Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 m were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised Ϸ133,000 individuals, yielded a 48% reduction in cholera (P < 0.005) compared with the control. C holera is a disease that continues to ravage developing countries and reemerges sporadically elsewhere throughout the world. According to the World Health Organization (WHO), 58 countries have officially reported cholera in 2001, with a total of 184,311 cases and 2,728 deaths (1). However, there were 293,113 cases of cholera worldwide in 1998, with 10,586 deaths. These annual figures of WHO actually represent the tip of the iceberg, because the morbidity and mortality caused by Vibrio cholerae is grossly underreported owing to surveillance difficulties and also for fear of economic and social consequences (2). In fact, several cholera endemic countries, e.g., Bangladesh, are not included in the WHO report. In 1991, after almost 100 years without cholera, outbreaks in 16 Latin American countries resulted in Ϸ400,000 reported cases of cholera and Ͼ4,000 reported deaths (3).That cholera is a waterborne disease has long been known (4-6). Furthermore, surface water has been linked with transmission of cholera since the pioneering work of Snow in 1854 (7). Demonstration of the potential for water to transmit cholera was provided by Koch, who, after Pacini first described the Vibrio (8), isolated and characterized the bacterium, which he named Vibrio comma, and was able to find it in pond water used by an Indian community suffering a cholera epidemic (9).The association of pathogenic vibrios with zooplankton was reported in 1973 by Kaneko and Colwell (10) and of V. cholerae with copepods by Huq et al. in 1983 (11). Commensal occurrence of Vibrio spp. in the copepod gut was demonstrated by Sochard et al. in 1979 (12). A few years later, preferential attachment of V. cholerae to copepod surfaces, egg cases, and the copepod oral region was reported by Huq et al. (11). Extensive data have since been accumulated showing that planktonic copepods play a major role in the multiplication, survival, and transmission of cholera (13-17). That environmental V. cholerae O1 can cause cholera has been established by molecular genetic evidence (18).During spring and late summer in Bangladesh, phytoplankton blooms occur, followed by zooplankton, with heaviest blooms occurring in September and October (13,19). Each year, the seasonal zooplankton blooms, in turn, are followed by cholera outbreaks (11, 13). It has been determined that a single copepod, depending on species and size, can carry up to 10 4 cells of V. cholerae (11,17). Thus, a copepod bloom ca...

Objective To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. Design Cluster randomised comparison. Setting Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. Participants 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. Intervention Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. Main outcome measures Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. Results About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to > 80% (364/434) in month 7 and was sustained at that level. Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). Conclusions The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease.

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We assessed the adequacy of nutrient intakes of 135 rural Bangladeshi breast-fed infants 6-12 mo of age and examined nutritional trade-offs due to possible displacement of breast milk by complementary foods. Observers completed 12-h daytime measurements of breast milk and complementary food intakes; data for the previous 12 h were obtained from maternal recall, yielding estimates of total 24-h intakes. On average, infants were mildly wasted (mean +/- SD weight-for-length Z-score = -0.92 +/- 0.88) and moderately stunted (length-for-age Z-score = -1.49 +/- 0.96). Total energy intakes at 6-8 and 9-12 mo were 88 and 86% of absolute energy requirements (kJ/d), 106 and 105% of requirements per kg body weight, and 97 and 94% of requirements per kg median weight-for-length, respectively. Breast milk contributed 78% of energy intake at 6-8 mo and 75% at 9-12 mo. Mean meal frequency and energy density of complementary foods were generally consistent with recommendations, but only small amounts of food were offered. Nevertheless, only 72% of the food energy offered was consumed. Total energy intake was positively correlated with meal frequency, quantity consumed per meal, and energy intake from breast milk, but not with energy density of complementary foods. Energy intake from complementary foods was inversely related to energy intake from breast milk. The diets fell short of recommended intakes for numerous vitamins and minerals. We conclude that although greater intakes of complementary foods were associated with higher total energy intake, micronutrient intake remained low due to the low micronutrient density of the complementary foods consumed and the partial displacement of breast milk.

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).

The effects of maternal postpartum vitamin A or beta-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1-3 wk postpartum, women were randomly assigned to receive either (1) a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of beta-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The beta-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (/=0. 06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status.

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Background: Vitamin A supplementation of mothers postpartum may improve infant health, not only by increasing vitamin A delivery to the infant through breast milk but also by increasing delivery of milk immune factors. Our hypothesis was that postpartum supplementation with vitamin A increases milk concentrations of certain soluble immune factors. Design: In a double-blind trial conducted in Matlab, Bangladesh, women at 1-3 wk postpartum were randomly assigned to receive until 9 mo postpartum 1) a single dose of 60 mg retinol as retinyl palmitate followed by daily placebos (n = 69), 2) daily doses of 7.6 mg ␤-carotene (n = 72), or 3) daily placebos (n = 71). Milk samples collected at baseline and 3 mo postpartum were analyzed by enzyme-linked immunosorbent assay for secretory immunoglobulin A, lactoferrin, lysozyme, and interleukin 8; by HPLC for total retinol; and by atomic absorption spectroscopy for sodium and potassium. Results: After mammary epithelial permeability (defined as an elevated Na:K) and baseline immune factor concentrations were controlled for, there were no significant treatment effects on immune factors at 3 mo. Increased mammary permeability was common (25% of women at baseline and 12% at 3 mo) and was associated with higher concentrations of milk immune factors. Low body vitamin A stores at baseline, as assessed by the modified-relative-dose-response test, were associated with a higher Na:K, but neither retinol nor ␤-carotene supplementation affected the prevalence of increased mammary permeability. Conclusions: Postpartum vitamin A supplementation does not increase milk concentrations of immune factors. The causes of increased mammary epithelial permeability in this population require further study.Am J Clin Nutr 1999;69:953-8.