Efficacy of Oral Cholera Vaccine

Abstract & Commentary

Synopsis: Orally administered cholera vaccines have offered the promise of controlling cholera epidemics during prior studies in Bangladesh.1,2 However, the high prevalence of HIV co-infection in sub-Saharan Africa has raised doubts about the level of protection an oral cholera vaccine could generate in this setting.

Source: Lucas M, et al.Effectiveness of Mass Oral Cholera Vaccination in Beira, Mozambique. N Engl J Med. 2005; 352:757-767.

This article evaluates a mass immunization program with recombinant cholera-toxin B subunit, killed whole cell (rBS-WC) cholera vaccine in Beira, Mozambique, a city where seroprevalence of HIV infection is 20-30%. Lucas and colleagues, 5 of whom were associated with the Ministry of Health in Mozambique, were able to mass immunize (2-dose regimen) approximately 19,550 non-pregnant individuals over 2 years of age before the anticipated cholera outbreak that coincides with every rainy season. Seroprevalence for HIV amongst pregnant women in this area is known to be 20 -30%. Each dose of the rBS-WC vaccine (Dukoral, SBL Vaccines) consisted of recombinant cholera-toxin B subunit and approximately 1 x 10" inactivated whole cells of the classic and El Tor biotypes of Vibrio cholerae 01, serotypes of Inaba and Ogawa. Surveillance for cholera was then begun at the Cholera Treatment Center in Beira, where all cases of acute non-bloody diarrhea requiring medical care are referred. The total population of Beira is 450,000. A case-control study was conducted during the predicted outbreak of El Tor, Ogawa, for this particular year, by recruiting neighborhood controls of the same sex and age living next to the case subject’s house. To estimate the level of vaccine protection, antecedent rates of vaccination were compared between persons with culture-confirmed cholera, severe enough to seek treatment, and age and sex-matched neighborhood controls without diarrhea. Receipt of 1 or more doses of rBS-WC vaccine was associated with 78% protection (95 % CI, 39-92%; P = .004). The vaccine was equally effective in children younger than 5 years of age and in older persons.

Comment by Michele Barry, MD

This is an ambitious landmark study of a cholera vaccine that appears to be highly protective against a severe form of disease necessitating medical treatment in a highly impacted HIV area in sub-Saharan Africa. Here, periodic flooding, difficult access to safe water, and the common practice of open defecation and drainage of municipal waste into water supplies contribute to epidemic cholera. Although this study did not include HIV testing, and vaccine protection could not be directly evaluated in such a population, the seroprevalence rate for HIV infection of 20-30% of pregnant women in this area indicates that this vaccine likely offered significant protection for HIV-infected persons. In addition, the safety of this oral vaccine in an HIV population can be inferred. No clinically significant adverse reactions to the vaccine were reported during the mass immunization campaign. In prior trials in Sweden, Brazil, and Kenya, the vaccine was not associated with adverse reactions or progression of HIV disease, although a transient increase in HIV viremia was observed in one study.3

Of interest to travel medicine practitioners, a parallel case-control study was performed of non-choleraic diarrhea presenting for medical treatment.

There was no evidence that the vaccine conferred any protection against non-choleraic diarrhea 3 months after oral cholera vaccination. This is an intriguing finding given that rBS-WC has been shown to provide cross-protection against heat-labile toxin producing E. coli, albeit only for a few months after vaccination.4 However, no cultures were reported for ETEC, and all these cases were severe enough to be referred for medical treatment. Perhaps they simply do not reflect prevention of mild disease.

References

1. Clemens JD, et al. Field Trial of Oral Cholera Vaccines in Bangladesh. Lancet. 1986;2:124-127.

2. Clemens JD, et al. Field Trial of Oral Cholera Vaccines in Bangladesh: Results From 3-Year Follow-Up. Lancet. 1990;335:270-273.

3. Ortigao-de-Sampaio MB, et al. Increase in Plasma Viral Load After Oral Cholera Immunization of HIV-Infected Subjects. AIDS. 1998;12:F145-F150.

4. Peltola H, et al. Prevention of Travellers’ Diarrhea By Oral B-Subunit/Whole-Cell Cholera Vaccine. Lancet. 1991;338-1285-1289.