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Summary Typhoid fever is estimated to have caused 21·6 million illnesses and 216 500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings. [ABSTRACT FROM AUTHOR]

Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children < 7 months of age (13%). VP7 genotypes G1 and G2 were most commonly isolated although significant heterogeneity of serotypes was observed. P[11], G9 strains were most frequently isolated among neonates. In 1998; approximately 98,000 childhood deaths were caused by rotavirus. These data underscore the urgent need for safe and effective interventions against rotavirus such as vaccines. The significant diversity of rotavirus strains and young age of hospitalization pose unique challenges to the formulation of a rotavirus immunization program in India, but raise the possibility of utilizing a neonatal vaccine to provide effective coverage. [ABSTRACT FROM AUTHOR]

Two hundred and five cases (mean age 13.4, SD 9.5) of persistent diarrhoea (PD) of 14–28 days duration, attending an urban slum clinic and treated according to standard WHO guidelines, were monitored at weekly intervals to obtain an estimate of treatment failure rates and to identify its clinical predictors. Vitamin and micronutrients (daily 2RDA) were additionally provided. Only 9 (8.2%) of 109 children with criteria for hospital care accepted in-patient care. Weight gain was considered inadequate if the daily increment between enrolment and day 7 of follow up was < 10 g at age 0–3 months, < 5 g at 4–6 months, and any weight loss for those older than 6 months. Recovery was considered delayed if diarrhoea ceased 7 days after enrolment. Overall, 28.3 % cases had inadequate weight gain and 25.6% had delayed recovery. The non-breast milk calorie intake was 11.2 % during infancy and 40.6 % at later ages of the recommended intakes. In a logistic regression model, initial watery stool frequency greater than median (adjusted OR 2.30, p=0.01), age < 6 months (adjusted OR 2.24, p=0.04) and low consumption of micronutrient mixture (adjusted OR 2.62, p=0.01) were associated with an increased risk of delayed recovery. In a Cox proportional hazards model for time to recovery from diarrhoea, low consumption of the micronutrient mixture and age < 6 months reduced the chances of recovery by 29 % and 37 % respectively. Low consumption of the prescribed micronutrient mixture (adjusted OR 2.21, p=0.04), fever (adjusted OR 1.91, p=0.05) and diarrhoea continuing beyond study day 7 (adjusted OR 2.29, p=0.03) increased the risk of inadequate weight gain. Breast feeding status and animal milk consumption did not influence weight gain or recovery. Due to the low compliance for advised hospitalisation, approaches for care at community level itself need to be evolved. Focus should be on increasing the overall dietary intake and provision of generous but safe amount of micronutrients; our findings do not support need for routine elimination of animal milk. The efficacy of individual micronutrients needs evaluation in controlled trials. [ABSTRACT FROM AUTHOR]

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs. [ABSTRACT FROM AUTHOR]

The national Diarrheal Disease Control Program was launched with the aim of improving the knowledge and practice of appropriate case management among caretakers of young children as well as health care providers. The National Family Health Survey (1992-3) revealed that 42.7% of mothers knew about ORS packets and 25.9% had ever used them. ORS use rates in children who suffered from diarrhea during the previous two weeks varied from 8.3% in Rajasthan to 50.1% in West Bengal. These findings represent substantial accomplishment, and also are a reminder that we still have to reach more than half of the households. Further analysis of the NFHS data showed that exposure to electronic mass media had a significant impact on mothers' awareness about ORS packets (56% in exposed, 32% in unexposed) and ORT use rates (38% in exposed, 25% in unexposed). In this review, future strategies for increasing the impact of the program are discussed. These include involvement of licensed and unlicensed medical practitioners, greater use of the electronic mass media, ORS standardization, greater focus on poorly performing states and resolving residual issues in the case management of diarrhea in malnourished children and infants under 6 months of age. [ABSTRACT FROM AUTHOR]

In an empiric approach to develop the definition of persistent diarrhea, we evaluated the relationship between diarrheal duration and risk of ensuing clinically significant decline in nutritional status, in a cohort of 395 children < 24 mo. Weights were obtained at the onset of diarrhea (wt I) and after three months interval (wt II). The occurrence of an adverse outcome (AO) was defined as a decline of -- 5% in NCHS weight for age (% WFA) between weights I and II or death in this interval. The risk of AO was similar for episodes of / or > 7 days while it was substantially higher in episodes with > 14 days duration (45%) than for shorter duration episodes, relative risk (RR) = 2.5 (p < 0.001). Relative risk remained similar for duration thresholds of 21 (2.3) and 28 days (2.6). As episode durations greater than 14 days are associated with substantial elevation of the risk of clinically cogent sequelae, such episodes may be termed 'persistent' at least in terms of poor prognostic expectations. [ABSTRACT FROM AUTHOR]

In order to relate etiology of diarrhea to the duration of the episode, a cohort of 452 children up to 36 months of age was visited once weekly at their households for 18 consecutive months to record diarrheal morbidity. Fecal specimens were obtained in 453 diarrheal episodes occurring in 354 children during this period. The common putative agents as single isolations associated with diarrhea were EA-AggEC (17.2%), ETEC (14.1%), EPEC (6.0%) and rotavirus (4.0%). The pathogens with higher median duration of diarrhea were Shigella (13.5; mean +/- SD 13.7 +/- 2.7), Salmonella (8.8: 15.3 +/- 4.5) and EA = AggEC (12.0: 15.1 +/- 1.8). Of 55 episodes with duration of greater than 14 days, the main pathogens isolated were EA-AggEC (32.7%), ETEC (9.0), Salmonella, G. lamblia (5.5% each) and Shigella (3.5%). These data provide a preliminary evidence to suggest that EA = AggEC may well be the main long sought microbial agent responsible for diarrhea of long duration. [ABSTRACT FROM AUTHOR]