ATOMIC IONIZATION ENERGIES OF LOW ATOMIC NUMBER ELEMENTS CALCULATED BY SEMICLASSICAL METHOD

Purpose of review Almost half of all childhood deaths worldwide occur in children with malnutrition, predominantly in sub-Saharan Africa and South Asia. This review summarizes the mechanisms by which malnutrition and serious infections interact with each other and with children’s environments. Recent findings It has become clear that whilst malnutrition results in increased incidence, severity and case fatality of common infections, risks continue beyond acute episodes resulting in significant postdischarge mortality. A well established concept of a ‘vicious-cycle’ between nutrition and infection has now evolving to encompass dysbiosis and pathogen colonization as precursors to infection; enteric dysfunction constituting malabsorption, dysregulation of nutrients and metabolism, inflammation and bacterial translocation. All of these interact with a child’s diet and environment. Published trials aiming to break this cycle using antimicrobial prophylaxis or water, sanitation and hygiene interventions have not demonstrated public health benefit so far. Summary As further trials are planned, key gaps in knowledge can be filled by applying new tools to re-examine old questions relating to immune competence during and after infection events and changes in nutritional status; and how to characterize overt and subclinical infection, intestinal permeability to bacteria and the role of antimicrobial resistance using specific biomarkers.</p

Pooling as a strategy for the timely diagnosis of soil-transmitted helminths in stool: value and reproducibility

Background The strategy of pooling stool specimens has been extensively used in the field of parasitology in order to facilitate the screening of large numbers of samples whilst minimizing the prohibitive cost of single sample analysis. The aim of this study was to develop a standardized reproducible pooling protocol for stool samples, validated between two different laboratories, without jeopardizing the sensitivity of the quantitative polymerase chain reaction (qPCR) assays employed for the detection of soil-transmitted helminths (STHs). Two distinct experimental phases were recruited. First, the sensitivity and specificity of the established protocol was assessed by real-time PCR for each one of the STHs. Secondly, agreement and reproducibility of the protocol between the two different laboratories were tested. The need for multiple stool sampling to avoid false negative results was also assessed. Finally, a cost exercise was conducted which included labour cost in low- and high-wage settings, consumable cost, prevalence of a single STH species, and a simple distribution pattern of the positive samples in pools to estimate time and money savings suggested by the strategy. Results The sensitivity of the pooling method was variable among the STH species but consistent between the two laboratories. Estimates of specificity indicate a ‘pooling approach’ can yield a low frequency of ‘missed’ infections. There were no significant differences regarding the execution of the protocol and the subsequent STH detection between the two laboratories, which suggests in most cases the protocol is reproducible by adequately trained staff. Finally, given the high degree of agreement, there appears to be little or no need for multiple sampling of either individuals or pools. Conclusions Our results suggest that the pooling protocol developed herein is a robust and efficient strategy for the detection of STHs in ‘pools-of-five’. There is notable complexity of the pool preparation to ensure even distribution of helminth DNA throughout. Therefore, at a given setting, cost of labour among other logistical and epidemiological factors, is the more concerning and determining factor when choosing pooling strategies, rather than losing sensitivity and/or specificity of the molecular assay or the method.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Calculating the prevalence of soil-transmitted helminth infection through pooling of stool samples: Choosing and optimizing the pooling strategy

Prevalence is a common epidemiological measure for assessing soil-transmitted helminth burden and forms the basis for much public-health decision-making. Standard diagnostic techniques are based on egg detection in stool samples through microscopy and these techniques are known to have poor sensitivity for individuals with low infection intensity, leading to poor sensitivity in low prevalence populations. PCR diagnostic techniques offer very high sensitivities even at low prevalence, but at a greater cost for each diagnostic test in terms of equipment needed and technician time and training. Pooling of samples can allow prevalence to be estimated while minimizing the number of tests performed. We develop a model of the relative cost of pooling to estimate prevalence, compared to the direct approach of testing all samples individually. Analysis shows how expected relative cost depends on both the underlying prevalence in the population and the size of the pools constructed. A critical prevalence level (approx. 31%) above which pooling is never cost effective, independent of pool size. When no prevalence information is available, there is no basis on which to choose between pooling and testing all samples individually. We recast our model of relative cost in a Bayesian framework in order to investigate how prior information about prevalence in a given population can be used to inform the decision to choose either pooling or full testing. Results suggest that if prevalence is below 10%, a relatively small exploratory prevalence survey (10–15 samples) can be sufficient to give a high degree of certainty that pooling may be relatively cost effective

Defining stopping criteria for ending randomized clinical trials that investigate the interruption of transmission of soil-transmitted helminths employing mass drug administration

The current World Health Organization strategy to address soil-transmitted helminth (STH) infections in children is based on morbidity control through routine deworming of school and pre-school aged children. However, given that transmission continues to occur as a result of persistent reservoirs of infection in untreated individuals (including adults) and in the environment, in many settings such a strategy will need to be continued for very extended periods of time, or until social, economic and environmental conditions result in interruption of transmission. As a result, there is currently much discussion surrounding the possibility of accelerating the interruption of transmission using alternative strategies of mass drug administration (MDA). However, the feasibility of achieving transmission interruption using MDA remains uncertain due to challenges in sustaining high MDA coverage levels across entire communities. The DeWorm3 trial, designed to test the feasibility of interrupting STH transmission, is currently ongoing. In DeWorm3, three years of high treatment coverage—indicated by mathematical models as necessary for breaking transmission—will be followed by two years of surveillance. Given the fast reinfection (bounce-back) rates of STH, a two year no treatment period is regarded as adequate to assess whether bounce-back or transmission interruption have occurred in a given location. In this study, we investigate if criteria to determine whether transmission interruption is unlikely can be defined at earlier timepoints. A stochastic, individual-based simulation model is employed to simulate core aspects of the DeWorm3 community-based cluster-randomized trial. This trial compares a control arm (annual treatment of children alone with MDA) with an intervention arm (community-wide biannual treatment with MDA). Simulations were run for each scenario for both Ascaris lumbricoides and hookworm (Necator americanus). A range of threshold prevalences measured at six months after the last round of MDA and the impact of MDA coverage levels were evaluated to see if the likelihood of bounce-back or elimination could reliably be assessed at that point, rather than after two years of subsequent surveillance. The analyses suggest that all clusters should be assessed for transmission interruption after two years of surveillance, unless transmission interruption can be effectively ruled out through evidence of low treatment coverage. Models suggest a tight range of homogenous prevalence estimates following high coverage MDA across clusters which do not allow for discrimination between bounce back or transmission interruption within 24 months following cessation of MDA

Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections. Parasitic infections with helminths (intestinal worms) are common in Africa and affect over half of the population in some areas. There are plausible biological reasons why treating helminth infections in people with HIV may slow down the progression of HIV to AIDS. Thus, treating people with HIV for helminths in areas with a high prevalence of both HIV and helminth infections may be a feasible strategy to help people with HIV delay progression of their disease or initiation of antiretroviral therapy. After a comprehensive review of the available literature, we conclude that there is not enough evidence to determine whether treating helminth infections in people with HIV is beneficial

Schistosoma mansoni Enhances Host Susceptibility to Mucosal but Not Intravenous Challenge by R5 Clade C SHIV

Parasitic infections have been postulated to increase host susceptibility to HIV-1. We previously demonstrated that rhesus monkeys with active schistosomiasis were significantly more likely to become systemically infected after intrarectal exposure to an R5-tropic clade C simian-human immunodeficiency virus then were parasite-free control animals. However, we could not address whether parasites exert their effect at the mucosal level or systemically. To address the latter possibility, we measured the virus doses needed to achieve systemic infection after intravenous exposure of parasite-free or parasite-positive monkeys using the identical virus stock. None of the viral parameters tested in these two groups of monkeys were statistically significantly different. These results suggest that schistosomiasis modulates susceptibility to immunodeficiency virus acquisition predominantly at the mucosal level. Treatment for parasitic infections in populations at higher risk for HIV-1 acquisition could represent a cost-effective approach to slow the spread of HIV-1, which is predominantly transmitted through mucosal routes

Herpes Simplex Virus Type 2, Genital Ulcers and HIV-1 Disease Progression in Postpartum Women

Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2

Deterministic processes structure bacterial genetic communities across an urban landscape

Land-use change is predicted to act as a driver of zoonotic disease emergence through human exposure to novel microbial diversity, but evidence for the effects of environmental change on microbial communities in vertebrates is lacking. We sample wild birds at 99 wildlife-livestock-human interfaces across Nairobi, Kenya, and use whole genome sequencing to characterise bacterial genes known to be carried on mobile genetic elements (MGEs) within avian-borne Escherichia coli (n=241). By modelling the diversity of bacterial genes encoding virulence and antimicrobial resistance (AMR) against ecological and anthropogenic forms of urban environmental change, we demonstrate that communities of avian-borne bacterial genes are shaped by the assemblage of co-existing avian, livestock and human communities, and the habitat within which they exist. In showing that non-random processes structure bacterial genetic communities in urban wildlife, these findings suggest that it should be possible to forecast the effects of urban land-use change on microbial diversity