J. Chakraborty

Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up

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%).

Field trial of oral cholera vaccines in Bangladesh.

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

Maternal mortality in Matlab Bangladesh: 1976-85.

This paper reports findings from a study of maternal mortality in Matlab, Bangladesh during the 1976-85 period. The study employed a multiple-step procedure to identify maternity-related deaths to all reproductive-aged women within the study area during this period. A total of 387 maternal deaths were identified, resulting in an overall maternal mortality ratio of 5.5 per 1,000 live births. The introduction of a family planning program in half of the Matlab study area led to a moderate but significant reduction in maternal mortality rates, relative to the comparison area. This appears to have been primarily due to a reduction in the overall number of pregnancies in the treatment area, since among women who became pregnant, mortality risks remained high. The results of this study underscore the need for a broad-based service strategy that includes but is not limited solely to family planning, in order to achieve significant reductions in maternal mortality levels in settings such as rural Bangladesh.

Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

Contraceptive use in Matlab Bangladesh in 1990: levels trends and explanations.

The results of a 1990 knowledge, attitudes, and practice survey in Matlab, Bangladesh, indicate that contraceptive prevalence has risen to 57 percent in the maternal and child health/family planning project area. Between 1984 and 1990 significant increases were registered in the proportions of women using contraceptives for the purposes of spacing and limiting births. By 1990 fertility control in the intervention area had become so widely diffused that educational differentials in contraceptive practice were no longer evident. Although significant gains in contraceptive use were also evident in the neighboring comparison area during this period, at 27 percent, prevalence there still remained substantially below the levels in the intervention area. The disparity in contraceptive use between the two areas is adequately explained neither by differences in socioeconomic conditions nor in the demand for family planning, but rather by differences in the intensity, coverage, and overall quality of their family planning programs.

Biotype as determinant of natural immunising effect of cholera

To test the hypothesis that clinical Vibrio cholerae O1 infections protect against recurrent cholera, treated cholera episodes in a rural Bangladesh population of 188,153 people who were followed between 1985 and 1988 were analysed. Of the 2214 people with initial episodes of cholera, 7 had a second episode. The incidence of cholera was 61% lower in subjects who had had an earlier episode than in those without such an episode. Whereas initial episodes of classical cholera were associated with complete protection against subsequent cholera, initial episodes of El Tor cholera were associated with negligible protection.

Persistent diarrhea as a cause of childhood mortality in rural Bangladesh.

To determine the importance of persistent diarrhea in childhood mortality a multiple‐step verbal autopsy method was used to study 1934 deaths in Matlab, Bangladesh. We found that most of the deaths from acute watery diarrhea occurred in infancy, whereas the peak of non‐watery diarrhea deaths was in children over 12 months of age. Children suffering from persistent diarrhea and malnutrition were at highest risk of dying during their third year of life. Children with infectious diseases have a two to four times higher risk of dying if they are malnourished, and for diarrhea the risk is 17 times as high. Forty‐nine percent of the diarrheal deaths were in children with malnutrition associated with persistent diarrhea. These results imply that fluid and dietary management are key aspects in the treatment of diarrhea, particularly for those episodes which persist. We conclude that attempts to reduce diarrhoeal deaths with vertical ORT programmes will not have a major impact unless other interventions are directed to the persistent diarrhoea‐malnutrition complex.

Nutrition and post-partum amenorrhoea in rural Bangladesh.

Summary A cross-sectional survey of 2048 breastfeeding women in rural Bangladesh was conducted in 1975 to explore factors affecting the duration of post-partum amenorrhoea. Information on menstrual status, infant supplementation, socio-economic status and anthropometric measurements was collected for lactating women with infants 13–21 months of age. The median length of amenorrhoea was observed to be over 18 months. There was a higher probability of being amenorrhoeic for older women and those of lower socio-economic status. Maternal malnutrition extended the duration of amenorrhoea slightly. Women feeding their infants higher-quality supplements were less likely to be amenorrhoeic than those supplying their infants with less adequate supplements. The figures suggest that the pattern of breastfeeding plays the primary role in determining lengths of lactational amenorrhoea for this rural population.

Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines

In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti-lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01.

Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. II: Field evaluation of cross-protection against other members of the Vibrionaceae family

Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae (NCV), the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a randomized, double-blind field trial in Bangladesh. Children aged 2-15 years and women aged greater than 15 years (62,285 in number) received three doses of BS-WC vaccine, WC-only vaccine, or a placebo consisting of Escherichia coli K12 strain (K12). During 1 year of follow-up, the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens (non-01 Vibrio cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus) in the placebo group was low (1.9 cases per 10,000 recipients) and identical to that for the two vaccine groups combined. The incidence (per 10,000 recipients) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher, but nearly identical in the three groups (26.1 cases for BS-WC, 26.0 cases for WC; 25.9 cases for K12). Pleisiomonas shigelloides was not isolated from any participant. It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms.