‘Targeting the feast of a sleeping beast’: Nutrient and mineral dependencies of encysted Acanthamoeba castellanii

Acanthamoeba spp. cause a corneal infection, Acanthamoeba keratitis (AK), and a cerebral infection, granulomatous amoebic encephalitis (GAE). Though aggressive chemotherapy has been able to kill the active trophozoite form of Acanthamoeba, the encysted form of this parasite has remained problematic to resist physiological concentrations of drugs. The emergence of encysted amoeba into active trophozoite form poses a challenge to eradicate this parasite. Acanthamoeba trophozoites have active metabolic machinery that furnishes energy in the form of ATPs by subjecting carbohydrates and lipids to undergo pathways including glycolysis and beta‐oxidation of free fatty acids, respectively. However, very little is known about the metabolic preferences and dependencies of an encysted trophozoite on minerals or potential nutrients that it consumes to live in an encysted state. Here, we investigate the metabolic and nutrient preferences of the encysted trophozoite of Acanthamoeba castellanii and the possibility to target them by drugs that act on calcium ion dependencies of the encysted amoeba. The experimental assays, immunostaining coupled with bioinformatics tools show that the encysted Acanthamoeba uses diverse nutrient pathways to obtain energy in the quiescent encysted state. These findings highlight potential pathways that can be targeted in eradicating amoebae cysts successfully.     

Phylogenetic analysis and prevalence of urosepsis strains of Escherichia coli bearing pathogenicity island-like domains

We characterized 100 Escherichia coli urosepsis isolates from adult patients according to host compromise status by means of ribotyping, PCR phylogenetic grouping, and PCR detection of papG alleles and the virulence-related genes sfa/foc, fyuA, irp-2, aer, hly, cnf-1 and hra. We also tested these strains for copies of pap and hly and their direct physical linkage with other virulence genes in an attempt to look for pathogenicity islands (PAIs) described for the archetypal uropathogenic strains J96, CFT073, and 536. Most of the isolates belonged to E. coli phylogenetic groups B2 and D and bore papG allele II, aer, and fyuA/irp-2. papG allele II-bearing strains were more common in noncompromised patients, while papG allele-negative strains were significantly more frequent in compromised patients. Fifteen ribotypes were identified. The three archetypal strains harbored different ribotypes, and only one-third of our urosepsis strains were genetically related to one of the archetypal strains. Three and 18 strains harbored three and two copies of pap, respectively, and 5 strains harbored two copies of hly. papGIII was physically linked to hly, cnf-1, and hra (reported to be PAI II(J96)-like genetic elements) in 14% of the strains. The PAI II(J96)-like domain was inserted within pheR tRNA in 11 strains and near leuX tRNA in 3 strains. Moreover, the colocalized genes cnf-1, hra, and hly were physically linked to papGII in four strains and to no pap gene in three strains. papGII and hly (reported to be PAI I(CFT073)-like genetic elements) were physically linked in 16 strains, pointing to a PAI I(CFT073)-like domain. Three strains contained both a PAI II(J96)-like domain and a PAI I(CFTO73)-like domain. Forty-two strains harbored papGII but not hly, in keeping with the presence of a PAI II(CFT073)-like domain. Only one strain harbored a PAI I(536)-like domain (hly only), and none harbored a PAI I(J96)-like domain (papGI plus hly) or a PAI II(536)-like domain (papGIII plus hly). This study provides new data on the prevalence and variability of physical genetic linkage between pap and certain virulence-associated genes that are consistent with their colocalization on archetypal PAIs.     

Household waste and health risks affecting waste pickers and the environment in low- and middle-income countries

Household waste has evolved into a core urban challenge, with increased quantities of waste being generated and with more complex material compositions, often containing toxic and hazardous elements. Critical systems theory understands cities as urban metabolisms, with different material and energy flows, highlighting the circularity in production, consumption, and discard. Waste pickers in low- and medium-income countries work on dumps and landfills, sifting through highly contaminated household waste and are exposed to health hazards. This paper discusses the risk factors, hazards, and vulnerabilities waste pickers are exposed to during collection and separation of recyclables, based on the review of literature on waste and environmental health and on findings from participatory research with waste pickers conducted in Brazil. We take a social and environmental justice perspective and identify the vulnerabilities and waste-borne hazards of household waste, associated with these workers, their communities, watersheds, and the environment. Household waste, although not always per se toxic or hazardous, can become a hazard if not collected or inadequately managed. Those communities where household waste is not collected or waste collection is insufficient are the most critical places. Informal and organized waste pickers, municipal or private waste collectors/workers, small waste traders and sometimes residents, particularly small children, may be considered vulnerable if exposed to waste-borne hazards. The results include recommendations to address household waste-borne hazards and vulnerabilities, according to waste workers involved in this research.     

Correction: Lifetime direct healthcare costs of treating colorectal cancer: a systematic review

The European Journal of Health Economics -     

Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children

Background

Immune responses to the inactivated oral whole cell cholera toxin B (CTB) subunit cholera vaccine, Dukoral^®, as well as three childhood vaccines in the national immunization system were compared in children living in high and low arsenic contaminated areas in Bangladesh. In addition, serum complement factors C3 and C4 levels were evaluated among children in the two areas.

Vaccinations

Toddlers (2–5 years) were orally immunized with two doses of Dukoral 14 days apart. Study participants had also received diphtheria, tetanus and measles vaccines according to the Expanded Program on Immunization (EPI) in Bangladesh.

Results

The mean level of arsenic in the urine specimens in the children of the high arsenic area (HAA, Shahrasti, Chandpur) was 291.8 μg/L while the level was 6.60 μg/L in the low arsenic area (LAA, Mirpur, Dhaka). Cholera specific vibriocidal antibody responses were significantly increased in the HAA (87%, P < 0.001) and the LAA (75%, P < 0.001) children after vaccination with Dukoral, but no differences were found between the two groups. Levels of CTB specific IgA and IgG antibodies were comparable between the two groups, whereas LPS specific IgA and IgG were higher in the LAA group, although response rates were comparable.Diphtheria and tetanus vaccine specific IgG responses were significantly higher in the HAA compared to the LAA group (P < 0.001, P = 0.048 respectively), whereas there were no differences in the measles specific IgG responses between the groups.Complement C3 and C4 levels in sera were higher in participants from the HAA than the LAA groups (P < 0.001, P = 0.049 respectively).

Conclusions

The study demonstrates that the oral cholera vaccine as well as the EPI vaccines studied are immunogenic in children in high and low arsenic areas in Bangladesh. The results are encouraging for the potential use of cholera vaccines as well as the EPI vaccines in arsenic endemic areas.     

Self-rated health and social capital in transitional countries: Multilevel analysis of comparative surveys in Armenia, Azerbaijan, and Georgia

The objective of this study is to analyze the effect of social capital on self-rated health in transitional countries of the South Caucasus region. The study is based on recent, 2009, cross-sectional nationally-representative surveys of 2082 respondents in Armenia, 2014 in Azerbaijan, and 1837 in Georgia with response rate of 78-80%. Two-level random-coefficient ordered logistic regression, modeling individual and community variations in subjective health was estimated to account for the hierarchical structure of the data set which includes individuals nested within communities. The results allow several interesting conclusions to be drawn. First, a proportion of the total variation in self-rated health explained at the community level is 0.23 for Azerbaijan, 0.10 for Georgia, and 0.08 for Armenia. These findings highlight the importance of more decentralized community-based healthcare interventions in the region. Second, human capital covariates remained significant predictors of health status even after controlling for social capital both at individual and community levels. Likewise, social capital variables are significant predictors of health status when used alone and when they are controlled by human capital covariates. These findings suggest that human capital and social capital influence health status independently of each other. Finally, this study sheds light on whether social capital collectively benefits members of a community in transitional countries beyond the individual benefits. In Armenia and Azerbaijan, community level differences in health status are rooted in "compositional" differences between social capital of individuals in the communities rather than at the community "contextual" level. In Georgia, by contrast, the beneficial effect of social capital can be simultaneously observed at the individual "compositional", and community "contextual" levels. These findings suggest that neither "compositional" nor "contextual" models of the social capital effect of health status can apply to all transitional societies universally.