Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

HIV/AIDS among youth in urban informal (slum) settlements in Kenya: What are the correlates of and motivations for HIV testing?

<p>Abstract</p> <p>Background</p> <p>Although HIV counseling and testing (HCT) is widely considered an integral component of HIV prevention and treatment strategies, few studies have examined HCT behavior among youth in sub-Saharan Africa-a group at substantial risk for HIV infection. In this paper we examine: the correlates of HIV testing, including whether associations differ based on the context under which a person gets tested; and the motivations for getting (or not getting) an HIV test.</p> <p>Methods</p> <p>Drawing on data collected in 2007 from 4028 (51% male) youth (12-22 years) living in Korogocho and Viwandani slum settlements in Nairobi (Kenya), we explored the correlates of and motivations for HIV testing using the Health Belief Model (HBM) as a theoretical framework. Multinomial and binary logistic regression analyses were employed to examine correlates of HIV testing. Bivariate analyses were employed to assess reasons for or against testing.</p> <p>Results</p> <p>Nineteen percent of males and 35% of females had been tested. Among tested youth, 74% of males and 43% of females had requested for their most recent HIV test while 7% of males and 32% of females reported that they were required to take their most recent HIV test (i.e., the test was mandatory). About 60% of females who had ever had sex received an HIV test because they were pregnant. We found modest support for the HBM in explaining variation in testing behavior. In particular, we found that perceived risk for HIV infection may drive HIV testing among youth. For example, about half of youth who had ever had sex but had never been tested reported that they had not been tested because they were not at risk.</p> <p>Conclusions</p> <p>Targeted interventions to help young people correctly assess their level of risk and to increase awareness of the potential value of HIV testing may help enhance uptake of testing services. Given the relative success of Prevention of Mother-to-Child Transmission (PMTCT) services in increasing HIV testing rates among females, routine provider-initiated testing and counseling among all clients visiting medical facilities may provide an important avenue to increase HIV status awareness among the general population and especially among males.</p

Overview of migration, poverty and health dynamics in Nairobi City's slum settlements

The Urbanization, Poverty, and Health Dynamics research program was designed to generate and provide the evidence base that would help governments, development partners, and other stakeholders understand how the urban slum context affects health outcomes in order to stimulate policy and action for uplifting the wellbeing of slum residents. The program was nested into the Nairobi Urban Health and Demographic Surveillance System, a uniquely rich longitudinal research platform, set up in Korogocho and Viwandani slum settlements in Nairobi city, Kenya. Findings provide rich insights on the context in which slum dwellers live and how poverty and migration status interacts with health issues over the life course. Contrary to popular opinions and beliefs that see slums as homogenous residential entities, the findings paint a picture of a highly dynamic and heterogeneous setting. While slum populations are highly mobile, about half of the population comprises relatively well doing long-term dwellers who have lived in slum settlements for over 10 years. The poor health outcomes that slum residents exhibit at all stages of the life course are rooted in three key characteristics of slum settlements: poor environmental conditions and infrastructure; limited access to services due to lack of income to pay for treatment and preventive services; and reliance on poor quality and mostly informal and unregulated health services that are not well suited to meeting the unique realities and health needs of slum dwellers. Consequently, policies and programs aimed at improving the wellbeing of slum dwellers should address comprehensively the underlying structural, economic, behavioral, and service-oriented barriers to good health and productive lives among slum residents

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.&lt;/p&gt

Striving to promote male involvement in maternal health care in rural and urban settings in Malawi - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Understanding the strategies that health care providers employ in order to invite men to participate in maternal health care is very vital especially in today's dynamic cultural environment. Effective utilization of such strategies is dependent on uncovering the salient issues that facilitate male participation in maternal health care. This paper examines and describes the strategies that were used by different health care facilities to invite husbands to participate in maternal health care in rural and urban settings of southern Malawi.</p> <p>Methods</p> <p>The data was collected through in-depth interviews from sixteen of the twenty health care providers from five different health facilities in rural and urban settings of Malawi. The health facilities comprised two health centres, one district hospital, one mission hospital, one private hospital and one central hospital. A semi-structured interview guide was used to collect data from health care providers with the aim of understanding strategies they used to invite men to participate in maternal health care.</p> <p>Results</p> <p>Four main strategies were used to invite men to participate in maternal health care. The strategies were; health care provider initiative, partner notification, couple initiative and community mobilization. The health care provider initiative and partner notification were at health facility level, while the couple initiative was at family level and community mobilization was at village (community) level. The community mobilization had three sub-themes namely; male peer initiative, use of incentives and community sensitization. The sustainability of each strategy to significantly influence behaviour change for male participation in maternal health care is discussed.</p> <p>Conclusion</p> <p>Strategies to invite men to participate in maternal health care were at health facility, family and community levels. The couple strategy was most appropriate but was mostly used by educated and city residents. The male peer strategy was effective and sustainable at community level. There is need for creation of awareness in men so that they sustain their participation in maternal health care activities of their female partners even in the absence of incentives, coercion or invitation.</p

Women's sexual health and contraceptive needs after a severe obstetric complication ("near-miss"): a cohort study in Burkina Faso

BACKGROUND: Little is known about the reproductive health of women who survive obstetric complications in poor countries. Our aim was to determine how severe obstetric complications in Burkina Faso affect reproductive events in the first year postpartum. METHODS: Data were collected from a prospective cohort of women who either experienced life threatening (near-miss) pregnancy-related complications or an uncomplicated childbirth, followed from the end of pregnancy to one year postpartum or post-abortum. Documented outcomes include menses resumption, sexual activity resumption, dyspareunia, uptake of contraceptives, unmet needs for contraception and women's reproductive intentions.Participants were recruited in seven hospitals between December 2004 and March 2005 in six towns in Burkina Faso. RESULTS: Reproductive events were associated with pregnancy outcome. The frequency of contraceptive use was low in all groups and the method used varied according to the presence or not of a live baby. The proportion with unmet need for contraception was high and varied according to the time since end of pregnancy. Desire for another pregnancy was highest among near-miss women with perinatal death or natural abortion. Women in the near-miss group with induced abortion, perinatal death and natural abortion had significantly higher odds of subsequent pregnancy. Unintended pregnancies were observed mainly in women in the near-miss group with live birth and the uncomplicated delivery group. CONCLUSIONS: Considering the potential deleterious impact (on health and socio-economic life) of new pregnancies in near-miss women, it is important to ensure family planning coverage includes those who survive a severe complication

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk