Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Niño-Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.

ATERNAL AND CHILD UNdernutrition is estimated to be the underlying cause of 3.5 million annual deaths and 35% of the total disease burden in children younger than 5 years. 1 The potential long-term consequences of nutritional imbalance or insult in fetal or early life also include cognitive impairment 2 and chronic diseases in adulthood. 3 Effective child nutrition interventions are available to reduce stunting, prevent consequences of micronutrient deficiencies, and improve survival. 4 The knowledge base is weaker regarding prenatal nutrition interventions of benefit for mother and offspring. Supplementation with balanced protein-energy supplements in low-income countries has resulted in increased birth weight, especially in periods of food insecurity. 5,6 A recent meta-analysis 7 of balanced proteinenergy supplementation to pregnant women estimated a mean effect on birth weight of 60 g (95% CI, 33-87 g). Recent meta-analyses of prenatal multiple micronutrient trials have demonstrated small increases in birth weight in comparison with iron-folic acid supplementation alone, 8,9 and a small reduction in the occurrence of smallfor-gestational-age outcomes, 10 but no reduction in risk of stillbirth, perina-For editorial comment see p 2094. Author Affiliations and the MINIMat Study Team are listed at the end of this article.

Antimicrobial resistance is becoming increasingly important in the treatment of enteric infections, particularly those due to Shigella, Vibrio cholerae, enterotoxigenic Escherichia coli (associated with traveler's diarrhea), and Salmonella typhi. The rate of antimicrobial resistance is highest in the developing world, where the use of antimicrobial drugs is relatively unrestricted. Of greatest immediate concern is the need for an effective, inexpensive antimicrobial that can be used safely as treatment for small children with dysentery due to Shigella, primarily Shigella dysenteriae type 1.

Maize was first domesticated in a restricted valley in south-central Mexico. It was diffused throughout the Americas over thousands of years, and following the discovery of the New World by Columbus, was introduced into Europe. Trade and colonization introduced it further into all parts of the world to which it could adapt. Repeated introductions, local selection and adaptation, a highly diverse gene pool and outcrossing nature, and global trade in maize led to difficulty understanding exactly where the diversity of many of the local maize landraces originated. This is particularly true in Africa and Asia, where historical accounts are scarce or contradictory. Knowledge of post-domestication movements of maize around the world would assist in germplasm conservation and plant breeding efforts. To this end, we used SSR markers to genotype multiple individuals from hundreds of representative landraces from around the world. Applying a multidisciplinary approach combining genetic, linguistic, and historical data, we reconstructed possible patterns of maize diffusion throughout the world from American "contribution" centers, which we propose reflect the origins of maize worldwide. These results shed new light on introductions of maize into Africa and Asia. By providing a first globally comprehensive genetic characterization of landraces using markers appropriate to this evolutionary time frame, we explore the post-domestication evolutionary history of maize and highlight original diversity sources that may be tapped for plant improvement in different regions of the world.

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In December 1979, a Vibrio cholerae O1 resistant to tetracycline, ampicillin, kanamycin, streptomycin, and trimethoprim-sulfamethoxazole was obtained from a patient with cholera at the Matlab Hospital, Bangladesh. All 256 isolates of V. cholerae O1 stocked in the previous six months were tested for antibiotic sensitivity: 54 were resistant to tetracycline, and 44 of these were resistant to all five antibiotics. The clinical presentation and hospital course for 51 patients with resistant strains of V. cholerae O1 and 102 patients with sensitive strains were compared by their medical records. Patients with resistant strains were indistinguishable from controls by age, sex, or severity of symptoms at presentation. All were treated with tetracycline, and patients with the resistant strains purged longer (mean, 37 vs. 25 hr; P less than 0.01) and in greater volume (mean 4.3 vs. 2.3 liters; P less than 0.01) and their controls with cholera due to susceptible strains. A resistance plasmid was identified. Based on these results, antibiotic use in the areas with resistant vibrios must be reconsidered.

To improve the understanding of the relative importance of serotypes of rotavirus in dehydrating diarrhea, we examined the correlation of clinical characteristics and disease severity with serotype in 2,441 diarrheal episodes among children younger than 2 years of age in rural Bangladesh. Of 764 rotavirus-associated episodes, a single G type (serotype 1, 2, 3, or 4) was determined by oligonucleotide probe in 485 (63%), while 233 episodes were nontypeable. Episodes with G types 2 and 3 were associated with more-severe dehydration than episodes associated with G type 1 or 4 or with nontypeable rotavirus. Episodes did not differ by G type in prevalence of vomiting, copious diarrhea, fever, abdominal pain, or length of treatment center stay. Rotavirus reinfections were detected in seven children, with homologous reinfection (G type 2) in one. Twelve children with diarrhea who died had rotavirus detected in stool specimens within 30 days of death. Children who died were more likely to be malnourished than were surviving children with rotavirus diarrhea. Of 40 specimens tested by polymerase chain reaction, 29 (72.5%) were P type 1, 9 (22.5%) were P type 2, 1 (2.5%) was P type 3, and 1 (2.5%) was nontypeable. One severely symptomatic diarrheal episode was associated with P type 3 rotavirus, a serotype usually found in asymptomatic nursery infections. Although G types 2 and 3 were associated with more-severe dehydration than other serotypes, the differences do not appear to be of major clinical importance. Effective vaccines should protect against all four major G types.

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