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High mortality rates among asymptomatic cryptococcal antigen (CrAg)-positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%-43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%-96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P < .001) and patients with headache only (P = .003). The optimal titer for predicting cryptococcal meningitis was >160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3-143.1; P < .001). About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis.

Since February 2022, Malawi has experienced a cholera outbreak of >54,000 cases. We investigated 6 cases in South Africa and found that isolates linked to the outbreak were Vibrio cholerae O1 serotype Ogawa from seventh pandemic El Tor sublineage AFR15, indicating a new introduction of cholera into Africa from south Asia.

Background: Staphylococcus aureus bacteraemia (SAB) is associated with a high mortality. Data on SAB cases in South Africa (SA) are limited.Objectives: This study aimed to establish the demographic profile, risk factors and complications of patients with SAB in a tertiary inpatient setting.Method: We conducted a retrospective record review of inpatients above the age of 13 with SAB from October 2015 to November 2022 at Helen Jospeh Hospital (HJH) in Gauteng, SA.Results: A total of 126 patients with SAB were reviewed. The case fatality ratio among these patients was 20.6% (95% confidence interval [CI]: 13.9–28.8); this was similar for methicillin-sensitive S. aureus and methicillin-resistant S. aureus (p = 0.154). Almost half (49.2%) were community acquired, and these were chiefly associated with skin and soft tissue infections (45.2%), while most healthcare-associated community-acquired infections (18.3%) and nosocomial-related infections (32.5%) were associated with short-term venous catheterisation (40.6%). The most common risk factors for acquiring a SAB were prior hospitalisation in the last 90 days (27.8%), the presence of an invasive device (26.2%) and receipt of haemodialysis (15.1%). Having hypertension (adjusted odds ratio: 5.55 [95% CI: 1.31–23.55]) and being recently hospitalised (adjusted odds ratio: 11.88 [95% CI: 1.84–26.99]) were associated with statistically significant increased odds of death.Conclusion: SAB-associated all-cause mortality remains high in a middle-income tertiary hospital setting, albeit with a case fatality ratio comparable to that seen in high-income countries.Contribution: Our study suggests that acceptable outcomes are achievable in tertiary middle-income settings provided there is access to resources including infectious diseases consultation, echocardiograms and basic infection control practices.

Background Despite the expansion of antiretroviral treatment programmes, the incidence and mortality of HIV-associated cryptococcal meningitis remain high in Africa. Cryptococcal antigen (CrAg) in the blood precedes meningitis. CrAg screening of individuals with advanced HIV disease, combined with pre-emptive fluconazole treatment, reduces the risk of cryptococcal meningitis and associated mortality. However, mortality among individuals with antigenaemia treated with fluconazole is higher than that of CD4-matched individuals with a CrAg-negative test. Autopsy studies have found that cryptococcal disease remains an important cause of death in people with antigenaemia despite pre-emptive antifungal treatment. This suggests a need for more potent treatment for antigenaemia. Flucytosine, combined with fluconazole, is an effective and safe oral treatment for cryptococcal meningitis, and flucytosine has become more widely available as a generic formulation. This trial aims to determine whether combination treatment of fluconazole plus flucytosine is superior to fluconazole monotherapy in reducing all-cause mortality among adults with antigenaemia without evidence of meningitis. Methods This multi-centre, open-label phase III randomised-controlled trial embedded in routine CrAg screening programmes in South Africa and Tanzania will compare 14 days of fluconazole (1200 mg/day) plus flucytosine (100 mg/kg/day) to fluconazole (1200 mg/day) alone for the treatment of adults with advanced HIV disease, a blood CrAg-positive test and without evidence of meningitis. Following this 2-week induction therapy, all participants are given fluconazole consolidation and maintenance therapy per local guidelines. The primary endpoint is all-cause mortality at 6 months (superiority analysis). Secondary endpoints include time to all-cause mortality, cryptococcal meningitis-free survival and incidence of symptomatic cryptococcal meningitis, proportion of participants with grade 3 or 4 adverse events, efficacy outcomes by baseline CrAg titre/CrAg semi-quantitative assay score, and health service and household costs per life year saved. A total of 600 participants will be enrolled, 300 per arm, sufficient to detect a 40% relative reduction in mortality with 91% power. Discussion An all-oral combination regimen of flucytosine with fluconazole, tested in adults with early cryptococcal disease across a range of baseline CrAg titres, could be an easy-to-administer, safe, and implementable alternative if found to be superior to the current World Health Organization recommended standard of fluconazole monotherapy. Trial registration ISRCTN30579828, registered 04 March 2021, and SANCTR DOH-27-122021-6511, registered 06 December 2021.

We retrospectively reviewed the Determine TB-LAM lateral flow assay (LF-LAM) results among human immunodeficiency virus–infected patients with disseminated nontuberculous mycobacterial (NTM) disease. LF-LAM was positive in 19 of 21 patients without evidence of tuberculosis (TB) coinfection. Although TB-NTM coinfection may have been underdiagnosed, our results suggest that disseminated NTM disease may cause false-positive LF-LAM results.

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2014 and the update on when to initiate antiretroviral therapy in 2015. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in southern Africa has continued. New antiretroviral drugs have become available with improved efficacy, safety and robustness. The guidelines are intended for countries in the southern African region, which vary between lower and middle income.

Background: Carbapenem-resistant Enterobacterales (CRE) are associated with significant morbidity and mortality. Carbapenem-resistant Enterobacterales colonisation is an important prerequisite for infection, and its surveillance is crucial to reduce spread. However, data from South Africa are limited.Objectives: We aimed to determine CRE colonisation prevalence, the incidence of subsequent CRE infections and the risk factors associated with each.Method: We retrospectively reviewed hospital records from 686 patients admitted to a medical high-care ward at a tertiary hospital in Gauteng, South Africa, between October 2019 and May 2022. Patients were grouped by CRE colonisation status on arrival and discharge. Data on comorbidities, indwelling devices and antibiotic exposure were collected.Results: The prevalence of CRE colonisation was 12.4% (95% confidence interval [CI]: 10.1–15.1), with Klebsiella pneumoniae (81.2%) being the most common CRE isolated and OXA-48-like enzymes (94.5%) being the most frequent carbapenemase detected. Risk factors for CRE colonisation on the univariate analysis included exposure to antibiotics (odds ratio [OR]: 2.21; 95% CI: 0.98–4.96, P = 0.048) and presence of a central venous line (OR: 6.33; 95% CI: 1.78–22.46, P = 0.001). Of patients colonised with a CRE, 21.2% subsequently developed a culture-positive infection within 180 days from the initial colonisation result and the majority within 30 days. These infections were mostly CREs (OR: 4.0, 95% CI: 1.3–12.7), and where the infections were CREs, the causative CRE organism and carbapenemase subtype were identical in each case.Conclusion: Our study documented higher CRE prevalence rates than those previously reported from South Africa. Given the association between CRE colonisation and subsequent infection, urgent measures are required to reduce CRE colonisation rates. As the organism and carbapenemase detected in the initial colonisation and subsequent CRE infection were closely related, knowledge of prior CRE colonisation may assist clinicians with antibiotic choice if patients present with an infection within 30 days of CRE colonisation.Contribution: This study reports higher CRE colonization rates in South Africa than previously documented, highlighting the urgent need to reduce colonization. The close genetic link between CRE colonization and subsequent infection suggests that knowledge of prior colonization can guide clinicians in selecting effective antibiotics, particularly for infections occurring within 30 days. These findings support targeted interventions to address the rising CRE threat.