A cheap, locally produced oral cholera vaccine has been proven safe and effective in young children in a part of India where the disease is endemic. Pending the results of follow-up studies, this vaccine, now manufactured to WHO standards, could be rolled out across developing nations where cholera remains endemic. The findings are discussed in an Article published Online First (www.thelancet.com) and in an upcoming Lancet, written by Dr John D. Clemens, International Vaccine Research Institute (IVI), Seoul, South Korea, and colleagues*.
While an earlier version of this vaccine had been used in Vietnam, and was effective there, it has not been approved for use worldwide because the manufacturing process in Vietnam did not reliably remove cholera toxin from the vaccine; nor is Vietnam's national regulatory authority approved by WHO. To facilitate use of this cheap oral vaccine, the International Vaccine Institute worked with the Vietnamese manufacturer VaBiotech to improve vaccine quality. The manufacturing has also now been transferred to Shantha Biotechnics (Hyderabad, India), where the national regulatory authority is approved by WHO. The authors assessed the safety and efficacy of this vaccine in Kolkata, India.
In this randomised controlled trial, over 107,000 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (52 212 people) or heat-killed Escherichia coli placebo (55 562 people), both delivered orally. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae diarrhoea severe enough for the patient to seek treatment in a health-care facility. The researchers undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo, and assessed first episodes of cholera that occurred between 2 weeks and 2 years after receipt of the second dose.
A total of 31,932 participants assigned to vaccine and 34,968 assigned to placebo received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%). The vaccine protected individuals in age-groups 1•0•9 years, 5•0•9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups. No vaccine-related serious adverse events were recorded.
The authors say: "This interim analysis of a double-blind, placebo-controlled trial shows that the modified killed-whole-cell oral vaccine is safe and efficacious, providing nearly 70% protection against clinically significant cholera for at least 2 years after vaccination. Protection was seen in children vaccinated at ages under 5 years, as well as in older individuals."
They conclude: "Although the protection reported in this trial might itself be sufficient to justify the public health use of the modified killed-whole-cell oral vaccine, the public health value of the vaccine would be increased by demonstration of a longer duration of protection and of vaccine herd protection. Both of these features will be assessed in subsequent follow-up analyses."
In an accompanying Comment, Dr Saranya Sridhar, School of Public Health, University of California, Berkeley, CA, USA, says the most impressive aspect of this vaccine is the story of its development—namely how successfully public-private partnerships can work with academics. He concludes: "This success story ought to be an example for other vaccine initiatives especially against malaria and HIV, to similarly engage industry and academia towards solving an urgent public health need."
Dr John D. Clemens, International Vaccine Research Institute, Seoul, South Korea. T) +82-872-2801 E) jclemens@ivi.int
Dr Saranya Sridhar, School of Public Health, University of California, Berkeley, CA, USA. (currently in UK) T) +44 (0) 207 594 0884 E) saranya.sridhar@gmail.com
For full Article and Comment, see: http://press.thelancet.com/cholera.pdf
*Note to editors: This study was funded by the Bill and Melinda Gates Foundation. Additional funding was provided to the IVI by the Swedish International Development Cooperation Agency and the Governments of South Korea, Sweden and Kuwait.
Journal
The Lancet