constância ayres - apeir · 18 mosquito surveillance sentinel - ovitrap network * santos et al...
TRANSCRIPT
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Anticipating future emerging infectious diseases through collaborative research: a reflection on
the Zika outbreak
Constância [email protected]
Roundtable Meeting on Zika Virus: Improving Detection, Preparedness, and Response, Through Surveillance and
Research
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Vector control
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Vector control
Integrated control;Sustainable strategies;Permanent;Monitoring through surveillance;Choice of a good tool (sensitivity);
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CICLO BIOLÓGICO
15 to 30 days
Qu
iesc
ent
eggs
Dis
per
sed
Ovi
po
siti
on
Passive Dispersion
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Biological traits of Aedes aegypti
• Highly antropophilic females;
• Monogamy (breeding can occur in 24 hours after emergence);
• Adapted to the urban environment (preference for premises);
• Prefer temporary breeding sites;
• Colonize reservoirs of potable water (>80% of breeding sites are inside houses).
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National Program for Dengue Control(PNCD)
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PNCD components
1. Epidemiological surveillance
2. Vector control
3. Patients assistance
4. Integration of Agents (PACS/PSF)
5. Sanitation
6. Social mobilization and comunication
7. Training
8. Legislatioin
9. Social and political approach
10. Evaluation
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Methods of control
• Focal – treatment of breeding sites.
• Perifocal – residual treatment of
surfaces.
• Space spray -Ultra Low Volume spray.
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Focal treatment (larvicides)
Larvae
Pupae
Adult
Egg Temephos Bti Diflubenzuron Pyriproxifen
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Perifocal: Insecticide Residual Spraying (adulticides)
“strategic points”
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PNCD guidelines: use of larvicide only when necessary
Powder
Use in the field - aplication
IPE
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Space- Spray
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Rede Nacional de Monitoramento
- Morena
Regiões
N
NE
SE
S
CO
Laboratório de
Entomologia/CE
Laboratório de
Entomologia CPqAM
(Fiocruz/RJ)
Laboratório de criação de
Aedes aegypti Geraldo
Magella Buralli/SP
(*) Rede Nacional de Monitoramento de Aedes aegypti a Inseticidas
Processo de avaliação para ingresso
de dois novos laboratórios:
1. Medicina Tropical – UnB
2. Universidade Federal do Paraná
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Temephos resistance in Brazil
Chediak, M. et al., 2016
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2002 - Programa Nacional de Controle da Dengue- PNCD
Aedes aegypti – Histórico de Controle no Brasil
•PNCD measures have not been enough to reduce Ae. aegypti populations, andconsequently, to minimize the endemic-epidemic transmission of dengue,chikungunya and zika;
• Natural Ae. aegypti populations are highly resistant to chemical insecticide;
• Low coverage of larvicide control associated to: high percentage of closedpremises/or refusal to inspection by the Health Agents (pendencies) and a highnumber of vacant lands;
Aedes aegypti control in Brazil
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SMCP-Aedes
Pernambuco - Northeastern
Sites – Real-Scale trials
3,000 inhabitants
Area: 17 km2 (15 villages)
Fernando de Noronha Island
.Archipelago 500 Km
87,538 inhabitants
Area: 335.5 km²
Santa Cruz do Capibaribe
Arid region 200 Km
Ipojuca
76,000 inhabitants
Area: 527.3 km²*
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18
Mosquito surveillance
Sentinel - Ovitrap Network
* Santos et al 2003. Field Evaluation of Ovitraps Consociated with Grass Infusion and Bacillus thuringiensis var. israelensis to determine Oviposition
Rates of Aedes aegypti. Dengue Bulletin, 27: 156-161.
SMCP-Aedes
Fixed sampling stations
262 – Santa Cruz do Capibaribe
76 – Ipojuca Centro
103 – Fernando de Noronha
Period in the field: 30 days
Containing Bti*
The sentinel-ovitrap (S-Ovt)
Araújo et al., 2007; Melo-Santos et al 2009. Long lasting persistence of Bacillus thuringiensis israelensis larvicidal activity in Aedes aegypti breeding sites.
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19
Social Mobilization - Information
Public health authorities
SMCP-Aedes
Technical staff of health services
Vídeo FIOCRUZ
Community mobilization
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Information Flow
Egg collection Counting Data analysis
Intervention Actions Planning Kernel Maps
SMCP-Aedes
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21
Control-ovitrap (C-Ovt) Production
Non-Govermental Organization - ICRIAC
collective ovitraps
manufactoring
SMCP-Aedes
* Regis et al 2013. Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian
Cities. PLoS ONE 8(7): e67682. doi:10.1371/journal.pone.0067682.
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22
Areas with high concentration of mosquito (hot spots).
SMCP-AedesKernel-Maps as decision support
Eg
g D
en
sit
y
Lo
w
Hig
h
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Site infestation SMCP-Aedes
Infestation found after >10 years of temephos** or Bti treatments (6 cycles/year) – PNCD.
May 2008
Santa Cruz**
POI = 100%
EDI = 1,597 eggs/trap/month
Ipojuca**
POI = 92.6%
EDI = 561.2 eggs/trap/month
Fernando de Noronha
POI = 84%
EDI = 180,6 eggs/trap/month
• POI: Positive Ovitrap Index• EDI: Egg Density Index (Mean number of eggs/OVT-S/ 30 days)
Jan 2011
Araujo et al 2013. The susceptibility of Aedes aegypti populations displaying temephos resistance to Bacillus thuringiensis israelensis: a basis for
management. Parasites & Vectors, v. 6, p. 297-305, 2013.
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SMCP-Aedes - Sensitivity to detect the A. aegypti presence
Egg laid = presence of blood fed Aedes females
The system detects continuous mosquito oviposition in most sites.
POI = 63 % – 100 %
SMCP-Aedes
* Regis et al 2013. Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian
Cities. PLoS ONE 8(7): e67682. doi:10.1371/journal.pone.0067682.
House Index
Santa Cruz = 3.8 to 12%
Ipojuca = 0 to 0.8%
Fernando de Noronha = 0 to 0.5%
Index based on larval surveys are not sensible enough to revel the true level of infestation by A. aegypti
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25
Befo
re
Co
ntr
ol
SMCP-Aedes
* Regis et al 2013. Sustained Reduction of the Dengue Vector Population Resulting from an Integrated Control Strategy Applied in Two Brazilian
Cities. PLoS ONE 8(7): e67682. doi:10.1371/journal.pone.0067682.
90% in Santa Cruz
77% in Ipojuca
Egg density
Egg densities decreased progressively during the control intervention period, however the POI remained higher than 80%.
Aft
er
C
on
tro
l
Egg suppression >7,500,000
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The tools and strategies used in SMCP-Aedes allowedquantification of the active population of A. aegypti, indicatingperiods and places with high virus transmission risk.
Final Considerations
The methods and tools used motivated the assimilation ofknowledge and encouraged social participation.
SMCP-Aedes16
The strategy using control-ovitrap is cost-effective and compatiblewith other control measures.
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Surveillance will enable control programs to:
Identify vectors;
Evaluate the impact of vector control strategies;
Management of insecticide resistance;
Generate risk maps for exposure to arboviruses;
Define priority areas for vector control;
Predict outbreaks.
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Why mosquito surveillance is important in SE Asia?
Zika virus has been present in areas of Southeast Asia for manyyears, and several countries have reported occasional cases orsmall outbreaks of Zika virus infections. Zika virus isconsidered endemic in some countries, and a large number oflocal residents are likely to be immune;
infections have occurred among travelers to Southeast Asia; Recent variations have been observed in the number of cases
reported in Southeast Asia. This can reflect changes inawareness of Zika virus, surveillance and testing for Zika virus,or changes in intensity of Zika virus transmission.
CDC
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The surveillance efforts are focused on identifyingarbovirus infections in mosquitoes as predictors of thepotential risk of transmission to humans;
to monitor the further expansion of the viruses; To provide base-line information for increment surveillance
programs and initiating control activities in the event that ZIKV is introduced into the region.
Aims:
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May 2013 May 2014
Monitoring of Ae. aegypti in the City of Praia, Cape Verde by Positive Ovitrap Index (POI) for 2013 and 2014.
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• Demonstration that members of the suspected populationcommonly feed upon vertebrate hosts of the pathogen;
• Demonstration of efficient transmission of the identifiablepathogen by the suspected vectors under controlledexperimental conditions;
• Repeated demonstration that suspected vector collectedunder natural conditions, harbor the identifiable, infectivestage of the pathogen;
• Demonstration of a convincing biological association intime and space between the suspected vectors and clinicalor subclinical infections in vertebrate hosts.
(Barnett, 1962)The incrimination of arthropods as vectors of disease
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RT-qPCR results
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Electronic Microscopy
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ZIKV in salivary gland cell of Culex
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ZIKV detected by FTA cards
Ae. aegypti 106
Cx. quinquefasciatus 106
Ae. aegypti 104
Cx. quinquefasciatus 104
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Surveillance
Field work
Diagnostic
Analysis and Outcomes
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Collection Transportation Storage
Surveillance
Field work material
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Aspiration
• indoor
• outdoor
FTA cards
• Inactivate the virus
• RNA extraction
Collection
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RNAlater
alive
Transportation
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Registration
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Sampling proportionality
Need to reduce the error
Need to increase the chance of detection
Vector infection is a rare event
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MIR Density
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Feedingbehavior
• Number of bites
• mosquito/person
Collection
• Time period
• Samplingmethods
• area
Phase of outbreak
• Few humaninfections
• peak
• post-peak
We need to take into account:
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the sampling process has to be adjusted to the most rare event
• MIR
Considering ecological and biological factors
• Time of outbreak, habits
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Vector ZIKV Infection Rate
Local Aedes Culex MIR
N Pools ZIKV+ Total Pools ZIKV+ Aedes Culex
Recife-PE (2016) 408 02 1496 03 4.9 2,0
Vitória-ES 14 01 286 04 71.4 13.98
Rio de Janeiro 315 03 385 0 9.5 0
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Vector ZIKV Infection Rate
Local Aedes Culex MIR
N Pools ZIKV+ Total Pools ZIKV+ Aedes Culex
Cabo Verde 100 0 20 0 0 0
Mexico 279 15 151 0 53,7 0
Malaysia 1277 01 - - 0,78 -
French Polynesia 2039 01 286 0 0,49 0
Micronesia (Yap) 41.2% 0 28.1% 0 0 0
Gabon 853 0 690 0 - -
Senegal* 250 1 22* 1 4.08 45.45
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ZIKV Diagnostic
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Nature Reviews Microbiology , S30-S37
Direct and Indirect Laboratory Diagnostic Methods
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Detection of ZIKV by RT-qPCR and RT-PCR
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Bad!
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RT-qPCR
Lanciotti, 2016
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Primary x Secondary Flavivirus Infection
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ZIKV Serology Summary
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Other Samples?
• N=6 patients• ZIKV RNA is detectable in urine at a higher load and with a longer duration than in serum
Serum
Urine
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Other Samples?
• 182 patients• ZIKV was more frequently detected in saliva compared to blood.• The use of saliva sample increased the rate of molecular detection of ZIKV at the acute phase of the disease but did NOT enlarge the window of detection of ZIKV RNA.
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ZIKV in Semen
•In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia.
•Eight weeks after first signs of Zika, he described a second episode of symptoms compatible with ZIKV infection
• 2 weeks after second episode: RNA loads were: 2.9 × 107 copies/mL and 1.1 ×107 copies/mL in the first and second semen samples, respectively, and 3.8 ×103 copies/mL in the urine sample. • ZIKV was isolated from his semen.
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Sample Collection and Shipment
Refrigerate biological fluids and tissues at 4 °C immediately after collection; Tissue fragments should be fixed in 10% formalin (1 part of tissue + 9 of formalin)
Transport • 4-8oC if transport within 3 days • Freeze at -80°C if storage for weeks or months before processing and shipment to reference laboratory
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How to Destroy Your Sample
Keep samples without refrigeration Repeated freeze-thaw cycles
- Destroys IgM- Kills the virus
To avoid hemolysis: do not freeze unseparated blood
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Obrigada!
Thanks!