Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study.

BackgroundSymptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis.MethodsFor this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard.FindingsBetween July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10).InterpretationThe performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy.FundingNational Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health

Readiness of Ugandan health services for the management of outpatients with chronic diseases.

OBJECTIVE: Traditionally, health systems in sub-Saharan Africa have focused on acute conditions. Few data exist on the readiness of African health facilities (HFs) to address the growing burden of chronic diseases (CDs), specifically chronic, non-communicable diseases (NCDs). METHODS: A stratified random sample of 28 urban and rural Ugandan HFs was surveyed to document the burden of selected CDs by analysing the service statistics, service availability and service readiness using a modified WHO Service Availability and Readiness Assessment questionnaire. Knowledge, skills and practice in the management of CDs of 222 health workers were assessed through a self-completed questionnaire. RESULTS: Among adult outpatient visits at hospitals, 33% were for CDs including HIV vs. 14% and 4% at medium-sized and small health centres, respectively. Many HFs lacked guidelines, diagnostic equipment and essential medicines for the primary management of CDs; training and reporting systems were weak. Lower-level facilities routinely referred patients with hypertension and diabetes. HIV services accounted for most CD visits and were stronger than NCD services. Systems were weaker in lower-level HFs. Non-doctor clinicians and nurses lacked knowledge and experience in NCD care. CONCLUSION: Compared with higher level HFs, lower-level ones are less prepared and little used for CD care. Health systems in Uganda, particularly lower-level HFs, urgently need improvement in managing common NCDs to cope with the growing burden. This should include the provision of standard guidelines, essential diagnostic equipment and drugs, training of health workers, supportive supervision and improved referral systems. Substantially better HIV basic service readiness demonstrates that improved NCD care is feasible

Prevalence of high blood pressure and associated factors among adolescents and young people in Tanzania and Uganda.

We conducted a cross-sectional study among school/college students in Tanzania and Uganda to determine the prevalence of high blood pressure (BP) and associated factors. Participants were classified to have high BP if they had pre-hypertension or hypertension. Interviews were done using the WHO STEPS instrument. Using data from both countries (n = 1596), the overall prevalence of high BP was 40% (95% CI: 37-42). The prevalence of pre-hypertension was 29% (95% CI: 26-31) and that of hypertension was 11% (95% CI: 10-13). High BP was independently associated with obesity (aOR = 6.7, 95% CI: 2.2-20.0), male sex (aOR = 3.2, 95% CI: 2.4-4.4), and among males aged above 20 years (aOR = 5.5, 95% CI: 2.9-10.5). Consumption of fruits/vegetables was associated with decreased odds for high BP (aOR = 0.7, 95% CI: 0.50-0.98). The increasing burden of pre-hypertension across age groups could explain the early onset of hypertension and cardiovascular diseases (CVDs) among young African adults. There is a need for longitudinal studies to explore the drivers of pre-hypertension in East African adolescents

Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

Background: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT0093134

Situational analysis of teaching and learning of medicine and nursing students at Makerere University College of Health Sciences

<p>Abstract</p> <p>Background</p> <p>Makerere University College of Health Sciences (MakCHS) in Uganda is undergoing a major reform to become a more influential force in society. It is important that its medicine and nursing graduates are equipped to best address the priority health needs of the Ugandan population, as outlined in the government’s Health Sector Strategic Plan (HSSP). The assessment identifies critical gaps in the core competencies of the MakCHS medicine and nursing and ways to overcome them in order to achieve HSSP goals.</p> <p>Methods</p> <p>Documents from the Uganda Ministry of Health were reviewed, and medicine and nursing curricula were analyzed. Nineteen key informant interviews (KII) and seven focus group discussions (FGD) with stakeholders were conducted. The data were manually analyzed for emerging themes and sub-themes. The study team subsequently used the checklists to create matrices summarizing the findings from the KIIs, FGDs, and curricula analysis. Validation of findings was done by triangulating information from the different data collection methods.</p> <p>Results</p> <p>The core competencies that medicine and nursing students are expected to achieve by the end of their education were outlined for both programs. The curricula are in the process of reform towards competency-based education, and on the surface, are well aligned with the strategic needs of the country. But implementation is inadequate, and can be changed:</p> <p>• Learning objectives need to be more applicable to achieving competencies.</p> <p>• Learning experiences need to be more relevant for competencies and setting in which students will work after graduation (i.e. not just clinical care in a tertiary care facility).</p> <p>• Student evaluation needs to be better designed for assessing these competencies.</p> <p>Conclusion</p> <p>MakCHS has made a significant attempt to produce relevant, competent nursing and medicine graduates to meet the community needs. Ways to make them more effective though deliberate efforts to apply a competency-based education are possible.</p

High prevalence of hypertension and of risk factors for non-communicable diseases (NCDs): a population based cross-sectional survey of NCDS and HIV infection in Northwestern Tanzania and Southern Uganda.

BACKGROUND: The burden of non-communicable diseases (NCDs) is increasing in sub-Saharan Africa, but data available for intervention planning are inadequate. We determined the prevalence of selected NCDs and HIV infection, and NCD risk factors in northwestern Tanzania and southern Uganda. METHODS: A population-based cross-sectional survey was conducted, enrolling households using multistage sampling with five strata per country (one municipality, two towns, two rural areas). Consenting adults (≥18 years) were interviewed using the WHO STEPS survey instrument, examined, and tested for HIV and diabetes mellitus (DM). Adjusting for survey design, we estimated population prevalences of hypertension, DM, obstructive pulmonary disease, cardiac failure, epilepsy and HIV, and investigated factors associated with hypertension using logistic regression. RESULTS: Across strata, hypertension prevalence ranged from 16 % (95 % confidence interval (CI): 12 % to 22 %) to 17 % (CI: 14 % to 22 %) in Tanzania, and from 19 % (CI: 14 % to 26 %) to 26 % (CI: 23 % to 30 %) in Uganda. It was high in both urban and rural areas, affecting many young participants. The prevalence of DM (1 % to 4 %) and other NCDs was generally low. HIV prevalence ranged from 6 % to 10 % in Tanzania, and 6 % to 12 % in Uganda. Current smoking was reported by 12 % to 23 % of men in different strata, and 1 % to 3 % of women. Problem drinking (defined by Alcohol Use Disorder Identification Test criteria) affected 6 % to 15 % men and 1 % to 6 % women. Up to 46 % of participants were overweight, affecting women more than men and urban more than rural areas. Most patients with hypertension and other NCDs were unaware of their condition, and hypertension in treated patients was mostly uncontrolled. Hypertension was associated with older age, male sex, being divorced/widowed, lower education, higher BMI and, inversely, with smoking. CONCLUSIONS: The high prevalence of NCD risk factors and unrecognized and untreated hypertension represent major problems. The low prevalence of DM and other preventable NCDs provides an opportunity for prevention. HIV prevalence was in line with national data. In Tanzania, Uganda and probably elsewhere in Africa, major efforts are needed to strengthen health services for the PREVENTION, early detection and treatment of chronic diseases

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

CGRP in Primary Headaches

Introduction: Anemia is a common problem in HIV in sub-Saharan Africa. We describe the contribution of antiretroviral therapy (ART) regimen to the incidence of anemia and changes in hemoglobin (Hb) in HIV-infected patients in Uganda. Methods: This study was nested in a prevention of cryptococcal disease trial (CRYPTOPRO; ISCRTN7648152). Patients received 3 different backbones of nucleoside reverse transcriptase inhibitor in a nonrandomized manner. Results: Of the 852 patients (161 on zidovudine [ZDV], 628 on stavudine [d4T], and 63 on tenofovir [TDF]; all received lamuvidine), the risk of developing grade 4 anemia was higher (adjusted hazard ratio 2.7) for those receiving ZDV than those receiving d4T. Those receivingd4T had a higher average increase in Hb than those receiving ZDV ( P = .024) or TDF ( P = .014). Conclusion: In this observational study, ZDV was associated with severe anemia compared to d4T or TDF; those receiving ZDV and TDF had smaller increases in Hb after ART initiation. We encourage publication of data on cohorts using TDF from Africa