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An autopsy study describing causes of death and comparing clinico-pathological findings among hospitalized patients in Kampala, Uganda
BACKGROUND: Information on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda. METHODS: Between May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus. RESULTS: Fifty-three complete autopsies were performed in 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown HIV serological status. Infectious diseases caused death in 83% of HIV-positive patients, with disseminated TB as the main diagnosis causing 37% of deaths. The spectrum of illness and causes of death were substantially different between HIV-positive and HIV-negative patients. In HIV-positive patients 12% of postmortem diagnoses were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. In HIV-negative patients 17% of postmortem diagnoses were clinically highly suspected, 42% considered and 42% not considered. CONCLUSION: Autopsy examination remains an important tool to ascertain causes of death particularly in settings with limited access to diagnostic testing during life. HIV-positive patients continue to die from treatable and clinically undiagnosed infectious diseases. Until rapid-point of care testing is available to confirm common infections, empiric treatment should be further investigated
Comparison of bovine cysticercosis prevalence detected by antigen ELISA and visual inspection in the North East of Spain
A cross-sectional serological study on cattle less than 2years old, using an antigen ELISA for the detection of bovine cysticercosis was carried out between November 2009 and February 2010 in 10 slaughterhouses from the Catalonia region (North-Eastern Spain). Circulating antigen was detected in 23 of 2073 animals, i.e. a sero-prevalence of 1.11% (CI95%: 0.76-1.75%). The determined sero-prevalence was about 50 times higher than the prevalence obtained by visual inspection within the same period: 19 positive animals of 90,891 slaughtered animals (0.02%) in the same slaughterhouses. None of the animals with positive result in the Ag-ELISA was detected by meat inspection
Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine Visfatin/NAMPT
BACKGROUND: The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations. RESULTS: We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as a putative mechanism for this differential effect. Possible in vivo relevance of visfatin induction is illustrated by its association with the dominance of CXCR4-using HIV in the plasma. CONCLUSIONS: As an innate factor produced by monocytes, visfatin is capable of inhibiting infections by R5 but not X4 strains, reflecting a potential selective pressure against R5 viruses
Surface-engineered polyelectrolyte multilayer capsules-synthetic vaccines mimicking microbial structure and function
Immunizing: To evoke highly potent immune responses against recombinant antigens, hollow capsules consisting of layers of dextran sulphate and poly-L-arginine that encapsulate the antigen ovalbumin (orange circles) were coated with immune-activating CpG-containing oligonucleotides (green). These capsules were readily internalized by dendritic cells and showed activity in further immunization experiments
A health systems research mapping exercise in 26 low- and middle-income countries: narratives from health systems research, policy brokers and policy-makers
Low castes have poor access to visceral leishmaniasis treatment in Bihar, India
Objectives Bihar, the poorest state in India, concentrates most of the visceral leishmaniasis (VL) cases in the country. A large proportion of the poor rural communities where VL is endemic are marginalized by their socio-economic status, intrinsically related to the caste system. In this study, we evaluated whether people from low socio-economic strata had difficulties accessing VL treatment in Bihar. As a secondary outcome, we evaluated whether people delaying their VL treatment had poorer clinical indicators at admission. Methods Data on 2187 patients with VL treated by Medecins Sans Frontieres (MSF) in Vaishali district from July 2007 to December 2008 were analysed. Patients who reported having onset of symptoms >/=8 weeks before admission were defined as 'late presenters'. Logistic regression models were used to evaluate whether low castes had higher risk to be 'late presenters' compared to the rest of castes and whether 'late presenters' had poorer indicators at admission (i.e. haemoglobin level, spleen size). Results After adjusting for age, gender and distance to VL treatment facility, Mushars (the lowest caste in Bihar) had twice the odds to be 'late presenters' compared to the rest of castes (OR 2.05, 95% CI: 1.24-2.38). Subjects that had VL symptoms for >/=8 weeks had a larger spleen and lower haemoglobin level than those that were treated earlier. Conclusion Low castes have poor access to VL treatment in Bihar, and late presenters have poorer clinical indicators at admission. These findings have implications at individual and community levels and should stimulate targeted VL control programmes to ensure that marginalized communities in Bihar are properly treated
A reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood
Depressed cell mediated immunity in human visceral leishmaniasis (VL), revealed as the inability of peripheral blood mononuclear cells (PBMCs) to respond to Leishmania antigen, remains a hallmark of and is thought to underlie the progressive nature of this disease. We have recently reported the ability of a whole blood, IFN-gamma release assay to detect sub-clinical infections amongst healthy individuals living in the kala-azar endemic zone in Bihar, India, and the surprising result that patients with active VL also secreted significant levels of antigen-specific IFN-gamma in this assay. We were interested to extend these findings to a larger cohort of subjects, and to employ the whole blood assay to detect additional cytokines that might better correlate with the disease status of infected individuals. We evaluated IFN-gamma, TNF-alpha and IL-10 release in 35 patients with active VL, 54 cured VL, 27 patients with other diseases, 52 Non-Endemic Healthy Controls (NEHC), and 147 Endemic Healthy Controls (EHC). The cellular response of the EHCs was correlated with their serological antibody titers against L. donovani and Phlebotomus argentipes saliva. The whole blood cells from the majority of both active (80%) and cured (85%) VL patients, as well as 24% of EHCs with presumed sub-clinical infections, produced significantly elevated levels of IFN-gamma. The findings do not support a severe Th1 response defect in kala-azar. Importantly, only the active VL patients also produced IL-10, which in conjunction with IFN-gamma better reflects the immune responses that distinguish active cases from cured or sub-clinically infected, immune individuals
Effectiveness of preventive school-based obesity interventions in low- and middle-income countries: a systematic review
BACKGROUND: The prevalence of childhood obesity is increasing rapidly in low- and middle-income countries, and informed policies to tackle the problem must be defined. OBJECTIVE: We systematically reviewed the evidence on the effectiveness of school-based interventions targeting dietary behavior and/or physical activity for the primary prevention of obesity in children and adolescents aged 6-18 y in low- and middle-income countries. DESIGN: We searched the MEDLINE, EMBASE, Web of Science, CENTRAL, ERIC, Cochrane Library, and Centre for Reviews and Dissemination databases for peer-reviewed controlled studies published in English, Spanish, French, German, or Dutch between January 1990 and July 2011. The quality of the included studies was appraised independently by 2 authors who used the Effective Public Health Practice Project tool. RESULTS: From a total of 7218 unique references, we retained 22 studies. Most of the interventions (82%) had a positive effect on dietary behavior and physical activity behavior (effect size ranged from -0.48 to 1.61). BMI decreased in 8 studies (effect size ranged from -0.7 to 0.0). Effective interventions targeted both diet and physical activity, involved multiple stakeholders, and integrated educational activities into the school curriculum. CONCLUSIONS: School-based interventions have the potential to improve dietary and physical activity behavior and to prevent unhealthy body weights in low- and middle-income countries. To reach their full potential, interventions should conduct process evaluations to document program implementation. The effect and the pathways through which interventions have this effect need to be better documented through rigorous evaluation studies