December 14, 2006

We are pleased to share with you a summary of the conclusions and recommendations prepared by an independent expert committee investigating adverse events following immunization (AEFIs) with the live, attenuated SA 14-14-2 Japanese encephalitis (JE) vaccine during campaigns held in India's high-risk districts from May to July 2006. This committee was composed of representatives from respected national bodies and led by Dr. Jacob John, professor emeritus of Vellore Medical College. It was convened by the Government of India immediately following the campaigns to address any risks associated with administration of the vaccine.

Following an extensive investigation of 504 adverse events reported through the AEFI system (including 22 deaths) and 29 additional cases identified through active case-finding, the committee found no link between the vaccine and the serious illnesses or deaths temporally associated with immunization. The primary recommendation of the committee's final report states that "No direct causality has been established between the reported illnesses and the JE vaccine. Therefore, no stricture on the further use of the vaccine is warranted."1

The committee's findings were recently presented in conjunction with a summary of the 2006 Indian JE immunization campaigns at key global health events, including the Global Vaccine Research Forum and a meeting of the World Health Organization's Global Advisory Committee on Vaccine Safety (GACVS). A report from the GACVS meeting will be published in an upcoming issue of the Weekly Epidemiological Record.

As a result of the expert committee's findings, the Government of India will move forward with phased immunization against JE in high-risk districts, using the live, attenuated SA 14-14-2 vaccine manufactured by the Chengdu Institute of Biological Products in China. The next round of campaigns and routine immunization will start in mid-2007, before the JE season begins in endemic districts.

Further conclusions from the committee's report are summarized below:

  • 9.3 million children from 11 districts in 4 states were vaccinated in 2006 campaigns. Of these beneficiaries, 533 total adverse events (including 22 deaths) were recorded.
  • The most common adverse events (75% of reported cases) involved mild systemic reactions (fever, acute respiratory infection, vomiting, and/or rash).
  • Case investigations and laboratory tests following adverse events reported during the 2006 campaigns were inadequate, and the committee recommends strengthening case recording, sample collection, data analysis, epidemiological investigation, and causality assessment.
  • The frequency of 22 deaths among the vaccinated cohort of 9.3 million children aged 1 to 15 years calculates to a rate of 0.00024%. By comparison, the probable frequency of death among children of this age range in the general population is 0.009%.2 Therefore, adverse events following JE vaccination do not seem to cause excess mortality.
  • Seasonal outbreaks of JE and acute encephalopathy in targeted districts (specifically those in Northern India) may have caused infection prior to vaccination and resulted in deaths due to naturally occuring infection rather than infection caused by vaccination with the live, attenuated virus.
  • Consensus statements from several global meetings of the World Health Organization have identified human vaccination as the only effective long-term control measure against JE and have recommended that at-risk populations receive a safe and efficacious vaccine through the national immunization program.3
  • The Government of India is currently conducting a follow-up study to evaluate long-term vaccine safety and serious adverse events occurring up to 12 months following vaccination. During the first 4 weeks following vaccine administration, no serious adverse events were recorded among the study population. Subjects will be monitored at several intervals throughout the 12 months following vaccination.

The following contacts are available to provide further information and answer any questions related to vaccination with the live, attenuated SA 14-14-2 JE vaccine:

Dr. Julie Jacobson; Director, PATH JE project; jjacobson@path.org

Dr. Rajshankar Ghosh; Program Officer (Delhi), PATH JE project; ghosh@pathindia.org

Dr. P. Biswal; Assistant Commissioner (EPI), Ministry of Health and Family Welfare, Government of India; drpbiswal@rediffmail.com

Dr. P. Haldar; Assistant Commissioner (UIP), Ministry of Health and Family Welfare, Government of India; pradeephaldar@yahoo.co.in

Dr. Sobhon Sarkar; National Technical Advisor for Immunization, Ministry of Health and Family Welfare, Government of India; polioindia@yahoo.com

 References:

1. National level committee of experts (Government of India). Report of the national-level committee of experts to review state investigation reports and to investigate the adverse events following immunization following vaccination against Japanese encephalitis in high risk districts. September 2006.

2. Office of the Registrar General, India. 2001 Census.

3. WHO. Japanese encephalitis vaccines. Weekly Epidemiological Record. 2006; 81(34/35):331-340.

 

 The PATH JE project is supported by the Bill & Melinda Gates Foundation.