Abstract: Between 23 August and 15 December 1990 an epidemic of cholera affected Mozambican refugees in Malawi causing 1931 cases (attack rate = 2.4%); 86% of patients had arrived in Malawi < 3 months before illness onset. There were 68 deaths (case-fatality rate = 3.5%); most deaths (63%) occurred within 24 h of hospital admission which may have indicated delayed presentation to health facilities and inadequate early rehydration. Mortality was higher in children < 4 years old and febrile deaths may have been associated with prolonged i.v. use. Significant risk factors for illness (P < 0.05) in two case-control studies included drinking river water (odds ratio [OR] = 3.0); placing hands into stored household drinking water (OR = 6.0); and among those without adequate firewood to reheat food, eating leftover cooked peas (OR = 8.0). Toxigenic V. cholerae O1, serotype Inaba, was isolated from patients and stored household water. The rapidity with which newly arrived refugees became infected precluded effective use of a cholera vaccine to prevent cases unless vaccination had occurred immediately upon camp arrival. Improved access to treatment and care of paediatric patients, and increased use of oral rehydration therapy, could decrease mortality. Preventing future cholera outbreaks in Africa will depend on interrupting both waterborne and foodborne transmission of this pathogen.

Abstract: During development of Peru-15, a new live oral vaccine for cholera, the role of buffer needed to be evaluated. Generally, oral bacterial vaccines are acid labile and need to be administered by using a formulation which protects them from gastric acid. We compared three different buffers for use with Peru-15, including a standard bicarbonate-ascorbic acid buffer, Alka-Seltzer, and a new electrolyte-rice buffer, CeraVacx. Saline served as the control. Thirty-nine healthy adult volunteers received Peru-15 (10(8) CFU) with one of the three buffers or saline in a double-masked study. The volunteers were monitored for symptoms for 7 days after the dose, serum was tested for antibody responses by vibriocidal antibody and immunoglobulin G antitoxin enzyme-linked immunosorbent assays, and stool samples were tested for excretion of the vaccine strain. Side effects were minimal in all groups. All 30 volunteers who took Peru-15 with a buffer showed significant rises in vibriocidal antibody titer. The magnitude of the rises was higher in the CeraVacx group than in the other two buffer groups. Four of nine volunteers who took the vaccine with saline also showed increased titers, but they were lower than those in any of the three buffer groups. Excretion of the vaccine strain was similar in the buffer groups, but excretion was not associated with the magnitude of the vibriocidal responses. Excretion of Peru-15 was not detected in the saline group. We conclude that buffer does amplify the serological response to Peru-15 and that CeraVacx may provide benefits not provided by other buffers.

Abstract: Background Cholera spread to Latin America in 1991; subsequently, cholera vaccination was considered as an interim intervention until long-term solutions involving improved water supplies and sanitation could be introduced. Three successive summer cholera outbreaks in northern Argentina and the licensing of the new single-dose oral cholera vaccine, CVD 103-HgR, raised questions of the cost and benefit of using this new vaccine. Methods This study explored the potential benefits to the Argentine Ministry of Health of treatment costs averted, versus the costs of vaccination with CVD 103-HgR in the relatively confined population of northern Argentina affected by the cholera outbreaks. Water supplies and sanitation in this area are poor but a credible infrastructure for vaccine delivery exists. Results In our cost-benefit model of a 3-year period (1992-1994) with an annual incidence of 2.5 case-patients per 1000 population and assumptions of vaccine efficacy of 75% and coverage of 75%, vaccination of targeted high risk groups would prevent 1265 cases. Conclusion Assuming a cost of US$602 per treated case and of US$1.50 per dose of vaccine, the total discounted savings from use of vaccine in the targeted groups would be US$132,100. The projected savings would be altered less by vaccine coverage (range 75-90%) or efficacy (60-85%) changes than by disease incidence changes. Our analysis underestimated the true costs of cholera in Argentina because we included only medical expenditures; Indirect losses to trade and tourism had the greatest economic impact. However, vaccination with CVD 103-HgR was still cost-beneficial in the base case.

Abstract: Various cellular fractions of Vibrio cholerae O139 were prepared and evaluated in the rabbit ileal loop model of experimental cholera for identification of the protective antigen(s) relevant for vaccine development. Lipopolysaccharides (LPS) and capsular polysaccharides (CPS) of O139 strains and its cell surface, membrane and cytosolic fractions were assayed for antibacterial immunity, whereas the cholera toxin was examined for antitoxic immunity. The lipopolysaccharides, membrane fraction and cholera toxin induced moderate protection, however there was a significant synergistic effect when cholera toxin was combined with membrane proteins or lipopolysaccharides. The O139 strains strongly resembled O1 strains in the profile of proteins and immunological cross reactivity, yet there was no cross protection. The results warrant further investigation of the pathogenesis of O139 strains and identify the critical somatic antigens relevant to protection.

Abstract: In 1995, the WHO Global Programme for Vaccines and Immunization established a Vaccine Trial Registry. As of September 1996, this registry included 50 WHO-supported vaccine trials, of which 25 (50%) were completed studies. The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials). Nearly 80% of these trials have been conducted in developing countries, with the largest number being in Africa. Among the 25 completed trials, outcomes measured were immune response (24 trials), adverse reactions (13 trials), morbidity (4 trials), and mortality (1 trial). WHO's contributions to these studies include direct funding, assistance with study design, site visits, data analysis, vaccine procurement, and vaccine potency testing.

Abstract: Although epidemic cholera was first described in 1817, the disease probably has been common in the Indian subcontinent since ancient times.1 Until recently, a single bacterial type (Vibrio cholerae 01) has been responsible for each of the seven recorded cholera pandemics. The current epidemic began in Celebes (Sulawesi), Indonesia, in 1961, and is currently raging through all continents.2 During the 1990s, over 1 million cholera cases have been reported from Latin America, 2000 from Ukraine and the Russian Republic during 1994 alone (GIDEON computer software, C.Y. Informatics, Ramat Hasharon, Israel). Of the 208,755 cases of cholera (5034 fatal) officially reported to the World Health Organization in 1995,3 41.1% were from Latin America, 34.0% from Africa, 24.4% from Asia, and 0.5% from Europe and Oceania. Interest in our own country of Israel stems from the popularity of tourism (over 1 million travelers exit Israel yearly) and the presence of disease in neighboring areas. Following an epidemic of 397 cases in Jerusalem during 1970, periodic outbreaks have occurred in Gaza, Judea and Samaria.4 Three tourists returned with the infection to Israel during the 1980s, all from Egypt (which officially claims to have no cholera).5 Despite universal interest in this ancient disease, medical science has long been frustrated in its search for an effective vaccine. The most important 'vaccine' against cholera is common sense, and consists of intelligent eating and drinking while in endemic areas. For example, local raw fish (ceviche) is a common source of the disease in Latin America, while shellfish (particularly oysters) are often implicated along the American Gulf Coast. Virtually all forms of water purification are effective against Vibrio cholerae. Although antibiotic prophylaxis might be considered in some circumstances (doxycycline; or a quinolone in areas of tetracycline resistance), it is not routinely advocated.

Abstract: Two oral cholera vaccines-inactivated WC/rBS and live CVD 103 HgR-have recently been marketed in Europe. Though the efficacy of the live vaccine is yet to be supported by field trials, the inactivated oral vaccine has shown encouraging results in field trails on different population groups. Since the role of cholera vaccines-including oral vaccines-as a public health tool in epidemic situations is debatable and cholera immunization for travellers will result in a high cost-benefit ratio, endemic cholera remains the main area of their application. The questions raised in the Bangladesh trial about the protective efficacy of WC/rBS vaccine in people infected with the EI Tor biotype, in 'O' blood group people and in those having no previous immunity to cholera have been reconsidered and explored during the recent field trail in South America, with satisfactory results. However, none of these vaccines provide protection against Vibrio cholerae 0139 Bengal. With their widely demonstrated safety and efficacy, oral cholera vaccines are set to make injectable vaccines obsolete.

Abstract: Researchers in Vietnam have produced a cheap and effective oral vaccine against cholera, reducing the incidence of the disease in an endemic area of the country by 60%. To test the efficacy of an oral killed cholera vaccine that had been produced locally the Vietnamese team performed an open field trial in 22 653 households in the central coastal city of Hue ( Lancet 1997;349:231-5). They found that the number of cases of cholera during an outbreak …

Abstract: A process for the isolation of nontoxinogenic V cholerae strain and a process for preparing a cholera vaccine from said V cholerae strain, said process comprising (a) isolating V cholerae from the stool of a patient suffering from cholera by spreading the stool on a selector medium specific for V cholerae , (b) separating the non-toxinogenic V cholerae strain from the population of the V cholerae strains isolated in step (a), the strain having been deposited at Microbial Type Culture Collection (MTCC) at the Institute of Microbial Technology (IMT), Chandigarh, India, a constituent laboratory of the applicants and having the Accession no MTCC B0010 which has also been deposited at American Type Culture Collection, Rockville, Maryland, USA and having Accession no ATCC 202010, and (c) incorporating immunogenic cholera toxin (ctx) B subunit gene into the chromosome of the strain having the Accession no MTCC B0010 (ATCC 202010) by conventional methods to produce the vaccine

Abstract: A live oral cholera vaccine should ideally protect against both classical and El Tor biotypes of Vibrio cholerae 01. An El Tor biotype vaccine strain, therefore, would complement classical cholera vaccine strain CVD 103-HgR, a strain already in use in some countries. In this study, 25 healthy adult volunteers received a single dose of 10 g colony-forming units of El Tor vaccine strain CVD 111, a derivative of El Tor Ogawa strain N16117 deleted in the virulence cassette. Three (12%) volunteers developed mild diarrhea (mean stool volume = 813 ml) but no systemic symptoms; 23 (92%) of the 25 volunteers developed serum vibriocidal antibodies (geometric mean titer = 1: 2,291). Five weeks after vaccination, 18 vaccinees and eight unimmunized control volunteers underwent wild-type challenge with El Tor Ogawa strain 3008. Three (16.7%) of 18 vaccinees and seven (87.5%) of eight controls developed diarrhea (P = 0.001) (vaccine efficacy = 80.9%). Further studies are underway to determine a dosage of CVD 111 that will be more clinically acceptable but equally immunogenic and protective.

Abstract: A new live oral cholera vaccine, Peru-15, was studied for safety, immunogenicity, and excretion in 2 groups of healthy volunteers. Twelve inpatient volunteers received freshly harvested vaccine in doses of either 10 7 or 10 9 cfu. Subsequently 50 outpatient volunteers received freeze-dried vaccine in doses of 10 8 or 10 9 cfu or placebo in a three-cell, double-masked, placebo-controlled trial. The strain was well tolerated at all dose levels, and it stimulated high levels of vibriocidal antibodies in most inpatient volunteers and in all outpatient volunteers. Although antitoxin responses were less frequent and of lower magnitude than the vibriocidal responses, antitoxin responses were seen in >60% of the outpatient volunteers. About 60% of the volunteers excreted the vaccine in their feces; however, fecal excretion did not correlate with serologic responses. It is concluded that Peru-15 is a safe and immunogenic oral vaccine for cholera.