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      The High Burden of Cholera in Children: Comparison of Incidence from Endemic Areas in Asia and Africa

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          Abstract

          Background

          Cholera remains an important public health problem. Yet there are few reliable population-based estimates of laboratory-confirmed cholera incidence in endemic areas around the world.

          Methods

          We established treatment facility–based cholera surveillance in three sites in Jakarta (Indonesia), Kolkata (India), and Beira (Mozambique). The annual incidence of cholera was estimated using the population census as the denominator and the age-specific number of cholera cases among the study cohort as the numerator.

          Findings

          The lowest overall rate was found in Jakarta, where the estimated incidence was 0.5/1000 population/year. The incidence was three times higher in Kolkata (1.6/1000/year) and eight times higher in Beira (4.0/1000/year). In all study sites, the greatest burden was in children under 5 years of age.

          Conclusion

          There are considerable differences in cholera incidence across these endemic areas but in all sites, children are the most affected. The study site in Africa had the highest cholera incidence consistent with a growing impression of the large cholera burden in Africa. Burden estimates are useful when considering where and among whom interventions such as vaccination would be most needed.

          Author Summary

          Cholera is an often forgotten disease affecting the world's forgotten people. When a large cholera outbreak occurs, the disease appears briefly on the radar of public attention. Some unfortunate populations around the world suffer recurrent episodes of cholera but their plight goes unnoticed. We established cholera surveillance in impoverished areas in Jakarta (Indonesia), Kolkata (India), and Beira (Mozambique) where the disease is known to occur regularly. The cholera burden was calculated using the site population as the denominator and the number of cholera cases as the numerator. The lowest overall rate was in Jakarta with 0.5 cases per 1000 population per year. The incidence was three times higher in Kolkata (1.6/1000/year) and eight times higher in Beira (4.0/1000/year), adding to the growing impression of the large cholera problem in Africa. In all sites, children are the most affected. Estimates such as these are useful when considering where and among whom interventions against the disease are most needed. Improvement of water supply and sanitation is the best strategy against cholera and other diarrheal diseases but may not be achievable in these impoverished areas in the near future. Other immediate, short- to medium-term strategies such as vaccination against cholera may be useful.

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          Most cited references15

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          Cholera.

          Intestinal infection with Vibrio cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Cholera toxin, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity. Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V cholerae serogroup O1, biotype El Tor, has moved from Asia to cause pandemic disease in Africa and South America during the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. Research on case management of cholera led to the development of rehydration therapy for dehydrating diarrhoea in general, including the proper use of intravenous and oral rehydration solutions. Appropriate case management has reduced deaths from diarrhoeal disease by an estimated 3 million per year compared with 20 years ago. Vaccination was thought to have no role for cholera, but new oral vaccines are showing great promise.
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            Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis.

            Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines. We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables. Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7.01 cases per 1000 in the lowest quintile of coverage vs 1.47 cases per 1000 in the highest quintile; p<0.0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% [95% CI 41-66], p<0.0001). In addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings.
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              Effectiveness of mass oral cholera vaccination in Beira, Mozambique.

              New-generation, orally administered cholera vaccines offer the promise of improved control of cholera in sub-Saharan Africa. However, the high prevalence of human immunodeficiency virus (HIV) infection in many cholera-affected African populations has raised doubts about the level of protection possible with vaccination. We evaluated a mass immunization program with recombinant cholera-toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in Beira, Mozambique, a city where the seroprevalence of HIV is 20 to 30 percent. From December 2003 to January 2004, we undertook mass immunization of nonpregnant persons at least two years of age, using a two-dose regimen of rBS-WC vaccine in Esturro, Beira (population 21,818). We then assessed vaccine protection in a case-control study during an outbreak of El Tor Ogawa cholera in Beira between January and May 2004. To estimate the level of vaccine protection, antecedent rates of vaccination were compared between persons with culture-confirmed cholera severe enough to have prompted them to seek treatment and age- and sex-matched neighborhood controls without treated diarrhea. We assessed the effectiveness of the vaccine in 43 persons with cholera and 172 controls. Receipt of one or more doses of rBS-WC vaccine was associated with 78 percent protection (95 percent confidence interval, 39 to 92 percent; P=0.004). The vaccine was equally effective in children younger than five years of age and in older persons. A concurrently conducted case-control study designed to detect bias compared persons with treated, noncholeraic diarrhea and controls without diarrhea in the same population and found no protection associated with receipt of the rBS-WC vaccine. The rBS-WC vaccine was highly effective against clinically significant cholera in an urban sub-Saharan African population with a high prevalence of HIV infection. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                February 2008
                20 February 2008
                : 2
                : 2
                : e173
                Affiliations
                [1 ]International Vaccine Institute, Seoul, Korea
                [2 ]National Institute of Cholera and Enteric Diseases, Kolkata, India
                [3 ]National Institute of Health Research and Development, Jakarta, Indonesia
                [4 ]Ministry of Health, Maputo, Mozambique
                National Institute of Allergy and Infectious Diseases, United States of America
                Author notes

                Analyzed the data: D. Kim. Responsible for overall coordination of the studies: J. Deen L. von Seidlein A. Lopez. Provided statistical support: D. Kim. Responsible for the comparative analysis across the three study sites: J. Deen M. Ali. Developed the multi-country study design and wrote the study protocols: J. Deen L. von Seidlein D. Sur M. Agtini M. Lucas A. Lopez M. Ali J. Clemens. Wrote the manuscript: J. Deen L. von Seidlein J. Clemens. In charge of the field work and data collection in the Indian, Indonesian, and Mozambican sites, respectively: D. Sur M. Agtini M. Lucas.

                Article
                07-PNTD-RA-0105R4
                10.1371/journal.pntd.0000173
                2254203
                18299707
                67580dc1-e215-4542-93ad-3180ca75cec3
                Deen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 25 May 2007
                : 26 December 2007
                Page count
                Pages: 5
                Categories
                Research Article
                Pediatrics and Child Health
                Public Health and Epidemiology

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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