Transition from JE outbreaks to sporadic cases in Sri Lanka : a tale of two JE vaccines

Country presentation for the 5th Bi-regional meeting on JE prevention and control

Dr. Pushpa Ranjan WijesingheNational Surveillance Focal Point

Principal investigator- study on safety and immunogenicity of the LJEV - SA 14 -14-2 in Sri Lankan children

Epidemiology Unit, Ministry of Health

Overview

• Campaign of JE immunization with the mouse brain derived vaccine

• Challenges to the immunization campaign• An alternative vaccine - the solution to new

challenges – the decision making – Introduction – Challenges/issues during introduction – Program monitoring and evaluation– AEFI surveillance and challenges

Immunization against JE

• Major outbreaks in 1985-1988• Phased introduction in 1988• Campaign approach • Timing - inter epidemic period (Sep-Oct)• Mouse brain derived inactivated JE vaccine– Nakayama strain

• Target group – children aged 1-10years• Three primary doses and 1 booster• Beijing strain in 1994 • High coverage - decreased incidence of JE

Challenges to the JE immunisation programme

• Sporadic cases and outbreaks in districts without immunization – Expansion of immunisation to 18 districts

• High rates of AEFI relative to other EPI vaccines – The highest rates of reported AEFI after DTP– Role of overall improvement of AEFI reporting ??– Poor quality of the mouse brain derived vaccine ( Japanese experience)

• Repercussions on the acceptability of the JE vaccine– Negative feedbacks from paediatricians

Challenges to the JE immunisation programme

• Increasing cost of the JE vaccine over the years– Annual cost for 4 doses – 9.1 million US $– ¾ of the entire government budget for all EPI

vaccines • Prohibitive factor on self funded EPI – Sustainability of JE immunisation programme– Sustainability of other EPI vaccines

• Shortage of vaccines for procurement • high demand and pressure for JE vaccination– Political, public and media pressure

Decision maker’s dilemma • What was the answer to challenges ? – Essence of an alternative to the inactivated JE vaccine

• affordable , safe , immunogenic

• Was there an alternative ?– Availability of LJEV for consideration

• Not considered in 2003 due to lack of information

• Was LJEV the appropriate choice ? – Evaluation of JE core working group– WHO SAGE recommendation– Translated literature from China by PATH

• Were safety and immunogenicity information available ? – Empirical evidence from China, Nepal, India

• Was the choice financial ly sustainable ?

– Cost saving potential of the LJEV vaccine with the low price • At 0.20 US $ ( India) – 8.8 million US $• 0.40 US $ ( Nepal) – 8.6 million US $

– Cost saving potential with• The single dose • ability to deliver through the EPI through out the year • abandoning the campaign approach

Challenges to decision making • Scepticism of the medical fraternity on safety and

immunogenicity– Open expression in the annual immunization stakeholder’s meeting

• Demand of the National Advisory Committee on Communicable Diseases (NACCD) for local evidence – Local study to assess the safety and immunogenicity

• Mobilizing financial resources for the study – Involvement of PATH as the sponsor of the study– MRI’s unwillingness to acquire skills and perform PRNT

• Policy of using only WHO pre qualified vaccines n the EPI • Sustain the achievements of over 2 decades

– Ensuring access to JE vaccination – avoiding accumulation of a susceptible population

Issues/ Challenges during implementation• Cost of a vaccine dose > the anticipated price

– Attempt s of direct procurement through government to government – The role of a middle company

• Operational difficulties with contraindications in the product insertion – Untypical contraindications for a pediatric vaccine – Generic nature ( renal, hepatic , cardio-vascular disorders)– Not listed in current WHO position papers – Need of clarifying the scientific rationale from the Chengdou and WHO

• Plan of the WHO/HQ for a detailed analysis at the GACVS– WHO’s Dialogue with chengdou

• WHO –HQ response to Sri Lanka– Contra-indications – not clinically revised recently in China – Based on local precautionary practices – Persistence with obsolete Chinese pharmacopeia due to need for complying with Chinese regulations– No documented risk of immunizing children with mentioned conditions– Sri Lanka to determine contra indication for the NPI

• A local set of pragmatic contra-indications by the NACCD

Implementation of LJEV

• NACCD approval - 07.03.2008• Implemented - 01.07.2009• Public sector- Live JE vaccine - SA 14-14 -2• Private sector- inactivated and LJEV • Single dose at the completion of 12 months– Shifting to 9 months with MMR introduction

• Through the EPI program in all districts – Through the immunization clinics in the primary

health care network

Issues/ Challenges during implementation

• Discrepancy with the product insertion – Potential legal repercussions/media interest– Repercussions on the NIP – Discussion with Chengdou Biologicals – Local insertion to be prepared and enclosed– Permission from the Drug evaluation Sub-committee

of the NDRA • Chengdou’s inability to supply the required

amount – Inability to cover those needing boosters– Inability to cover all districts

Programme monitoring and evaluation

• At the national, district and divisional level

• Integrated with the MIS of the EPI

• Quarterly review with 26 regional epidemiologists (RE)

• Quarterly review at the NACCD• Monthly review at the districts

by RE• Annual EPI review meetings in

districts • Annual EPI survey of a selected

district

Field staff

Divisional Level / MOH

District Level/

DPDHS/ RE/ MOMCH

National Level/

Epid Unit, FHB

National Expert Committee on AEFI

AEFI surveillance of LJEV • Integrated with other EPI activities • Field and clinic based activated passive

notification to the Medical officer of Health

• Consolidated AEFI returns to the district and center

• All serious AEFI – detailed investigations • Deaths following a vaccine – AEFI

advisory committee • Recommendations to the NACCD for

policy decisions • Challenges

– more involvement of the private sector in reporting

– Pacifying the effects of adverse media publicity to AEFI

– Risk benefit communication skills of the PHC staff

– Anaphylaxis management capabilities for the PHC staff

Year No of doses

Solicited AEFI

Allergic reactions

seizures Severe local reactions

Fever > 38 C

Others

2009 249758 285 172 20 14 56 23

Rate/100 000 doses

114 68.9 8.0 5.6 22.4 9.0

2010 579007 674 379 31 28 137 99

Rate/100 000 doses

116.4 65.5 5.4 4.8 23.7 17.0

2011 453175 470 272 36 11 112 39

Rate/100 000 doses

103.7 60.0 7.9 2.4 24.7 8.6

Total 1281940 1429 823 87 53 305 161

Rate/100 000 doses

111.5 64.2 6.8 4.1 23.8 12.6

Evaluation of the JE immunization campaign with the killed vaccine

• A collaborative project by the JE immunization focal point and a doctoral student in 2005-6

• Financial support by the PATH/USA • Area of study – the epicenter of former major outbreaks • Effectiveness of the immunization campaign

– Cases prevented -97%– Deaths prevented – 100%– Disabilities prevented – 98%

• Incremental cost per averting a – JE case = 315 US $– Death= 2437 US $– Disability = 1072.5 US $

Acknowledgement

• For the far seeing vision of Dr Nihal Abeysinghe ( Regional Advisor/IVD –SEAR ) whose leadership as the Chief Epidemiologist /Sri Lanka made LJEV a reality amidst many challenges …..

• All former epidemiologists for bold decisions in – Establishing surveillance and initiating vaccination

• Dr. Paba Palihawadana – Chief Epidemiologist • Dr. Sudath Peiris – EPI focal point • Dr. Nayana De Alwis for evaluating the program• PATH for a long standing partnership in many endeavors • Julie , Susan, Chris and Mansur of the PATH team • Cyril, Twinkle , Chesmal and the Quintiles/Singapore team • Sri Lankan parents for the faith in JE vaccination