Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.

Anaemia and malnutrition in children aged 0-59 months on the Bijagós Archipelago, Guinea-Bissau, West Africa: a cross-sectional, population-based study.

BACKGROUND: Childhood malnutrition is the leading risk factor for the global burden of disease. Guinea-Bissau is a politically unstable country with high levels of childhood malnutrition and mortality. AIM: To determine the nutritional status of children on three remote islands of the Bijagós Archipelago, Bubaque, Rubane and Soga, and to identify factors associated with malnutrition and anaemia in this population in order to provide a baseline for future public health interventions. METHODS: A cross-sectional, population-based, door-to-door household survey of randomly selected households was undertaken to collect data on children aged 0-59 months (n = 872). Dietary information was collected using a validated questionnaire. Anthropometric measurements were collected using World Health Organization techniques. Capillary blood samples were analysed using a Hemocue®, with anaemia defined as Hb<11 g/dl. RESULTS: The prevalences of stunted, wasted and underweight children were 21.8%, 9.4% and 3.7%, respectively. These figures indicate moderate chronic malnutrition. The significant predictor variables for stunting were: age in months (OR 1.03), rural residence (OR 2.32), anaemia (OR 3.55) and residence on Soga island (OR 0.44). Stunting was more prevalent in males (25.4%) than in females (18.6%) (P = 0.03). The prevalence of anaemia was 80.2%. Age (OR 0.96), male gender (OR 1.81) and stunting (OR 2.87) were significant predictors. The Minimum Acceptable Diet was achieved by only 8.7% of children. CONCLUSION: The prevalence of malnutrition on the Bijagós Archipelago is less than half that on the mainland. This study is the first to determine the prevalence of anaemia in Guinea-Bissau, which, at 80.2%, is of severe public health concern. Future research should focus on the aetiology of stunting and anaemia, especially the contribution of infectious diseases and mother-child interaction. Iron supplementation should be strongly considered in this population.

Species- and sex-related differences in metabolism of trichloroethylene to yield chloral and trichloroethanol in mouse, rat, and human liver microsomes.

Trichloroethylene (TRI) has been shown to cause a variety of tumors, particularly in mouse liver and lung and rat kidney. However, a clear association between exposure to TRI and cancer development in humans has not been established. Because TRI metabolism by cytochrome P450s has been implicated in the mechanisms of TRI-induced carcinogenicity in mice, the purpose of the present study was to characterize the kinetics of TRI oxidation in male and female mouse, rat, and human liver microsomes to possibly allow for a better assessment of human risk. Methods were developed to detect and quantitate chloral, trichloroethanol, trichloroacetic acid, dichloroacetic acid, chloroacetic acid, glyoxylic acid, and oxalic acid, known TRI metabolites in rodents or humans. However, only chloral and its further metabolite, trichloroethanol, were consistently detected in the various liver microsomes in the presence of NADPH. Chloral was the major metabolite detected, and its levels were species- and sex-dependent; the amounts of trichloroethanol detected were also species- and sex-dependent but never exceeded 15% of total metabolites. Double-reciprocal plots of metabolite formation with male and female rat and human liver microsomes indicated biphasic kinetics, but this trend was not observed with microsomes from male or female mouse liver. The Vmax data are consistent, with male and female mice being more susceptible to TRI-induced liver carcinogenicity than male rats. However, the Vmax/Km ratios in male and female rat liver microsomes, in comparison with the male mouse liver microsomes, did not correlate with tumor incidences in these tissues. Furthermore, as only two out of six human liver samples examined exhibited Vmax/Km ratios similar or higher than the ratio obtained with male mouse liver, humans may vary in their toxic response after TRI exposure.