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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is the latest virus to cause global health panic. Due to the rapidly escalating numbers of new infections outside China, COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020, in a message delivered by Dr. Tedros Adhanom Ghebreyesus, the WHO Director-General [ 1 ]. As of March 21, about 166 countries globally had recoded cases of the COVID-19 in only 4 months since its outbreak in Wuhan, Hubei Province, China [ 2 , 3 ]. With the Antarctic continent unaffected, Africa, in particular Sub-Saharan Africa (SSA), has recorded the least number of cases, despite the cited moderate-to-high risk of infection [ 4 ]. The biggest challenge is whether Sub-Saharan Africa is ready for this pandemic.

Data continue to emerge that suggest treating HIV infection as early as possible is beneficial. In this trial assessing the timing of antiretroviral therapy initiation in patients with acute cryptococcal meningitis and newly diagnosed HIV infection, early initiation was associated with increased mortality. Cryptococcus neoformans is the most common cause of meningitis in adults in sub-Saharan Africa, 1 – 5 and meningitis caused by C. neoformans accounts for approximately 20 to 25% of deaths from the acquired immunodeficiency syndrome (AIDS) in Africa. 6 – 9 Determining when antiretroviral therapy (ART) should be initiated after a diagnosis of cryptococcal meningitis involves balancing the survival benefit conferred by ART against the risk of the immune reconstitution inflammatory syndrome (IRIS), a paradoxical reaction that occurs during immunologic recovery with ART despite effective therapy for the opportunistic infection. Since 2009, the international standard of care has shifted toward earlier ART . . .

Health workers' failure to adhere to guidelines for screening, diagnosis and management of HIV-associated cryptococcal meningitis (CM) remains a significant public health concern. We aimed to assess adherence to the standards of care and management of HIV patients at risk of CM per the MoH guidelines and assess stock management of CM supplies in the period of January to June 2021 at selected public health facilities (HFs) in Uganda. The study employed an observational cross-sectional design to assess the level of adherence of health workers to standards of clinical care and management of HIV positive patients at risk of CM as per the clinical guidelines for Uganda, and stock management of CM supplies in the period of January to June 2021in selected public health facilities. The study team used a survey guide designed by MoH to assess and score the screening, diagnosis and management practices of Health Facilities towards CM. Scoring was categorized as red (< 80%), light green (80%-95%), and dark green (˃95%) in the order from worst to best adherence. The data was transcribed into a spread sheet and analysed using STATA-v15. The study team visited a total of 15 public health facilities including 5 general hospitals, 9 regional referral hospitals (RRHs) and 1 National Referral hospital (NRH). The mean score for adherence to screening and management of CM for all the combined facilities was 15 (64.7%) classified as red. 10 (66.7%) HFs had not performed a baseline CD4 test for eligible patients within 2 weeks of ART initiation. With regards to treatment, 9 (60%) of the HFs were scored as light green on knowledge of the procedure for reconstituting intravenous Liposomal Amphotericin B. None of the HFs visited had potassium chloride tablets in stock. Major MoH guidelines are generally not being adhered to by health workers while managing cryptococcal meningitis. It is vital that government and implementing partners regularly support HFs with training, mentorship, and support supervision on CM management to improve adherence to CM screening and treatment guidelines.

WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50–70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47–87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23–66; 10/23) for Xpert and 43% (23–66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77–99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24–68]; 10/22; p=0·0010) or culture (45% [24–68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.

Tuberculous meningitis accounts for 1–5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5–87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6–96·2; 153 of 165), compared with 55·6% sensitivity (44·0–70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9–91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5–75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4–91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5–98·5; 39 of 42), higher than Xpert at 65·8% (48·6–80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9–86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases.

Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown. Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7–11 days; thus, follow-up stopped at time of death, randomization, or 11 days. Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12–.82). The association was observed regardless of opening pressure at baseline. Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.

A trial involving HIV-infected patients with CD4+ T-cell counts below 100 cells per cubic millimeter compared strategies of systematic treatment for TB and treatment only if testing revealed infection. Systematic treatment was not better than treatment guided by testing with respect to the rate of death or bacterial infection.

Background The World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations. Methods We reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption. Results The distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline. Conclusion National guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards.

BackgroundSickle cell disease (SCD) is associated with significant mortality and morbidity, especially in low- and middle-income countries.ObjectivesWe determined the indications for hospitalisation and predictors of 30-day re-admission among patients with SCD in Northern and Central Uganda.DesignRetrospective chart review.SettingMulago National Referral Hospital in Kampala, St. Mary’s Hospital Lacor in Gulu and Gulu Regional Referral Hospital in Gulu, Uganda.ParticipantsPatients with confirmed SCD admitted between January 2020 and January 2025 were included.OutcomesPrimary outcome: indication for hospitalisation. Secondary outcomes: rate and predictors of 30-day hospital re-admission. Socio-demographic, clinical history and hospitalisation data were extracted using a pretested data extraction tool.ResultsWe enrolled 505 patients, accounting for 714 hospital admissions, with a mean age of 8.1±6.2 years. Most participants (n=489, 96.8%) had less than four admissions per year, with a median of 1 admission (IQR: 0–2). The most common indications for hospitalisation were infection (n=375, 52.5%), painful crisis (n=366, 51.3%) and anaemia (n=186, 26.1%). Malaria was the most prevalent infection (n=244, 65%). The median length of hospital stay was 4 days (IQR: 3–6), with a 30-day re-admission rate of 6.9% (n=49). Admission with painful crisis (adjusted OR (AOR): 0.45, 95% CI: 0.23 to 0.89, p=0.021), receiving a blood product (AOR: 0.32, 95% CI: 0.16 to 0.66, p=0.002) and having four or more admissions per year (AOR: 0.84, 95% CI: 0.04 to 0.17, p<0.001) were inversely associated with re-admission within 30 days of last admission.ConclusionsInfections, especially malaria, and painful crises were the leading causes of hospitalisation among Ugandan patients with SCD. Frequent admissions, painful crises and blood transfusions were associated with lower 30-day re-admission risk. There is an urgent need to strengthen malaria prevention strategies and optimise access to disease-modifying therapy, such as hydroxyurea, to improve patient outcomes.

Background Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support. Purpose The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma. Methods We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma. Results Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations. Conclusions Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.