Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome.

Abstract.Children in poor environmental conditions are exposed early and often to enteric pathogens, but within developing countries, heterogeneity in enteropathogen exposure in different settings and communities is rarely addressed. We tested fecal samples from healthy infants and children from two different environments in the same Indian town for gut enteropathogens and biomarkers of gut inflammation. A significantly higher proportion of infants and children from a poor semi-urban neighborhood (93%) had one or more enteropathogens than those from a medical college campus (71.7%). Infants and children from the poor neighborhood had an average of 3.3 (95% confidence interval [CI]: 2.9–3.7) enteropathogens compared with an average of 1.4 (95% CI: 1.0–1.7) enteropathogens in campus infants/children. Viral and bacterial infections, including enteroviruses, adenoviruses, Campylobacter spp., and diarrhegenic Escherichia coli were more common and fecal biomarkers of inflammation were higher in the poor neighborhood. The findings demonstrate significant difference in the asymptomatic carriage of gut enteropathogens and gut inflammatory biomarkers in infants and children from two different environments within the same town in south India.

The epidemiology of typhoid fever in South Asia has changed. Multi-drug resistant (MDR) Salmonella typhi ( S. typhi) is now frequently resistant to nalidixic acid and thus labelled NARST. Treatment failure with the use of fluoroquinolones has been widely noted, forcing clinicians to adopt alternative treatment strategies. In this observational study, we looked at various treatment regimens and correlated clinical and microbiological outcomes. In 146 hospitalised adults, the median minimum inhibitory concentration (MIC) for ciprofloxacin was 0.38 µg/mL with a median fever clearance time (FCT) of eight days (range = 2-35 days). Of the regimens used, gatifloxacin and azithromycin had a shorter FCT of six days compared to ceftriaxone (ten days; P < 0.001). Though mortality and relapse in our cohort was low, NARST seemed to correlate with mortality ( P = 0.006). Gatifloxacin or azithromycin clearly emerge as the drugs of choice for treatment of typhoid in South India.

Cerebrotendinous xanthomatosis is a lipid storage disease characterized by diarrhea, cataract, tendon xanthoma and neurological regression if untreated. CYP27A1 is the only gene in which mutations are known to cause Cerebrotendinous xanthomatosis. We report two Indian families from different regions of India who underwent molecular testing of CYP27A1. The first family from Eastern India consisting of two affected individuals was found to have the c.526delG homozygous mutation in exon 3, previously reported from our laboratory, also in a patient from Eastern India. However the second affected individual from Southern India that we studied and two previously reported cases from Northern India have different mutations. Interestingly the only previous report of c.526delG mutation was in a Surinamese individual from the Netherlands. To date most of the pathogenic mutations for Cerebrotendinous xanthomatosis have been confined to single population except for R362C mutation which was reported from the Netherlands and the USA (Black). To our knowledge this is the second causal mutation for Cerebrotendinous xanthomatosis which has been reported in two different populations. As human trading was prevalent from Eastern India to Surinam by the Dutch settlers this mutation might suggest a common founder mutation in these populations.

Spondylodiscitis due to typhoidal Salmonella presents a therapeutic challenge for clinicians. Factors that complicate treatment include drug-resistant strains, poor antibiotic bone penetration, potential for neurological compromise and lack of established protocols and guidelines. We discuss a 57-year-old man with Salmonella paratyphi A spondylodiscitis involving lower thoracic vertebrae and discuss various aspects of management.