National Health Laboratory Service

While South African guidelines recommend a lumbar puncture (LP) to exclude cryptococcal meningitis (CM) among all people with a newly positive cryptococcal antigen (CrAg) test, irrespective of CM symptoms, this is not always feasible. High blood CrAg lateral flow assay (LFA) titers are associated with concurrent CM and increased mortality. Single-strip CrAg semi-quantitative (SQ) tests could risk-stratify people with antigenemia. Consecutive fresh LFA-positive remnant plasma samples from a CD4 laboratory network collected between April and July 2021 were retested. We described LFA titers, CrAgSQ scores, and the proportion with cerebrospinal fluid (CSF) collected 28 days before or after a positive CrAg screening test. Of 2,240 re-tested plasma samples from unique patients, 2,166 (97%) were confirmed LFA-positive. The median LFA titer was 640 (IQR, 40-5,120), 63% (1,354/2,166) had a titer of ≥160, and 52% (1,124/2,166) had SQ scores of ≥3+. Only 31% (662/2,166) had a CSF sample collected 28 days before or after a CrAg LFA-positive test; 60% (398/662) had confirmed CM. More than half of the people with cryptococcal antigenemia had a blood CrAg titer of ≥160 or a CrAgSQ score of ≥3+, both previously shown to confer a high risk of concurrent CM. Of 3 in 10 who had an LP, most had CM, suggesting that meningitis symptoms prompted LP. Healthcare worker support/training is required to improve adherence to the universal LP recommendation. When immediate LP is not feasible, blood CrAgSQ testing can rapidly identify people at the highest risk of CM who require urgent referral for LP. IMPORTANCE:A majority of patients with HIV-associated cryptococcal antigenemia identified through a large screening program in South Africa had high cryptococcal antigen titers and thus an elevated risk of concurrent meningitis and death. Despite this, a relatively small proportion had a lumbar puncture to definitively exclude meningitis. Routine CrAg semi-quantification can help to stratify patients at higher risk for meningitis and guide clinicians' management, but performing a full range of titers for all CrAg-positive blood samples increases costs and is labor-intensive. An alternative approach is to use a single test strip, which yields a semi-quantitative score.

Our knowledge of Cryptococcus neoformans and cryptococcal disease spans many years. Yet, despite numerous clinical studies and revisions to treatment protocols, the burden of cryptococcal disease remains alarmingly high, more so in endemic regions like Africa. Thus, the inclusion of this organism in the World Health Organization's (WHO) Fungal Priority Pathogens List (FPPL) in part underscores the unmet need to respond to cryptococcal infections and antifungal resistance adequately. To this end, this contribution interrogates the available literature, highlighting emerging treatment strategies to manage infections. Some of these strategies include drug repurposing, immunomodulating therapies and medicinal plants. Although some of the highlighted strategies are still only in the preclinical stages, these studies provide promising evidence of potential alternatives to currently available antifungals.

PURPOSEEsophageal squamous cell carcinoma (ESCC) remains a major cause of cancer mortality in South Africa. Understanding locally relevant and modifiable risk factors is crucial for prevention. This study clarifies the syndemic role of lifestyle and environmental factors, such as alcohol, tobacco, socioeconomic indicators (rurality and education), and fuel use, in ESCC.METHODSWe analyzed 939 histologically confirmed ESCC cases and 3,089 cancer controls from the Johannesburg Cancer Study. Multivariable logistic regression estimated adjusted odds ratios (aORs), with interaction terms for alcohol, tobacco, and sex. Population attributable fractions were calculated using both study-control and national prevalence estimates.RESULTSVery high alcohol intake (≥840 g ethanol/wk) showed a modest independent association with ESCC (aOR, 1.56 [95% CI, 1.14 to 2.12]). Smoking was a strong risk factor, with aOR = 2.82 (95% CI, 2.20 to 3.62) for ex-smokers and 6.71 (95% CI, 5.15 to 8.76) for current smokers. Among never-smokers, alcohol showed little dose response. Among smokers, risks were high across all alcohol levels, with no consistent increase at higher intakes. Additional risks included rural origin or residence (aOR approximately equal to 1.22-2.38), lower educational attainment (aOR approximately equal to 1.45-1.69), and use of biomass or other fuels (aOR, 1.50 [95% CI, 1.21 to 1.87]).CONCLUSIONIn this high-burden setting, tobacco remains the principal modifiable driver of ESCC. Alcohol showed only a modest independent effect, limited to very high intake, and did not increase the risk among smokers beyond the high risk from smoking. Socioeconomic and environmental disadvantages cluster with behavioral risks, underscoring a syndemic context. These findings, consistent with prior Johannesburg Cancer Study reports yet offering greater exposure granularity, support targeted prevention strategies focused on smoking cessation, mitigation of hazardous drinking patterns, and reduction of household environmental exposures.

Background:Repeated monitoring of viral load (VL) among pregnant women living with HIV (WLWH) is critical in vertical transmission prevention. For women who are newly diagnosed with HIV during pregnancy, a subsequent VL is recommended three months after ART initiation, and for all women living with HIV, follow-up VL is required every six months throughout pregnancy and breastfeeding. Here, we describe the uptake and timing of VL testing and frequency and distribution of viraemic episodes during pregnancy. Methods:We linked prospective cohort data from WLWH whose infants were born at Rahima Moosa Mother and Child Hospital (RMMCH) in Johannesburg, South Africa (2013-2018) to laboratory data from the National Health Laboratory Services national HIV cohort. We report the uptake and timing of VL testing, and frequency of viremia and viral suppression. We applied the log binomial regression, to explore factors associated with having at least one or more VL test. Crude relative risks (RR) and adjusted relative risks (aRR) with 95% confidence intervals (CI) relative risk were reported. Results:Data from 4064 women with known dates of entry into antenatal care and delivery during the study period were analysed. Overall, less than half (46%) completed VL testing during pregnancy. Most VLs were conducted during the third trimester (67%). Only 5% (n = 100) were during the first trimester and 11% within 7 days of delivery. Three-quarters of tests during pregnancy indicated viral suppression (VL < 400 copies/mL), 7% viraemic (VL 400-1000 copies/mL), and 19% high-grade viraemia (VL > 1000 copies/mL). We found that being older (≥35) and being engaged in HIV care prior to pregnancy were significantly associated with VL testing during pregnancy. Conclusion:With less than half of pregnant women living with HIV in this study having a VL measure during their pregnancy, and VL testing occurring late in pregnancy, this study highlights critical gaps in providing quality HIV care to women and prevention of vertical transmission.

In regions where both Mpox virus (MPXV) and varicella zoster virus (VZV) are co-circulating, overlapping clinical manifestations can complicate clinical diagnosis. During the MPXV outbreak declared in Uganda on July, 2024, symptomatic suspected cases tested PCR negative for Mpox. To determine the cause of symptoms, we employed metagenomic sequencing with a targeted Viral Surveillance panel in 284 Mpox negative samples. VZV was identified as the predominant pathogen in 86% of MPXV-negative cases, suggesting a concurrent chickenpox surge. Using the VaricellaGen pipeline for variant calling, clade typing, and phylogeny, 118 (42%) samples that achieved ≥70% genome coverage were of clade 5 based on the single-nucleotide polymorphism (SNP) dataset. This data confirms co-circulation of chickenpox during the Mpox outbreak in Uganda. Our results underscore the need for laboratory confirmation of Mpox and the inclusion of VZV in the testing algorithm during the Mpox outbreak.