Fatigue was a common problem after stroke. There was a lack of awareness in both patients and clinicians and little advice being given to patients with fatigue.

Abstract Background Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts. Methods We conducted a cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among asymptomatic CrAg-positive and CrAg-negative (ratio of 1:2) patients living with HIV with CD4 counts <100 cells/µL attending 2 hospitals in Johannesburg, South Africa. When possible, minimally invasive autopsy (MIA) was performed on participants who died. Results Sixty-seven CrAg-positive and 134 CrAg-negative patients were enrolled. Death occurred in 17/67 (25%) CrAg-positive and 12/134 (9%) CrAg-negative participants (hazard ratio for death, adjusted for CD4 count, 3.0; 95% confidence interval, 1.4–6.7; P = .006). Cryptococcal disease was an immediate or contributing cause of death in 12/17 (71%) CrAg-positive participants. Postmortem cryptococcal meningitis and pulmonary cryptococcosis were identified at MIA in all 4 CrAg-positive participants, 3 of whom had negative cerebrospinal fluid CrAg tests from lumbar punctures (LPs) at the time of CrAg screening. Conclusions Cryptococcal disease was an important cause of mortality among asymptomatic CrAg-positive participants despite LPs to identify and treat those with subclinical cryptococcal meningitis and preemptive fluconazole for those without meningitis. Thorough investigation for cryptococcal disease with LPs and blood cultures, prompt ART initiation, and more intensive antifungals may reduce mortality among asymptomatic CrAg-positive patients identified through screening.

BackgroundEarly mortality among HIV-positive adults starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis (TB) the leading cause of death. However, current methods to estimate TB-related deaths are inadequate and most autopsy studies do not adequately represent those attending primary health clinics (PHCs). This study aimed to determine the autopsy prevalence of TB and other infections in adults enrolled at South African PHCs in the context of a pragmatic trial of empiric TB treatment (“TB Fast Track”).Methods and FindingsAdults with CD4 ≤150 cells/μL, not on ART or TB treatment, were enrolled to TB Fast Track and followed up for at least six months. Minimally invasive autopsy (MIA) was conducted as soon as possible after death. Lungs, liver, and spleen were biopsied; blood, CSF, and urine aspirated; and bronchoalveolar lavage fluid obtained. Samples underwent mycobacterial, bacterial, and fungal culture; molecular testing (including Xpert® MTB/RIF); and histological examination. 34 MIAs were conducted: 18 (53%) decedents were female; median age was 39 (interquartile range 33–44) years; 25 (74%) deaths occurred in hospitals; median time from death to MIA was five (IQR 3–6) days. 16/34 (47%) had evidence of TB (14/16 [88%] with extrapulmonary disease; 6/16 [38%] not started on treatment antemortem); 23 (68%) had clinically important bacterial infections; four (12%) cryptococcal disease; three (9%) non-tuberculous mycobacterial disease; and two (6%) Pneumocystis pneumonia. Twenty decedents (59%) had evidence of two or more concurrent infections; 9/16 (56%) individuals with TB had evidence of bacterial disease and two (13%) cryptococcal disease.ConclusionsTB, followed by bacterial infections, were the leading findings at autopsy among adults with advanced HIV enrolled from primary care clinics. To reduce mortality, strategies are needed to identify and direct those at highest risk into a structured pathway that includes expedited investigation and/or treatment of TB and other infections.

Background Tuberculosis, often undiagnosed, is the major cause of death among HIV-positive people. We tested an algorithm enabling nurses in South African primary healthcare clinics (PHCs) to initiate empirical tuberculosis treatment among adults with advanced HIV disease. Methods In an open-label cluster-randomised trial, 24 PHCs were randomised 1:1 to intervention or control (routine care) using computer-generated random numbers. HIV-positive adults were eligible if they had CD4 count ≤150 cells per µL; no antiretroviral therapy (ART) or tuberculosis treatment in the last six or three months respectively; and did not require urgent hospital referral. In intervention clinics, study nurses assessed participants based on tuberculosis symptoms, body mass index (BMI), pointof-care haemoglobin, and urine lipoarabinomannan assay (Determine TB-LAM, Alere). A study algorithm assigned tuberculosis probability as high (positive urine TB-LAM or BMI <18•5 kg/m 2 or haemoglobin <100 g/L), to start tuberculosis treatment immediately then ART two weeks later; medium (tuberculosis symptoms, no high probability criteria), to have symptom-guided investigation; or low (no tuberculosis symptoms or high probability criteria), to start ART immediately. The primary outcome was all-cause mortality at six months. (ISRCTN35344604) Findings 3091 individuals were screened; 3053 assigned a study identifier; and 3022 (1507 intervention, 1515 control; median age 37 years, 55•2% female, median CD4 72 cells per µL) analysed. 930/1507 (61•7%) versus 172/1515 (11•4%) of participants in the intervention versus control arm started tuberculosis treatment by two months. The mortality rate was 19•0 (134 deaths/704 person-years [pyrs]) versus 21•6 (151/699 pyrs) per 100 pyrs in the intervention versus control arm (unadjusted hazard ratio [HR] 0•92, 95% CI 0•67-1•26; adjusted HR 0•87, 95% CI 0•61-1•24, p=0•41). There were 29 versus 11 serious or severe adverse events in the intervention versus control arm. 4 Interpretation Our intervention substantially increased coverage of tuberculosis treatment in this high-risk population, but did not reduce mortality.

Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an ongoing project entitled Umoya omuhle ("good air"), conducted in two provinces of South Africa, that adopts an interdisciplinary, 'whole systems' approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs, as well as opportunities to address the problem holistically. A 'whole systems' approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission.