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Background Forcibly Displaced Myanmar Nationals (FDMNs) fled into Cox’s Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. The purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrheal patients from FDMNs and host community. Methods A total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox’s Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory for culture. Results A total of 8134 participants with diarrhea were enrolled from 2017 to 2019: 4881 were FDMNs and 3253 were from the Bangladeshi host community. Among the FDMNs, the proportion of Vibrio cholerae was 0.7%, the proportion of enterotoxigenic Escherichia coli (ETEC) was 4.9%, and the proportion of Shigella was 1.5%. The distributions from host community were 1.2% V cholerae, 1.8% ETEC, and 1.1% Shigella. Similar risk factors have been identified for the diarrheal pathogens for both communities. Conclusions This surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policymakers to take immediate preventive measures.

Background Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension. Methods A post hoc analysis of a 2-year cluster-randomized controlled trial including 2,645 hypertensives aged ≥40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants’ self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: (i) the therapeutic intensity score (TIS) for all (and class-specific) antihypertensive medications; (ii) the number of antihypertensive medications in all trial participants. Results At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% confidence interval (CI, 0.03, 0.12); P = 0.002). In MCI compared with controls, a greater increase in the TIS of renin–angiotensin–aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P < 0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05); P = 0.031), and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19); P = 0.016) was observed. Conclusions In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared with the usual care among adults with hypertension. Clinical trials registration Trial Number NCT02657746.

Background In a cluster randomized trial (CRT) of a Vi polysaccharide vaccine against typhoid in the slums of Kolkata we found evidence of vaccine herd protection. However, transmission of typhoid into clusters from the outside likely occurred in this densely populated setting, which could have diminished our estimates of vaccine herd protection. Methods Eighty clusters (40 in each arm) were randomised to receive a single dose of either Vi or inactivated hepatitis A vaccine. We analysed protection for the entire cluster and for subclusters consisting of residents of the innermost households. Results During 2 y of follow-up, total protection was 61% (95% CI 41 to 75), overall protection was 57% (95% CI 37 to 71) and indirect protection was 44% (95% CI 2 to 69). Analyses of the innermost 75% and 50% of households of the clusters showed similar findings. However, in the innermost 25% of households of the clusters, total protection was 82% (95% CI 48 to 94) and overall protection was 66% (95% CI 27 to 84). There was not a sufficient sample size to demonstrate such a trend for indirect protection in these innermost households. Conclusions The findings suggest that analyses of the entire cluster may have led to underestimation of herd protection against typhoid by Vi vaccine and that restriction of the analyses to the inner subclusters may have led to a more accurate estimation of vaccine herd effects.

Background Faecal-oral carriage via hands is an important transmission pathway for diarrhoeal pathogens. The level of faecal contamination of commuters' hands in Dhaka, Bangladesh, was examined in this study. Methods A total of 900 hand washing samples, including both left and right hands, were collected during one year to cover three different seasons in Bangladesh: winter, summer and rainy seasons. Standard membrane filtration technique was used to quantify total coliforms (TC), faecal coliforms (FC), faecal streptococci (FS), Escherichia coli (EC) and Clostridium perfringens (CP). Results The hands of the commuters were contaminated with TC, FC, FS, CP and EC. The TC, FC, FS, CP and EC counts were 1.95, 1.65, 4.04, 1.54 and1.46 log10 colony forming units (cfu) in the left hand; and 2.13, 1.82, 4.11, 1.52 and 1.61 log10 cfu in the right hand, respectively. There were no statistically significant differences in counts of left and right hands. The highest counts were observed for FS in all seasons. Conclusions This evidence based study may be used to provide interventions to reduce the contamination of commuters' hands through washing with detergent and, thus, help to prevent the spread of infectious diseases.

Background. Chronic and convalescent carriers play an important role in the transmission and endemicity of many communicable diseases. A high incidence of Salmonella enterica serovar Typhi and invasive nontyphoidal Salmonella (NTS) infection has been reported in parts of sub-Saharan Africa, yet the prevalence of Salmonella excretion in the general population is unknown. Methods. Stool specimens were collected from a random sample of households in 2 populations in West Africa: Bissau, Guinea-Bissau, and Dakar, Senegal. Stool was cultured to detect presence of Salmonella, and antimicrobial susceptibility testing was performed on the isolated organisms. Results. Stool was cultured from 1077 and 1359 individuals from Guinea-Bissau and Senegal, respectively. Salmonella Typhi was not isolated from stool samples at either site. Prevalence of NTS in stool samples was 24.1 (95% confidence interval [CI], 16.5–35.1; n = 26/1077) per 1000 population in Guinea-Bissau and 10.3 (95% CI, 6.1–17.2; n = 14/1359) per 1000 population in Senegal. Conclusions. Evidence of NTS excretion in stool in both study populations indicates a possible NTS transmission route in these settings.

Background New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Methods Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Results Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. Conclusions By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs.

The Typhoid Fever Surveillance in Africa Program (TSAP) estimated adjusted incidence rates (IRs) for Salmonella enterica serovar Typhi and invasive nontyphoidal S. enterica serovars (iNTS) of100 cases per 100 000 person-years of observation (PYO) for children aged15 years in Asante Akim North Municipal (AAN), Ghana, between March 2010 and May 2012. We analyzed how much these rates differed between rural and urban settings.Children recruited at the Agogo Presbyterian Hospital and meeting TSAP inclusion criteria were included in the analysis. Towns with32 000 inhabitants were considered urban; towns with populations5200 were considered rural. Adjusted IRs for Salmonella bloodstream infections were estimated for both settings. Setting-specific age-standardized incidence rates for children aged15 years were derived and used to calculate age-standardized rate ratios (SRRs) to evaluate differences between settings.Eighty-eight percent (2651/3000) of recruited patients met inclusion criteria and were analyzed. IRs of Salmonella bloodstream infections in children15 years old were100 per 100 000 PYO in both settings. Among rural children, the Salmonella Typhi and iNTS rates were 2 times (SRR, 2.2; 95% confidence interval [CI], 1.3-3.5) and almost 3 times (SRR, 2.8; 95% CI, 1.9-4.3) higher, respectively, than rates in urban children.IRs of Salmonella bloodstream infections in children15 years old in AAN, Ghana, differed by setting, with 2 to nearly 3 times higher rates in the less populated setting. Variations in the distribution of the disease should be considered to implement future studies and intervention strategies.

BACKGROUND The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. METHODS Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (

Background In Bangladesh, cholera is endemic and maintains a regular seasonal pattern. The role of phytoplankton in maintaining endemicity and seasonality of cholera was monitored in Matlab, Bangladesh. Methods Phytoplankton and water samples were collected from two ponds bi-weekly for 1 year. The association of Vibrio cholerae O1 with phytoplankton was studied by culture and direct fluorescent antibody techniques. The bio-physicochemical parameters of water were measured and data for cases of cholera were collected from the records of Matlab hospital. The correlation of cholera cases with levels of phytoplankton, V. cholerae and bio-physicochemical parameters of water was carried out using Pearson's correlation coefficients. Results V. cholerae O1 survived for 48 days in association with Anabaena variabilis in a culturable state, but survived for a year in a viable but non-culturable (VBNC) state. V. cholerae survived for 12 and 32 days in a culturable state in control water (without algae) and water with algae, respectively. There was a significant correlation between changing levels of cholera cases in the community and the blue green algae and total phytoplankton in the aquatic environment. A significant correlation was also found between the cholera cases and chlorophyll-a and VBNC V. cholerae O1 in the aquatic environment. Conclusions This study demonstrated the role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh.

BACKGROUND This study describes phenotypic, genotypic and antibiotic susceptibility patterns of the strains isolated from the 2012 Sierra Leone cholera outbreak. Rectal swabs were collected from patients and cultured for Vibrio cholerae O1. METHODS The isolates were subjected to multiplex PCR, mismatch amplification mutation assay (MAMA) PCR, pulsed field gel electrophoresis (PFGE), and antibiotic sensitivity tests using disk diffusion and minimum inhibitory concentration (MIC) E-test following standard procedures. RESULTS Out of 17 rectal swabs tested, 15 yielded V. cholerae O1 biotype El Tor, serotype Ogawa. All the strains belonged to 'altered' variants as MAMA PCR result showed the presence of classical cholera toxin B. PFGE result revealed four pulse types. Using antibiotic disk diffusion, all the isolates were resistant to erythromycin, chloramphenicol, furazolidone, and trimethoprim/sulfamethoxazole (SXT) except SL1 which was sensitive to chloramphenicol and SXT. All the isolates were sensitive to nalidixic acid, tetracycline, doxycycline, azithromycin, and ciprofloxacin except SL2 which was resistant to nalidixic acid. However, variable sensitivity patterns were observed for kanamycin. The ranges of MIC were 0.125-0.50 mg/l, 0.003-0.023 mg/l and 0.38-0.75 mg/l for azithromycin, ciprofloxacin and tetracycline, respectively. CONCLUSIONS This study demonstrates that altered variants of V. cholerae O1 of four clonal types were responsible for the 2012 outbreak of cholera in Sierra Leone.

In this article, we review the feasibility of mass vaccination against cholera and estimate the global population at risk for epidemic cholera. We then examine the cost of establishing and managing a cholera vaccine stockpile and summarize published mathematical models of the estimated impact of reactive vaccination campaigns developed for the current Haitian outbreak and a recent outbreak in Zimbabwe. On the basis of these evaluations, we recommend a stockpile that starts at 2 million doses, with an estimated annual cost of $5.5-$13.9 million in 2013, and grows to 10 million doses per year by 2017, with an annual cost of $27-$51 million. We believe that the stockpile can enhance efforts to mitigate future cholera outbreaks by guaranteeing the availability of cholera vaccines and, through use of the stockpile, by revealing knowledge about the efficient use of cholera vaccines during and after crises.

The current seventh pandemic of cholera, caused by serogroup O1, El Tor biotype, has now involved almost the entire developing world. The ongoing dynamic epidemiology of cholera, involving evolution of new strains, prolonged and more frequent epidemics, increased antimicrobial resistance, and awareness of the role of climate change upon the global burden has returned cholera to the forefront of global public health discussions. Improved water and sanitation should continue to be the mainstays of cholera-prevention efforts, but major improvements are a far-off goal for much of the cholera-affected developing world. The advent of safe and effective, new-generation oral vaccines against cholera has created renewed interest in the use of vaccines as a tool to control cholera.

The Heerenveen batholith exemplifies an aerially extensive group of � 3·1 Ga felsic potassic batholiths that mark the final magmatic event associated with the cratonization of the central^eastern Kaapvaal Craton, and the transition from the earlier sodic tonalite^ trondhjemite^granodiorite (TTG) to the more recent style of monzogranitic and granitic magmatism. As is typical of these bodies, it is geochemically and mineralogically heterogeneous, sheeted in structure, and was assembled incrementally, with eight main units in four assembly stages. Apart from a metaluminous quartz monzonite, all the Heerenveen rocks are peraluminous.There are few identifiable geochemical lineages among the rocks of the batholith. The geochemical heterogeneity is largely due to protolith internal heterogeneity, tapping of multiple sources, pulsed magma extraction related to sequential occurrence of discrete melting reactions, and varying degrees of entrainment of peritectic minerals formed during partial melting of the crustal protoliths, together with varying structural controls on magma extraction and ascent, which allowed distinct magma sources to be tapped, at different periods during batholith assembly. Fractional crystallization, magma mixing and wall-rock assimilation were not significant processes. TTG rocks are not suitable source materials for any of the Heerenveen magmas; nor are highly aluminous metasediments. For magmatic rocks with SiO2570 wt %, the likely source rocks were intermediate to mafic igneous rocks, with variable degrees of K-enrichment. For those rocks with SiO2472 wt %, the sources were K-enriched intermediate to felsic rocks. It seems likely that the partial melting reactions that produced the Heerenveen magmas occurred at moderate temperatures and that hornblende was present in the residues. This suggests that initial melting may have occurred in the presence of an H2O-rich fluid. There is no evidence that the genesis of the potassic granitic magmas involved either recycling of TTG crust or the presence of aluminous metasediments in the deep crust. The K-enrichment in the protoliths was most probably due to their ultimate derivation from mantle rocks metasomatized by fluids evolved in subduction-like processes. The monzonite in the batholith may have been derived directly by partial melting of this metasomatized mantle.

Previous studies have shown that cost of illness (COI) measures are lower than the conceptually correct willingness-to-pay (WTP) measure of the economic benefits of disease prevention. We compare COI with stated preference estimates of WTP associated with shigellosis in a rural area of China. COI data were collected through face-to-face interviews at 7 and 14 days after culture-confirmed diagnosis. WTP to avoid an episode similar to the one the respondent just experienced was elicited using a sliding-scale payment card. In contrast to previous studies' findings, average COI estimates (2002 PPP adjusted US dollars 28.2) approximate an upper bound estimate of WTP, rather than a lower bound. One explanation for the similarity between COI and WTP is that preventive expenditures and disutility due to pain and suffering are low for shigellosis. WTP to avoid additional cases in children aged 0-5 years is higher than in adults. Also, average COI (2002 PPP adjusted US dollars 28.4) for children is similar to a lower bound estimate of WTP (2002 PPP adjusted US dollars 16.4) and lies within the WTP range. Because the monetary loss associated with another episode in children is small, caregivers' higher WTP may be attributable to the disutility of illness due to the children's pain and suffering. These findings suggest that for some diseases, COI may approximate more comprehensive measures of economic benefits.

Recent research has indicated that the malaria burden in Asia may have been vastly underestimated. We conducted a prospective community-based study in an impoverished urban site in Kolkata, India, to estimate the burden of malaria and typhoid fever and to identify risk factors for these diseases. In a population of 60452 people, 3605 fever episodes were detected over a 12-month period. The blood films of 93 febrile patients contained Plasmodium (90 P. vivax, 2 P. falciparum and 1 P. malariae). Blood cultures from 95 patients grew Salmonella enterica serotype Typhi. Malaria patients were found to be significantly older (mean age 29 years) compared with patients with typhoid fever (15 years; P

The effectiveness of vaccines in populations must consider both direct and indirect protection. This study reanalyses data from a large individually randomized oral cholera vaccine trial that was conducted in rural Bangladesh from 1985 to 1990. A recent analysis of the results of that trial showed that the proportion of people in household clusters who received the vaccine was inversely related to placebo incidence during the first year of surveillance, which was attributed to herd immunity.In this study we measure the relationship between neighbourhood-level oral cholera vaccine coverage and protective efficacy (PE) during a 2 year follow-up period, controlling for known effect modifiers. We link trial data to a household geographic information system to facilitate the neighbourhood-level analysis. Findings Neighbourhood-level PE can be partially explained by vaccine coverage after adjusting for ecological variables.The inverse relationship between vaccine coverage and efficacy illustrates that people living in high-coverage areas may be indirectly protected from cholera because people living around them are vaccinated.

In July 2002 and June 2003, cholera outbreaks were detected by a diarrhoea surveillance system in a village outside Karachi, Pakistan. Specimens were culture confirmed. The first outbreak was caused by Vibrio cholerae O139 (n = 30) and the second outbreak by V. cholerae O1 (n = 39). Demographic and clinical features of patients were recorded and case-control studies were conducted following each outbreak. Clinical information was obtained for 29 of the 30 patients in the first outbreak, and 2 of the patients in the second outbreak were either out of the area or lost to follow-up, leaving 29 and 37 cases in the analysis for the first and second outbreak, respectively. Eighteen (49%) of the 37 V. cholerae O1 patients were under 2 years of age compared with 6 (21%) of the 29 V. cholerae O139 patients (P = 0.02). Vibrio cholerae O139-infected patients were more likely to be febrile (16/29) than those infected with V. cholerae O1 (2/37; P

Background. We conducted a nested case-control study in 397 rural Egyptian children

To design an efficacy trial of a killed oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea in Egyptian children, we derived for ETEC diarrhea an empirical definition that increased the probability that diarrhea associated with excretion of ETEC was caused by the detected ETEC.We conducted a cohort study of 397 Egyptian children24 months old and monitored them until they were 3 years old. Vaccine-preventable (VP) ETEC was defined as ETEC expressing/=1 of the toxin- (heat-labile [LT] toxin) and colonization-factor antigens (CFA I, II, and IV) in the vaccine.Although fecal excretion of VP-ETEC was highly associated with diarrhea, excretion of LT-ETEC per se was not related to diarrhea (adjusted odds ratio [OR(A)], 1.16 [95% confidence interval [CI], 0.90-1.49]). The fecal excretion of antigenic types of VP-ETEC other than LT-ETEC (non-LT VP-ETEC) was highly associated with diarrheal symptoms (OR(A), 3.91 [95% CI, 2.78-5.49]; P.001), and this association was greater for nonbloody than for bloody diarrhea.Because the vaccine had been anticipated to protect primarily against symptomatic ETEC diarrhea, these results indicate that the primary-outcome definition of ETEC diarrhea for the trial should be restricted to nonbloody diarrheal episodes associated with fecal excretion of non-LT VP-ETEC.

The Huntly Gabbro is one of a suite of large, Ordovician, syn-orogenic, mid-crustal, layered, mafic intrusions, emplaced into Proterozoic metaclastic rocks of NE Scotland soon after the thermal peak of static, high-T, low-P regional metamorphism. This gabbro and its associated contact metamorphic rocks illustrate a variety of processes operating during contact anatexis and subsequent melt segregation and extraction. These processes may closely mirror those occurring at much larger scales in the deep crust during high-grade regional metamorphism and the generation of granitic magmas. The emplacement of the Huntly mafic magma resulted in high-grade contact metamorphism and, locally, anatexis of metapelites, leading to the formation of migmatites. The migmatites and country-rock schists were studied to establish the physical conditions of metamorphism and anatexis, the nature of the melting reactions, the compositions of the melts produced, and the extent to which melting was a closedor open-system process. The country-rock schists immediately to the south of the Huntly Complex contain mineral assemblages characteristic of the regional andalusite zone. Thermobarometry of an andalusite schist yields regional metamorphic conditions of 537 42 C and 0 27 0 12 GPa, consistent with previously published P±T estimates. The contact metamorphic rocks include sillimanite hornfelses, metatexites and diatexites. The metatexites consist of cordierite±K-feldspar hornfels melanosomes and K-feldspar-rich garnetiferous leucosomes. The diatexites consist of schollen of fine-grained granoblastic hornfels and metatexite suspended in igneous-textured matrix rocks composed of abundant sub/euhedral garnet, cordierite, plagioclase and, locally, orthopyroxene, with minor interstitial biotite, K-feldspar and quartz. The hornfels melanosomes and schollen retained their structural integrity during partial melting, but the matrix rocks did not. In the highestgrade diatexites, the assemblage Grt ‡ Opx ‡ Crd‡ Hc ‡ Pl characterizes both the hornfels schollen and the sub/euhedral minerals of the matrix rocks. Application of phase equilibria to Opx-bearing rocks yields estimated peak-metamorphic conditions of 900 50 C, 0 45 0 1 GPa and aH2O5 0 3. The pressure estimate implies an emplacement depth of 16 3 km. The prograde P±T path of contact-metamorphic rocks had a low, positive dP/dT slope, indicating that the gabbro intrusion increased the lithostatic load on the country rocks by overplating. Pseudomorph textures involving Al-silicates provide strong evidence that the diatexites evolved from andalusite schists via a sillimanite hornfels stage. Mineralogical changes reflect a sequence of dehydration reactions, followed by fluid-absent partial-melting reactions involving biotite breakdown. It was the fluid-absent reactions that generated the sub/euhedral minerals in the diatexites, as peritectic phases. In many of the highestgrade diatexites, quartz-free anhydrous solid assemblages were produced via reactions such as Bt ‡ Sil ‡ Grt ˆ Crd ‡ Hc ‡ Kfs ‡ melt and Bt‡ Grt ‡ Crd ˆ Opx ‡ Hc ‡ Kfs ‡ melt. Whole-rock major-element geochemical studies indicate that the Opx±Crd hornfelses and diatexite matrices are depleted in Si and K relative to their schist protoliths. Mass-balance calculations indicate that (1) the Opx±Crd hornfels xenoliths represent solid Ca-, Mg-, Fe-, Al-, Na-rich residues left after extraction of 60% melt; (2) the Opx-bearing diatexite matrix rocks are also residual, and represent restite-enriched crystal±liquid mushes left after extraction of 55% melt; (3) the Opx-free diatexite matrix rocks probably represent restite-enriched mushes that retained a higher proportion of residual melt; (4) the anatectic melts were of H2O-undersaturated, peraluminous, JOURNAL OF PETROLOGY VOLUME 44 NUMBER 6 PAGES 995±1029 2003

To investigate whether micronutrient supplementation could improve the vibriocidal antibody response of children to a killed oral cholera vaccine, 2-5-year-old children were randomly assigned to receive vitamin A and zinc (AZ group), vitamin A and a placebo (A group), zinc and a placebo (Z group), or both placebos (P group). All children received 2 doses of the vaccine. The number of children who had a > or = 4-fold increase in vibriocidal antibody was significantly greater in the AZ group than in the P group (P = .025-.028). Factorial analysis suggested that the proportion of children with a > or = 4-fold increase in vibriocidal antibody titer was significantly greater in the zinc-supplemented groups than in the groups that did not receive zinc (P = .013-.048) and that vitamin A supplementation did not have a significant effect. Thus, supplementation with zinc improves seroconversion to vibriocidal antibody and, hence, has the potential to improve the efficacy of oral cholera vaccine in children.

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

From 1996 onward, a pandemic spread of Vibrio parahaemolyticus infections due to one clone has been reported in several Asian countries. During a population-based study that relied on passive surveillance, 548 cases of V. parahaemolyticus infection were detected between 1997 and 1999 in the Khanh Hoa province of Vietnam. Detection of cases of V. parahaemolyticus infection abruptly stopped in November 1999, although Vibrio species other than V. parahaemolyticus continued to be isolated throughout 2000. Of the infections, 90% occurred in individuals >5 years old; 53% of the patients presented with watery stools, and 6% reported blood in their stools. All patients had recovered by the time of discharge. A surprising risk factor for V. parahaemolyticus infections was high socioeconomic status. Like the interruption of the transmission of V. cholerae infections that had been observed earlier, the transmission of V. parahaemolyticus came to a halt without meteorological changes or changes in water supply and sanitation.

Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995--1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6--12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development.

To evaluate the effectiveness of Vi polysaccharide vaccine (Vi vaccine) in preventing typhoid fever, an analysis was done of an outbreak of typhoid fever among students attending a middle school in the People's Republic of China, where Vi vaccine is licensed for use. Vi vaccine effectiveness was analyzed by using Cox proportional hazards modeling to account for the time-dependent nature of vaccination and illness status during the outbreak. Among 1260 students who had been immunized before the outbreak, receipt of Vi vaccine was associated with 73% (95% confidence interval [CI], 32%-89%) protection. Among the additional 441 students immunized during the outbreak, receipt of Vi vaccine was associated with 71% (95% CI, -9% to 92%) protection. These results provide the first evidence about the effectiveness of Vi vaccine when deployed routinely in a typhoid-endemic area and support the use of Vi vaccine as a public health tool to control typhoid fever.

show that post-collisional wrenching in this part of the Variscides The Querigut mafic–felsic rock association comprises two main was under way by 310 Ma. magma series. The first is felsic comprising a granodiorite–tonalite, a monzogranite and a biotite granite. The second is intermediate to ultramafic, forming small diorite and gabbro intrusions associated with hornblendites and olivine hornblendites. A U–Pb zircon age

Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were2.0 microg/mL, and 95% were5.0 microg/mL. Homologous seroresponses (/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders.

Two randomized, double-blinded trials assessed the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli (ETEC) plus cholera toxin B subunit vaccine in Egyptian children. Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds. Safety was monitored for 3 days after each dose. Blood was collected before immunization and 7 days after each dose to measure immune responses. Few children reported postdosing symptoms, with no differences in the frequency of symptoms between treatment groups. Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I (100%, 6-12 years; 95%, 2-5 years), coli surface antigen 2 (92%, 6-12 years; 83%, 2-5 years), and coli surface antigen 4 (93%, 6-12 years). Vaccination evoked a >/=4-fold rise in antitoxic IgA and IgG titers in 93% and 81% of children, respectively. In conclusion, the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children, justifying further evaluation in infants.

This paper discusses considerations in public health for the introduction of tetravalent rhesus rotavirus-based reassortant vaccine (RRV-TV) for infants. RRV-TV contains a mixture of G1, G2, and G4 reassortants with a parent strain of MMU 18006. Field trials were performed to evaluate the protective efficacy of RRV-TV in infants and to determine the efficacy of RRV-TV higher-dose regimen. The use of RRV-TV in infant immunization brings about the following relevant issues: 1) availability of alternative or complementary non-vaccine interventions; 2) burden of disease; 3) epidemiologic features of rotavirus disease; 4) protective characteristics of the vaccine in efficacy trials; 5) clinical effectiveness of the vaccine; and 6) balance between costs and benefits of vaccination. Moreover, due to its high cost, RRV-TV would not be a cost-saving public health tool in developing countries unless it is made affordable. An effective vaccine against rotavirus is needed due to the following factors: 1) immense burden of rotavirus; 2) persistence of disease burden despite the promotion of rehydration therapy for acute diarrheas in childhood; and 3) lack of effectiveness of nonvaccination approaches.

In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune responses to these infections. After severe V. cholerae 01 infections (n = 70) in subjects5 years of age, the age group in which both vaccines were efficacious, a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients (p0.01). Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p0.01). The authors conclude that subjects who failed to be protected by BS-WC and WC, despite being in the age group for which these vaccines were protective, exhibited poor immune responses even to the vigorous stimulus of natural infection. These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in populations with endemic cholera.Natural infections by Vibrio cholerae 01 are known to confer substantial protection against recurrent infections in populations where cholera is endemic. This suggests that it may one day be possible to develop a highly effective oral vaccine against cholera. It is, however, curious that cholera continues to occur into adulthood in populations which have endemic cholera. This phenomenon could be the result of an inability among some individuals in endemic populations to mount suitable immune responses to natural infections. If such immune hyporesponsiveness is truly at work, it may be an important barrier against the development and use of an effective oral cholera vaccine. The authors evaluated whether deficient immune responses to natural infection were associated with the risk of vaccine failure among recipients of killed oral cholera vaccines in a field trial in Bangladesh during 1985. Their findings support the hypothesis that immune hyporesponsiveness, even after the vigorous stimulus of natural infection, may have limited the protection conferred by the vaccines studied in the trial.

To evaluate the relationship between Helicobacter pylori infection and the subsequent risk and severity of endemic Vibrio cholerae O1 diarrhea among rural Bangladeshis, 285 children and adults with cholera (cases) and 881 contemporaneously selected community controls were studied. Cases and controls were contrasted for H. pylori infection, as manifested by serum IgG anti-H. pylori antibodies. Although the overall risk of cholera was not significantly increased among H. pylon-infected subjects, the risk of cholera of life-threatening severity was significantly elevated (relative risk [RR] = 1.61 ; 95% confidence interval [CI] = 1.07-2.42). A significant increase in the risk of severe cholera was seen in subjects who lacked natural serum vibriocidal antibodies (RR = 2.88 ; 95% CI = 1.28-6.48) but not in those with such antibodies. Thus, H. pylori infection was associated with a significant increase in the risk of life-threatening cholera, but only among persons lacking natural vibriocidal immunity.

Background A protective effect of breastfeeding on childhood lymphoma has been indicated but supportive evidence is limited. Method Data from a population-based case-control study of childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukaemia cases and their age- and sex-matched community controls, were analysed. Results After adjustment for potentially confounding variables, a slight, although non-significant, reduction in risk of lymphoma was observed among children who were breastfed as infants versus those who were not (odds ratio [OR] = 0.69; 95% CI: 0.3-1.7). The reduction was somewhat greater for children who had been breastfed longer and appeared to pertain primarily to Hodgkin's disease and to cases diagnosed before the age of 6 years. As expected, there was no reduction in risk of acute leukaemia associated with breastfeeding. Conclusions Although providing neither strong support for nor refuting the study hypothesis, these data suggest that if breastfeeding does reduce the risk of lymphoma, its protective effect among Chinese children is likely modest in magnitude and concentrated in certain subgroups defined by length of breastfeeding, age at diagnosis and histological subtype of cancer.

Background. \ud Diarrhea is a leading cause of illness and death among children aged

The purpose of this study was to determine whether moderately low birth weight, singleton babies without congenital anomalies are at increased risk for postperinatal infectious disease mortality. The study cohort consisted of 54,795 live births assembled at 12 medical school-affiliated hospitals in different regions of the United States between 1959 and 1966 and followed prospectively. After exclusions of multiple gestation births, very low birth weight (less than 1,500 g) births, births with major congenital anomalies, and first-week deaths, 51,931 children remained for analysis. Postperinatal infectious disease mortality was assessed through age 7 years. Causes of death were classified independently by two pediatricians, blinded to birth weight status, according to an algorithm developed for the study. Moderately low birth weight infants and children were at increased risk of infectious disease mortality (relative risk (RR) = 2.49, 95% confidence interval (CI) 1.74-3.55). The risk persisted among those whose deaths met our strictest criteria for infectious etiology and was sustained beyond infancy throughout the age interval under analysis. Among those with moderate low birth weight, there was an increased risk among those with preterm birth (RR = 2.77, 95% CI 1.19-6.46) but not among those who were born small-for-gestational age (RR = 1.19, 95% CI 0.37-3.83). The data suggest that moderate low birth weight renders individuals vulnerable to infectious disease mortality during both infancy and childhood. Among moderately low birth weight infants and children, this vulnerability appeared to be attributable primarily to preterm birth rather than to intrauterine growth retardation.

Prevention of excessive heat loss is fundamental to survival of low birthweight (LBW) newborns. The use of infant incubators (INC) is beyond the resources of developing countries, and the space-heated room (SHR) has been the only feasible means of providing thermal protection to LBW newborns. Recently a thermostatically controlled, heated, water-filled mattress (HWM) has been developed as a potentially simpler and affordable alternative.In a neonatal care ward of a referral hospital in Addis Ababa, 621 week old newborns, weighing 1000-1999 g, who were well enough to breathe comfortably in room air and tolerate oral feeds, were randomly allocated to INC, HWM or SHR and followed for 3 weeks. The level of cold stress as assessed by core-to-skin temperature gradient and the rate of weight gain were the main outcome measures.The level of cold stress was lowest in the INC, intermediate in the HWM and highest in the SHR. Relative to the INC group, the HWM group exhibited a modest increase in the occurrence of clinically important hyperthermic or hypothermic deviations in core temperature (rate ratio (RR) = 2.3; 95% CI: 0.9, 5.6), and the SHR displayed a definite increase (RR = 4.0; 95% CI: 1.7, 9.3). During the first week, the rate of weight gain was highest in the INC group (3.6 g/kg/day), lowest in the SHR group (-2.3 g/kg/day, P0.05 versus INC) and intermediate in the HWM group (1.6 g/kg/day, P0.1 versus INC).Care in the SHR produced clinically significant thermal stresses and was associated with deficient early neonatal growth, but the use of HWM may constitute a feasible and clinically acceptable alternative in providing warmth to LBW newborns during the neonatal period.

BACKGROUND The potential benefits of installing excreta disposal facilities on the burden of paediatric diarrhoea in less-developed settings remain controversial. We conducted a longitudinal study to evaluate whether family latrines are associated with interruption of the transmission of shigellosis to younger children in rural Bangladesh. METHODS We prospectively studied 1529 children under 5 years of age exposed to index cases of Shigella dysentery. In all 219 children with culture-proven shigellosis detected during 1 month of follow-up were compared with 1310 control children who did not develop shigellosis or Shigella-negative dysentery. RESULTS Overall, the presence of a family latrine appeared to be associated with a higher, not a lower, risk of paediatric shigellosis (adjusted odds ratio (ORa) = 1.37, 95% confidence interval (CI): 0.99-1.89). While use of a pit or sanitary latrine revealed no evidence of a protective association (ORa = 0.96, 95% CI: 0.43-2.15), use of a hanging latrine in which faeces were discharged directly onto the ground or into a body of water was associated with a notable increase of risk (ORa = 1.42, 95% CI: 1.02-1.98, P < 0.05). CONCLUSIONS While cautioning that installation of sanitary latrines may not be sufficient to reduce the burden of paediatric shigellosis in less-developed settings, these data suggest that eliminating unsanitary latrines constitutes a potentially important intervention in its own right in these settings.

of opx, through partial melting of heterogeneous, highPREAMBLE K, biotite-bearing, lower-crustal source rocks. We inKlotzli et al. (2001) present a genetic model for a particular terpreted the orthopyroxenes in the SQMD rocks as granitic rock unit within the Variscan (Carboniferous) having crystallized early, and probably at somewhat South Bohemian Batholith. We studied and published higher P than the final emplacement of the magma. In on these same rocks some years previously (Finger & the course of protracted cooling and magmatic crysClemens, 1995). The interpretations of Klotzli et al. (2001) tallization, in a crustal section already heated by regional contrast so significantly with our own that we consider metamorphism, the orthopyroxenes were affected by it necessary to comment briefly on their paper. various exsolution and recrystallization processes. They The rock unit in question is the so-called Sarleinsbach quartz monzodiorite (SQMD), first described by Frasl & reacted with the residual melts and became marginally Finger (1988). This unit is an opx-bearing facies of the overgrown and replaced by clinopyroxene, amphibole Weinsberg granite—a very coarse-grained biotite granite and biotite–quartz symplectites (Haunschmid & Finger, and the most prominent rock type in the batholith. As 1994). Such magmatic overgrowths are to be expected with all granitic units assigned to the Weinsberg type, because aH2O and aKAlSi3O8 both increase in the the SQMD contains large K-feldspar phenocrysts. On residual liquids as crystallization proceeds toward the chemical variation diagrams, the data for the SQMD solidus. join smoothly with the other Weinsberg points, at the In contrast with this, Klotzli et al. (2001) hypothesize more mafic end of the compositional spectrum. Although that the pyroxenes are xenocrystal in origin, derived from such a variation is by no means definitive, this and the a Cadomian magmatic rock that crystallized some 200 field and textural evidence suggest that the SQMD is Myr earlier, and accidentally incorporated into the part of the Weinsberg granite. This has long been held Weinsberg magma. Klotzli et al. arrive at this conclusion to be the case. mainly through a geochronological study of the zircons of the SQMD. This work reveals the existence of a population of zircons with Variscan ages (interpreted as dating the formation and intrusion of the granite magma), ORIGIN OF PYROXENES IN THE and morphologically distinct (so-called J4-type) zircons SQMD with Cadomian ages (>520 Ma), clearly pre-dating the Variscan magmatic cycle. They observed the relationship We (Finger & Clemens, 1995) considered that the that pyroxene-rich variants of SQMD have a sysWeinsberg magma (as a whole) originated under granulite-facies conditions, i.e. within the P–T stability field tematically greater proportion of J4-type zircons than

To evaluate the safety and efficacy of passive immunotherapy for advanced human immunodeficiency virus (HIV) infection, a randomized, double-blind, controlled trial of human anti-HIV hyperimmune plasma was conducted. Sixty-three subjects with stage IV HIV disease (AIDS) were randomized to received 250 mL of either HIV-immune plasma or HIV antibody-negative plasma every 4 weeks. Although nonsignificant trends toward improved survival and delayed occurrence of a new opportunistic infection were noted, no significant effects on absolute CD4 lymphocyte counts or quantitative HIV viremia were seen. The only notable toxicity was the allergenicity to be expected from infusing plasma products, usually manifesting as urticaria. Thus, results do not rule out the potential usefulness of passive immunization with different preparations, but did fail to demonstrate clinical benefit of the product studied.

The recent spread of cholera to Latin America, together with the persistent burden of this disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus El Tor cholera.It is important to predict cholera incidence for clinical trials, but it is hard to do so, even in areas where there is a regular endemic pattern. In Matlab, Bangladesh, cholera tends to occur seasonally, right before and after the summer monsoon. Various host facts affect cholera incidence, e.g., insufficient natural immunity and exposure to infected persons. Passive surveillance data in Matlab demonstrate that cholera occurs in a temporo-spatially clustered, multifocal pattern within a community. Ineligibility, refusal to participate, and absenteeism have a strong filtering effect on the population in a field trial. For example, in a field trial of killed oral cholera vaccines in Bangladesh, only 62.285 of the original 124,035 people completed the trial. As a result of nonparticipation, the expected incidence for nonvaccinees was overestimated. The definition of cholera used also determines incidence. For example, if a trial in endemic areas uses the classical definition (watery diarrhea with excretion of cholera vibrios but no copathogens), it would miss those cases with atypical symptoms (e.g., 21% of treated cholera episodes in the oral vaccine trial were clinically atypical or microbiologically mixed). Age related distinctions, ABO blood group, and biotype of the infecting organisms all influence vaccine efficacy. The above issues were considered when designing field trails of killed oral cholera vaccines in Colombia and Peru, but most people in these countries lack preexisting natural immunity, these areas have only E1 for cholera, and it will be very difficult to predict incidence among nonvaccines. This review of epidemiological studies of cholera in Bangladesh, including a large-scale field trial of killed oral cholera vaccines, describes the significance of these considerations.

This case-control study sought to determine whether protection against clinically significant rotavirus diarrhea in children aged 4-35 months correlated with titers of serum neutralizing antibody and, if so, whether this protection was serotype-specific. Titers of acute-phase sera from 156 cases of treated rotavirus diarrhea in rural Bangladesh were contrasted with titers from 312 contemporaneously selected, age-matched controls. Analyses of the culture-adapted rotaviruses from the cases revealed that 24%, 15%, 43%, and 17% belonged to serotypes 1-4, respectively. Titers of both homologous and heterologous neutralizing antibody in acute blood specimens of cases were significantly lower than those of matched controls. However, multivariate logistic regression models demonstrated that only antibody titers to heterotypic rotaviruses were independently associated with protection against rotavirus disease. These data, which indicate that the correlation of protection with neutralizing antibody titers is not serotype-specific, suggest that immunity to rotavirus disease may be mediated by other factors.

The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators.

The relationship of serum vibriocidal (VC) and IgG anti-cholera toxin (CT) antibodies to the risk of cholera was evaluated during the first year of follow-up of recipients of three oral doses of B subunit (BS)-whole-cell vaccine, whole-cell vaccine, or Escherichia coli K12 strain placebo in Bangladesh. Acute sera from 121 cholera patients were compared with sera from 2592 contemporaneous community controls. Each doubling of VC titer was associated, on average, with a 22%-47% reduction of cholera risk in the three groups. In contrast, in the two groups that did not receive BS, anti-CT titers were directly associated with cholera and thus served as markers of higher cholera risk. Each vaccine conferred approximately 65% protective efficacy against cholera, but antibody titers did not correlate with vaccine efficacy, indicating that serum VC and anti-CT antibodies are poor markers of the longitudinal pattern of vaccine efficacy.

To evaluate the seroprevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among undergraduate college students, the authors simultaneously conducted three types of surveillance on a large university campus (27,902 undergraduates) in the Baltimore-Washington metropolitan area: a voluntary HIV-1 serosurvey with a linked risk assessment questionnaire (n = 3,394), a blinded serosurvey using blood specimens collected for routine purposes in the Student Health Center (n = 1,829), and a random sample risk assessment and case identification mail survey (n = 1,017 respondents of 3,000 solicited). The proportion of students belonging to a known risk group (a homosexual or bisexual man, intravenous drug user, or a sexual partner of a bisexual man, an HIV-1-infected person, a female prostitute, or an intravenous drug user) was 5.9% in the mail survey and 8.8% in the voluntary serosurvey. Whereas no infections were detected in the blinded serosurvey, two infected persons were identified in the mail survey (0.2%) and two in the voluntary serosurvey (0.06%), all among high-risk persons. Although derived from independent samples and subject to different biases, these three survey methods yielded a consistent pattern of HIV-1 epidemiology on this campus, whereby the overall prevalence of infection was low and confined to members of high-risk groups, despite the common occurrence of behaviors that might facilitate sexual transmission of HIV-1 among many other students.

The association between persistent diarrhoea and 'recent morbidity' defined as that occurring within the two-month period immediately preceding the onset of persistent diarrhoea was investigated in a population-based case-control study in rural North India. In two separate matched case-control analyses children with persistent diarrhoea (cases) were compared to population controls (five controls matched to each case) and acute diarrhoeal controls (three controls matched to each case). After correcting for possible confounding variables, comparing children with persistent diarrhoea and matched population controls, presence of a recent diarrhoeal illness was significantly associated with persistent diarrhoea with an odds ratio (OR) 2.6 (95%) confidence interval (CI): 1.1-7.1; p less than 0.05); during infancy this OR was 5.2 (95% CI: 1.0-31.9; p less than 0.01). Comparing children with persistent diarrhoea to matched acute diarrhoeal controls, presence of recent diarrhoeal illness was associated with an OR of 5.1 (95% CI: 1.3-20.3) in favour of the episode becoming persistent; in infants this OR was 10.4 (95% CI: 1.1-132.4; p less than 0.001).

To evaluate serologic immunity against clinical infections by heat-labile enterotoxin-producing Escherichia coli (LT-ETEC) in rural Bangladesh, 124 children and adult women with LT-ETEC diarrhea (cases) were compared with 347 age-matched community controls. In paired acute-convalescent sera from the cases, IgG anti-CFA I and anti-CFA II antibody titers increased eight-to ninefold after infection by LT-ETEC with the homologous CFA, and IgG anti-LT antibody titers increased fourfold for all LT-ETEC infections. Anti-CFA and anti-LT titers peaked in controls aged 12-23 months, the age group with the highest incidence of ETEC infections. However, antibody titers were similar in acute sera from cases and in sera from controls. Although serum IgG anti-CFA and anti-LT antibodies rose in response to LT-ETEC infections and paralleled the age-specific incidence of ETEC in the community, these antibodies were not associated with a lower risk of LT-ETEC diarrhea.

The association between breast feeding and the risk of severe cholera was examined in a case-control study of rural Bangladeshi children under 36 months of age who were studied in 1985-1986 during a field trial of killed oral cholera vaccines. A total of 116 cases who were treated for severe cholera were compared with 464 age-matched community controls without severe cholera. Overall, the odds ratio relating breast feeding to severe cholera (0.30, p less than 0.0001) reflected a 70% reduction in the risk of severe cholera among breast-fed children. The estimated reduction of risk declined with age, but was clearly evident in children up to 30 months of age. Although the association between breast feeding and a reduced risk of severe cholera was not significantly greater in children of mothers who had received cholera vaccine than in children whose mothers had received placebo during the trial, maternal vaccination per se was suggestively associated with a reduced risk of severe cholera in their nonvaccinated children (odds ratio = 0.53, p = 0.05). These results indicate that breast feeding was associated with a substantial reduction of the risk of severe cholera and raise the possibility that vaccination of mothers may provide protection to their young children in endemic settings.

The distribution of serotypes of group B streptococci (GBS) isolated from 67 infants with early-onset sepsis are described. Case-infants were assembled from 13 hospitals across the United States from 15 July 1995 to 5 February 1997 through prospective active surveillance. The distribution of GBS serotypes was Ia, 40%; Ib, 9%; II, 6%; III, 27%; V, 15%; and nontypeable, 3%. Type V occurred more frequently in the northeast region (New York and New Jersey) than in other regions (29% vs. 9%, P = .06). Conversely, type III occurred significantly less frequently in the northeast region than other regions (10% vs. 35%, P = .04). GBS types Ia, III, and V accounted for 82% of the isolates. This report supports previous observations about the emergence of GBS type V, but our data caution that conclusions about serotype distributions based on one geographic location or on a small number of patients may not be generally applicable. Continued monitoring seems necessary for the design of a GBS vaccine.