Risk Screening Tools Could Potentially Miss HIV-Positive Individuals Who Seek Testing Services: A Secondary Program Data Analysis on the Performance Characteristics of an Adolescent and Adult HIV Risk Screening Tool in Uganda.

Improving HIV testing efficiency saves financial and material resources for health. We conducted a secondary data analysis of routinely collected HIV risk-screening program data in Uganda, from October to November 2019, to determine the performance characteristics of the adolescent and adult HIV risk screening tools in public health facilities. A total of 19,854 clients had been screened for HIV testing eligibility and tested for HIV. The overall positivity rate (cluster-weighted prevalence of HIV) among those screened was 4.5% (95% CI: 4.1-4.8) versus 3.71% (95% CI: 3.06-4.50) among those not screened. The sensitivity and specificity of the risk screening tool were 91% (95% CI: 89-93) and 25% (24.2-26), respectively. With screening, the number needed to test to identify one PLHIV was reduced from 27 to 22. Although risk screening would have led to a 24.5% (4825/19,704) reduction in testing volume, 9.3% (68/732) of PLHIV would have been missed and be misclassified as not eligible for testing. The cost saving per PLHIV identified was minimally reduced by 3% from USD 69 without screening to USD 66.9 with screening. Since the treatment-adjusted prevalence of HIV is dropping globally, overzealous use of risk screening tools to determine who to test or not carries the potential of missing PLHIV due to their limited specificity. We recommend the use of scientifically validated HIV risk screening tools, and a need to explore the use of HIV self-testing as a test for tirage to minimize misclassification of people who seek HIV testing services.

Double burden of malnutrition among women in reproductive Age (15-49 years) in Sierra Leone: a secondary data analysis of the demographic health survey 2019 (SLDHS-2019).

BACKGROUND: The double burden of malnutrition (DBM) is rising globally, particularly in sub-Saharan Africa. In Sierra Leone, the incidence of overweight, obesity (OWOB), and overnutrition among women has sharply increased. This finding accompanies the high incidence of undernutrition, which has been prevalent for decades. This study aimed to determine the prevalence of different malnutrition categories (underweight, overweight, obesity, and overnutrition) and associated factors among women of reproductive age (15-49 years) in Sierra Leone using secondary data analysis of the Sierra Leone Demographic Health Survey of 2019 (SLDHS-2019). METHODS: We conducted secondary data analysis of the SLDHS-2019 of 7,514 women aged 15-49 years. We excluded pregnant, post-natal, lactating, and post-menopausal women. Data was collected using validated questionnaires, and respondents were selected through a multistage stratified sampling approach. A multivariable logistic regression analysis was used to determine factors associated with malnutrition among 15-49-year-old women in Sierra Leone. RESULTS: Among 15-49-year-old women in Sierra Leone, the prevalence of underweight was 6.7% (95%CI: 4.5-8.9%); overweight at 19.7% (95%CI: 17.7-21.7%); obesity was 7.4% (95% CI: 5.2-9.6%); and overnutrition, 27.1% (95%CI: 25.2-29.0%). Women aged 25-34 years were more likely to be underweight (adjusted Odds Ratios, aOR = 1.670, 95%CI: 1.254-2.224; p < 0.001) than those aged 15-24 years; women who were not married were less likely to be underweight (aOR = 0.594, 95%CI: 0.467-0.755; p < 0.001) than married women. Women from the North were less likely to be underweight (aOR = 0.734, 95%CI: 0.559-0.963; p = 0.026) than the East, and those who did not listen to the radio were less likely to be underweight (aOR = 0.673; 95%CI: 0.549-0.826; p < 0.001) than those who did. Overweight was less likely among 25-34 years (aOR = 0.609, 95%CI: 0.514-0.722; p < 0.001) and 35-49 years (aOR = 0.480, 95%CI: 0.403-0.571; p < 0.001) age-groups than 15-24 years; more likely among not married women (aOR = 1.470, 95%CI:1.249-1.730; p < 0.001) than married; less likely among working-class (aOR = 0.840, 95%CI: 0.720-0.980; p = 0.026) than not working-class; most likely in women from the North (aOR = 1.325, 95%CI:1.096-1.602; p = 0.004), and less likely among women from the South (aOR = 0.755, 95%CI: 0.631-0.903; p = 0.002) than the East; less likely among women of middle-wealth-index (aOR = 0.656, 95%CI: 0.535-0.804; p < 0.001), richer-wealth-index (aOR = 0.400, 95%CI: 0.309-0.517; p < 0.001), and richest-wealth-index (aOR = 0.317, 95%CI: 0.234-0.431; p < 0.001) than the poorest-wealth-index; and more likely among women who did not listen to radios (aOR = 1.149; 95%CI:1.002-1.317; p = 0.047) than those who did. The predictors of overweight among women 15-49 years are the same as obesity and overnutrition, except overnutrition and obesity were less likely in female-headed households (aOR = 0.717,95%CI: 0.578-0.889; p < 0.001). CONCLUSION: The prevalence of all categories of malnutrition among women of reproductive age in Sierra Leone is high, affirming a double burden of malnutrition in this study population. Underweight was more likely among the 25-34-year age group than 15-24-year. The predictors of overweight, obesity, and overnutrition were being unmarried/single, residing in the North, and not listening to the radio. There is an urgent need for policymakers in Sierra Leone to design comprehensive educational programs for women of reproductive age on healthy lifestyles and the dangers of being underweight or over-nourished.

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Background: Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. Methods: We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. Results: We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). Conclusions: CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

The practice of pilot/feasibility studies in informing the conduct of HIV related clinical trials in sub-Saharan Africa: A scoping review.

Introduction: Pilot/feasibility studies represent a fundamental phase of the research process and play a vital role in the preliminary planning of a full size HIV clinical trial. Published HIV clinical trial protocols were reviewed to establish the extent to which the proposed HIV clinical trials are informed by a prior pilot/feasibility study. Methods: The JBI methodology for scoping reviews was followed. Six databases were systematically searched to identify articles for inclusion. Results: Thirty two (32) published HIV study protocols were included. Articles were in the English language and were published in the past 10 years (2011-2020). The review results showed that the majority of HIV-related clinical trials in sub-Saharan Africa were not informed by pilot/feasibility studies. The results further indicated that the number of HIV clinical trials informed by a pilot/feasibility study have been on the increase in the 8 years' period since 2012, a trend that indicates positive uptake of pilot studies in HIV related studies. A few select countries (South Africa, Uganda, Zimbabwe, Malawi and Kenya) comprised more than 70% of all clinical trials that were informed by a pilot/feasibility study, conducted in sub Saharan Africa. Conclusions: Although there is an increasing interest among researchers to integrate pilot/feasibility studies in HIV related research, limited countries in sub-Saharan Africa appear to have embraced this trend. Strategies that can motivate researchers to engage in a culture of incorporating pilot/feasibility studies in HIV related research should be implemented.

Developing and Validating an Effective Pediatric and Adolescent HIV Testing Eligibility Screening Tool for High-Volume Entry Points in Uganda.

INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents.

Sex Differences in HIV Testing - 20 PEPFAR-Supported Sub-Saharan African Countries, 2019.

Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

Low proportion of women who came knowing their HIV status at first antenatal care visit, Uganda, 2012-2016: a descriptive analysis of surveillance data.

BACKGROUND: HIV testing is the cornerstone for HIV care and support services, including Prevention of Mother to Child Transmission of HIV (PMTCT). Knowledge of HIV status is associated with better reproductive health choices and outcomes for the infant's HIV status. We analyzed trends in known current HIV status among pregnant women attending the first antenatal care (ANC) visit in Uganda, 2012-2016. METHODS: We conducted secondary data analysis using District Health Information Software2 data on all pregnant women who came for ANC visit during 2012-2016. Women who brought documented HIV negative test result within the previous 4 weeks at the first ANC visit or an HIV positive test result and/or own HIV care card were considered as knowing their HIV status. We calculated proportions of women with known current HIV status at first ANC visit, and described linear trends both nationally and regionally. We tested statistical significance of the trend using modified Poisson regression with generalized linear models. For known HIV positive status, we only analyzed data for years 2015-2016 because this is when this data became available. RESULTS: There was no significant difference in the number of women that attended first ANC visits over years 2012-2016. The proportion of women that came with known HIV status increased from 4.4% in 2012 to 6.9% in 2016 and this increase was statistically significant (p < 0.001). Most regions had an increase in trend except the West Nile and Mid-Eastern (p < 0.001). The proportion of women that came knowing their HIV positive status at first ANC visit was slightly higher than that of women that were newly tested HIV positive at first ANC visit in 2015 and 2016. CONCLUSION: Although the gap in women that come at first ANC visit without knowing their HIV positive status might be reducing, a large proportion of women who were infected with HIV did not know their status before the first ANC visit indicating a major public health gap. We recommend advocacy for early ANC attendance and hence timely HIV testing and innovations to promptly identify HIV positive women of reproductive age so that timely PMTCT interventions can be made.

Mobile digital fluorescence microscopy for diagnosis of tuberculosis.

Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is limited by a scarcity of microscopes and experienced technicians. We evaluated the accuracy of CellScope, a novel digital fluorescence microscope that may expand access to microscopy. The study utilized smear microscopy slides prepared from sputum specimens submitted by consecutive adults with ≥ 2 weeks of cough who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light-emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were performed by experienced technicians. Two U.S.-based postgraduate researchers without prior microscopy experience restained, imaged, and interpreted the slides using CellScope. We assessed whether sensitivity and specificity of CellScope-based LED FM was noninferior to conventional LED FM by using a preselected margin of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and 39% had culture-confirmed TB. The proportions of positive results were similar with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32), and agreement was substantial. CellScope accuracy was within the noninferiority margin for both sensitivity (63% versus 70%; difference, -7%; 95% confidence interval [CI], -13% to -1%) and specificity (85% versus 92%; difference, -7%; 95% CI, -12% to -3%). A subanalysis of 43 slides evaluated by each CellScope reader found substantial interreader reliability (custom-weighted kappa, 0.65) and variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48). CellScope offers promise for expanding microscopy services. Future studies should evaluate the device when operated by health workers in low-resource settings, the feasibility of image transmission and analysis by experienced microscopists, and the accuracy of automated image analysis algorithms.

Integrated strategies to optimize sputum smear microscopy: a prospective observational study.

RATIONALE: Smear-positive tuberculosis (TB) case detection rates are far below targets in most low-income countries. The standard approach to smear microscopy involves sputum collection over multiple days and examination of sputum smears by light microscopy (LM), an insensitive and time-consuming technique. OBJECTIVE: To determine whether two alternative approaches can increase smear-positive case detection by increasing the efficiency (single-specimen microscopy) or sensitivity (light-emitting diode [LED] fluorescence microscopy [FM]) of TB suspect evaluation. METHODS: We enrolled patients with cough of 2 weeks or more admitted to Mulago Hospital in Kampala, Uganda and collected spot and early morning sputum specimens. We compared the diagnostic accuracy of four prespecified strategies based on the number of sputum specimens collected (one specimen versus two specimens) and the type of microscopy (LM versus LED FM) using mycobacterial culture as a reference standard. MEASUREMENTS AND MAIN RESULTS: Two hundred thirty-three of 464 (50%) patients had culture-positive TB. There was no difference in sensitivity between single-specimen and two-specimen strategies when smears were examined with LM (55 vs. 56%; difference, -1%; 95% confidence interval [CI], -5 to +2%) or LED FM (61 vs. 64%; difference, -3%; 95% CI, -7 to +1%). LED FM was more sensitive than LM with both the single-specimen (61 vs. 55%; difference, 6%; 95% CI, 2-10%) and two-specimen strategies (64 vs. 56%; difference, 8%; 95% CI, 3-12%). Findings were similar among the HIV-infected patient subset (n = 321 patients). CONCLUSIONS: In low-income, high TB burden settings, single-specimen microscopy and LED FM, either alone or in combination, could considerably increase identification of smear-positive TB cases.

Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis.

BACKGROUND: Sputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals. METHODS: We performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture. RESULTS: Of 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months. CONCLUSION: Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.

Poor performance of universal sample processing method for diagnosis of pulmonary tuberculosis by smear microscopy and culture in Uganda.

Laboratory methods to improve smear microscopy are an urgent priority for global tuberculosis control. The novel universal sample processing (USP) method has been reported to improve conventional diagnostic testing for tuberculosis while also providing inhibitor-free specimens for molecular assays. However, no studies evaluating the method in the field have been conducted. In this study, we compared the performance of the USP method to that of the standard N-acetyl-L-cysteine-NaOH (NALC) method for conventional diagnosis of tuberculosis in 252 adults admitted to Mulago Hospital in Kampala, Uganda, with a clinical suspicion of pneumonia. A single early-morning sputum specimen collected from each patient was divided into two aliquots, each of which was assigned a random identification number. One randomly numbered specimen was processed by the USP method and the other by the NALC method. Mycobacterial cultures were more frequently negative in USP compared to NALC specimen aliquots (58% versus 43%; P < 0.001). There was no difference in the proportion of contaminated mycobacterial cultures (12% versus 11%; P = 0.87). The sensitivity and specificity of smear microscopy for the USP method were 52% and 86%, respectively, and were not significantly different from those for the NALC method (56% and 86%, respectively) using mycobacterial culture results as a reference standard. These results suggest that the USP method did not provide any significant advantage over the standard NALC method for conventional diagnosis of tuberculosis in our setting and illustrate the importance of well-designed, field-level evaluations of novel diagnostic techniques.