Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Fulani cattle productivity and management in the Kachia grazing reserve, Nigeria

Kachia Grazing Reserve (KGR) in northern Nigeria was home to some 10,000 Fulani pastoralists and their 40,000 cattle in June 2011. This study examines productivity and management of cattle belonging to livestock keepers within the reserve before and after a mass immigration event when 3,000 refugees moved into the reserve with their cattle to escape inter-community violence during May 2011. Data, on livestock management strategies (transhumance) and production parameters (herd size, composition, fertility, dynamics), were collected in March, June and October 2011.Cattle productivity in KGR is geared to supporting Fulani households while maintaining herd wealth. High offtake of young animals, especially the selling of heifers, was an unusual finding and may indicate that KGR pastoralists have been restricting their herd size voluntarily as well as limiting milk production to household requirements. This is probably due to the absence of a commercial milk market and a higher reliance on the sale of young stock to meet cash needs.Despite the widespread perception that grazing reserves are promoting sedentarisation of Fulani pastoralists and curbing transhumance, the inhabitants of the KGR were observed to practise wide-ranging transhumance both during wet and dry seasons driven by the limited availability of grazing. Some households selected a sub-sample of animals for transhumance rather than sending their whole herd, and some maintained cattle on alternative land-holdings outside the reserve. KGR households described modifying their usual transhumance practices in response to the mass immigration event and insecurity.Nevertheless, the herd demography results from this study are broadly similar to data obtained from other studies over the past 40 years, indicating that productivity and management practices have remained relatively unchanged

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

Objective: This article compares trends in CD4+ T-cell recovery and proportions achieving optimal restoration (>=500 cells/µl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4+ less than 200 cells/µl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4+ T-cell count at cART start (baseline), rapid progressors experienced faster CD4+ T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1–18 [-0.05 (-0.06; -0.03)] and no significant differences in 18–60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4+ T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4+ T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4+ T-cell counts at cART initiation

Genome Scan of M. tuberculosis Infection and Disease in Ugandans

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFα) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10−3) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal α = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFα p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFα p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P \u3c .001), and a steeper rate of decline through the first 5 days (P \u3c .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978

High acceptance of home-based HIV counseling and testing in an urban community setting in Uganda

<p>Abstract</p> <p>Background</p> <p>HIV testing is a key component of prevention and an entry point into HIV/AIDS treatment and care however, coverage and access to testing remains low in Uganda. Home-Based HIV Counseling and Testing (HBHCT) has potential to increase access and early identification of unknown HIV/AIDS disease. This study investigated the level of acceptance of Home-Based HIV Counseling and Testing (HBHCT), the HIV sero-prevalence and the factors associated with acceptance of HBHCT in an urban setting.</p> <p>Methods</p> <p>A cross-sectional house-to-house survey was conducted in Rubaga division of Kampala from January-June 2009. Residents aged ≥ 15 years were interviewed and tested for HIV by trained nurse-counselors using the national standard guidelines. Acceptance of HBHCT was defined as consenting, taking the HIV test and receipt of results offered during the home visit. Multivariable logistic regression analysis was performed to determine significant factors associated with acceptance of HBHCT.</p> <p>Results</p> <p>We enrolled 588 participants, 408 (69%, 95% CI: 66%-73%) accepted testing. After adjusting for confounding, being male (adj. OR 1.65; 95%CI 1.03, 2.73), age 25-34 (adj. OR 0.63; 95% CI 0.40, 0.94) and ≥35 years (adj. OR 0.30; 95%CI 0.17, 0.56), being previously married (adj. OR 3.22; 95%CI 1.49, 6.98) and previous HIV testing (adj. OR 0.50; 95%CI 0.30, 0.74) were significantly associated with HBHCT acceptance. Of 408 who took the test, 30 (7.4%, 95% CI: 4.8%- 9.9%) previously unknown HIV positive individuals were identified and linked to HIV care.</p> <p>Conclusions</p> <p>Acceptance of home-based counseling and testing was relatively high in this urban setting. This strategy provided access to HIV testing for previously untested and unknown HIV-infected individuals in the community. Age, sex, marital status and previous HIV test history are important factors that may be considered when designing programs for home-based HIV testing in urban settings in Uganda.</p

The Role of Mobile Phones in Governance-Driven Technology Exports in Sub-Saharan Africa

This study assesses how the mobile phone influences governance to improve information and communication technology (ICT) exports in Sub-Saharan Africa with data from 2000-2012. The empirical evidence is based on Generalised Method of Moments and three main governance concepts are used, namely: (i) institutional (comprising the rule of law and corruption-control); (ii) political (involving political stability/no violence and voice & accountability) and (iii) economic (including regulation quality and government effectiveness) governance. The following findings are established. First, there are positive net effects on ICT goods exports from independent interactions between mobile phones and ‘political stability’ ‘voice and accountability’ and corruption-control. Second, significant net effects are not apparent from independent interactions between mobile phones and government effectiveness, regulation quality and the rule of law. Theoretical and practical implications are discussed

African ancestry of New World, Bemisia tabaci-whitefly species

Bemisia tabaci whitefly species are some of the world’s most devastating agricultural pests and plant-virus disease vectors. Elucidation of the phylogenetic relationships in the group is the basis for understanding their evolution, biogeography, gene-functions and development of novel control technologies. We report here the discovery of five new Sub-Saharan Africa (SSA) B. tabaci putative species, using the partial mitochondrial cytochrome oxidase 1 gene: SSA9, SSA10, SSA11, SSA12 and SSA13. Two of them, SSA10 and SSA11 clustered with the New World species and shared 84.8‒86.5% sequence identities. SSA10 and SSA11 provide new evidence for a close evolutionary link between the Old and New World species. Re-analysis of the evolutionary history of B. tabaci species group indicates that the new African species (SSA10 and SSA11) diverged from the New World clade c. 25 million years ago. The new putative species enable us to: (i) re-evaluate current models of B. tabaci evolution, (ii) recognise increased diversity within this cryptic species group and (iii) re-estimate divergence dates in evolutionary time