@article{259a9b5f1dfa454c976e9b50d3191f92,
title = "Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up",
abstract = "The protective efficacy (PE) of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind field trial among children aged 2-15 years and women over 15 years in rural Bangladesh. Among the 62 285 subjects who received three doses of BS-WC, WC, or Escherichia coli K12 strain placebo, cumulative PE at 3 years of follow-up was 50% for BS-WC and 52% for WC. PE was similar against severe and non-severe cholera, but was significantly lower in children who were vaccinated at 2-5 years (26% for BS-WC; 23% for WC) than in older persons (63% for BS-WC; 68% for WC). Among persons vaccinated at 2-5 years, protection at 4-6 months of follow-up was similar to that for older persons, but rapidly waned thereafter and was not evident during the third year of follow-up. In contrast, persons vaccinated at older ages were protected even in the third year of follow-up (PE 40% for BS-WC; 62% for WC). PE was substantially higher against classical cholera (58% for BS-WC; 60% for WC) than against El Tor cholera (39% and 40%).",
author = "Clemens, {J. D.} and Sack, {D. A.} and Harris, {J. R.} and {van Loon}, F. and J. Chakraborty and F. Ahmed and Rao, {M. R.} and Khan, {M. R.} and Md Yunus and N. Huda and Stanton, {B. F.} and Kay, {B. A.} and R. Eeckels and Clemens, {J. D.} and Rao, {M. R.} and Kay, {B. A.} and Sack, {D. A.} and Harris, {J. R.} and Stanton, {B. F.} and S. Walter and R. Eeckels and Svennerholm, {A. M.} and J. Holmgren",
note = "Funding Information: vaccines. If such vaccines are to include cholera toxin B subunit-this addition may be worthwhile because it augments short-term protection against cholera and cross- protects against heat-labile toxin producing enterotoxigenic E coli—it will be necessary to devise techniques that do not rely upon expensive and technically demanding biochemical procedures for extraction and purification of this component.2 Recombinant DNA techniques have lately been employed to place the structural gene for B subunit under the control of a strong promoter in a plasmid, so that extremely high concentrations of recombinant B subunit are secreted during the growth phase of the organisms before inactivation procedures.17 With this approach, it is possible to envisage greatly simplified procedures for inclusion of B subunit that could be accomplished at low cost in developing countries. Also needed are strategies to improve overall levels of protection, particularly long-term protection in young children, and to augment protection against El Tor cholera. In this regard, consideration should be given to booster doses for young children, in whom protection was initially comparable with that for older persons but declined rapidly. Moreover, a more balanced formulation of El Tor and classical organisms (three-quarters of the current formulation consists of classical organisms) might increase protection against El Tor cholera. Finally, better clinical protection may come from use of immunological adjuvants designed to augment mucosal immunity and from growth and inactivation of organisms in a fashion that permits expression of TCP pilus18 and of El Tor-specific colonisation factor antigens.1 We gratefully aknowledge the technical assistance and support of Arabinda Banik, Dr M. Giasuddin, Moqbul Hossian, Dr N. Huda, Anwarul Hug, A. K. M. Nurul Islam, M. A. H. Miah, M. A. Satter Miah, Liaquat Mondal, Md Noorullah, Badrul Prodhan, Anisur Rahman, Siddiqur Rahman, A. M. Sarder, K. Shaikh, Charles Simons, and the additional 407 field, laboratory, and data management staff who worked so diligently. Dr Jane Menken, Dr Michael Merson, Dr Henry Mosley, Dr Nathaniel Pierce, Dr Bogdan Wojtyniak, and Mr Andrew Foster provided helpful advice on design and analysis. Dr William B. Greenough gave support and encouragement. Institut Merieux, Lyon, France, in collaboration with the National Bacteriology Laboratory, Stockholm, Sweden, produced the vaccine and placebo agents for the study. Dr James Kaper kindly provided the E coli K12 strain used for the placebo. ACO Ltd, Stockholm, Sweden, prepared antacid tablets for administration with the vaccines and placebo. Mr M. A. Mazed provided expert secretarial assistance. This work was supported by funds from the United States Agency for International Development, the Government of Japan, the Swedish Agency for Research Cooperation with Developing Countries, and the World Health Organisation.",
year = "1990",
month = feb,
day = "3",
doi = "10.1016/0140-6736(90)90080-O",
language = "English (US)",
volume = "335",
pages = "270--273",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "8684",
}