sixth meeting of vaccine-preventable diseases ...during the globally synchronized switch from 17...
TRANSCRIPT
12–15 September 2016
Manila, Philippines
Meeting Report
SIXTH MEETING OF VACCINE-PREVENTABLE DISEASES LABORATORY NETWORKS IN THE
WESTERN PACIFIC REGION
Sixth Meeting of Vaccine-Preventable Diseases Laboratory Networks in the Western Pacific RegionPolio Session
12–13 September 2016Manila, Philippines
Sixth Meeting of Vaccine-Preventable Diseases Laboratory Networks in the Western Pacific RegionMeasles and Rubella Session
14–15 September 2016Manila, Philippines
RS/2016/GE/30(PHL) English only
REPORT
SIXTH MEETING OF VACCINE-PREVENTABLE DISEASES
LABORATORY NETWORKS IN THE WESTERN PACIFIC REGION
Convened by:
WORLD HEALTH ORGANIZATION
REGIONAL OFFICE FOR THE WESTERN PACIFIC
Manila, Philippines
12–15 September 2016
Not for sale
Printed and distributed by:
World Health Organization
Regional Office for the Western Pacific
Manila, Philippines
December 2016
2
NOTE
The views expressed in this report are those of the participants of the Sixth Meeting of
Vaccine-Preventable Diseases Laboratory Networks in the Western Pacific Region and do not
necessarily reflect the policies of the conveners.
This report has been prepared by the World Health Organization Regional Office for the Western
Pacific for Member States in the Region and for those who participated in the Sixth Meeting of
Vaccine-Preventable Diseases Laboratory Networks in the Western Pacific Region in Manila,
Philippines from 12 to 15 September 2016.
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CONTENTS
ABBREVIATIONS ................................................................................................................................ 5
SUMMARY ............................................................................................................................................ 7
1. INTRODUCTION .............................................................................................................................. 7
1.1 Meeting organization ................................................................................................................................ 7
1.2 Meeting objectives .................................................................................................................................... 7
2. PROCEEDINGS ................................................................................................................................. 8
2.1 Polio LabNet .............................................................................................................................................. 8
2.1.1 Polio endgame strategy and regional update on the polio eradication initiative and next
steps ..................................................................................................................................................... 8
2.1.2 Update of global wild poliovirus transmission and status of polio laboratory network .......... 8
2.1.3 Regional updates of Polio laboratory network in the Western Pacific Region-expansion of
ITD laboratories and environmental surveillance (ES) update ................................................... 9
2.1.4 Methodologies for VDPV detection, characterization and virologic classification ................. 9
2.1.5 Country reports ................................................................................................................................. 11
2.1.6 Follow-up on recommendations from the 2015 regional polio laboratory network meeting 16
2.1.7 Report on 2015 virus isolation PT and an update on 2016 virus isolation PT ........................ 17
2.1.8 Report on 2015 ITD PT and report/update on 2015 sequencing PT ........................................ 17
2.1.9 Global and regional update on implementation of GAPIII ........................................................ 17
2.1.10 Review of new ITD algorithm post-switch work in PI, PII, PIIS, PEF and non-PEF referral
of samples post-switch and work in line with GAPIII ............................................................... 18
2.1.11 Review of CDC rRT-PCR assays ver. 4.1 and 5.0 for ITD and VDPV screening ............... 18
2.1.12 Experience and challenges in rolling out new ITD version 4.0 and 4.1 assay ..................... 18
2.1.13 How to implement Annex 6, compliance and understanding for polio laboratories ............ 18
2.1.14 Global perspective on Environmental surveillance .................................................................. 19
2.1.15 GPLN management system (GPLNMS) .................................................................................... 22
2.1.16 Data management and reporting .................................................................................................. 23
2.1.16 Quality assurance and quality control ......................................................................................... 23
2.2 Measles and Rubella LabNet ................................................................................................................. 24
2.2.1 Global and regional updates on measles and rubella elimination ............................................. 24
2.2.2 Global measles and rubella LabNet .............................................................................................. 25
2.2.3 Progress of regional measles and rubella laboratory network ................................................... 25
2.2.4 Global specialized laboratories (GSLs) and regional reference laboratories .......................... 29
2.2.5 Molecular Epidemiology overview and lessons learned ............................................................ 29
2.2.6 Country presentations ...................................................................................................................... 30
2.2.7 Strengthening rubella and congenital rubella syndrome (CRS) surveillance .......................... 34
2.2.8 Measles and rubella recommendations from the Fifth Meeting on VPD LabNet in the
Western Pacific Region .................................................................................................................. 36
2.2.9 Update on quality assurance for molecular proficiency testing ................................................ 37
2.2.10 Measles and rubella IgM Proficiency Test and confirmatory testing ..................................... 37
2.2.11 China LabNet confirmatory testing and EQA for provincial laboratories ............................. 38
2.2.12 Data management and reporting .................................................................................................. 39
3. CONCLUSIONS AND RECOMMENDATIONS ........................................................................... 40
3.1 Conclusions .............................................................................................................................................. 40
3.1.1 Polio ................................................................................................................................................... 40
3.1.2 Measles and Rubella ........................................................................................................................ 41
3.2 Recommendations ................................................................................................................................... 43
3.2.1 Polio ................................................................................................................................................... 43
3.2.2 Measles and rubella ......................................................................................................................... 45
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ANNEXES:
Annex 1. List of participants
Annex 2. Timetable
Keywords:
Laboratories – organization and administration / Measles / Poliomyelitis / Rubella / Vaccines
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ABBREVIATIONS
AFP acute flaccid paralysis
aVDPV ambiguous vaccine-derived poliovirus
bOPV bivalent oral polio vaccine
CV Coxsackie virus
cVDPV circulating vaccine-derived poliovirus
CRS congenital rubella syndrome
DBS dried blood spot
ECHO enteric cytopathic human orphan
EOC Emergency Operating Centre
EV enterovirus
ELISA enzyme-linked immunosorbent assay
EPI Expanded Programme on Immunization
EQA external quality assessment
ES environmental surveillance
ESR Institute of Environmental Science Research
FTA fast technology analysis
GAPIII Global Action Plan to minimize poliovirus facility-associated risk after
type-specific eradication of wild polioviruses and sequential cessation
of OPV use
GCC Global Commission for the Certification of Poliomyelitis Eradication
GPEI Global Polio Eradication Initiative
GPLN Global Polio Laboratory Network
GPLNMS Global Polio Laboratory Network Management System
GSL global specialized laboratory
HFMD hand, foot and mouth disease
IgG immunoglobulin G
IgM immunoglobulin M
IHR International Health Regulations
IPV inactivated poliovirus vaccine
ISO International Organization for Standardization
ITD intratypic differentiation
iVDPV immunodeficiency-related vaccine-derived poliovirus
JICA Japan International Cooperation Agency
LabNet laboratory network
LBS laboratory strengthening and biorisk management
L20B a mouse cell line (L-cells), genetically engineered to express the
human poliovirus receptor
LQC laboratory quality control
MCV measles-containing vaccine
MeaNS Measles Nucleotide Surveillance
mEQA molecular External Quality Assessment
MMR measles, mumps and rubella
MRSRS Measles and Rubella Surveillance Reporting System
NEW Next Generation and Extended Sequencing Working Group
NIBSC National Institute for Biological Standards and Control
NIHE National Institute of Hygiene and Epidemiology
NIID National Institute of Infectious Diseases
NML national measles laboratory
NMRL national measles and rubella laboratory
NPEV non-polio enterovirus
NPL national polio laboratory
OPV oral polio vaccine
PAEDS Paediatric Active Enhanced Disease Surveillance
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PASRS Polio AFP Surveillance and Reporting System
PCR polymerase chain reaction
PHLC Public Health Laboratory Centre
POLIS Polio Information System
PT proficiency test
PV poliovirus
RCV rubella containing vaccine
RD human rhabdomyosarcoma
RT-PCR reverse transcription polymerase chain reaction
RITM Research Institute for Tropical Medicine
RIVM National Institute for Public Health and the Environment
RLC regional laboratory coordinator
RRL regional reference laboratory
RVC Regional Verification Commission for Measles Elimination
RubeNS Rubella Nucleotide Surveillance
SAGE Strategic Advisory Group of Experts
SL Sabin-like
tOPV trivalent oral polio vaccine
UNICEF United Nations Children's Fund
US CDC United States Centers for Disease Control and Prevention
VDPV vaccine-derived poliovirus
VIDRL Victorian Infectious Diseases Reference Laboratory
VP1 viral capsid protein
VPD vaccine-preventable disease
WHO World Health Organization
WPV wild poliovirus
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SUMMARY
The Sixth Meeting on Vaccine-Preventable Diseases Laboratory Networks in the Western Pacific
Region was held in Manila, Philippines from 12 to 15 September 2016 to review the performance and
identify the challenges of the poliomyelitis (polio) and measles and rubella network laboratories in the
Region. The meeting reviewed ways to further strengthen the performance of network laboratories
and followed up on recommendations from the fifth vaccine-preventable diseases (VPD) laboratory
networks meeting in May 2015. The meeting also provided an opportunity to discuss ways to improve
the quality and timeliness of laboratory testing in countries experiencing large measles outbreaks and
the importance of improving molecular surveillance for measles and rubella. The implications of the
switch to bivalent oral polio vaccine (OPV) and of the containment of poliovirus type 2 (PV2) on the
laboratory networks were deliberated. This meeting was funded by Korea Centers for Disease Control
and Prevention.
1. INTRODUCTION
1.1 Meeting organization
Seventy participants from network laboratories, advisers, observers and WHO staff attended the
meeting, including 44 representatives from 16 countries (12 polio network laboratories and
18 measles and rubella network laboratories). The list of participants is available at Annex 1.
The meeting was organized in two sessions over four days to cover poliomyelitis (12–13 September)
and measles and rubella (14–15 September). The meeting programme is available at Annex 2.
1.2 Meeting objectives
The objectives of the meeting were:
1) to discuss and review the performance and the implementation status of the requirements of the
polio network laboratories;
2) to identify challenges and define the way forward for the expanding roles of the polio network
laboratories in the implementation of the WHO Global Action Plan to minimize poliovirus
facility-associated risk after type-specific eradication of wild polioviruses and sequential
cessation of OPV use (GAPIII) and Polio Eradication and Endgame Strategic Plan 2013–2018;
3) to review the progress and identify the challenges of the measles and rubella network laboratories
to support initiatives on measles and rubella; and
4) to develop plans to strengthen molecular detection capacity and data reporting and to ensure the
quality of performance of network laboratories.
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2. PROCEEDINGS
2.1 Polio laboratory network
2.1.1 Polio endgame strategy and regional update on the polio eradication initiative and next
steps
The World Health Organization (WHO) Western Pacific Region was the second of the six WHO
regions to be certified as polio free in October 2000. The last indigenous case was reported from
Cambodia in 1997. Since certification, the Western Pacific Region has had several imported cases of
both wild poliovirus (WPV) and circulating vaccine-derived poliovirus (cVDPV), but transmission
was halted each time and polio-free status was retained. The last imported WPV case was detected in
China in 2011, and the last cVDPV was detected in the Lao People’s Democratic Republic in January
2016.
Polio risk assessments at national level were carried out in 2015. While most countries were classified
as low risk, China, Cambodia and the Lao People's Democratic Republic were classified as medium
risk, and Papua New Guinea and the Philippines as high risk. The non-polio acute flaccid paralysis
(AFP) rate in the Region from 2014 to 2016 (week 36) reached or exceeded the minimum requirement
of 1 case per 100 000 children under 15 years of age for all countries with the exception of
Papua New Guinea, while adequate stool specimen collection rates of ≥80% were achieved by 10 of
16 (62.5%) countries and areas. Objective 2 of the polio endgame plan recommends introduction of at
least one dose of inactivated poliovirus vaccine (IPV) into the routine immunization along with
withdrawal of the type 2 component of OPV. Seventeen Member States in the Region were using an
all-OPV schedule in 2015 and planned to switch to bivalent oral polio vaccine (bOPV) and introduce
at least one dose of IPV. Fifteen of the 17 Member States have since introduced at least one dose of
IPV into their routine immunization schedule. Mongolia and Viet Nam delayed introduction to the last
quarter of 2017 due to IPV global supply constraints. Sixteen of 16 Member States in the Region
using any OPV in 2016 successfully switched from trivalent oral polio vaccine (tOPV) to bOPV
during the globally synchronized switch from 17 April to 1 May 2016.
2.1.2 Update on global WPV transmission and status of Global Polio Laboratory Network
During 2014, WPV cases were identified in Pakistan, Afghanistan and Nigeria, and outbreaks
occurred following importation into previously polio-free countries in Central Africa (Equatorial
Guinea and Cameroon), the Horn of Africa (Somalia and Ethiopia), and the Middle East (Iraq and
Syria). In 2015, wild poliovirus type 1 (WPV1) was found only in Afghanistan and Pakistan; it was
the first year that WPV was not seen in the African Region. After more than 2 years without WPV in
Nigeria, the Government reported that three WPV1 cases had been detected in the northern
Borno State. Genetic sequencing of the three WPV1 cases suggested that the new cases were most
closely linked to a WPV strain last detected in Borno State in 2011. In 2016, 52 WPV1 cases were
identified; 15 (28%) were detected in Afghanistan, three (5%) in Nigeria and 34 (65%) in Pakistan.
During the previous 12 months, a total of 18 cVPDV cases from outbreaks were reported from three
countries: Guinea (n=6), the Lao People’s Democratic Republic (n=11), and Myanmar (n=1). Sabin
type 2 poliovirus from sewage specimens was also reported in Afghanistan, Kenya, Nigeria and
Pakistan. Though 36 countries with 105 sites reported environmental surveillance data, data collection
and management needs to be improved.
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The Global Polio Laboratory Network (GPLN), with 98 (67%) intratypic differentiation (ITD)
laboratories and 24 (16%) sequencing laboratories, continues to perform at a very high level. Once a
year, each laboratory is required to submit an annual report via the GPLN platform. In 2015, 112 out
of 146 laboratories (76.7%) completed the report, and 10 laboratories in the Western Pacific Region
did not complete the report. It is planned that the Global Polio Laboratory Network Management
System (GPLNMS) will be linked with the Polio Information System (POLIS). Global Action Plan
(GAPIII) introduction was implemented and monitored by enhancing biosafety and biosecurity
through biorisk training programmes since 2015. Operational Guidance for Polio Diagnosis post
OPV2 withdrawal was provided to the GPLN. Steps are under way to provide clear operational
guidance to all laboratories with GAPIII requirements, strengthen quality assurance and direct support
to all laboratories, and improve communication with the programme. Current threats to GPLN
performance include: workload of regional laboratory coordinators (RLCs), complacency,
uncoordinated requests/demands from the Global Polio Eradication Initiative (GPEI) or national
authorities, and communication with the programme.
2.1.3 Update on polio laboratory network in the Western Pacific Region: expansion of ITD
laboratories and environmental surveillance update
The Western Pacific Region's polio laboratory network consists of 43 laboratories, 38 of which
perform ITD. Four laboratories are performing environmental surveillance (Australia, China, Japan
and Malaysia), and all four are also performing enterovirus surveillance, including hand, foot and
mouth disease (HFMD) and AFP. The Philippines will introduce environmental surveillance soon.
From October 2015 to date, a total of 11 confirmed cVDPV1 cases have been reported from an
outbreak in the Lao People’s Democratic Republic. In China, cVDPV was last detected in 2012.
Small numbers of ambiguous vaccine-derived poliovirus (aVDPV) cases and immunodeficiency-
related vaccine-derived poliovirus (iVDPV) cases were detected in China each year from 2012 to
2015, and an aVDPV was found in the Philippines in December 2014, the first since 2001. The
Strategic Advisory Group of Experts (SAGE) on immunization noted that a small number of cVDPV2
outbreaks are expected within 12 months after the switch; hence, all polio laboratories are requested
to comprehensively and timely report all PV2 from all sources after the switch, 24 hours after
completing the ITD and sequencing, starting on 1 May 2016.
Laboratories in the polio laboratory network continue to perform well. All of the laboratories passed
the virus isolation proficiency test (PT). Two laboratories experienced challenges with the 2015 ITD
PT, while two others experienced challenges with the 2015 sequencing PT. The laboratories are
currently addressing the issues identified. Three rounds (two in China and one in Manila) of
ITD/VDPV training were completed, and an optimized ITD version 4.1 assay and updated algorithm
to accelerate the detecting all type 2 were introduced in 2016. Four provincial polio laboratories in
China will be accredited for ITD capacity as they have completed the ITD implementation and passed
the PT. WHO will conduct annual accreditation through on-site review or desk review/by
correspondence.
2.1.4 Methodologies for VDPV detection, characterization and virological classification
In October 2015, SAGE decided to move ahead with the tOPV–bOPV switch. The key precondition
was absence of persistent cVDPV2. The switch occurred in April 2016. The new VDPV guidelines
were to clarify and standardize definitions, roles and responsibilities, particularly at regional and
country levels, and to reduce delays in obtaining final classification for VDPVs. The definitions for
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VDPV, cVDPV, iVDPV and aVDPV were developed, taking into account both virological and
epidemiological considerations. A VDPV isolate should only be classified as 'ambiguous' once
additional investigations have excluded that it is derived from an iVDPV or part of an ongoing chain
of transmission, i.e. a cVDPV. A VDPV classified as 'ambiguous' may need to be reclassified as 'c' or
'i' if there is subsequent evidence of circulation or of derivation from an immunodeficient individual.
To improve global surveillance for VDPVs, the WHO regional office polio teams should submit to
WHO headquarters a weekly line listing of all VDPV isolates reported from GPLN sequencing
laboratories. This weekly reporting of VDPVs will be similar to the weekly reporting of WPV
isolates, and should include all VDPV isolates regardless of source (AFP cases, healthy child, and
environmental samples) and current classification status. Standardized format/variables should be
used for the weekly reports. More complete and timely VDPV surveillance data will allow timely
detection of and response to cVDPV outbreaks. The WHO headquarters polio team will include
detailed and timely VDPV data and information in reports and weekly updates provided to the GPEI
and to the public. A standardized reporting template should be used.
The GPLN uses standardized laboratory algorithms to screen poliovirus isolates obtained from any
source for possible VDPV status. All isolates that are non-vaccine-like or discordant in ITD tests are
referred to a WHO-accredited polio sequencing laboratory for genetic sequencing. The only way to
confirm VDPV status is through sequencing of the viral capsid protein (VP1) region of the poliovirus
genome. VDPV reporting from sequencing laboratories needs to be harmonized by adopting standard
language for emails accompanying the reports. The approach to establish VDPV emergence groups
and nomenclature should also be harmonized. Reports should include a VDPV on trees and/or maps.
By 1 August 2016, all type 2 isolates must be referred for sequencing. Standard operating procedures
describe the post-switch response to all types and type 2 poliovirus events and outbreaks.
VDPV circulation in the Lao People’s Democratic Republic
The Lao People’s Democratic Republic has maintained its polio-free status for nearly 15 years. The
last polio case due to WPV1 was identified in 1996. According to the national polio endgame plan,
IPV was introduced in October 2015, and the switch from tOPV to bOPV was performed in
April 2016 to minimize the risk for an outbreak of VDPV2. In October 2015, a type 1 poliovirus was
isolated at National Institute of Infectious Diseases (NIID) from a child who had AFP onset on
7 September 2015 in Bolikhamxay Province. The isolate was identified as a type 1 VDPV (VDPV1)
with 30 nucleotide differences from the parental Sabin 1 strain (3.3% nucleotide diversity) by VP1
sequencing. Under intensified surveillance activities, a growing number of cVDPV1 isolates were
identified from AFP cases and contacts in three geographically distinct areas in the
Lao People’s Democratic Republic. Eleven confirmed cVDPV1 cases (two patients died) were aged
between 8 months and 44 years (average: 15 years). They had generally inadequate OPV
immunization histories, suggesting immunity gaps even in adults in the affected areas/communities.
Phylogenetic analysis based on the VP1 sequences of 38 cVDPV1 isolates from the AFP cases and
contacts revealed seven distinct genetic clusters with considerable genetic diversity among the
cVDPV1 isolates. Recombination with non-polio enteroviruses (species C) or Sabin 2/Sabin 3 strains
has not been identified for cVDPV1. The date of onset of the last case of laboratory-confirmed
cVDPV1 was 11 January 2016; thereafter, cVDPV1 has not been detected from any AFP case. These
results highlight the remaining risk for polio outbreaks due to VDPVs in areas/communities with low
immunization coverage with OPV or IPV including the current setting following the switch from
trivalent to bivalent OPV.
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VDPV surveillance in China
Three VDPV cases were detected in China in 2015. The first case was iVDPV type 2 from
Guangdong, the second case was aVDPV type 2 (aVDPV2) from Liaoning, and the third case was
aVDPV type 1 (aVDPV1) from Zhejiang. All of the VDPV isolates detected in China were very
young isolates. The polio immunization strategy in China was effective in preventing sustained
transmission of VDPVs. No VDPV was isolated from January to August 2016.
2.1.5 Country reports
Australia
AFP cases in Australia are ascertained via: (1) a monthly report card submitted by clinicians to the
Australian Paediatric Surveillance Unit, and (2) nurses screening case admission codes as part of the
Paediatric Active Enhanced Disease Surveillance (PAEDS) system based in tertiary paediatric
hospitals in five of the six state capital cities. Using these two systems, Australia has reached the
WHO non-polio AFP rate for the last eight consecutive years. Gaps in AFP surveillance have been
identified at the subnational level, and Australia has never met the WHO surveillance criterion for
adequate stool collection from AFP cases. However, at least one stool per case was collected from
more than 70% of cases in 2015–2016. EV-A71 sub-genogroups B5 and C2 were isolated from AFP
cases in 2015–2016. A single detection of EV-D68, which shares a common ancestor by phylogenetic
analysis with the United States of America outbreak in 2013–2014, was reported from an AFP case in
early 2016.
The master cell bank has 83 ampoules of RD-A at passage 226 and 99 ampoules of L20B (53 at
passage 17 and 46 at passage 18). Mycoplasma was not detected in the master cell bank or routine
passages using the VenorGeM PCR-based mycoplasma detection kit, but difficulty with the kit’s
internal control was experienced in 2015. The laboratory scored 100% for the most recent virus
isolation, ITD and sequencing PTs in 2015–2016. The laboratory was designated as a poliovirus-
essential facility by the Australian Government in 2015 and has contained wild and Sabin poliovirus
type 2.
China
The Chinese Center for Disease Control and Prevention (China CDC) received 179 and 82 poliovirus
strains sent by provincial laboratories in 2015 and 2016, respectively. In 2015, there were two
aVDPV1 strains isolated in Zhejiang Province, two aVDPV2 strains isolated in Liaoning Province,
and five iVDPV isolated in Guangdong Province. In 2016, there was no VDPV isolated until August.
As part of the WHO quality assurance programme, the regional reference laboratory (RRL) in China
CDC and all 31 provincial polio laboratories received the virus isolation PT from the National Institute
for Public Health and the Environment (RIVM)/WHO and the ITD PT from the United States Centers
for Disease Control and Prevention (US CDC)/WHO. They all passed both PTs. The national polio
laboratory (NPL) at China CDC passed the sequencing PT that was provided by US CDC/WHO. In
June 2016, six provincial polio laboratories – Hainan, Chongqing, Tianjin, Jiangsu, Jilin and Inner
Mongolia – passed the on-site review. Hainan provincial laboratory received and passed only the virus
isolation accreditation, while the other five laboratories received and passed the virus isolation and
ITD accreditation with very high scores. China’s polio laboratory network was performing good
quality control on cell sensitivity testing and mycoplasma testing. Some training courses and
workshops were held in 2015 and 2016. These included a real-time training course on the new
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algorithm for virus isolation and ITD, a laboratory network workshop, a training course on
environmental surveillance technology (two-phase separation for sewage concentration and ITD 4.0
were tested in this training course), a hands-on training course of ITD 4.0 kits, and a workshop on
environmental surveillance in 2016.
China’s polio laboratory network tests more than 10 000 stools from 5000 AFP cases annually with an
adequacy rate of more than 90% every year since 2000. Though the number of polioviruses isolated
per year has gradually declined since 2002, the non-polio enterovirus (NPEV) rate is constant at
around 10% every year. The new real-time PCR for ITD and VDPV screening was introduced in
January 2013 with 23 provincial laboratories performing reverse transcription polymerase chain
reaction (RT-PCR). All passed the ITD and VDPV PT for 2014. The other eight provincial
laboratories (except Tibet) have now finished the two quality assurance steps and will complete ITD
in their own laboratories shortly. Capacity of the laboratory network is maintained through regular
training. Training in September 2014 focused on use of the new algorithm to improve reporting
timeliness to 14 days in 2015. Accreditation review of six to eight laboratories is carried out each year
by a team of international experts, and all provincial and national laboratories are currently fully
accredited. Nine provinces carry out environmental surveillance and two more will start shortly.
Hong Kong SAR (China)
All the indicators for AFP surveillance in Hong Kong SAR (China) met the targets from 2014 to 2016
(up to August). Eighteen AFP cases were detected in 2015 and the first eight months of 2016. No
poliovirus or NPEV was isolated in the 52 stools specimens received from AFP cases. One Sabin-like
type 3 poliovirus was detected from a non-AFP stool specimen in 2016.
The Public Health Laboratory Centre (PHLC), the NPL in Hong Kong SAR (China), obtained perfect
scores in virus isolation, ITD and sequencing PTs from 2013 to 2015. Quality assurance is also
indicated by the valid results in cell sensitivity testing and absence of mycoplasma in L20B and RD
cells.
With the introduction of IPV in 2007, the latest serosurvey conducted in 2010 showed that over 95%
of the subjects had antibody to all three types of poliovirus among children aged 1–10 years. PHLC is
evaluating a Luminex assay to replace the neutralization test for serosurvey to determine population
immunity.
In March 2015, the Department of Health conducted an inventory of facilities holding polioviruses.
An action plan was formulated in the event of detection of any WPV importation or cVDPV. A
contingency plan for prevention and control of poliovirus infection was also formulated.
Japan
An apparent decline in routine immunization coverage with tOPV was identified during the OPV–IPV
transition period in 2011–2012. However, according to several different surveys, routine IPV
immunization coverage was sufficiently high, and some unimmunized children in 2011–2012 were
immunized with standalone cIPV or DTP-IPV after the introduction of IPV since September 2012,
filling the immunity gap in Japan. The laboratory of enteroviruses at NIID is functioning as the NPL
for Cambodia, the Lao People's Democratic Republic and Japan, as the WHO RRL for Mongolia, the
Republic of Korea and Viet Nam, and as the global specialized laboratory (GSL) for the Western
Pacific Region. The GSL at NIID has been fully accredited since 2014. The laboratory scored 100%
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on the most recent poliovirus isolation PT, and the cell sensitivity of L20B and RD cells is
appropriately maintained and monitored. For ITD of poliovirus isolates, real-time RT-PCR assays
were implemented in 2010, and the score on the most recent ITD PT in 2015 was 95%. The score on
the sequencing PT in 2015 was 100%. A type 1 VDPV isolate was identified at NIID from an AFP
case in the Lao People's Democratic Republic in October 2015. A growing number of genetically
related type 1 VDPVs were isolated from AFP and contact samples at NIID in 2015–2016.
In December 2014, GAPIII was published, and accordingly, poliovirus containment and biorisk
management activities in Japan have to be re-established and encouraged, particularly for PV2
infectious materials. The previous national inventory of facilities with poliovirus materials in Japan
was reviewed and revised to identify GAPIII-based poliovirus-essential facilities. NIID (Murayama
branch) will be one of the poliovirus-essential facilities in Japan for laboratory diagnosis,
seroprevalence study, quality control of the IPV products, and reference activities.
Malaysia
AFP surveillance is part of the activities carried out by the NPL. Based on an incidence rate of 1 per
100 000 of population under the age of 15 years, it is estimated to be about 95–96 cases per year. The
laboratory reported 165 cases in 2014, 148 in 2015, and 101 in 2016 (up to 10 August). Also in 2015,
at least 90% of cases referred to the laboratory had adequate samples due to active and continuous
engagement of laboratory personnel from the peripheral hospitals. Currently, IPV coverage among the
target groups is almost 100%. The vaccine schedules are at 2, 3 and 5 months of age and a booster at
7 years of age. Overall, there were more non-AFP cases than AFP cases in 2014–2016. In addition,
there were more NPEVs isolated from AFP and HFMD cases in 2014–2016. For 2016, the NPEVs
identified among AFP cases included E5, E6 and E16. For HFMD, they were mostly CAV16, EV71
and E2, and for EV cases, CVA16 was the common NPEV. No polioviruses were isolated in 2012–
2016.
Cell sensitivity testing was conducted using two cells, L20B and RD, for all three polio viruses. It was
done two to three times on a yearly basis, and results were within the acceptable limits. This assay
was stopped for poliovirus type 2 in April 2016. Mycoplasma testing was also carried out routinely
for all cells according to ISO 15189 standards, and so far, there are no contaminations due to
mycoplasma. The laboratory achieved satisfactory results in the PT panels, but for the 2015 ITD and
VDPV PTs, the scores were below the passing rate. For those PTs, an older algorithm was used. Once
rectified, the laboratory scored 100% thereafter. Environmental surveillance was not carried out in
2015 due to logistical problems, but surveillance was started again in June 2016. Samples were
collected from two sites on a monthly basis, and results indicated the detection of NPEV for both June
and July samples. Results for August are in progress. Biosafety training for staff is an ongoing
process. The laboratory plans to participate in sequencing PT.
Mongolia
Almost one third of Mongolia’s population of 3 million is under 15 years of age. As of July 2016,
coverage with full doses of OPV vaccination was at 97.8%. The national Expanded Programme on
Immunization (EPI) team analyses data on AFP surveillance reported from all 330 soums of 21
provinces and the capital city. There were 11 reported cases of AFP for this reporting period. All AFP
cases were laboratory confirmed to be non-polio. The national preparedness plan (2016–2020) for
detection of and response to WPV is ongoing. For this reporting period, the laboratory’s NPEV rate
was 18.2%. No poliovirus was isolated from any of the AFP cases or from the healthy children stool
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samples. ITD laboratory set-up is close to completion. The laboratory is planning to calibrate the RT-
PCR machine in September 2016.
Also, an inventory of laboratories handling human faeces was conducted; the inventory involved 140
laboratories from Mongolian provinces and Ulaanbaatar City. The inventory revealed that only the
NPL had samples containing poliovirus in Mongolia. All materials containing the Sabin 2 and
potential infectious materials, which were stored in the NPL, were disinfected. Moreover, Mongolia
finalized the national switch plan. The switch day was discussed and reviewed by the National
Immunization Technical Advisory Group (NITAG) in January 2015 and issued by Ministry of Health
in Mongolia. The nationwide switch took place on 27 April 2016. Mongolia is planning to introduce
IPV in 2017.
New Zealand
New Zealand’s population is 4.4 million. About 800 000 people are under 15 years of age. Eight to
nine AFP cases are expected each year. A national response plan for WPV importation was developed
in 2009. OPV was used from 1960 to 2001 and was replaced by IPV in 2002. Sabin virus was shown
to disappear very quickly over six months through enterovirus and environmental surveillance. Of the
three polioviruses that have been detected since then, two were associated with OPV vaccine directly
or through a contact and one had unknown origin. AFP case detection improved in 2013 (10 cases)
and 2016 (eight cases as of August); however, AFP detection was low in 2014 and 2015. Cell
sensitivity testing results are within acceptable range, indicating that the cell lines are viable and
sensitive. The use of PV2 in cell sensitivity testing was stopped following the global switch in May
2016.
NPEV rates have exceeded 10% for the past 4 years, and all laboratory performance indicators meet
the minimum requirements. Sequencing was established in 2014, and the laboratory scored 100% in
the sequencing PT.
The Philippines
The NPL of the Philippines reported the following performance indicators to be very low despite
efforts in the field: (1) NPEV rate remains below 10%, dropping from 9.9% in 2015 to 6.6% in
January–June 2016; (2) adequacy rate averaged 64% from 2015 to June 2016 due to collection of
stool specimens more than 14 days after onset; and (3) collection to receipt of samples remains at
around 60%. The laboratory was accredited for virus isolation and ITD this year, and it passed the
proficiency testing for virus isolation (100%) and ITD (95%). The turnaround time for reporting was
about 90% until mid-2016. Quality controls were also being monitored; the laboratory noted no
contamination of mycoplasma for either RD or L20B cell lines. Cell sensitivity testing indicated that
the laboratory is using viable and sensitive cell lines. The use of PV2 in cell sensitivity testing was
stopped following the global switch in May 2016.
Other laboratory activities include HFMD testing, planning for environmental surveillance and
laboratory containment. For HFMD, the laboratory has tested 2320 samples with Coxsackie virus
(CV) A6 as the prevalent etiologic agent since 2014. In 2015, the NPL began its planning for ES.
Start-up equipment, supplies and materials were made available through WHO funding. There are 19
possible sites for the pilot ES; however, due to limited funding, environmental surveillance will be
phased in and will start in five sites beginning 2017 on a monthly basis. For the laboratory
containment of poliovirus, the following activities were done in early 2016: (1) identification of a
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national coordinator; (2) declaration of the NPL as a non-essential facility; (3) funding secured for the
start-up activities; (4) finalized listing of facilities to be included in the survey; (5) creation and
amendment of circulars pertaining to polio including membership of the National Task Force for the
Laboratory Containment of Poliovirus, and Department of Health Memorandum No. 2006-0102
requiring all clinical and diagnostic facilities to complete and submit survey questionnaires online as a
licensing requirement and encouraging them to destroy/dispose properly all materials that are no
longer needed (https//labcontainmentsurvey.com); (6) destruction of all PV2 isolates on
29 January and 11 August 2016; and (7) attendance and conduct of several orientation programmes on
laboratory containment.
Several challenges remain for the implementation of environmental surveillance. For example, the
dedicated room is still under renovation, only one staff is person has been trained, and no budget has
been allocated from the national level; all funds come from WHO. The laboratory is continuously
submitting proposals to the Department of Health for funding. For containment, the new online survey
should be implemented as the Task Force is expecting participation of more than 6000 facilities
nationwide and other facilities that are not under the Department of Health.
Singapore
National preparedness for WPV importation includes established AFP surveillance, high poliomyelitis
vaccination coverage (>95%), and high standards of environmental hygiene and sanitation.
Notification to the Ministry of Health of all patients with diseases that could lead to AFP, whether or
not AFP is present, is required. The “at risk” diagnoses include: poliomyelitis, acute polyneuritis,
Guillain-Barré Syndrome, mononeuritis, monoplegia, transverse myelitis and all cases of AFP. Of the
451 samples processed from May 2015 to August 2016, 18 were AFP stool samples.
The laboratory has been performing routine RD and L20B cell sensitivity monitoring as required by
WHO. The results have been satisfactory. Cultures used in the laboratory are tested for mycoplasma
contamination immediately after purchase and after recovery from the freezer. In addition, cultures
are tested for mycoplasma contamination after 7–8 passages. No mycoplasma contamination was
noted since 2004. The 2015 PT results for virus isolation, ITD and sequencing were all 100%.
All PV2 materials were autoclaved on 22 July 2016 and collected by a licensed waste contractor on 29
July 2016 for incineration when the final result of the biological indicator was negative after seven
days of incubation.
Viet Nam (Hanoi)
From January 2011 to June 2016, routine immunization coverage for OPV ranged from 93% to 97%,
while campaign immunization coverage ranged from 97% to 98%. AFP surveillance index always
achieved more than 1/100 000 children under 15 years old. From January 2015 to August 2016, 344
AFP cases were detected; two stool specimens were collected from 341 AFP cases and one stool was
collected from three AFP cases. It was also noted that 92% of stool samples were collected within 14
days since onset, and that 25.7% and 76.6% of stool samples arrived in the laboratory within three
days and seven days, respectively. Results of virus isolation showed 10% and 13% of samples with
cytopathic effect on cell culture in 2015 and in 2016 (up to August), respectively.
Results of poliovirus identification by real-time RT-PCR of two AFP cases in 2015 revealed one SL
PV1 and one SL PV1 + PV2. Four AFP cases tested in 2016 detected one SL PV1 and three SL PV3.
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Virologic test results in all AFP samples were reported within 14 days of receipt, and ITD testing was
done in all L20B isolates and results reported within seven days of detection.
PT results for virus isolation in 2013, 2014 and 2015 were 95%, 95% and 100%, respectively. PT
results for ITD and VDPV screening using real-time RT-PCR in 2013, 2014 and 2015 were 97.5%, 90%
and 100%, respectively. Cell sensitivity testing results on L20B and RD cell lines were always within
the acceptable range. Mycoplasma was often tested in the middle of cell culture passages (7-8
passages) and the results were always negative. All PV2 isolates and PV2 strains that were used for
RD and L20B cell sensitivity testing were destroyed on Tuesday, 25 October 2015.
Viet Nam (Ho Chi Minh City)
The Laboratory of Enteroviruses, Pasteur Institute of Ho Chi Minh City, Viet Nam, has been a
member of the regional polio laboratory network in the Western Pacific Region since 1992. The
laboratory is ISO 15189 compliant and has been accredited since 2011. The laboratory is responsible
for detecting enteroviruses from AFP and HFMD surveillance in the southern half of Viet Nam. In
2015, the NPEV isolation rate was 10%, EV71 was 41% (7/17), and there was no L20B positive case.
However, in the 2016, there were two polio cases: one SL PV2 + PV3, and one SL PV3. All PV2
isolates were destroyed by the end of 2015.
Testing of specimens from severe and fatal HFMD cases in 2015 showed the presence of EV71 and
other enteroviruses (EVs) in 20% and 17% of specimens, respectively. In 2015, CVA6 made up 45%
of the other EVs; however, in 2016, CVA10 made up 50% of other EVs. With EV71 strains,
subgenotypes B5 (75%) and C4 (25%) were identified by sequencing for the VP1 region.
For quality assurance, cell sensitivity testing using the RD-A and L20B cell lines are being done on a
regular basis and still need to be evaluated. Sabin 2 reference strains from National Institute for
Biological Standards and Control (NIBSC) and laboratory quality control (LQC) were no longer used
for cell sensitivity testing in 2016. PT samples for virus isolation and ITD/VDPV were implemented
and reported; the score on both PTs was 100%. The laboratory met all criteria given by WHO for
accreditation.
2.1.6 Follow-up on recommendations from the 2015 regional polio laboratory network meeting
Twenty-two polio-specific recommendations were proposed at the regional VPD laboratory network
meeting in May 2015. Only 36% of the recommendations were completed. Of the partially
implemented recommendations (32%), most were 80–90% completed. Some laboratories had
challenges in meeting reporting timeliness. Only three countries were reporting non-AFP data in
2016. ITD version 4.0 has been distributed since 2015. ITD version 4.1, for which training was
conducted for all polio laboratories, is currently being used in the network. For all poliovirus-non-
essential laboratories: all NIBSC Sabin 2 reference strains used in cell sensitivity testing have been
discontinued and destroyed. Any sample with PV2 was destroyed. The 2015 annual report was
completed by 36 laboratories through GPLNMS. The Access database for data management was used
by most laboratories.
2.1.7 Report on 2015 virus isolation PT and an update on 2016 virus isolation PT
A review of the most recent virus isolation PT test was reported. Each annual PT panel consists of
10 stool samples with single or combination of polio and enteroviruses. Some samples may be
negative. Reporting is required within the standard 14 days, and laboratories must attain a score of
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90% to pass. Any laboratory that fails to pass must submit their worksheets for a full investigation to
identify deficiencies to resolve any problem; then, a new PT is provided. In 2015, all 43 polio
laboratories in the Region received the virus isolation PT panel. All laboratories in the Western
Pacific Region passed, with 42 scoring 100% and one scoring 95% (reduced L20B and RD sensitivity,
respectively, in PT samples 6 and 7). Three laboratories in three WHO regions failed the virus
isolation PT with a score of 80%. The laboratories have been informed of the 2016 virus isolation PT
to be distributed within the year.
2.1.8 Report on 2015 ITD PT and report/update on 2015 sequencing PT
The PT for polio molecular diagnostic methods assesses the proficiency of GPLN ITD laboratories in
RT-PCR, including interpretation and reporting. The PT is used to field-test the reliability and
durability of polio molecular reagents and helps to identify GPLN training needs. The minimum
passing score is 90% based on the WHO GPEI standards. The new scoring system is based on the
accuracy of the final result with deductions for technical issues and timeliness of reporting and will
heavily penalize failure to detect WPV and VDPV. In 2015, 38 laboratories in the Region received the
ITD PT that was assessed under the new scoring scheme; 36 laboratories passed and two failed with
scores of less than 90% (75% and 80%). For the 2015 sequencing PT, seven laboratories in the
Western Pacific Region participated and two failed with scores of less than 90%. One laboratory was
unable to amplify sample B, one laboratory had sequence editing issues, some failed sequencing
primers, and some had reporting issues. A mandatory but unscored evaluation using the Fast
Technology Analysis (FTA) card was also included in the sequencing PT; however, acquiring
materials needed for FTA card processing is a challenge. WHO headquarters provided the RNA
processing buffer components, glycogen and dithiothreitol (DTT). Twenty of 25 laboratories in GPLN
reported high-quality results and files for the FTA card. For the failed laboratories, extensive
troubleshooting and training has occurred and a repeat PT will be provided.
2.1.9 Global and regional update on implementation of GAPIII
Poliovirus containment is one of the five readiness criteria for the tOPV–bOPV switch and sequential
cessation of OPV use. Poliovirus containment activities, described in GAPIII and endorsed by the
World Health Assembly in May 2015, address the risk of release and transmission of poliovirus from
facilities. In 2015, the Global Commission for the Certification of Poliomyelitis Eradication (GCC)
concluded that wild poliovirus type 2 (WPV2) had been eradicated worldwide. Of current relevance
are: Phase I: Reduction in the number of facilities handling or storing PV2, involving identification of
facilities and destruction of unneeded PV2 materials, and designation of poliovirus-essential facilities
planning to retain PV2 for critical international functions; Phase II: appropriate containment of PV2 in
poliovirus-essential facilities and certification of containment. The global strategy for minimizing
poliovirus facility-associated risks consists of risk elimination by destroying poliovirus materials in all
but certified poliovirus-essential facilities and biorisk management of these facilities by strict
adherence to required safeguards. The Western Pacific Region was the first WHO region to submit all
reports for WPV2 and VDPV type 2 (VDPV2). Biorisk management trainings were held in May 2015
for regional polio laboratories and in February 2016 for the national polio containment coordinators,
national authority for containment, vaccine manufacturers and polio laboratories. Challenges observed
in the implementation of GAPIII included lack of coordination with non-polio laboratory networks in
early development of the plan (measles, influenza, rotavirus, etc.), time for completing
inventory/preparation is very short, and an issue whether full-length RNA is infectious or not.
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2.1.10 Review of new ITD algorithm post-switch work in referral of samples and work in line
with GAPIII
Progressive changes within the network, such as changes in diagnostic methods for all capacities
(viral isolation, ITD and sequencing), capacity-building to align polio diagnosis to programme needs,
and adjustments to changes in shipping regulations and courier’s requirements, are bringing the
network in line with the new containment requirements. The GAPIII requirements will have a
profound effect on all members of the GPLN; hence, clear guidance for each procedural step is
needed. The GLPN will implement a phased approach to tackle complex issues. Focus for
containment will be given to more than 90% of polio laboratories that will not be poliovirus-essential
facilities and will work under Annex 6 and on the diagnosis of poliovirus in potentially infectious
materials. Appropriate tools for the polio laboratories will be designed and disseminated. Issues faced
by the polio laboratories that intend to be poliovirus-essential laboratories and non-polio laboratories
will be addressed.
All laboratories in the Region should adopt the new algorithm for poliovirus isolation and choose one
of the following referral schemes: polio isolation laboratory, polio isolation and identification
laboratory, and polio isolation identification and sequencing laboratory. The scheme for biological
materials handling and referral depends on the polio laboratory’s capacity and whether the polio
laboratory is a poliovirus-essential facility or non-essential facility. This new algorithm will require
development of new standard operating procedures, worksheets and reporting forms. A
comprehensive biorisk management system should be implemented to mitigate the likelihood and
consequences of unintentional release of poliovirus into the environment.
2.1.11 Review of US CDC real-time RT-PCR assays for ITD and VDPV screening
Protocols for ITD real-time RT-PCR are continuously being updated. There is a constant demand for
improved sensitivity and specificity to rapidly identify viruses for sequencing and to allow direct
screening during outbreaks. In 2014–2015, US CDC stopped making ITD version 3.0 and introduced
ITD version 4.0, which is more sensitive, cost-effective and the master mix is commercially available.
In 2016, US CDC launched a further revision, ITD version 4.1, which includes adjustments to the
WPV probes and primers used with new reaction conditions and instructions. ITD version 5.0 has
been developed and will include an assay to detect PV2 after the switch to bOPV. Additional ITD 4.1
and ITD 5.0 kits are available upon request. The WHO Regional Office for the Western Pacific will
work with laboratories to prepare a distribution plan of the kits and will send a request to US CDC.
2.1.12 Experience and challenges in rolling out new ITD version 4.0 and 4.1 assay
In China, 27 provincial laboratories (not including Tibet, Qinghai, Liaoning and Hainan) have been
accredited as ITD laboratories and performed ITD assay as routine work in 2016. The virus data from
2014–2016 were analysed. There were one type 1, 49 type 2 and 11 type 3 indicated as VDPV by ITD
assay, but only nine type 2 indicated as VDPV were confirmed by sequencing assay. The results of
the sequencing and ITD assays were cross-analysed. There were two type 1 VDPV, 11 type 2 VDPV
and two type 3 VDPV; respectively, the SL results of the ITD assay were two type 1, two type 2 and
two type 3. There are much more space for improvement of the target design.
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2.1.13 How to implement Annex 6, compliance and understanding for polio laboratories
Annex 6 of the GAPIII relates to biorisk management standards for safe handling of new samples
potentially containing poliovirus material in poliovirus-non-essential facilities. A facility-associated
poliovirus infection or release into the environment during the polio endgame strategy period and
following eradication and cessation of OPV use would be a public health event of international
proportions. The GAPIII addresses that risk by establishing a post-eradication/post-OPV cessation
goal of not retaining poliovirus in poliovirus-non-essential facilities worldwide. Introduction of
biorisk management training within the GPLN increased interest/demand for emerging and re-
emerging infectious diseases as many institutions hosting a GPLN laboratory lack a structured
biosafety and biosecurity programme. A GPLN biosafety campaign raises awareness of biosafety and
biosecurity issues in the GPLN. An extended training programme for GPLN laboratories is organized
in order to debate and address biorisk issues, stimulate discussion on the risks associated with the
work, and encourage the exchange of ideas and feedback on relevant biorisk issues. During the first
phase of biosafety training, six video modules in four languages were produced and successfully used
to train polio laboratory staff in five WHO regions. The second phase adopted new concepts towards
implementation of a comprehensive biorisk management programme in GPLN laboratories. The
WHO Biorisk Management Advanced Trainer Programme (BRM-ATP), which has been held in
collaboration with WHO/LBS/IHR since 2011, is based and designed on theories and principles of
adult learning styles and techniques. Full training in all regions was completed during the second
quarter of 2015. Biosafety and biosecurity practices were also emphasized during on-site visits to the
laboratories. However, implementation within laboratories depends on institutional support and/or
commitment and availability of adequate tools.
For the third phase, all six WHO regions have already implemented BRM/GAPIII training in 2015
and 2016. However, compliance with GAPIII annexes (including Annex 6) will be a long journey.
2.1.14 Global perspective on environmental surveillance
Environmental surveillance, which is used to supplement AFP surveillance, increases the sensitivity
of the surveillance system, especially in areas where AFP surveillance is under-performing.
Polioviruses can be detected by a variety of laboratory methods after sewage concentration.
Environmental surveillance will be geographically expanded to help identify any residual
transmission in poliovirus-endemic areas, to provide early indication of new importations into
recurrently re-infected areas, and to ensure early detection of any new emergence of VDPV and
document the elimination of Sabin viruses following the tOPV–bOPV switch and eventual cessation
of tOPV use.
The priorities for expanding environmental surveillance are based on risk of emergence and
circulation of WPV and VDPV in four tiers of countries. Tier 1 includes WPV-endemic countries or
countries that have reported cVDPV2 since 2000;Tier 2 includes those that have reported
cVDPV1/cVDPV3 since 2000 OR large and medium-sized countries with DTP3 coverage less than
80% in 2009, 2010 and 2011, as per WHO/UNICEF Estimates of National Immunization Coverage
(WUNIC); Tier 3 includes large and medium-sized countries adjacent to Tier 1 countries that reported
WPV since 2003 OR countries that have experienced a WPV importation since 2011; and Tier 4
includes all other OPV-only countries. Of 17 Tier 1 countries, 11 countries are performing
environmental surveillance, two countries are starting environmental surveillance, and four countries
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plan to do it. Only two Tier 2 countries, Azerbaijan and Indonesia, are performing environmental
surveillance; however, environmental surveillance implementation is planned in most of the countries.
During the phase 2 expansion (2016–2018), environmental surveillance will be extended to the
remaining Tier 1 countries (Ethiopia, South Sudan, Somalia and Yemen), to priority countries holding
type 2 viruses (Iran, South Africa, Mexico and Viet Nam), and to sites chosen according to regional
priorities and “freelance” countries. A series of training activities were conducted in 2015 to build
laboratory capacity to support expansion of environmental surveillance. Environmental surveillance
technologies/methodologies were also improved. In the Western Pacific Region, Australia, China,
Japan and Malaysia are already implementing environmental surveillance, and expansion to the
Philippines and Viet Nam is being planned. Some of the hurdles in implementing environmental
surveillance are lengthy administrative and implementation processes, aligning GPEI partners’
visions, poor implications of surveillance personnel, and need for more (real-time) analytics. In the
pipeline are finalization of quality assurance procedures (including accreditation checklist for
environmental surveillance laboratory, proficiency testing for environmental surveillance, data
dictionary harmonization) and improving the quality of environmental surveillance sites and
sampling.
Environmental and enterovirus surveillance in Australia
Australia introduced enterovirus and environmental surveillance as a means of addressing the gaps in
AFP surveillance. Environmental surveillance was initially performed at four sites in regional
New South Wales between 2010 and 2012, with population catchments ranging from 10 000 to
180 000. No poliovirus was detected, and 81% (29/36) of the samples were positive for NPEVs. In
2014–2015, the site of collection was moved to metropolitan Melbourne with a population catchment
of 1.5 million. Two Sabin-like (SL) polioviruses were isolated in February–March 2015 (one SL PV1
and one SL PV1 + PV2. Four AFP cases tested in 2016 detected one SL PV1 and three SL PV3) and
97% (31/32) of the samples were positive for NPEVs. The WHO two-phase separation protocol was
used, but a bottle broke while mixing the sewage with PEG/dextran/NaCl in 2015. Plastic-coated
bottles for reagent mixing and plastic funnels for the phase separation step have been purchased.
Testing will recommence in Melbourne.
The Enterovirus Reference Laboratory Network of Australia consists of 11 public sector diagnostic
virology laboratories that either provide enterovirus typing results or refer enterovirus-positive RNA
for typing to the polio RRL at Victorian Infectious Diseases Reference Laboratory (VIDRL), which is
also designated as the National Enterovirus Reference Laboratory for Australia. The laboratory also
serves as the National Polio Reference Laboratory for Brunei Darussalam, Pacific island countries and
areas and Papua New Guinea. The laboratory’s cell sensitivity results have been in range for both cell
lines except when tape lifted causing cell degeneration for Sabin 2 in L20B in September 2015. New
stocks of Sabin 1 and Sabin 3 LQC are being validated.
Environmental surveillance of poliovirus and non-polio enteroviruses in China
Nine provinces in China have been performing environmental surveillance since 2008. In July 2016,
the seventh environmental surveillance workshop was held in Fujian Province. A workshop on new
environmental surveillance technology, which was held in China CDC in late 2015, trained
participants on two-phase separation for sewage concentration and ITD 4.0. From the sewage samples
collected in the nine provinces, 626 and 358 polioviruses were isolated in 2015 and in 2016 (up to
July), respectively. There were 340 and 220 polioviruses isolated in Xinjiang in 2015 and in January–
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July 2016, respectively; all of them were Sabin-like. In 2015, there was one VDPV2 isolated in
Guangdong Province. Environmental surveillance is a very important supplement for AFP
surveillance in China.
Environmental surveillance in Japan
To intensify the infectious agent surveillance for polioviruses after the IPV introduction in Japan in
September 2012, nationwide environmental surveillance using influent water at sentinel wastewater
treatment plants (WWTPs) was officially started in July 2013. In the first year, the network consisted
of eight Public health Institutes (PHIs) under National Epidemiological Surveillance of Vaccine-
Preventable Diseases (NESVPD) and five PHIs supported by a Ministry of Health, Labour and
Welfare research grant. In 2014, the number of local PHIs increased to 14 under NESVPD, and total
19 PHIs conducted environmental surveillance. In 2015, the network consisted of 18 PHIs. Sixteen
PHIs conducted environmental surveillance under NESVPD, and the other two conducted
environmental surveillance as their own research project. The period of environmental surveillance,
which is organized within the national programme, is 6 months. The sampling sites (18 sites in total)
cover different geographical areas in Japan, and accordingly, a size of population reached to
approximately six million. Any poliovirus isolated from the environmental samples at PHIs will be
forwarded to the GSL at NIID for intratypic differentiation of the poliovirus isolates. Thereafter,
detection of WPV or VDPV from the environmental samples will be also reported from NIID to
national authorities and WHO. In 2014, Sabin 3 isolates were detected from the environmental
samples, but no poliovirus has been isolated in 2015. Except for poliovirus, a number of enteric
viruses including enteroviruses from the environmental samples were identified as by-products.
HFMD surveillance in China
HFMD was listed as the 38th class C notifiable disease on 2 May 2008. The major pathogens of
HFMD in China were EV71 and Coxsackie virus (CV) A16. Other enteroviruses isolated in HFMD
cases were CVA6, CVA10, CVA5, CVA7 CVA2, CVA4, CVB2, CVB5 and some enteric cytopathic
human orphan (ECHO) viruses. The molecular epidemiology of EV71 and CVA16 showed the
following: for EV71, C4 genotype was divided into C4a and C4b clade, and there were recombination
between EV71 and CVA16, 14, 4 in C4a and C4b, and the genetic divergence was becoming larger
through time; and for CVA16, it was divided into B1 and B2 subgenotypes, and B1 was epidemic in
China.
Non-polio enterovirus surveillance in Japan
Under the Infectious Diseases Control Law in Japan, some enterovirus infections are classified as
reportable infectious diseases in the National Epidemiological Surveillance. Poliomyelitis including
vaccine-associated paralytic polio (VAPP) is classified as Category II, and all the cases have to be
reported. Other common enterovirus-associated diseases such as HFMD, herpangina, acute
haemorrhagic conjunctivitis and aseptic meningitis are reported from sentinel clinics and hospitals,
and the infectious agents surveillance is conducted for some of the clinical samples at local public
health institutes. Although national surveillance and laboratory diagnosis systems have not been
established specifically for EV-D68 infections in Japan, the epidemiological and clinical
characteristics in Japan from 2005 to 2015 were characterized based on data from the National
Epidemiological Surveillance System. The number of EV-D68-positive cases was more than 100 in
2010, 2013 and 2015, higher than those in other years from 2005 to 2015. The number of EV-D68-
positive cases peaked in September during the EV-D68 endemic years. Approximately 80% of EV-
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D68-positive cases were 6 years of age or younger. Among EV-D68-positive cases, the majority were
patients with respiratory illness; however, EV-D68 was also detected from patients with neurologic
syndromes including paralysis (n=8). The majority of EV-D68-positive clinical samples were throat
swabs (97%), but EV-D68 was also detected from stool (n=10), blood (n=3) and conjunctival (n=1)
specimens. Diagnosis was made mainly by molecular detection methods. In September 2015, the
number of EV-D68-positive cases rapidly increased, resulting in the largest number in 2015 (n=258)
from 2005 to 2015 in Japan. Almost simultaneously, a growing number of AFP cases were reported
nationwide in Japan. The increasing number of AFP cases led the Ministry of Health, Labour and
Welfare to expand notification, survey and laboratory testing of AFP cases (A notification letter from
the Ministry of Health, Labour and Welfare on October 2015). Some of the AFP cases were identified
as EV-D68-positive, but no poliovirus has been detected. Although reporting and laboratory diagnosis
biases should be carefully considered, the results provide insights into the epidemiological and
clinical aspects of EV-D68 infections.
HFMD surveillance in northern Viet Nam
The National Institute of Hygiene and Epidemiology (NIHE), Hanoi, serves 28 provinces for HFMD
surveillance. Of the 2804 clinical samples collected from patients with HFMD from 2011 to
August 2016 in northern provinces of Viet Nam, 1870 (66.7%) were positive with enteroviruses,
including: 676 (36.1%) samples positive with EV71; 477 (25.5%) positive with CVA6; 376 (20.1%)
positive with CVA16; and 162 (8.7%) positive with other enteroviruses including other CVA
serotypes (domination of CVA10, CVA12, CVA24), ECHO viruses, polio-Sabin virus types 1, 2, 3
and enterovirus type 96. Also, 9.6% of enteroviruses were un-typed. Dominant viruses that arranged
from high to low, respectively, were EV71 and CVA6 and CVA16 in 2011–2013; CVA16, CVA6 and
EV71 in 2014; CVA6, EV71 and CVA16 in 2015. However, in 2016, CVA16, CVA10, EV71 and
CVA6 are in equal proportion. The three subgenotypes of EV71 were C4, C5 and B5. By year, the
dominant EV71 subgenotypes were C4 (86.5%) in 2011, C4 (57.8%) and B5 (36.7%) in 2012, B5
(100%) in 2013–2015, and C4 (35%) and B5 (65%) in 2016. HFMD is often concentrated in children
under 5 years old, with highest concentrations in children aged 1–2 years old. Cycle tendency of
EV71, CVA6 and CVA16 is 3 years.
2.1.15 Global Polio Laboratory Network Management System (GPLNMS)
The GPLNMS mission is to improve coordination by addressing gaps in the global management of
information. The aims are to provide comprehensive capture and archiving of laboratory data
generated by the GPLN; streamline key processes (annual reporting, accreditation, PTs); develop
online monitoring tools (facilities, equipment, staff, exchange of materials); and provide a space and
forum for standard documents, discussion and information exchange. Electronic sharing of
information with multiple partners is necessary, and the GPLNMS will gather all laboratory
information in one place. There will be a requirement to submit information on staff, equipment and
supplies, an annual report and the accreditation report. Annual and accreditation indicators will be
computed from laboratory files received at WHO headquarters in order to validate values/information
reported by the laboratory in GPLN and PTs (virus isolation, ITD and sequencing) will be added. The
status of the 2015 annual reports in the Western Pacific Region showed reports of 33 laboratories
were validated, six laboratories did not open the database, one laboratory opened but has to complete
the report, and three reports were returned due to incorrect data. Penalties will be applied to those
laboratories that do not comply with the requirements.
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2.1.16 Data management and reporting
Polio data (including AFP surveillance and polio laboratory data for AFP, non-AFP and
environmental specimens) are submitted to the WHO Regional Office for the Western Pacific in a
variety of formats. Specifically, polio laboratory data for AFP specimens are sent to the WHO
Regional Office for the Western Pacific in MS Access database format by 11 out of 12 laboratories.
NIID is the only laboratory that still submits data in MS Excel line list.
Submission of polio laboratory data in Access database format (feedforward file of the Access-based
database deployed in 2013) has been found to fix most, if not all, data quality issues of reported data.
On the other hand, when using Excel line lists, many data issues can be found such as the need to
manually link the laboratory line list to the AFP line list, segregation of AFP and non-AFP specimens,
linking of virus isolation to ITD/sequencing results, as well as sometimes needing to manually
segregate information into individual data elements when laboratory results are indicated in a single
but lengthy text field.
Participants were reminded that laboratory results from AFP specimens should be reported to the
WHO Regional Office for the Western Pacific on a weekly basis. However, there is much room for
improvement in this regard, as some laboratories still submit data on a biweekly or monthly basis.
Participants were also reminded of the various uses of the polio laboratory data that are submitted to
the WHO Regional Office for the Western Pacific. For example, data are shared in the WHO
Regional Office for the Western Pacific Polio Bulletin, which is distributed to a large number of
subscribers as well as uploaded onto the WHO Regional Office for the Western Pacific website on a
biweekly basis. As such, the various tables in the Polio Bulletin that reflect polio laboratory data were
explained, as they were found to be a major source of inquiry in the past year.
Similar to the previous year, participants were once again introduced to the Polio/AFP Surveillance
and Reporting System (PASRS), which is a web-based data entry and reporting system. The PASRS
has many advantages over the current Access database and Excel line list – most notably, the merging
of both AFP surveillance and polio laboratory data (virus isolation, ITD and sequencing) into one
single database. The most common complaint in polio laboratory data submission – re-entering
epidemiological data from AFP surveillance – is now completely removed, because with PASRS,
laboratories now only need to enter data relevant to them such as laboratory ID, date of receipt of
specimens and laboratory results. The PASRS has just been recently sent for review and testing for
use in Cambodia, and once successfully finalized, it is highly recommended for all other countries to
consider migrating onto this system.
2.1.17 Quality assurance and quality control
Network laboratories continue to report results of cell sensitivity tests and titration experiments to the
regional laboratory coordinator (RLC) for review and for implementation of appropriate corrective
actions early. Sabin 2 reference strains have been omitted from cell sensitivity testing (as per GLPN
recommendation in June 2015) since April 2016. The following cell sensitivity testing performance
issues and challenges were observed: invalid titration results without corrective action (not showing
100% or 0% for end-point dilutions); decreasing linear trend of CPE not observed; and stock-out of
low passage L20B and RD cells. These problems are being addressed by providing timely feedback to
the laboratories. VIDRL, Australia provided new authenticated cell lines to the Research Institute for
Tropical Medicine (RITM), Philippines in July 2015, and shipment of cells is being arranged for
NIHE, Viet Nam and the Institute of Environmental Science Research (ESR), New Zealand. Public
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Health Institute (PHI), Mongolia received cells in March 2016 from NIID Japan. Mycoplasma testing
is performed by most of the laboratories; however, no standardized protocol is being used in the
laboratory network.
The annual PT and assessment of laboratories continue to be critical for the quality assurance of the
performance in polio laboratories. Three different PT panels are in use for evaluating: 1) accuracy of
virus isolation; 2) ITD by real-time RT-PCR; and 3) sequencing poliovirus isolates. The PT
programme is coordinated by WHO in collaboration with the global specialized laboratories (GSLs)
in the United States of America and the Netherlands. For the laboratories that failed the 2015 ITD PT
and the 2015–2016 sequencing PT, new PT panels will be given during the meeting and will be hand-
carried by the participants. The 2016 virus isolation PT will be shipped to the laboratories via courier,
and shipment will be arranged when the instructions on the processing of the samples are reviewed
and revised by the Dutch National Institute for Public Health and the Environment (RIVM). As
indicated in GPLN Guidance Paper No. 2, the 2016 ITD PT panel must be run with ITD version 5.0.
The 2016 ITD/VDPV PT and ITD 5.0 kits from US CDC will be distributed as soon as they are
available. The WHO Regional Office in the Western Pacific will also provide Quanta ToughMix
enzymes to all laboratories.
In summary, the polio network laboratories continue to provide high-quality laboratory support to the
programme.
2.2 Measles and Rubella LabNet
2.2.1 Global and regional updates on measles and rubella elimination
All six WHO regions have set a target year for measles elimination: Region of the Americas in 2000,
European Region in 2015, Eastern Mediterranean Region in 2015, African Region in 2020, South-
East Asia Region in 2020, and Western Pacific Region in 2012. For rubella elimination, two regions
have set a target year for elimination: Region of the Americas in 2010 and European Region in 2015.
In 2014, the Western Pacific Region committed to eliminate rubella; in 2015, the Technical Advisory
Group on immunization and vaccine-preventable diseases in the Western Pacific Region (TAG)
recommended 2020 as the target year. However, a target year is not yet set for rubella elimination. As
of December 2015, 34 (97%) out of 35 countries in the Region of the Americas were verified to have
achieved measles elimination. An endemic transmission was re-established in Brazil from 2013 to
2015. All 35 countries (100%) were verified to have achieved rubella elimination. In the European
Region, out of 53 countries, 21 countries (40%) were verified to have achieved measles elimination,
and 20 countries (38%) were verified to have achieved rubella elimination. In the Western Pacific
Region, measles case-based surveillance was conducted in all 37 countries and areas, including 14
countries and two areas that report data individually, and 21 countries and areas of the Pacific islands
that report data as one epidemiologic block. Out of 14 countries, two areas and one epi-block, six
countries and one area (Australia, Brunei Darussalam, Cambodia, Japan, Macao SAR (China),
Mongolia and Republic of Korea) were verified to have achieved measles elimination.
To achieve and sustain measles elimination, the Western Pacific Regional Plan of Action for Measles
Elimination endorsed by the Regional Committee in 2003 proposed three core strategies:
immunization, surveillance and laboratory support. To support case-based surveillance, a measles and
rubella laboratory network was established in the Western Pacific Region. Currently, 386 laboratories
ranging from prefecture-level laboratories in China to the GSL in Japan are participating in the
regional laboratory network. Since 2000, some countries have conducted nationwide or subnational
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SIAs every year. From 2003 to 2015, 445 million children in the Region were reached by the national
immunization programme through supplemental immunization campaigns with measles-containing
vaccine (MCV-SIAs). Several countries (e.g. Lao People's Democratic Republic, Philippines, Papua
New Guinea and Solomon Islands) actively conducted MCV-SIAs with other child health
interventions (e.g. OPV-SIA, vitamin A supplementation and/or anti-helminthic treatment
[deworming]). Incidence of measles decreased from 81.6% in 2008, to 34% in 2009, 27% in 2010,
11.7% in 2011 and 5.9% in 2012. However, the Region experienced a resurgence of measles in 2013
(18%), 2014 (67.2%) and 2015 (35.3%) due to endemic transmission in several countries with large
populations; repeated importation from endemic countries to countries verified to have interrupted
endemic measles transmission (e.g. Australia, Japan, Republic of Korea) and to countries approaching
elimination (e.g. Singapore); and importation from endemic countries to countries with no or low
documented transmission (e.g. Mongolia, New Zealand, Papua New Guinea and Solomon Islands),
resulting in large outbreaks.
To address and overcome the issues and emerging challenges identified in the Region and to
accelerate achievement and promote sustainability of both measles and rubella elimination in the
Western Pacific, the new regional strategic document proposes 31 strategies with accompanying
activities in eight strategic areas: (1) overall planning and immunization system; (2) immunization; (3)
epidemiological surveillance; (4) laboratory support; (5) programme review and risk assessment; (5)
outbreak preparedness and response; (7) partnership, advocacy, information, education and
communication (IEC) and social mobilization; and (8) progress monitoring and verification of
elimination.
2.2.2 Global Measles and Rubella Laboratory Network (LabNet)
The Global Measles and Rubella LabNet is the largest globally coordinated laboratory network
providing high-quality laboratory support for surveillance to measure progress towards measles and
rubella elimination. Serological testing is performed by all network laboratories, with increasing use
of molecular methods for case confirmation. Molecular detection and characterization are done by
RRLs and some of the national measles and rubella laboratories (NMRLs), expanding QA/QC and
accreditation in the entire network and ensuring high-quality testing. There are seven working groups
supporting technical developments and guidance. A new laboratory manual is being developed,
training and workshops were held, and 61 laboratory staff were trained in 2015–2016 to ensure
proficiency.
The annual number of measles cases identified from either case-based or aggregate surveillance
systems are reported by countries to WHO and UNICEF through their Joint Reporting Form (JRF). In
2015, in the 160 countries that reported case-based surveillance data, 146 925 specimens were tested
for measles immunoglobulin M (IgM) antibodies and 112 461 specimens were tested for rubella IgM
antibodies. In 2016, approximately 60 000 specimens and 42 000 specimens were tested for measles
and rubella IgM antibodies, respectively. The quality of the LabNet remains high and most network
laboratories are fully accredited.
Genotype data are reported to the WHO Measles Nucleotide Surveillance (MeaNS) and Rubella
Nucleotide Surveillance (RubeNS) databases. During 2010–2015, eight measles genotypes (B3, D3,
D4, D6, D8, D9, G3 and H1) were reported. The outbreak in the Philippines in 2014 caused global
transmission of measles genotype B3 “Harare” and genotype D9. Eleven wild-type genotypes were
detected since 2005, and six genotypes are still circulating. Five rubella genotypes (1E, 1J, 1G, 1A
and 2B) were reported globally from 2010 to 2015.
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Introduction of RT-PCR based assays for rapid confirmation of vaccine reactions and new generation
and larger sequence “windows” that can distinguish separate importations from the same source are
the recent developments in the Global Measles and Rubella LabNet. In summary, the global network
has highly proficient laboratories with strong quality assurance and provides accurate and timely
laboratory confirmation and genotyping evidence to the programme.
2.2.3 Progress of regional measles and rubella laboratory network
The regional measles and rubella laboratory network plays an important role in measles and rubella
surveillance by providing timely and reliable laboratory confirmation and identification of virus
strains and genetic characterization of viral isolates. A quality assurance programme is being
implemented to maintain the high-quality laboratory network. In 2015 and 2016, VPD laboratory
network meetings were organized in Manila. A hands-on training workshop on laboratory molecular
diagnosis of measles and rubella was held in Hong Kong SAR (China), and on-site accreditation of
six provincial laboratories in China, namely, Hainan, Chongqing, Tianjin, Jiangsu, Jilin, Inner
Mongolia, was done on 30 May–6 June 2016. All 53 network laboratories participated in and passed
the 2015 IgM PT; 2016 IgM PT panels will be distributed during the meeting. Shipment of 2015–
2016 samples for confirmatory testing is ongoing. In 2015, 11 laboratories participated in the measles
and rubella molecular PT and all have passed. For the 2016 molecular PT, 13 laboratories will
participate; PT panels will be distributed in November 2016. Accreditation by on-site visit and by
correspondence/desk review was done in most of the laboratories in 2015 and 2016. On-site visits to
selected laboratories in 2017 were proposed.
This year, the Western Pacific Regional Plan of Action for Measles Elimination, which was issued in
2003, was updated to include rubella elimination. The draft plan of action on measles and rubella
elimination in the Western Pacific Regional proposes strategies and activities to support measles and
rubella elimination including laboratory support. Three strategies for laboratory support were
proposed: 1) ensure timely laboratory diagnostic confirmation of suspected measles and rubella cases;
2) assure collection of appropriate clinical specimens for obtaining genotype information from each
outbreak and transmission; and 3) collaborate with the WHO Regional Office for the Western Pacific
to further improve the performance of the regional measles and rubella laboratory network. The
proposed plan of action on laboratory support will be shared with the laboratories for review and
comments.
From 2013 to 2016, measles genotypes B3, D4, D8, D9, G3 and H1were reported. Genotype H1
continues to be the predominant genotype circulating in several countries in this Region. Genotype B3
was the second predominant genotype in 2013–2014, but genotype D8 became the second
predominant genotype in 2015–2016. Several countries and areas were verified as having eliminated
measles. In Australia, Japan, Macao SAR (China) and the Republic of Korea, genotype evidence
supports the interruption of endemic measles virus transmission. In Cambodia, the genotype
information supports the interruption and re-importation of genotype B3 and the outbreak still
ongoing. For Mongolia, genotyping data re-established the country’s endemic status after verification.
For rubella, genotype information was obtained from only a few Member States. The molecular
trainings held in Hong Kong SAR (China) strengthened the capacity of laboratories in performing
genotyping. Rubella genotypes 2B and IE were detected in 2014 and 2015; however, only 2B was
reported in 2016. Based on the reported genotypes, it is proposed that the Lao People’s Democratic
Republic and Papua New Guinea will work with surveillance colleagues to obtain virologic samples
and refer them to RRL for virus detection and genotyping or refer serum samples to RRL to get
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genotype information; the Philippines and Viet Nam will work with surveillance colleagues to get
more and qualified virologic samples and monitor the performance of the laboratory tests in
subnational laboratories.
2.2.4 Global specialized laboratories (GSLs) and regional reference laboratories (RRLs)
Japan as GSL
The GSL at NIID, Japan continues to be involved in strengthening the capacity of the regional
LabNet. The laboratory helped facilitate the Japan International Cooperation Agency (JICA) global
training on measles and rubella in 2016, carried out seroepidemiology for measles and rubella among
the general population in the Lao People's Democratic Republic using DBS, and performed vaccine
stability.
Commercial (private) laboratories perform the bulk of IgM testing for measles and rubella in Japan,
and prefectural laboratories perform PCR and sequencing tests. There are 73 prefectural institutes and
10 measles and rubella reference centres in Japan. In 2015, 1045 suspected measles cases were tested
by PCR, and 42 were positive. To build capacity and ensure quality in national surveillance, NIID
developed a molecular PT that was performed by 22 laboratories in 2014 and 20 laboratories in 2015.
Respectively, 95% and 80% of the laboratories passed the molecular PT in 2014 and 2015. Measles
and rubella IgM PT panels were also distributed to the private laboratories in 2015; all of the
laboratories passed the IgM PT with a score of at least 90%.
A total of 365 measles viruses were genotyped in 2014 and 24 in 2015. Genotype B3 was
predominant from 2013 to 2014 and D8 in 2015. Two other genotypes, D9 and H, were also detected
from 2013 to 2015. A limited number of measles cases were reported in 2015, and no endemic
measles transmission has been established. However, in 2016, large outbreaks occurred. Vaccination
campaigns in the patients’ neighbourhoods have been implemented.
Australia as RRL
Australia has maintained the interruption of endemic measles transmission in 2015. Evidence includes
low incidence, majority of cases imported or import-related, and a small number of outbreaks with
few cases of short duration. The quality of epidemiological and laboratory surveillance systems
remained high with indicators achieved. High vaccination coverage has been maintained above 90%
for both doses of measles, mumps and rubella (MMR) vaccine. Genotyping evidence supports
elimination with multiple genotypes detected and no sustained transmission of a single genotype for
more than 12 months. Australia will submit evidence of rubella elimination for verification in 2017.
VIDRL’s current molecular testing algorithms for measles and rubella remain unchanged from that
presented at the previous VPD LabNet meeting. Laboratory procedures to further improve quality
control have been implemented, including: weekly environmental contamination checks for measles
amplicon; reference sequencing control inclusion; and pre-testing of all PCR reagents prior to
diagnostic use. For quality assurance, VIDRL participates in a molecular External Quality Assessment
(mEQA) for measles through Quality Control for Molecular Diagnostics (QCMD). This is in addition
to the WHO/CDC mEQA for measles and rubella that VIDRL already participates in.
From January to August 2016, laboratory testing of 177 specimens for rubella virus and 634
specimens for measles virus by real-time RT-PCR has yielded one and 57 positive cases, respectively.
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A measles genotype was obtained in 51 of 57 positive cases; two genotypes, B3 and D8, were
identified. The single case of rubella was identified as genotype 2B. Measles virus isolation in vero
SLAM was successful in seven of 25 specimens.
Other RRL activities included measles genotyping of positive IgM samples from Brunei Darussalam,
measles testing for New Caledonia and confirmatory measles PCR and genotyping for New Zealand.
China measles LabNet (with 31 provincial laboratories)
The China measles LabNet was established in 2001. The China measles LabNet is composed of a
national measles laboratory (NML), 32 provincial laboratories and 339 prefectural laboratories. The
NML was certificated as a WHO RRL in the Western Pacific Region in 2003. The NML plays a
significant role in the control of measles in China, and as a RRL, it makes considerable contributions
to the regional and global measles control programme. It acts as a RRL for the provincial and
prefecture measles laboratories in China and also performs many GSL-type functions for China. The
NML plays a key role in quality assurance, preparing proficiency tests, providing supervision and
training, and developing guidelines that outline roles and responsibilities of measles laboratories at
various levels.
Throughout the China measles LabNet, more than 130 000 serum samples collected from suspected
sporadic measles cases were detected for measles IgM antibodies and for rubella IgM during 2015 and
January to June 2016. A total 629 suspected measles outbreaks were reported, and 84% were
confirmed as measles outbreaks during 2015 and January to June 2016.
Molecular epidemiological techniques for measles and rubella viruses have been well established in
the NML since 1993. Except for Tibet, all of the provincial laboratories have successfully done
measles isolation. The NML received more than 6000 measles isolates through the China measles
LabNet during 2015 and January to August 2016. All of the isolates have been identified using RT-
PCR and sequencing method; comparing with the known measles genotype sequences in the world,
all the virus isolates belong to H1 genotype,except for three D8, one D9 and 26 vaccine strains. The
H1 genotype is still the predominant endemic genotype in China.
The China NML plays a key reference and quality assurance role for the measles laboratory network
in China. The NML and 31 provincial laboratories (not including Tibet) received the serology PT
panel, and the NML accepted the molecular PT panel from WHO in 2015. All the participants passed
the tests with high scores. Six provincial laboratories had on-site accreditation in 2016, and all
participants passed with excellent marks. The 12th National Measles Laboratory Network Workshop
was held on 16-17 September 2015 in Beijing. All the participants were from the 32 provincial
laboratories. Experts from WHO attended the workshop and presented a global overview of measles
control and elimination.
Hong Kong SAR (China) as RRL
The testing algorithm of measles and rubella diagnosis and surveillance was presented. The laboratory
fulfilled measles and rubella elimination and verification criteria in terms of reporting serology results
within four days (89.1% in 2015, 94.5% in 2016), reporting monthly to WHO (100% completeness
and timeliness) and providing genotype information for clustered cases investigation. Quality
assurance measures adopted in the PHLC include monitoring of controls for enzyme immunoassays
(EIAs), participation in proficiency tests (with 100% score obtained) and laboratory accreditation
(ISO 15189 and WHO).
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The performance of national laboratories in IgM confirmatory testing has improved over the years,
with the concordance rate topping more than 90% for most of the national laboratories. Genotyping
was performed. Measles genotypes B3, D8, D9 and H1 were detected from January 2015 to
August 2016 in eight national laboratories. For rubella, only samples from the Philippines had
genotype results (1J and 2B). Shipment of samples from different countries mostly corresponded quite
well with the proposed shipment schedule. There were still problems and challenges to be resolved,
such as leakage of samples, prolonged shipment time, use of inconsistent date format, insufficient
volume of serum for both IgM testing and RT-PCR, and mislabelling of samples. Investigation of
discordant samples by the Philippines was used as an example for reference by other national
laboratories.
2.2.5 Molecular epidemiology overview and lessons learnt
Genetic characterization of measles viruses by the Global Measles and Rubella Laboratory Network
for more than 20 years has made substantial contributions to both the biology and evolution of
measles viruses, and has become an integral part of routine laboratory surveillance for measles.
Analysis of viruses from measles cases and outbreaks indicates that all measles vaccines belong to
genotype A, which is a genotype that is not associated with documented endemic transmission in any
part of the world. The wild-type viruses in genotype A are no longer circulated; hence, sequence
information allowed the development of RT-PCR based assays for rapid confirmation of vaccines
reactions. Also, the vaccine viruses are not associated with subacute sclerosing panencephalitis
(SSPE). There is no evidence for selective pressure on the H protein based on measurement of rates
on nonsynonymous/synonymous amino acid substitutions. The site directed mutagenesis of the
measles H protein shows structural constraints needed for binding to SLAM and nectin-4, and so,
antigenic drift will unlikely compromise vaccine efficacy. Genetic characterization allows tracking of
viral transmission pathways, and extended sequencing windows will be needed to increase the
resolution of molecular epidemiological studies. Some genotypes with apparent geographic restriction,
e.g. genotype B3 (once restricted to African countries) and genotype D8 (once endemic in India) now
have global distribution, while genotype H1 is still endemic in China only. In countries that have
eliminated measles, the pattern of genotypes reflects the sources of imported virus, and thus, lack of
endemic genotype is an essential criterion for verification of elimination. Countries with endemic
measles have multiple, co-circulating lineages of measles virus, while in countries where measles has
been reintroduced, often only a single lineage is detected. There has been an apparent decrease in
genetic diversity of circulating measles viruses based on a decrease in the number of genotypes
detected, and there has been a shift in genotypes over time in various regions. The shift in genotypes
and decrease in number of circulating genotypes suggest that measles transmission is interrupted
frequently. However, as the number of individuals susceptible to measles increases, the
country/region is re-seeded by imported viruses. Though interruption of transmission has been
suggested by epidemiological data in the past, the more recent application of molecular epidemiology
has helped to document these interruptions, e.g. C2, D6 and D4 genotypes in Europe have been
replaced by D8 and B3genotypes, and the circulation of endemic D3 genotype in the Philippines was
interrupted.
LabNet support for virological surveillance is now well established in all WHO regions; however, the
Global Measles and Rubella Laboratory Network needs to continue to build capacity for genetic
characterization of both measles and rubella and to integrate new testing schemes and new
technologies.
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2.2.6 Country presentations
All countries presented a summary of their achievements. All laboratories have passed the global PT,
have acceptable concordance with their confirmatory tests and are fully accredited. Most countries
presented their testing and reporting algorithms, which followed WHO recommendations.
Brunei Darussalam
The NMRL for Brunei Darussalam was accredited by WHO in 2014. In 2015, four measles cases
were found to be imported, and one case was genotype D8. Eight acquired rubella cases were reported
from 2008 to 2014, and no rubella case was reported in 2015. Since genotyping is not available
locally, specimens are sent to the WHO RRL at VIDRL, Australia for testing. Brunei Darussalam has
been verified by the Regional Verification Commission for Measles Elimination (RVC) as having
achieved measles elimination since March 2015.
Cambodia
No single measles case was confirmed by the NMRL from November 2011 to 2014. Cambodia has
been verified as having achieved measles elimination by the RVC since March 2015. However, in
2016, there was a measles outbreak reported with 20 laboratory-confirmed cases from January to
August. The Ministry of Health immediately launched an inspection and took all necessary measures,
including vaccination, to stop the transmission of the virus. From 2007 to 2011, measles genotypes
D9 and H1were detected in the country; however, from January to August 2016, genotype B3 was
reported to be circulating in Cambodia.
Fiji
The NMRL in Mataika House received a total of 234 samples in 2015; of these, 92 samples were sent
from Vanuatu and 20 samples were measles IgM positive. Currently, molecular diagnosis of measles
and rubella is not done in Fiji; it is conducted in VIDRL, Australia. However, there is a need for
assistance to set up such a facility for molecular testing.
There is also an urgent need for the development of a virus isolation room so that the NMRL can fulfil
its obligation in the active surveillance of measles, which may advance to its elimination. The facility
will also benefit Fiji in terms of communicable disease diagnosis and surveillance. Although funding
for the project was not secured from the government’s health budget allocation, there is still
anticipation that this important infrastructure development will continue to be part of Fiji’s future
development programme.
Lao People’s Democratic Republic
Outbreaks of fever and rash have occurred every year from 2011 to 2015 in different provinces. Fever
and rash cases are still confirmed for measles and rubella, but the numbers have remarkably decreased
since 2011. The majority of cases occurred in children under 15 years of age, with no significant
difference in gender. Cases occurred in areas with low measles and rubella immunization coverage
and hard-to-reach areas. In 2015, a total of 552 samples were tested for measles and rubella; 12
samples (2.2%) were measles IgM positive and 21 samples (3.8%) were rubella IgM positive. The
NMRL at the National Center for Laboratory and Epidemiology (NCLE) has no capacity for
molecular testing. The NCLE reported that they have a shortage of human resources, they lack
rubella-positive samples for the in-house control, and provincial and district staff require refresher
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training on field investigation and collection of blood specimens. The laboratory needs to strengthen
laboratory biosafety programmes, improve data management and coordinate with other sections.
Malaysia
Since 2011, measles incidence has increased with four deaths in 2011, one death in 2014 and two
deaths in 2015, but no deaths have been recorded so far in 2016. Starting in April 2016, a change in
the vaccination schedule will be implemented and a first-dose MMR vaccine will be given to
9-month-old children. In 2015, a total of 4864 samples were tested, and 1456 samples (29.9%) were
measles IgM positive. In 2016 (until June), a total of 3314 samples were tested, and 1000 samples
(30.2%) were measles IgM positive. Genotypes B3, D8 and D9 were circulating in Malaysia during
2015 and 2016. In Malaysia, the National Public Health Laboratory monitors the quality of the
subnational laboratory in Sabah, established in 2011, through EQA and confirmatory testing. Among
clinicians and health officials in Malaysia, awareness of the measles elimination programme is
growing as more cases are being reported/notified. Reducing the number of under-reported cases is a
major step towards achieving the main objective of this programme.
Mongolia
Mongolia was verified as having achieved measles elimination by the RVC in 2014; however, since
mid-March 2015, a measles outbreak is still ongoing. The highest age-specific attack rate is reported
among children under 1 year old, following young adults aged between 18 and 30 years old. In 2015
and 2016, there were eight and 132 deaths, respectively. The overall case fatality rate was 0.4%. The
SIAs carried out had shown positive results as a decreasing trend of cases are seen as the activities
were carried out extensively. In 2015 and 2016 (until August), a total of 14 462 samples were tested
for measles IgM, and 6962 samples (48%) were confirmed positive. Measles genotype H1 was
identified during the outbreak. Mongolia plans to develop and ensure implementation of the measles
and rubella outbreak preparedness and response plan, improve infection prevention and control
practices to prevent nosocomial transmission, establish a web-based immunization registry and
increase budget allocation for MCV SIAs every 4–5 years to ensure that herd immunity level reaches
the standard level,
New Zealand
MMR vaccine coverage following one dose of vaccine is 92.8% in children 24 months of age, while
coverage following two doses is 84.6% for children 5 years of age. Because of previous vaccine
distribution issues, teenagers aged 10 to 19 years remain at risk of contracting measles infection.
Measles and rubella diagnostic and confirmatory testing, genotyping, culture and serology are
performed by the New Zealand NMRL using the WHO-recommended test kits and CDC protocols.
With samples received from suspected cases, a diagnostic algorithm is followed. Real-time RT-PCR
has become the test of choice ahead of IgM and IgG serology. After a high rate of measles cases in
2014 (6.2 confirmed cases per 100 000 population), the numbers dropped significantly in 2015 to 0.2
per 100 000. No rubella-virus-positive samples were recorded in New Zealand in 2015. In 2016 (until
August) several measles outbreaks originating from imported cases from Asia have been reported.
Epidemiologically linked outbreaks have occurred in several regions. All of these outbreaks were
associated with a measles D8 genotype; however, several lineages, with sequences differing by up to
15 bps, have been identified. The laboratory participates in a range of quality assurance programmes
that include monitoring with both internal and external audits. Results are reported monthly to WHO
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and annually to the New Zealand Ministry of Health, and a selection of samples is sent regularly to
VIDRL (RRL) for confirmatory testing.
Papua New Guinea
A large measles outbreak took place in Papua New Guinea from March 2014 to April 2015. The
outbreak was confirmed in the National Capital District, in mountainous areas and in a densely
populated province in the Highlands Region. A total of 5056 samples were tested for measles IgM,
and 2393 (47.33%) samples were measles IgM positive. The most common measles genotype
detected was B3, and circulation of D9 at the border with Indonesia was also reported. The flourishing
mining industry and the liquefied natural gas (LNG) project brought an influx of foreign workers into
the country; hence, the outbreak was import-related. In 2016 (until August), only 32 samples were
tested, and all samples were negative for measles IgM. The laboratory plans to decentralize testing to
regional laboratories within Papua New Guinea during outbreaks, to have a better communication
with clinical and surveillance teams and to detect and report data in a timely manner.
Philippines
A total of 2330 cases were referred to the NMRL from May 2015 to August 2016, with the majority
of referrals coming from 2015. A decline in referrals from 2015 to 2016 coincided with a decline in
the positivity rate of measles (May to December 2015: 12.5%; January to August 2016: 2.9%). As for
rubella, more positive cases were detected in 2016 (6.2%) than in 2015 (3.2%). In terms of regional
distribution, during 2015, more measles cases were detected in southern Philippines (or the Mindanao
islands) than in central and northern Philippines. A few rubella cases were detected throughout the
country. In 2016, most of the referrals came from central Philippines, specifically Region 6, because
of a rubella outbreak in one of its province. A few measles cases were detected in 2016, with the
majority coming from Region 7 and Region 9. The NMRL shifted to parallel testing of measles and
rubella IgM in the start of 2016 to increase detection of rubella cases and to improve the turnaround
time of results (94.9% up to 99%). Consistent with IgM results, virus isolation and real-time PCR
yield more rubella positives than measles. The current circulating genotype according to available
data is B3 for measles and 2B for rubella. Measles genotyping is done on serum samples since no
virus isolation samples yielded positive results for measles, while rubella genotyping is done on virus
isolation samples. Quality assurance is implemented by: monitoring in-house controls and kit controls
and plotting them in quality control charts, sending samples to the RRL in Hong Kong SAR (China)
for validation of results, participating in annual proficiency testing for measles and rubella IgM and
molecular testing and participating in accreditation visits by WHO and CDC personnel. The NML is
accredited for 2015–2016.
Subnational laboratories are needed to make testing more accessible throughout the Philippines, to
facilitate rapid detection of cases through laboratory confirmation, and to improve surge capacity in
cases of outbreaks. Subnational laboratories would perform not only molecular-based testing but also
serology and bacterial culture. This would entail capacity-building through upgrade of infrastructure,
workshops for coordination and reporting, training on laboratory testing and shipment, and
development of platforms that would complement case- and event-based surveillance. With the
support of WHO and other partner organizations, RITM will spearhead the establishment of these
laboratories.
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Singapore
Singapore General Hospital was the NMRL from 2001 to 2016, until the National Public Health
Laboratory (NPHL) in Tan Tock Seng Hospital took over the responsibility from 2016 (overlapping)
onwards.
In Singapore, notification of measles is compulsory under the Infectious Diseases Act. Both
suspected/clinically diagnosed and laboratory-confirmed cases of measles are required to be notified
to the Ministry of Health. In June 2012, the measles surveillance system was enhanced by following
up suspected/clinically diagnosed cases to ensure that confirmatory laboratory tests for measles were
conducted for such cases (i.e. using PCR or serology). As part of the enhanced measles surveillance
framework, a higher proportion of measles cases with positive PCR results will be followed up with
genotypic analysis. This will lead to a better understanding of the measles genotypes circulating in
Singapore and will also support tracing epidemiological linkages among cases, especially in
outbreaks.
A total of 670 suspect cases were notified between January 2012 and August 2016. Of the 338 cases
that were laboratory confirmed, 87cases were imported, 49 cases were import-related, 196 cases had
an unknown source, 6 cases were vaccine-associated and 53 cases were clinically compatible; there
was no endemic case. The NPHL has not received any rubella-positive samples since 2011. There has
been a shift in the genotype distribution from the predominant circulating endemic D9 genotype in
2012, G3/D9 genotypes in 2013 and the B3 genotype in 2014. The B3 genotype was first detected in
2013, and a sharp surge was seen in 2014. This increase was probably due to the importation of cases
from the Philippines, where one of the main circulating genotypes is B3. Another endemic genotype,
D8, was seen in 2015. Genotype A is a vaccine genotype not associated with documented endemic
transmission in any country. Comparison of IgM testing results between NPHL and Singapore
General Hospital showed very good concordance. The laboratory is faced with challenges mainly in
serological testing. First, too few samples are received due to the low prevalence of measles and
rubella, and decentralized diagnostics capacity and molecular testing are widely available in most
public hospitals. Second, IgM in-house control is a challenge since there are very few IgM-positive
samples and it is difficult to prepare in-house positive controls in batch. The laboratory plans to
complete WHO EQA of both molecular and serological panels, to obtain WHO accreditation in
February 2017 and to conduct national serosurvey in 2017–2018.
Viet Nam
The measles vaccine coverage in Viet Nam was maintained at 95% for the first dose and 90% for the
second dose. NIHE is responsible for the measles and rubella surveillance in northern Viet Nam,
which consists of 28 provinces/cities. After the measles outbreak in 2014, during which there were
more than 4000 confirmed cases, the number of measles cases dropped to 100 cases in 2015 and three
cases in 2016 (up to August). There were eight rubella cases in 2015 and six in 2016. The genotypes
of measles circulating in Viet Nam were H1 and D8 and the genotype of rubella was 2B, all of which
were closely related to Chinese strains. The NIHE performed re-confirmatory testing for two
subnational laboratories in the Central Highlands of Viet Nam and provincial laboratories. The
concordant result for measles was more than 98%. In terms of congenital rubella syndrome (CRS)
surveillance, there was one sentinel site located in National Pediatrics Hospital, Hanoi, Viet Nam and
the number of CRS cases in 2016 was two. For quality assurance, NIHE monitors in-house controls
for measles/rubella enzyme-linked immunosorbent assay (ELISA) testing, performs PT panels on
ELISA and molecular tests (100% for both), and sends re-confirmatory samples to Hong Kong RRL
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(scheduled in August but still waiting export permit). NIHE has applied ISO15189: 2012 for measles
and rubella ELISA tests since March 2016. The number of throat swab specimens collected was very
low. To overcome this challenge, NIHE performed nested RT-PCR on serum samples to get more
genotype information and communicated with EPI staff to collect more throat swab specimens.
The NMRL at Pasteur Institute in Ho Chi Minh City performs virus isolation and identification of
measles and rubella viruses from 20 provinces. The laboratory has participated in CRS surveillance
since 2011. The laboratory also has the capacity to perform RT-PCR and sequencing. From May 2015
to August 2016, a total of 1585 samples were tested for both measles and rubella IgM. Of these, 130
samples (8.2%) were positive for measles IgM, while 813 (51.3%) were rubella IgM-positive. CRS
data from Children’s Hospital No.1 showed 11 (4.1%) cases were rubella positive, and eight (3.9%)
rubella-positive cases were reported in Children’s Hospital No. 2. Genotyping results showed that the
circulating measles virus strains were genotypes D8 and H1 during the 2014 outbreak. Eight rubella
virus isolates were sequenced in 2015, and the results indicated genotype 2B. The laboratory needs to
train the provinces on specimen collection including throat swabs since receiving throat swab samples
is rare.
The Pasteur Institute in Nha Trang is a subnational laboratory (SNL) providing laboratory
surveillance for measles and rubella in central Viet Nam. Serology diagnosis of measles and rubella is
done using the Siemens kit and IBL kit (Germany). The SNL also performs molecular testing and
genotyping with primers developed by US CDC. For quality control of the results, the SNL uses an
in-house control for IgM testing of measles and rubella. It also performs the WHO PT panel every
year and scores 100%. A large measles outbreak in 2014 resulted in 1765 serum samples being tested
for IgM, and of these, 1005 (56.9%) were positive. In addition, 99 PCR tests were performed of which
50 were positive. There were only 10 rubella-positive cases from 804 tests by serology method. The
SNL also tested rubella PCR for four cases, but all of them were negative. Central Viet Nam saw a
significant decrease in both the number of samples and positive cases of measles and rubella between
2015 and 2016. In 2015, out of 307 IgM tests performed, seven were positive with measles and 13
were positive with rubella. In 2016, 106 samples were tested in the first eight months of this year.
Only one case was measles IgM positive, while six cases were rubella IgM positive. There was no
PCR testing for measles and rubella in 2015 and 2016. In 2010, 40 measles samples were genotyped
and all of them were H1. In 2014, the SNL detected measles virus from 27 samples with H1, D8 and
B3 genotypes. This was the first time a genotype B3 was detected in Viet Nam.
2.2.7 Strengthening rubella and congenital rubella syndrome (CRS) surveillance
Global update of rubella and CRS surveillance
Molecular surveillance for rubella viruses is poor in most of the world; nevertheless, the major
genotypes now detected are 1E, 1G, 1J and 2B. Utility of rubella molecular epidemiology is
fundamentally limited by low number of available viral sequences. Molecular epi is an essential
component of documenting and verifying rubella and CRS elimination. A genotype baseline map of
viruses found in each state/district in the country should be developed and maintained. Lack of
collection of specimens is a major impediment. Use of archival serum specimens is a solution and is
effectively used in the Hong Kong RRL. Since virological surveillance is limited worldwide for
rubella viruses, laboratories in the network should work together on interpreting genotype
information. For virological surveillance in the elimination phase, laboratory and epidemiology teams
should review all laboratory results and epidemiological data relevant to case classification. Good
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epidemiological investigation can contribute to determining the source of a virus (exporting countries)
and can provide information from countries without genetic baselines.
WHO provides guidance for CRS case classification, which gives consistency to surveillance. CRS
surveillance is a challenge as clinical manifestations may not be manifested within the first year of life
(after which laboratory confirmation is not currently possible), the health-care system may not have
the technology (e.g. hearing testing) to detect the defect, chronic disability and death may be
underestimated in infants/children with CRS depending on the follow-up of the infants with CRS,
laboratory confirmation for infants more than 6 months may be challenging, adding viral isolation and
RT-PCR to the CRS laboratory confirmation algorithms, and development of global CRS surveillance
performance indicators. Another challenge, besides adequate CRS surveillance is that CRS
surveillance requires interactions between epidemiologists and laboratorians. Joint training courses
structured around case classification was effective in the WHO South-East Asian Region and may be
effective in the future.
China
In China, rubella incidence showed a gradually decreasing trend since 2008, and reached the lowest
level in recent years. An epidemic rubella cycle in China is about every 7 to 8 years, and it may
change due to the introduction of the rubella-containing vaccine (RCV). Since 2014, all provinces had
an incidence below 5/100 000, and 22 provinces were found with less than 1/100 000 rubella
incidence in 2015. During 2004–2013, reported rubella cases were mainly concentrated in the under-
15 years age group. While the proportion of this age group decreased in 2014 and 2015 (42.75% in
2015), the proportion of the 15–39 age group increased gradually (53.66% in 2015). This is a concern
due to the CRS problem.
In 2015, Chinese National Measles/Rubella Laboratory coordinated with 31 provinces and carried out
the molecular epidemiology of rubella virus in China. A total of 340 rubella virus isolates were
obtained from 19 provinces in 2015, and 51 rubella virus isolates from eight provinces were obtained
from January to August 2016. All of the rubella viruses were identified using real-time RT-PCR,
genotyping and sequencing. Phylogenetic analysis based on the 739nt sequences showed that all the
rubella virus sequences could be divided into two genotypes: 1E (2015: 4 strains, 1.2%; 2016: 1
strain, 2.0%) and 2B (2015: 336 stains, 98.8%; 2016: 4 strains, 1.2%). The results indicated that
genotypes 1E and 2B were co-circulating in China and 2B became the predominant in recent years.
The prevalence trends of rubella genotypes in China during 1999–2016 were analysed; two genotypes
replacement occurred in the last 18 years. The first genotype replacement was found in 2001, when
genotype 1E instead of genotype 1F became the predominant genotype, and 1F viruses were not
found after 2002. Genotype 2B viruses had been sporadically detected before 2010, and the detection
rate of genotype 2B gradually increased since 2011; genotype 2B, instead of genotype 1E, became the
predominant genotype during 2014–2016. Almost all Chinese 1E viruses (2001–2015) from Mainland
China grouped into a single lineage. Two closely related clusters including Cluster A (2002–2015)
and Cluster B (2001–2009) could be identified within the Chinese lineage. Cluster B seems to have
been replaced by Cluster A in recent years. Total of five genotype 1E rubella virus strains detected in
2015 to August 2016 belong to three different transmission chains. 1E detected in Tianjin city in 2015
continuously circulated in 2016.
Though the important genetic baseline data had been established in China, a surveillance gap still
existed (e.g. Xinjiang and Tibet). Continuous virological surveillance should be carried out in all
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provinces. The shipment of rubella viruses in some of the provinces was delayed because of the
airport transportation certification issue. For some provinces, need to timely transport the viruses
strains to national laboratory. Real-time RT-PCR method as routine detection method has been
introduced into the LabNet, and routine quality control should be also strengthened. Rubella virus
surveillance should be strengthened during the measles elimination stage.
Japan
Rubella and CRS are notifiable in Japan. A low number of rubella cases was reported between 2008
and 2011. However, rubella cases increased in 2012, and a relatively large outbreak occurred in Japan
in 2013 with 14 344 cases detected. Between 2011 and 2016, the rubella viruses were classified into
three genotypes (1E, 1J and 2B), but only genotype 1J virus was detected in 2011. During the
outbreak in 2012 and 2013, large numbers of rubella viruses were reported; about 90% of the viruses
were classified as genotype 2B and about 10% were genotype 1E viruses. After the outbreak, the
number of viruses decreased greatly; however, both types of virus continue to be detected. A
phylogenetic tree was constructed using genotypes 2B and IE viruses detected from 2014 to 2016, and
the results suggested that the rubella viruses detected during the outbreak have already disappeared in
Japan since 2015 and new viruses with different origins have entered Japan several times. In Japan, a
serosurvey against rubella is conducted annually by the national programme. In 2011, before the last
outbreak, the results of the serosurvey showed adult females with high immunity across most ages,
but there was a large immunization gap in adult males aged 30 to 50 years old. It was found that many
patients belonged to this group in the last epidemic.
Since the start of case-based surveillance for CRS in Japan in 1999, the largest number of CRS cases
was reported in 2013. Between 2012 and 2014, a total of 45 cases were associated with the rubella
outbreak. To understand the burden of CRS and the impacts on public health in Japan, physicians
attending to the 45 CRS patients were asked about the clinical and virological conditions of the
patients using a self-completion questionnaire. The results of the survey showed about three quarters
of mothers had no or unknown history of rubella vaccination and the rest received one dose
vaccination. This indicates that rubella vaccination is still important for prevention of CRS. About
70% of mothers were documented with any rubella symptoms during their pregnancy. This suggests
that appropriate diagnosis of rubella for pregnant women is important for picking up possible CRS
cases. Almost all of the CRS patients were diagnosed at the age of 0 month, while the last case was
diagnosed at 18 months. Twenty-four per cent were born prematurely, and 24% died within two years
after birth. Follow-up of children with CRS or congenital rubella infection (CRI) is important for
detection of late onset of diseases. Long-term preventive measures against transmission of rubella
virus should be considered.
2.2.8 Measles and rubella recommendations from the fifth meeting on VPD LabNet in the
Western Pacific Region
A total of 38 measles- and rubella-specific recommendations arose from the regional VPD LabNet
meeting in May 2015. Overall implementation of recommendations showed 26% were achieved by
the LabNet, 10.5% were partially implemented, 55% are on-going, and 7.9% pending.
A summary of the accreditation status of the measles and rubella LabNet showed that almost all
laboratories met the minimum criteria except for the timeliness of reporting within four days. Two
laboratories dealt with large outbreaks in their countries, and the logistics in testing and reporting
most samples within four days after receipt were very challenging. Both countries also had test kit
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stock outs that impacted testing turnaround time. The new Measles-Rubella Surveillance Reporting
System, a web-based measles and rubella database being proposed for the Region, has considerable
potential for enhancing the exchange of data between the laboratory and the Regional Office. It is now
being used by Cambodia and the Lao People’s Democratic Republic. There is a need for surveillance
to also use the MRSRS database which limits its wider implementation. Expansion into CRS
surveillance is also possible.
2.2.9 Update on quality assurance for molecular proficiency testing
In 2014, a molecular PT programme was initiated to assess proficiency of laboratories that were
routinely performing molecular testing for measles and rubella viruses. The molecular PT panels were
distributed to 22 reference laboratories in the LabNet; 21 laboratories returned the reports and passed
for both measles and rubella testing. For 2015 molecular PT, all RRLs and selected national and
subnational laboratories were included. The number of participating laboratories was expanded to 49
laboratories. Most laboratories use WHO methods, but many did not provide details for methods. In
the Eastern Mediterranean Region, two additional laboratories received the panels but dropped out
and one laboratory failed for measles and rubella testing due to serious problems with real-time PCR
assay. One laboratory in the South-East Asia Region failed the measles PT. All participating
laboratories in the Western Pacific Region passed both measles and rubella molecular PTs.
The European Region has a separate mEQA system. Collaboration between WHO and a commercial
vendor (INSTAND e.V.) on mEQA for measles and rubella for the European Region was initiated in
November 2015. The number of measles laboratories participating was 34 (from 33 countries), while
the number of rubella laboratories participating was 30 (from 28 countries). All laboratories reported
the results.
The 2016 mEQA panels using FTA cards will be distributed by the Wisconsin State Laboratory of
Hygiene to the WHO regions. The panels are redesigned to separate detection and genotyping. The
regional laboratory coordinators will keep track of the of the delivery dates of the panels and share
them with US CDC.
2.2.10 Measles and rubella IgM PT and confirmatory testing
VIDRL has implemented a web-based submission of results with the new PT score algorithm
including not only results, but also timeliness and completeness of assay data, and assay validation
data. The assessment of the 2015 measles and rubella IgM PT results is based on the revised and
weighted PT score. The Western Pacific Region had 53 laboratories that participated in the 2015
global measles and rubella PT. Siemens was the most commonly used kit in the Region for both
measles and rubella testing. Haitai and Virion/Serion kits were mostly used in China. Denka Seiken
kits (2%) were also used for both measles and rubella. Other kits used for rubella testing were
Kerunda and Roche. All laboratories in the Western Pacific Region passed the PT, with 41 (77.4%)
laboratories scoring 100% and 12 (22.6%) laboratories scoring more than 95%. Among the 53
laboratories, 50 (94.3%) laboratories submitted the results through the website and three (5.7%)
laboratories submitted the results via email in an MS Excel file.
VIDRL supports confirmatory testing for seven national laboratories in the Region (Brunei
Darussalam, Fiji, Guam, Malaysia, New Zealand, Papua New Guinea and the Republic of Korea). In
2015 and 2016, six national laboratories referred samples for confirmation. Three laboratories were
found to have acceptable concordance rates (more than 90%) for both measles and rubella test results.
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Three laboratories had less than 90% concordance for measles, and one laboratory had less than 90%
concordance with the reference laboratory.
2.2.11 China LabNet confirmatory testing and EQA for provincial laboratories
China’s NML and the 31 provincial measles participated in the 2015 WHO measles and rubella
proficiency test. The panel was composed of 20 samples. IgM tests for measles and rubella were
performed and results were reported to WHO within 14 days from receipt of the samples. The PT
results were submitted via VIDRL’s website by the laboratories. The NML translated WHO’s
instructions and distributed them to 31 provincial laboratories. All the provincial laboratories have
independently uploaded the PT results. All the laboratories passed the PT.
In the China LabNet, two commercial kits (Haitai kit and Virion/Serion kit) were widely used for
measles IgM antibody detection. The PT results of the two kits showed a good correlation. For rubella
IgM detection, three rubella kits (Haitai kit, Virion/Serion kit and Kerunda kit) were used. The
correlation among the rubella IgM kits was not good, and the kits should be re-evaluated by NML.
Only NML participated in the 2015 WHO molecular PT for measles and rubella. The samples have
been genotyped for both measles and rubella. Results were reported within 6 weeks from receipt of
the panel. The laboratory passed the 2015 WHO PT for molecular measles and rubella.
In 2012, real-time RT-PCR was introduced into the China LabNet. In order to assess the capability of
real-time RT-PCR detection, the quality assurance of China LabNet should be strengthened and the
quality of the commercial real-time RT-PCR kit should be evaluated. The first measles/rubella
molecular PT was developed in December 2014. PT panels were prepared containing 10 samples
including four wild-type measles viruses, four wild-type rubella viruses, and two negative samples for
both measles and rubella; they were distributed to all 31 provincial laboratories. The real-time RT-
PCR results were reported to NML within seven working days after sample receipt, and genotyping
results were be reported to NML within 15 working days. All 31 provincial laboratories passed the
2014 molecular PT for measles and rubella.
In the China LabNet, provincial laboratories receive WHO on-site review every 3–4 years. In 2016,
Jilin, Inner Mongolia, Jiangsu, Tianjin, Hainan, Chongqing provincial laboratories were selected for
on-site review; all the laboratories passed the accreditation. All the other provincial laboratories
should receive desk reviews from NML. The review period was from 1 May 2015 to 30 April 2016.
In order to update network laboratories on progress in recent years and to build the capacity of
measles laboratory staff, the 12th National Measles Laboratory Network Workshop was held on
16–17 September 2015 in Beijing. All the participants were from the 32 provinces. Provincial
laboratories presented reports on the status of the measles control in their provinces. Experts from
WHO attended the workshop and presented a global and regional overview of measles and rubella
control and elimination.
In 2015, China CDC provided support for laboratories participating in the China CDC/US CDC/WHO
enhanced measles surveillance project in 32 provinces and 339 prefectures. It coordinated and assisted
provincial laboratories in developing an accreditation process for prefecture laboratories. It
cooperated with WHO, US CDC and other international agencies on global measles elimination and
eradication strategies. It also ensured regular exchange of information between national and global
specialized laboratories and within the China measles LabNet and also with the EPI.
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2.2.12 Data management and reporting
In the current data reporting structure, the Regional Office for the Western Pacific receives separate
data from the measles and rubella surveillance teams and the laboratories. The surveillance teams
submit their data through the Measles and Rubella Surveillance Reporting System (MRSRS), the
Access database and the Excel reporting template. The laboratories submit their data using the same
formats. Data submitted to the Regional Office for the Western Pacific are used in several ways. Data
exchange files are generated from these reports and are submitted to WHO headquarters once a month.
A measles and rubella bulletin is produced once a month, and a measles and rubella country profile is
produced at least once a year. Data are also being used for other publications, reports and
presentations.
Currently, most of the laboratories submit data using the Excel reporting template; however, when
using this format, certain issues are encountered. For example, core variables cannot be required and
are thus not being reported, it is prone to typo errors, and different codes are being used by different
countries. This reporting format also does not have an automatic reporting function, and data cannot
be easily linked to surveillance data. To address these issues, the Access database was developed. Six
laboratories are now using the Access database to report measles and rubella laboratory data. The
issue remains though that the data cannot be easily linked to surveillance data. The MRSRS was
developed to address this specific issue. The MRSRS is a web-based system designed to contain data
from both surveillance and laboratories. It has the same basic features as the Access database, but data
are automatically linked to surveillance data. Since it is web based, data are instantly reported. Also,
multiple users can enter data at the same time. It is currently being used by Cambodia and the Lao
People's Democratic Republic.
We look forward to moving towards the use of a standardized system (MRSRS or Access) in order to
improve data quality, by including core variables in reports and minimizing typo errors. We also aim
to strengthen systems to enable linking of laboratory data with surveillance data.
2.2.13 New technologies (vaccine-specific RT-PCR, Extended Windows (M-F) and next
generation sequencing and serological markers of measles infection)
Approximately 5% of recently vaccinated individuals develop a rash about 10–12 days after
vaccination. These vaccine reactions are clinically indistinguishable from measles cases. Genotyping
is currently the only method to identify cases associated with measles virus (MeV) vaccine (genotype
A), but genotyping may take several days. To avoid unnecessary public health responses, rapid
confirmation of vaccine reaction is needed during outbreaks in which recently vaccinated individuals
may also have been exposed to measles. US CDC developed a rapid RT-PCR method to specifically
detect MeV genotype A (MevA). Vaccine/wild-type result can be obtained in a few hours. Platforms
used are: Roche 480 LightCycler (Canada National Microbiology Laboratory and Germany Robert
Koch Institute) and ABI 7500 (US CDC). Overall sensitivity is 94% and specificity is 99.5%. The
lower limit of detection is about 1 log higher that the MeV RT-PCR. It works with the Qiagen
QuantiTect Kit but not with the Invitrogen Superscript III kit. The current genotyping approaches
(N450 and the H gene for measles) are adequate for routine genotyping. However, as we approach
elimination of measles and rubella, more resolution is needed to map transmission pathways. The
standardized genotyping targets are often insufficient to distinguish repeated importations from local
transmission. The Next Generation and Extended Sequencing Working Group (NEW) plans to
develop an extended, practical, genotyping target to help document elimination and to track
transmission of measles and rubella viruses. NEW developed a set of recommendations and standards
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for obtaining and depositing measles sequences for the Global Measles and Rubella Laboratory
Network. National laboratories are encouraged to collect and store specimens (suited for culture
isolation, if possible) for extended sequencing and to collaborate with GSLs and RRLs that have
capacity for whole genome and/or extended sequencing. MeaNS and RubeNS eventually will be able
to accept measles and rubella whole genome sequences and measles M gene and F gene sequences
from the noncoding region (MF-NCR).
In the United States, 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated
individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM
assays can give inconclusive results. A positive RT-PCR assay result can provide confirmation.
Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past
immunologic response to measles from natural infection or immunization. High concentrations of
measles neutralizing antibody have been measured in samples from confirmed measles cases with
high-avidity IgG: reinfection cases (RICs). Measles neutralizing antibody concentrations of >40 000
mIU/ml identified RICs with 90% sensitivity and 100% specificity. When serological or RT-qPCR
results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be
confirmed as RICs by measles neutralizing antibody concentrations of >40 000 mIU/ml.
3. CONCLUSIONS AND RECOMMENDATIONS
3.1 Conclusions
3.1.1 Polio
A two-day session for the polio laboratory network in the Western Pacific Region was organized to
discuss global progress towards polio eradication, to identify challenges in maintaining polio-free
status in the Western Pacific Region, to share updates on global and regional polio laboratory
networks, to review the performances of the polio network laboratories and to discuss the
implementation of new polio containment requirements following the global switch to bivalent OPV
(bOPV). The session included presentations on the transmission of wild poliovirus (WPV) and
vaccine-derived poliovirus (VDPV), the polio endgame strategy, new enhanced intratypic
differentiation (ITD) techniques for the detection of poliovirus type 2 (PV2), a new algorithm for the
safe shipping of PV2 samples within the network, laboratory containment and the implementation of
the WHO global action plan to minimize inadvertent release of polioviruses, quality assurance,
detection of polioviruses from environmental surveillance, experiences of the polio laboratory
network for the laboratory diagnosis of hand, foot and mouth disease (HFMD), data management and
country reports.
The meeting concluded that the performance of the regional polio laboratory network has been
sustained at polio-free-certification standard and that acute flaccid paralysis (AFP) surveillance
activities have been efficiently supported. The network laboratories provided critical evidence in
support of the continued polio-free status of the Region. As of August 2016, all 43 network
laboratories are accredited including all 38 polio laboratories with ITD function. All 43 laboratories
passed the virus isolation proficiency test (PT); however, two of the 37 laboratories performing the
ITD/VDPV PT and two of the seven laboratories performing the sequencing PT did not reach the
passing score. These four laboratories have undergone further training to improve their capability and
will undergo further proficiency panel testing.
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Since the Western Pacific Region has been polio-free for more than 10 years, network laboratories
have been actively involved in supplementary enterovirus or environmental surveillance. China
established an extensive HFMD laboratory network based on existing polio laboratories, and Japan
and Viet Nam have also implemented HFMD surveillance. The polio laboratories in Australia, China,
Japan and Malaysia are involved in testing samples collected from environmental surveillance, and
the Philippines laboratory has undergone training and will start environmental surveillance in late
2016. In the Region in 2015, China detected three VDPVs in AFP cases, two of which were
determined to be “ambiguous” and one from an immunodeficient case. None showed spread after
extensive investigation. A number of circulating VDPV type 1 viruses were detected in the
Lao People's Democratic Republic in late 2015 and early 2016. Viruses were found in AFP cases
(N=11) and contacts (N=25). Extensive surveillance following eight rounds of supplemental
immunization has not detected cases since January 2016. The continued use of environmental and
enterovirus surveillance in a number of countries and areas in the Region has provided valuable data
to support evidence of the continued polio-free status of the Region.
Workshops continue to build capacity in the Region. Hands-on training workshops in China equipped
five more provincial laboratories with the capacity to perform ITD. Another workshop held at the
Research Institute for Tropical Medicine (RITM), Philippines enabled eight countries to introduce the
new ITD algorithm for enhanced detection of PV2 following the switch to bOPV.
The global switch to bOPV in April 2016 has had wide-reaching implications for all laboratory
networks, particularly the Global Polio Laboratory Network (GPLN). Poliovirus type 2 was declared
eradicated. Post eradication, all type 2 polioviruses or materials potentially infected with PV2 must be
destroyed or handled in poliovirus-essential facilities with biosafety level 3 plus capacity. It was
proposed that the Western Pacific Region would have three poliovirus-essential facilities: the polio
network laboratories in Australia, China and Japan. The algorithm for all other polio network
laboratories to safely send any PV2 detected in the future to the poliovirus-essential facilities was
communicated.
Considerable efforts have been made to achieve polio eradication in the Region with a critical
contribution from the polio laboratory network. Continuous strong quality assurance procedures and
training activities to enhance the sensitivity of detecting WPV and VDPV are being implemented in
the Region, ensuring high-performance, high-quality laboratory support.
3.1.2 Measles and rubella
A two-day session of the regional measles and rubella laboratory network was organized to review
progress, identify challenges and develop plans to further strengthen the performance of network
laboratories including molecular capacity in support of measles and rubella elimination. The session
included presentations on global and regional measles and rubella elimination initiatives, quality
assurance, enhancing molecular surveillance, methods for identifying possible vaccine failure,
strengthening rubella and congenital rubella syndrome (CRS) surveillance, data management, country
reports and strengthening laboratory management.
The meeting concluded that measles and rubella network laboratories have helped in working towards
the regional goal of measles and rubella elimination by confirming suspected cases and identifying
measles and rubella virus genotypes circulating in the Region. The laboratory network has played a
critical role in the recent verification of measles elimination of seven Member States by identifying
that measles cases found in these countries are imported rather than due to endemic circulation. The
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network consists of one global specialized laboratory (GSL) in Japan, three regional reference
laboratories (RRLs) in Australia, China and Hong Kong SAR (China), 13 fully functional national
measles and rubella laboratories (NMRLs), 31 provincial and 331 prefectural laboratories in China,
and three subnational laboratories in Malaysia and Viet Nam. A total of 16 laboratories were assessed
under the WHO accreditation process, 11 with on-site reviews and five by correspondence. Another
27 laboratories are currently undergoing review and four laboratories’ checklists are still pending
submission.
As the role of the measles and rubella laboratory network extends to molecular surveillance for
confirming and maintaining verification of measles elimination, laboratories with virus isolation,
molecular testing and sequencing capabilities were encouraged to collect samples for sequencing and
genotyping for measles and especially rubella. Genotype and sequence information for measles are
submitted to the WHO sequence database for measles, MeaNS, for 11 of the 13 countries reporting
laboratory-confirmed cases. For rubella, sequences are submitted to the RubeNS genotype database
for five of the 16 countries in the Region reporting confirmed rubella cases. A comprehensive global
quality assurance programme has been established, and 11 of the 12 laboratories conducting
molecular testing in the Region participated. All achieved a passing score for measles, and 10
laboratories passed the rubella component.
Countries that have experienced large measles outbreaks are considering establishing a subnational
network of laboratories to spread the workload and improve timeliness of reporting. China has had a
well-established subnational network since 2000. Viet Nam has two subnational laboratories, and
Malaysia has one. The Philippines is investigating the logistics and economics of establishing a
subnational network of laboratories that will test for measles and rubella as well as Japanese
encephalitis (JE) and participate in AES surveillance.
Establishing CRS surveillance in countries in the Region is a challenge; however, an appropriate
laboratory testing strategy is being developed in collaboration with the GSLs at the United States
Centers for Disease Control and Prevention (US CDC) and the National Institute of Infectious
Diseases (NIID), Japan.
The implementation of GAPIII containment of polioviruses and potentially infectious material will
have an impact on the measles and rubella laboratory network. Any respiratory or faecal sample
collected for any purpose in a time and geographic area of OPV use is presumed potentially infectious
for polioviruses (Sabin) unless otherwise demonstrated, under GAPIII guidelines. As many measles
and rubella laboratories have stored throat swabs collected during such a period, they may not be
aware that these samples are now considered as potentially infectious for polioviruses and the need to
meet the deadline for completing an inventory of such material. If considered a high risk, these
samples may have to be shipped to a poliovirus-essential facility, a poliovirus-non-essential facility or
destroyed.
The regional measles and rubella laboratory network has made considerable progress since its
establishment in 1998. The network now includes 386 laboratories that are all following WHO-
recommended methods and procedures under a strong environment of quality assurance. A total of
120 000 serum samples from suspected measles cases were tested in 2015 and reported timely and
accurately. More than 3200 measles virus sequences and 300 rubella sequences were reported to the
WHO genotype databases in 2015, allowing informed decisions on the molecular surveillance of
measles and rubella globally and in the Region.
43
3.2 Recommendations
3.2.1 Polio
1) As of January 2016, only poliovirus-essential facilities should handle and store WPV type 2
(WPV2) and VDPV type 2 (VDPV2); the same is true of OPV/Sabin type 2 materials as of
August 2016. Poliovirus-non-essential facilities that will continue to receive samples from AFP
and environmental surveillance originating from recent OPV-using countries must implement safe
and secure working practices based on a risk assessment and appropriate biorisk management
systems as described in GAPIII, Annex 6.
2) As of August 2016, all poliovirus laboratories in the Western Pacific Region must follow the new
algorithm for sample referral.
a) Virus isolation (VI) laboratory: all viruses growing in L20B cell must be transferred (by
FTA cards) to a designated poliovirus-essential facility that has capacity for virus isolation,
ITD and sequencing (VIIS).
b) Virus isolation and ITD laboratory: all new identified PV2 isolates must be transferred (by
FTA cards) to a designated poliovirus-essential facility that has capacity for VIIS for VP1
sequencing.
c) VIIS laboratory but poliovirus-non-essential facility: any new identified PV2 isolates must
be transferred (by FTA cards) to a designated poliovirus-essential facility that has capacity
for VIIS for VP1 sequencing.
d) Designated poliovirus-essential facilities with capacity for VIIS in the regional polio
laboratory network are:
• VIDRL, Australia: receiving PV2 for sequencing from Malaysia, New Zealand, the
Philippines and Singapore;
• China CDC: receiving PV2 for sequencing from provincial laboratories in China;
• NIID, Japan: receiving PV2 for sequencing from Hong Kong SAR (China), Mongolia
(also for ITD), Republic of Korea and Viet Nam (2).
3) After 1 August 2016, three months following the OPV2 switch in April 2016, all polio
laboratories are requested to report all type 2 polioviruses detected from any source within 24
hours after completing ITD and when completing sequencing tests. The following steps should be
implemented:
a) report all new PV2 to the Ministry of Health and WHO within 24 hours;
b) all original stool samples, stool extracts and cell-culture harvests to be packed, sealed and
kept under lock and key at -20 °C;
c) send isolate using FTA cards as soon as possible, and within seven days, for sequencing to
designated poliovirus-essential facility and track the shipment;
d) when sequencing results are received from the poliovirus-essential facility, immediately
notify the Ministry of Health and WHO (country office, Regional Office and headquarters)
within 24 hours (and get confirmation of receipt of message);
e) destroy sealed packages under the guidance of the regional laboratory coordinator (RLC)
and global laboratory coordinator (GLC); and
f) document everything and share reports with the Ministry of Health and WHO.
44
4) A new ITD kit (version 5.0), including PV2 primers to detect all Sabin 2-related viruses as well as
WPV2 used by IPV vaccine manufacturers, will be provided to ITD laboratories (either as a new
kit or as a supplement to version 4.1) by October. All viruses growing in L20B need to be tested
with the ITD 5.0 kit from date of receipt.
5) A new ITD PT panel, which will be tentatively distributed to all ITD laboratories in October 2016,
will need to be tested with the new ITD 5.0 kit.
6) All Sabin 2-positive reactions identified by ITD must be sequenced. It will not be necessary to run
an additional Sabin 2 VDPV assay. VDPV2 reactions will not be needed even if using the VDPV
4.1 kit.
7) All laboratories identifying VDPVs should share the VP1 sequences (FASTA file) with WHO.
WHO will make them available to other GPLN sequencing laboratories to allow rapid comparison
with other VDPVs detected worldwide. Provision will be taken to ensure confidentiality and
propriety of such sequences.
8) Laboratories having challenges in obtaining the minimum numbers of AFP stool specimens to
meet the accreditation criterion (i.e. 150 stools annually) should consider collecting stool samples
from other sources, including conducting healthy children surveys.
9) To maintain expertise in ITD procedures, laboratories that are not regularly detecting polioviruses
should perform ITD testing using National Institute for Biological Standards and Control (NIBSC)
sensitivity strains (laboratory quality control types 1 and 3 only) at least once a month.
10) Laboratories that do not achieve a passing score for isolation, ITD or sequencing PTs should
thoroughly explore the reasons for the variance and resolve any issues detected in collaboration
with the PT provider, the RLC and the GLC before repeating a new panel.
11) Environmental surveillance continues to provide valuable evidence of poliovirus circulation.
Polio network laboratories are requested to inform the WHO Regional Office if any other
laboratories in their countries are performing environmental surveillance in order to gain evidence
of presence or absence of polioviruses in the environment.
12) An environmental surveillance accreditation checklist is in the process of being developed and
should be ready for piloting by the end of 2016. All environmental surveillance laboratories can
expect to undergo environmental surveillance accreditation in 2017.
13) FTA cards have been validated for the shipment of sequencing PTs. All sequencing laboratories
should ensure procurement of supplies and reagents needed for FTA card elution and testing
(reference to FTA cards elution protocol). All laboratories should ensure they have sufficient
stock of FTA cards at all times.
14) The “polio legacy” of transitioning to the surveillance of HFMD or other non-polio enteroviruses
post eradication is a potential progression for many laboratories in the Region. All laboratories
currently carrying post-eradication surveillance should report their findings and budget
requirements to the RLC to be presented the next VPD LabNet meeting.
45
15) VDPV classification should be a coordinated decision-making process. All laboratory personnel
and national programme staff should be aware of the field investigation requirements described in
the Global Polio Eradication Initiative’s guidelines for the reporting and classification of VDPVs,
(http://www.polioeradication.org/Portals/0/Document/Resources/VDPV_ReportingClassification.
pdf). A sequencing laboratory should be familiar with the elements under the field investigation
section of the guidelines when communicating a VDPV result so that it can advise field staff of
the need to immediately conduct appropriate clinical and field investigations.
16) A standardized reporting text for email messages accompanying sequencing reports should be
used in the GPLN. US CDC and WHO will provide a consensus on genetic characterization,
categorization and reporting for VDPVs.
17) To allow finalization of global polio laboratory data gathering, all polio laboratories are requested
to complete their 2015 annual report in the Global Polio Laboratory Network Management
System by the end of September 2016. Compliance will be assessed during accreditation exercises.
18) All polio laboratories in the Western Pacific Region should obtain low passaged RD-A and L20B
from a master cell bank to prepare working cell bank stocks used for poliovirus surveillance
directly from authenticated sources such as NIBSC, VIDRL, NIID, US CDC or China CDC.
19) All laboratories are reminded that laboratory data submission for AFP specimens and
environmental samples are to be sent to the WHO Regional Office for the Western Pacific on a
weekly basis as feedforward files using the WHO Western Pacific Region polio Access database.
Zero reporting is to be used when no AFP specimens are received.
Aggregated laboratory data for non-AFP specimens are to be sent to the WHO Regional Office at
least on a monthly basis.
20) As soon as the polio AFP surveillance reporting system (PASRS) is up and running, all countries
should consider migrating to the web-based system.
21) The WHO Regional Office for the Western Pacific should consider holding annual polio
laboratory network meetings (at least for the next 2 years) while the implications of polio
endgame strategy requirements are being finalized.
22) The regional polio laboratory network may send serum or dried blood spot (DBS) samples for
staff handling potentially infectious poliovirus material, who have unknown poliovirus immunity,
to CDC for poliovirus serology.
23) All network laboratories are encouraged to use the laboratory self-assessment tools for GAPIII,
Annex 6.
3.2.2 Measles and rubella
1) IgM detection and molecular testing for confirmation of both rubella and measles needs to be
implemented or strengthened, especially in countries that have recently introduced rubella
vaccination. Laboratories will need to identify resources to cover the increased costs of the testing
required for integration of measles and rubella testing, and case-based surveillance.
46
2) In order to conserve laboratory resources, measles and rubella outbreak response plans should
include laboratory surge capacity and prioritization of sample collection and testing. The plans
should include methods for rapid acquisition of supplies, backup personnel, and coordination
between laboratory and surveillance. Efforts should be made to epidemiologically link cases to
laboratory-confirmed cases and during large outbreaks ensure specimens are collected from only
selected suspected cases (e.g. from first 5–10 suspected cases in a district or province or if the
outbreak lasts for more than 30 days), not all.
3) Laboratories unable to obtain baseline molecular data may consider using serum samples
collected from confirmed cases within the first three days after rash onset for rubella and within
five days of rash onset for measles. These serum samples should be sent to the designated RRL
after consultation with the RLC. National measles and rubella laboratories (NMRLs) without the
capacity for molecular analysis should send representative virological or serum samples to their
designated RRL after consulting with the RLC and RRL so that the country can obtain genetic
information on both outbreaks and sporadic cases. A serum volume of >200ul is required for
molecular testing and should be shipped under the appropriate cold chain.
4) Measles and rubella laboratories in the regional network should submit genotype and sequence
data to measles and rubella nucleotide surveillance databases (MeaNS and RubeNS) at least
monthly. Information published in the monthly Measles-Rubella Bulletin will reflect MeaNS and
RubeNS data submitted.
5) One of the lines of evidence for the verification of elimination is determining population
immunity through analysis of data on routine and supplementary immunization activities.
Alternatively, countries may include other sources of immunity data such as well-conducted
seroprevalence studies. WHO is currently developing guidelines for the assessment of population
immunity against measles and rubella through seroprevalence studies. However, countries should
carefully consider implementing such activities, as they are complicated, costly and time-
consuming, and the use of high-quality serology assays is critical.
6) The use of molecular testing for case classification can provide a useful addition to antibody
detection, and should be expanded. The ability to separate similar lineages of circulating viruses
may require new methods such as extended sequencing windows to enhance molecular
epidemiology. Next generation sequencing may provide supplementary information regarding
single or multiple importations during an outbreak. Because these techniques typically require
higher quantities of RNA, viral isolates are necessary. Countries requiring these techniques should
communicate with their RLC and GSL.
To ensure that the quality and performance of the regional measles and rubella laboratory network
meet the criteria outlined in the Measles and Rubella Elimination in the Western Pacific, Regional
Strategies and Plan of Action:
7) Participants are kindly requested to review and share comments on this document with the RLC
before 1 October 2016.
8) Member States are requested to allocate sufficient human and financial resources to support the
laboratories of the regional measles and rubella laboratory network.
47
9) All NMRLs in the Region should submit samples for confirmatory testing to their designated
RRL in a timely manner (one to two times a year). A schedule of suitable shipping dates can be
arranged in consultation with the RLC, RRL and the NMRLs. To avoid delays to the agreed
schedule, the NMRLs should arrange timely accession of import/export permit, if required.
Follow-up of discordant results should be made and findings shared with RLC, RRL and NMRLs
for future improvement.
10) If an NML is unable to prepare positive in-house control samples, they may request assistance
from the RLC and RRL.
11) To ensure the timely arrival of samples for PT, NMRLs should secure an import permit and liaise
with WHO country offices to facilitate receipt of PT samples in advance of the schedule of
distribution of PT panels. Laboratories should work with the RRL and RLC to evaluate results
and address any issues identified by the PT. Results should be submitted via the PT website
within the required 14-day timeline.
12) Laboratories that are routinely performing molecular testing should participate in the global
mEQA programme. PT panels should be requested by the RLC and testing by the NMRLs should
be completed within six weeks of receipt of the panel.
13) Laboratories should have regular communication with the RLC and WHO country offices to
update them on any change in workload and identify potential shortfalls in supplies that may
impact their testing turnaround time.
14) Where issues in quality are identified in subnational laboratories, the NMRL responsible for that
country should monitor the performance of subnational laboratories and provide support where
necessary.
15) All non-polio laboratories (including measles and rubella laboratories) are requested to complete
an inventory of potentially infectious materials in line with both the GAPIII and the WHO
guidance document (expected to be available in October), for classification of potentially
infectious materials having the likelihood of being contaminated with Sabin poliovirus type 2.
16) To improve rubella virus and CRS surveillance, collaboration between the epidemiology
surveillance staff and laboratory staff is particularly important. Joint meetings should be held
regularly and include a focus on improving CRS surveillance and collection of appropriate
samples (serum, urine and pharyngeal) for laboratory confirmation.
3.2.3 Recommendations for WHO Secretariat
1) To assist with the timely distribution of PT panels, test kits and other supplies/equipment, the
WHO Regional Office should prepare a timetable/schedule for distribution of PT samples and
supplies in advance and share this information with NMRLs.
ANNEX 1
LIST OF PARTICIPANTS, TEMPORARY ADVISERS, OBSERVERS, AND SECRETARIAT
POLIOMYELITIS SESSION, 12–15 September 2016
1. PARTICIPANTS
AUSTRALIA Dr Bruce Robinson Thorley, Senior Medical Scientist, Head,
WHO Polio Regional Reference Laboratory, Victorian Infectious
Diseases Reference Laboratory, 792 Elizabeth Street, Melbourne,
Victoria 3000. Tel no.: +613 9342 9607. Fax no.: +6139342 9665.
E-mail: [email protected]; [email protected]
Dr Linda Katherine Hobday, Medical Scientist, WHO Polio Regional
Reference Laboratory, Victorian Infectious Diseases Reference
Laboratory, 792 Elizabeth Street, Melbourne, Victoria 3000.
Tel no.: +61 3 9342 9607. Fax no.: +61 3 9342 9665.
E-mail: [email protected]
CHINA Dr Zhu Shuangli, Associate Chief Technician, National Institute
for Viral Disease Control and Prevention, Chinese Center for
Disease Control and Prevention, No 155 Changbai Road, Changping
District, Beijing 102206. Tel no.: +86 10 5890 0185.
Fax no.: +86 10 5890 0184. E-mail: [email protected]
Dr Wang Dongyan, Associate Senior Technologist, National Institute
for Viral Disease Control and Prevention, Chinese Center for
Disease Control and Prevention, No 155 Changbai Road, Changping
District, Beijing 102206. Tel no.: +86 10 5890 0185.
Fax no.: +86 10 5890 0184. E-mail: [email protected]
HONG KONG Ms To Pui-chi, Amanda, Scientific Officer (Medical), 9/F Public
SAR (CHINA) Health Laboratory Centre, 382 Nam Cheong Street, Shek Kip Mei,
Kowloon. Tel no.: +852 2319 8239. Fax no.: +852 2319 5989.
E-mail: [email protected]
JAPAN Dr Hiroyuki Shimizu, Chief, Laboratory of Enteroviruses,
Department of Virology II, National Institute of Infectious Diseases,
4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Tel no.: +81 42 561 0771. Fax no.: +81 42 561 4729.
E-mail: [email protected]
MALAYSIA Dr Ravindran Thayan, Head, Virology Unit, Infectious Diseases Research
Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur,
50588. Tel no.: +60 3 2616 2669/74. Fax no.: +60-3 2693 8094.
E-mail: [email protected]
Annex 1
MONGOLIA Dr Ariuntugs Sodnomjamts, Researcher, National Polio Laboratory,
Public Health Institute, Peace Avenue 17, Bayanzurkh District,
Ulaanbaatar City. Tel no.: +976 11 452664.
Fax no.: +976 11 452664. E-mail: [email protected]
NEW ZEALAND Dr Sue Qiu Huang, Senior Science Leader-Virology, Communicable
Disease Group, Institute of Environmental Science and Research,
66 Ward Street, Wallaceville, Upper Hutt. Tel no.: +64 4 529 0606.
Fax no.: +64 4 529 0601. E-mail: [email protected]
PHILIPPINES Dr Lea Necitas Apostol, Supervising Science Research Specialist,
Virology Department, Research Institute for Tropical Medicine,
9002 Research Drive, FCC Compound, Alabang, Muntinlupa City
Tel no.: +63 2 809 7120. Fax no.: +63 2 809 7120.
E-mail: [email protected]
SINGAPORE Ms Puong Kim Yoong, Senoir Science Officer, Virology Section
Department of Pathology, Singapore General Hospital
20 College Road, Singapore 169856. Tel no.: +65 6321 4940.
Fax no.: +65 6221 3689. E-mail: [email protected]
SOCIALIST Dr Nguyen Thi Hien Thanh, Head, Enterovirus Laboratory
REPUBLIC National Institute of Hygiene and Epidemiology, No. 1 Yersin
OF VIETNAM Street, Hanoi 10000. Tel no.: +84 4 3 972 6851 ext. 218.
Fax no.: +84 4 3 972 6850. E-mail: [email protected]
Dr Nguyen Thi Thanh Thao, Head, Laboratory of Enteric Viruses,
Pasteur Institute, 167 Pasteur Street, District 3, Ho Chi Minh City.
Tel no.: +84 8 38 202 878. Fax no.: +84 8 38 231 419.
E-mail: [email protected]
2. TEMPORARY ADVISERS
Dr Mark Steven Oberste, Chief, Polio and Picornavirus Laboratory Branch, Division of Viral Diseases (DVD), National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention, Atlanta, Georgia 30333, United States of America. Tel no.: 1 (404) 639 5497. Fax no.: 1 (404) 639 4011. E-mail: [email protected]
Dr Xu Wenbo, Acting Chief of National Laboratory of Poliomyelitis and Deputy Director of
National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control
and Prevention, 155 Changbai Road, , Changping Qu, Beijing 102206, People's Republic of
China.
Tel no.: +86 10 87102056. Fax no.: +86 10 58900187. E-mail: [email protected]
Dr Youngmee Jee, Director, Center for Immunology and Pathology, Korea National Institute of
Health, Korea Centers for Disease Control and Prevention, 187 Osongsaengmyeong 2(i)-ro
Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, South Korea.
Tel no.: +8243 7198400. Fax no.: +8243 7198402. E-mail: [email protected];
Annex 1
3. OBSERVERS
Ms Leonibel Reyes, Senior Science Research Specialist, Virology Department, Research Institute
for Tropical Medicine, 9002 Research Drive, Filinvest Corporation City Compound, Alabang,
Muntinlupa City 1781, Philippines. Tel no.: +63 2 8097120. Fax no.: +63 2 8097120.
E-mail: [email protected]
Ms Maria Melissa Ann Jiao, Science Research Specialist I, Virology Department, Research
Institute for Tropical Medicine, 9002 Research Drive, FCC Compound, Alabang, Muntinlupa
City 1781, Philippines. Tel no.: +63 2 8097120. Fax no.: +63 2 8097120. E-mail:
MEASLES SESSION, 14-15 September 2016
1. PARTICIPANTS
AUSTRALIA Dr Vicki Vasiliki Stambos, Scientist, WHO Measles Regional Reference
Laboratory, Victorian Infectious Diseases Reference Laboratory
The Doherty Institute, 792 Elizabeth Street, Melbourne, Victoria 3000.
Tel no.: +613 9342 9646. Fax no.: +613 9342 9676.
E-mail : [email protected]; [email protected]
Dr Thomas Tran, Scientist, WHO Measles Regional Reference
Laboratory, Victorian Infectious Diseases Reference Laboratory, The
Doherty Institute, 792 Elizabeth Street, Melbourne, Victoria 3000.
Tel no.: +61 3 9342 9626. Fax no.: +61 3 9342 9629. E-mail:
BRUNEI Dayang Hajah Mazmah Binti Haji Ahmad Morshidi, Scientific Officer, DARUSSALAM Biomedical Science Research, Ministry of Health, Jalan Sumbiling Bandar Seri Begawan 8511. Tel no.: +673 8881682.
E-mail: [email protected]
CAMBODIA Mr Am Chanthan, Head, Immunology Unit (Laboratory)
National Institute of Public Health, Lot #80, Samdach Penn Nouth Blvd.,
Sangkat Boeng Kok II, Khan Tuol Kork, Phnom Penh.
Tel no.: +855 12 881 196. Fax no.: +855 23 882 889.
E-mail: [email protected]
Mr Ung Serey Sopheak, Staff, Immunology Unit (Laboratory), National
Institute of Public Health, Lot # 80 Samdach Penn Nouth Blvd, Sankat
Boeng Kok II, Khan Tuol Kok, Phnom Penh. Tel no.: +855 12 669045.
Fax no.: +855 23 882 889. E-mail: [email protected]
Annex 1
CHINA Dr Xu Wenbo, Acting Chief of National Laboratory of Poliomyelitis and
Deputy Director of National Institute for Viral Disease Control and
Prevention, Chinese Centre for Disease Control and Prevention,
155 Changbai Road, Changping District, Beijing 102206.
Tel no.: +8610 58900187. Fax no.: +8610 58900187.
E-mail: [email protected]
Dr Li Yong, Chief of Bureau for Disease Control and Prevention
Yunan Provincial Health and Family Planning Commission, Room 533
Zhengtong Building, 309 Guomao Road, Kunming, Yunan.
Tel no.: (86 13) 577141458. Fax no.: (86 871) 67195186.
E-mail: [email protected]
Dr Cui Aili, Researcher, National Institute for Viral Disease Control and
Prevention, Chinese Center for Disease Control and Prevention,
No 155 Changbai Road, Changping District, Beijing 102206.
Tel no.: +86 10 5890 0188. Fax no.: +86 10 5890 0188.
E-mail: [email protected]
Dr Zhu Zhen, Associate Researcher, National Institute for Viral Disease
Control and Prevention, Chinese Center for Disease Control and
Prevention
No 155 Changbai Road, Changping District, Beijing 102206.
Tel no.: +86 10 5890 0188. Fax no.: +86 10 5890 0188.
E-mail: [email protected]
Dr Wang Huiling, Assistant Researcher, National Institute for Viral
Disease Control and Prevention, Chinese Center for Disease Control and
Prevention , No 155 Changbai Road, Changping District, Beijing
102206. Tel no.: +86 10 5890 0189. Fax no.: +86 10 5890 0188.
E-mail: [email protected]
Dr Wang Jinghui, Technician, Hebei Provincial Center for Disease
Control and Prevention, Huai’an East Road 97, Shijiazhuang.
Tel no.: +8618 9033 90332. E-mail: [email protected]
FIJI Dr Daniel Brian Faktaufon, Acting Senior Medical Officer, Fiji Center
for Communicable Disease Control, Mataika House Building, Princess
Road, Tamavua, Suva. Tel no.: +679 330 1967. E-mail:
HONGKONG SAR Dr Woo Kei-Sheng Gibson, Scientific Officer (Medical), Microbiology
(CHINA) Division, 9/F Public Health Laboratory Centre, 382 Nam Cheong Street,
Shek Kip Mei, Kowloon. Tel no.: +852 2319 8385.
Fax no.: +852 2549 5989. E-mail: [email protected]
Dr Chan Chi Wai Rickjason, Consultant Medical Microbiologist, Public
Health Laboratory Services Branch, Centre for Health Protection,
Department of Health, 9/F Public Health Laboratory Centre, 382 Nam
Cheong Street, Shek Kip Mei, Kowloon. Tel no.: +852 2319 8255.
Fax no.: +852 2549 2445. E-mail: [email protected]
Annex 1
JAPAN Dr Yoshio Mori, Chief of Rubella Laboratory, Department of
Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen,
Musashimurayama-shi, Tokyo 208-0011. Tel no.: +81 42 561 0771
Fax no.: +81 42 561 1960. E-mail: [email protected]
Dr Katsuhiro Komase, Head of Laboratory of Measles
Department of Virology III, National Institute of Infectious Diseases,
4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011.
Tel no.: +81 42 561 0771. Fax no.: +81 42 561 1960.
E-mail: [email protected]
LAO PEOPLE'S Dr Vongphrachanh Phengta, Director, National Center for Laboratory
DEMOCRATIC and Epidemiology, Ministry of Health, Km 3 Thadeua Road, Vientiane
Tel no.: +856 21 312351. Fax no.: +856 21 351006.
E-mail: [email protected]
Mr Som Oulay Virasack, Staff, Sero-Virology Section,
National Center for Laboratory and Epidemiology, Ministry of Health
Km 3 Thadeua Road, Vientiane. Tel no.: +856 21 312351.
Fax no.: +856 21 351006. E-mail: [email protected]
MALAYSIA Madam Norizah binti Ismail, Science Officer, National Public Health
Laboratory, Ministry of Health Malaysia, Lot 1853, Kg. Melayu,
47000 Sungai Buloh, Selangor. Tel no.: +60 3 6126 1200.
Fax no.: +603 6140 2249. E-mail: [email protected]
Madam Rashidah Mohammad, Science Officer, Kota Kinabalu Public
Health Laboratory, Kolam Road, Bukit Padang, Kota Kinabalu 88850,
Sabah. Tel no.: +60 88 250710. Mobile no.: +60 16 809 1076.
Fax no.: +60 88 243210. E-mail: [email protected]
MONGOLIA Dr Nyamaa Gunregjav, Physician, National Measles Laboratory,
National Center for Communicable Diseases, Ministry of Health and
Sports, Nam Yan Ju Street 1, Bayanzurkh District, Ulaanbaatar City
210-648. Tel no.: +976 88 703888. Fax no.: +976 11 455847.
E-mail: [email protected]
Dr Naranzul Tsedenbal, Virologist, Virology Laboratory, National Center
for Communicable Diseases, Ministry of Health and Sports, Government
Building VIII, Olympic Street-2, Sukhbaatar District, Ulaanbaatar City
51. Tel no.: +976 1 99911833. Fax no.: +976 11 455847.
E-mail: [email protected]
NEW ZEALAND Dr Meik Dilcher, Scientific Officer, Virology/Serology Department,
Canterbury Health Laboratory, P.O. Box 151, Christchurch 8011.
Tel no.: +64 3 364 1229. Fax no.: +64 3 364 0750.
E-mail: [email protected]
PAPUA NEW Mr Willie Porau, Laboratory Manager, Central Public Health
GUINEA Laboratory, National Department of Health, PO Box 807, Waigani,
National Capital District. Tel no.: +675 324 8199.
Fax no.: +675 325 6342. E-mail: [email protected]
Annex 1
PAPUA NEW Mr Saul Pembu, Scientific Officer, Serology and Sero-Surveillance
GUINEA Unit, Central Public Health Laboratory, National Department of Health,
PO Box 807, Waigani, National Capital District. Tel no.: +675 324
8202. Fax no.: +675 325 6342. E-mail: [email protected]
PHILIPPINES Mr Rex Centeno, Senior Science Research Specialist, Virology
Department, Research Institute for Tropical Medicine, 9002 Research
Drive, FCC Compound, Alabang, Muntinlupa City 1781.
Tel no.: +63 2 8097120. Fax no.: +63 2 809 120.
E-mail: [email protected]
Mr Daniel Villarico, Bacteriologist I, Virology Department, Research
Institute for Tropical Medicine, 9002 Research Drive, FCC Compound,
Alabang, Muntinlupa City 1781. Tel no.: +63 2 8097120.
Fax no.: +63 2 8097120. E-mail: [email protected]
SINGAPORE Dr Cui Lin , Senior Prinicpal Scientist, National Public Health
Laboratory General Hospital, Tan Tock Seng Hospital, 11 Jalan Tan
Tock Seng, Singapore 308433. Tel no.: +65 9338 7212; +65 6357
7301. Fax no.: +65 6251 5829. E-mail: [email protected]
VIET NAM Dr Nguyen Thanh Long, Director, National Influenza Center
Head, National Laboratory of Respiratory Viruses, Pasteur Institute
167 Pasteur Street, District 3, Ho Chi Minh City.
Tel no.: +84 8 202 878. Fax no.: +84 8 231 419.
E-mail: [email protected]
Dr Do Phuong Loan, Researcher, Laboratory for Respiratory Viruses,
National Institute of Hygiene and Epidemiology, No. 1 Yersin, Hai Ba
Trung District, Hanoi 112800. Tel no.: +844 39726851 ext. 110.
Fax no.: +844 39724624. E-mail: [email protected];
Dr Trieu Van Thi Thanh, Researcher, Laboratory for Respiratory Viruses
National Institute of Hygiene and Epidemiology, No. 1 Yersin, Hai Ba
Trung District, Hanoi 112800. Tel no.: +84 4 39726851 ext 110.
Fax no.: +84 4 39724624. E-mail: [email protected]
Dr Dang Thanh Giang, Staff, National Laboratory of Respiratory
Viruses, Pasteur Institute, 167 Pasteur Street, District 3, Ho Chi Minh
City. Tel no.: +84 098 937 3176. Fax no.: +84 8 231 419.
E-mail: [email protected]
Ms Lam Tu Quynh, Researcher, Pasteur Institute, No. 8 Tran Phu Street
Nha Trang City, Khanh Hoa Province. Tel no.: +84 58 382 9539.
Fax no.: +84 58 382 4058. E-mail: [email protected]
Mr Le Van Tuan, Researcher, Tay Nguyen Institute of Hygiene and
Epidemiology, 34 Pham Hung Street, Buon Ma Thuot, Dak Lak
Province. Tel no. : +84 5003 814878. E-mail:
Annex 1
2. TEMPORARY ADVISERS
Dr Paul Rota, Team Leader, Measles Team, Measles, Mumps, Rubella and Herpesvirus,
Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention ,
Mailstop C-22, 1600 Clifton Road , Atlanta, Georgia 30333, United States of America.
Tel no.: +1 404 639 3512. Fax no.: +1 404 639 4187. E-mail: [email protected]; [email protected]
Dr Makoto Takeda, Director, Department of Virology 3, National Institute of Infectious Diseases
4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan. Tel no.: 8142 848 7060.
Fax no.: 8142 562 8941. E-mail: [email protected]
Dr Youngmee Jee, Director, Center for Immunology and Pathology, Korea National Institute of
Health, Korea Centers for Disease Control and Prevention, 187 Osongsaengmyeong 2(i)-ro,
Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, South Korea.
Tel no.: 8243 7198400. Fax no.: 8243 7198402. E-mail: [email protected]; [email protected]
3. OBSERVERS
Ms Jhulie Anne Mangurali, Science Research Specialist II, Virology Department, Research
Institute for Tropical Medicine, 9002 Research Drive, FCC Compound , Alabang, Muntinlupa
City, 1781, Philippines. Tel no.: +63 2 862 2320. Fax no.: +63 2 8097120.
E-mail: [email protected]
Ms Chrissa Myrh Fuentes, Medical Technologist, Virology Department, Research Institute for
Tropical Medicine, 9002 Research Drive, FCC Compound , Alabang, Muntinlupa City, 1781,
Philippines. Tel no.: +63 2 8097120. Fax no.: +63 2 8097120.
E-mail: [email protected]
3. SECRETARIAT
Dr Mark Jacobs, Director, Division of Communicable Diseases, World Health Organization,
Regional Office for the Western Pacific, United Nations Avenue 1000, Manila, Philippines.
Tel no.: +63 2 5289701. Fax no.: +63 2 5211036. E-mail: [email protected]
Dr Sergey Diorditsa, Coordinator, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue, 1000 Manila,
Philippines. Tel no.: +63 2 5289745. Fax no.: +63 2 521 1036. E-mail: [email protected]
Ms Varja Grabovac, Scientist, Expanded Programme on Immunization , World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no.: +63 2 5289747. Fax no.: +63 2 5211036. E-mail: [email protected]
Dr Zhang Yan, Laboratory Virologist, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no.: +63 2 5289034. Fax no.: +63 2 5211036. E-mail: [email protected]
Annex 1
Dr W. William Schluter, Medical Officer (Group Lead, Accelerated Disease Control), Expanded
Programme on Immunization ,World Health Organization, Regional Office for the Western
Pacific, United Nations Avenue 1000, Manila. Philippines. Tel no.: +63 2 5289748.
Fax no.: +63 2 5211036. E-mail: [email protected]
Dr Yoshihiro Takashima, Medical Officer, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no.: +63 2 528 9746. Fax no.: +63 2 5211036. E-mail: [email protected]
Dr Roberta Pastore, Technical Officer, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no.: +63 2 5289018. Fax no.: +63 2 521 1036. E-mail: [email protected]
Dr David Alexander Featherstone, Consultant (Measles and Rubella Laboratory), Expanded
Programme on Immunization, World Health Organization, Regional Office for the Western
Pacific, United Nations Avenue 1000, Manila, Philippines. Tel no.: +63 2 5289019.
Fax no.: +63 2 521 1036. E-mail: [email protected], [email protected]
Dr Santosh Gurung, Consultant, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no. : +63 2 528 9704. Fax no.: +63 2 521 1036. E-mail: [email protected]
Ms Analisa Bautista, Consultant, Expanded Programme on Immunization, World Health
Organization, Regional Office for the Western Pacific, United Nations Avenue 1000, Manila,
Philippines. Tel no.: +63 2 5289025. Fax no.: +63 2 521 1036. E-mail: [email protected]
Mr Benjamin Bayutas, Informatics Assistant, Expanded Programme on Immunization, World
Health Organization, Regional Office for the Western Pacific, United Nations Avenue 1000,
Manila. Tel no.: +63 2 528 9739. Fax no.: +63 2 521 1036. E-mail: [email protected]
Ms Kayla Mae Mariano, Assistant (Informatics), Expanded Programme on Immunization, World
Health Organization, Regional Office for the Western Pacific, United Nations Avenue 1000,
Manila, Philippines. Tel no.: +63 2 528 9738. Fax no.: +63 2 521 1036.
E-mail: [email protected]
Dr Ousmane Diop, Scientist, Global Polio Laboratory Coordinator, Surveillance, Monitoring and
Information, Expanded Programme on Immunization Plus, World Health Organization, Avenue
Appia 20, 1211, Geneva 27, Switzerland. Tel no.: +41 22 791 2503. Fax no.: +41 22 791 0746.
E-mail: [email protected]
Dr Miguel Norman Mulders, Scientist, Global Measles/Rubella Laboratory Coordinator,
Expanded Programme on Immunization Plus, World Health Organization, Avenue Appia 20, CH
1211, Geneva 27, Switzerland. Tel no.: +41 22 79 14405. Fax no.: +41 22 79 0746. E-mail:
ANNEX 2 SIXTH MEETING ON VACCINE-PREVENTABLE DISEASES LABORATORY NETWORKS IN THE WESTERN PACIFIC REGION WPR/DCD/EPI(09)2016.1a Manila, Philippines, 12–13 September 2016 English only PART I. POLIOMYELITIS SESSION
PROVISIONAL TIMETABLE
Time Day 1, Monday, 12 September 2016 Day 2, Tuesday, 13 September 2016
08:00 – 08:30
08:30 – 09:00
Registration
Opening session
• Welcome remarks by the Responsible Officer
• Opening remarks of the Regional Director
• Self-introduction
• Election of Officers
• Administrative announcements
08:30 – 09:00
09:00 – 09:30
09:30 – 10:00
Session 6. Laboratory containment and GAP III
a) Global and regional update on implementation of GAP III
b) Review of new ITD/VDPV algorithm post-switch work in PI, PII, PIIS, PEF and non-PEF referral of samples post-switch and work in line with GAP III
Discussion
09:00 – 09:30 GROUP PHOTO AND COFFEE BREAK 10:00 – 10:30 COFFEE BREAK
09:30 – 09:50
09:50 – 10:10
10:10 – 10:30
10:30 – 10:45
10:45 – 11:00
11:00 – 11:15
11:15 – 11:30
11:30 – 11:45
11:45 – 12:00
12:00 – 12:15
Session 1. Polio endgame strategy and updates on maintaining polio-free status: global and regional
a) Polio endgame strategy and regional update on the polio eradication initiative and next steps
b) Update of global wild poliovirus transmission and status of polio laboratory network
c) Regional updates of polio laboratory network – expansion of ITD laboratories and environmental surveillance (ES) update
Session 2. Vaccine-derived poliomyelitis virus (VDPV)
a) Methodologies for VDPV detection, characterization and virologic classification
b) Regional update on VDPV circulation
c) VDPV surveillance in China
Discussion
Session 3. Report from global specialized laboratory (GSL) and regional reference laboratories (RRLs) in the Region
a) Japan
b) Australia
c) China
10:30 – 10:45
10:45 – 11:00
11:00 – 11:15
11:15 – 11:30
11:30 – 11:45
11:45 – 12:00
12:00 – 12:15
12:15 – 12:30
12:30 – 12:45
c) Review of CDC rRT-PCR assays ver. 4.1 and 5.0 for ITD and VDPV screening
d) Experience and challenges in rolling out of new 4.0 and 4.1 assay
e) How to implement Annex 6, compliance and understanding for polio laboratories
Discussion
Session 7. Detection of poliovirus from non-AFP specimens and environmental surveillance
a) Global perspectives on ES
b) ES of poliovirus and non-polio enteroviruses in China
c) Australia experience
d) Japan experience
Discussion
12:15 – 13:15 LUNCH BREAK 12:45 – 13:45 LUNCH BREAK
13:15 – 13:30
13:30 – 13:45
13:45 – 14:00
14:00 – 14:15
14:15 – 14:30
14:30 – 15:00
Session 4. Report from national poliomyelitis laboratories in the Region
a) Hong Kong SAR (China)
b) Malaysia
c) Mongolia
d) New Zealand
e) Philippines
Discussion
13:45 – 14:00
14:00 – 14:15
14:15 – 14:30
14:30 – 14:45
14:45 – 15:00
15:00 – 15:15
15:15 – 15:30
Session 8. Experience of polio laboratory network for the laboratory diagnosis of hand, foot and mouth disease (HFMD) and other enteroviruses
a) HFMD in China
b) HFMD in Japan
c) HFMD in Viet Nam
Discussion (including legacy and transition post eradication)
Session 9. Global polio laboratory network (GPLN) data management
a) GPLN management system
b) Data management and reporting
Discussion
Time Day 1, Monday, 12 September 2016 Day 2, Tuesday, 13 September 2016
15:00–15:30 COFFEE BREAK 15:30 – 16:00 COFFEE BREAK
15:30–15:45
15:45–16:00
16:00–16:15
16:15–16:30
f) Singapore
g) Viet Nam – Hanoi
h) Viet Nam – Ho Chi Minh City
Discussion
16:00–16:15
16:15–17:30
Session 10. Quality assurance and management
a) Quality assurance and quality control (cell sensitivity and authenticity, PT, confirmatory testing, etc)
Discussion
16:30 – 16:45
16:45 – 17:00
17:00 – 17:15
17:15 – 17:30
Session 5. Laboratory quality assurance
a) Follow-up on recommendations from 2015 regional polio laboratory network meeting
b) Report on 2015 virus isolation proficiency testing (VIPT) and an update on upcoming 2016 VIPT
c) Report on 2015 ITD and report/update on 2015 sequencing PT
Discussion
16:30–17:30
Session 11. Conclusions and recommendations
a) Draft conclusions and recommendations
17:30 – 18:00 Wrap up and close of the first day 17:30 – 17:45 Closing session
18:00 Regional Director's reception
SIXTH MEETING ON VACCINE-PREVENTABLE DISEASES LABORATORY NETWORKS IN THE WESTERN PACIFIC REGION WPR/DCD/EPI(09)2016.1a Manila, Philippines, 14-15 September 2016 English only PART II. MEASLES AND RUBELLA SESSION
PROVISIONAL TIMETABLE
Time Day 1, Wednesday, 14 September 2016 Day 2, Thursday, 15 September 2016
08:00 – 08:30
08:30 – 09:00
Registration
Opening session
• Welcome remarks by the Responsible Officer
• Opening remarks of the Regional Director
• Self-introduction
• Election of Officers
• Administrative announcements
08:30 – 08:45
08:45 – 08:55
08:55 – 09:05
09:05 – 09:15
09:15 – 09:30
09:30 – 9:45
09:45 – 10:00
10:00 – 10:15
10:15 – 10:30
Summary of day 1
Session 3: Country reports (cont.)
k) Lao People's Democratic Republic
l) Fiji
m) Papua New Guinea
Discussion
Session 4: Strengthening rubella and congenital rubella syndrome (CRS) surveillance
a) Global update of rubella virus surveillance and CRS surveillance, laboratory confirmation
b) Rubella and CRS surveillance in China
c) Rubella and CRS surveillance in Japan
Discussion
09:30 – 09:30 GROUP PHOTO AND COFFEE BREAK 10:30 – 11:00 COFFEE BREAK
09:30 – 09:50
09:50 – 10:10
10:10 – 10:30
10:30 – 10:40
10:40 – 10:55
10:55 – 11:10
11:10 – 11:25
11:25 – 11:45
11:45 – 11:55
11:55 – 12:10
Session 1. Overview of global and regional measles and rubella elimination initiatives
a) Global and regional updates on eliminating measles and rubella
b) Update of global measles and rubella laboratory network
c) Progress – regional measles and rubella laboratory network
Discussion
Session 2. Reports from global specialized laboratory (GSL) and regional reference laboratories (RRLs) in the Region
a) Japan
b) Australia
c) China
d) Hong Kong SAR (China)
e) CDC molecular epidemiological overview and lessons
Discussion
11:00 – 11:15
11:15 – 11:30
11:30 – 11:45
11:45 – 12:00
Session 5: Quality assurance
a) Follow-up on recommendations from 2015/2016 global and regional measles rubella laboratory network meeting
b) Update on quality assurance for molecular proficiency test
c) Measles and rubella IgM proficiency test and confirmatory testing
Discussion
12:10 – 13:10 LUNCH BREAK 12:00 – 13:00 LUNCH BREAK
13:10 – 13:25
13:25 – 13:40
13:40 – 13:55
13:55 – 14:10
14:10 – 14:40
14:40 – 14:50
Session 3: Country reports
a) Brunei Darussalam
b) New Zealand
c) Singapore
d) Cambodia
e) Mongolia
Discussion
13:00 – 13:15
13:15 – 13:30
13:30 – 13:40
13:40 – 13:50
13:50 – 14:00
14:00 – 14:10
14:10 – 14:20
d) China laboratory network: quality assurance for provincial laboratories
e) Data management and reporting
Discussion
Session 6. New technique
a) Extended windows (M-F) and next generation sequencing
b) Serologic markers of measles reinfection
c) Vaccine specific rRT-PCR
Discussion
Time Day 1, Wednesday, 14 September 2016 Day 2, Thursday, 15 September 2016
14:20 – 14:40
14:40 – 14:50
Session 7. The requirements of GAP III for polio containment
a) Polio laboratory containment and GAP III implementation for non-polio laboratories
Discussion
14:50 – 15:20 COFFEE BREAK 14:50 – 15:20 COFFEE BREAK
15:20 – 15:35
15:35 – 15:45
15:45 – 15:55
15:55 – 16:05
16:05 – 16:25
16:25 – 17:00
f) Malaysia
g) Viet Nam (Hanoi)
h) Viet Nam (Nha Trang)
i) Viet Nam (Ho Chi Minh City)
j) Philippines
Discussion
15:20 – 16:30
16:30 – 17:00
Video presentations: FTA card and sequence analysis
Session 8: Conclusions and recommendations
17:00 – 17:15 Wrap up and close of the first day 17:00 Closing session
17:30 Regional Director's reception
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