Imported Cholera Cases, South Africa, 2023.

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.

HIV Infection as Risk Factor for Death among Hospitalized Persons with Candidemia, South Africa, 2012-2017.

We determined the effect of HIV infection on deaths among persons >18 months of age with culture-confirmed candidemia at 29 sentinel hospitals in South Africa during 2012-2017. Of 1,040 case-patients with documented HIV status and in-hospital survival data, 426 (41%) were HIV-seropositive. The in-hospital case-fatality rate was 54% (228/426) for HIV-seropositive participants and 37% (230/614) for HIV-seronegative participants (crude odds ratio [OR] 1.92, 95% CI 1.50-2.47; p<0.001). After adjusting for relevant confounders (n = 907), mortality rates were 1.89 (95% CI 1.38-2.60) times higher among HIV-seropositive participants than HIV-seronegative participants (p<0.001). Compared with HIV-seronegative persons, the stratum-specific adjusted mortality OR was higher among HIV-seropositive persons not managed in intensive care units (OR 2.27, 95% CI 1.47-3.52; p<0.001) than among persons who were (OR 1.56, 95% CI 1.00-2.43; p = 0.05). Outcomes among HIV-seropositive persons with candidemia might be improved with intensive care.

Cross-reactivity of a Histoplasma capsulatum antigen enzyme immunoassay in urine specimens from persons with emergomycosis in South Africa.

Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi. LAY SUMMARY: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.

Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020.

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.

Mental health in South African adolescents living with HIV.

We examined the prevalence of mental health conditions, social support, and associated factors among adolescents living with HIV. We conducted a cross-sectional analysis with adolescents (ages 9-19) attending a primary care clinic in Johannesburg, South Africa. We analyzed the results of four self-report tools: Children's Depression Inventory-Short, Revised Manifest Anxiety Scale, Child Post-Traumatic Stress Disorder (PTSD) Checklist, and a modified version of the Medical Outcomes Study Social Support Scale. We used robust Poisson regression to quantify the association between social support and mental health. Among 278 adolescents, the majority were perinatally infected with HIV (92%), and had at least one deceased parent (59%). Depression symptom threshold scores were found among 8% of adolescents, and 7% screened positive for symptoms of anxiety. Few (1%) met the criteria for PTSD. Overall, 12% of adolescents screened positive for symptoms of depression, anxiety or PTSD. Older adolescents reported less social support than younger adolescents. Adolescents were less likely to have mental health symptoms if they had higher measures of social support (adjusted Prevalence Ratio 0.38, 95% CI 0.20-0.73). Attention should be paid to social support for adolescents living with HIV as this may play an important role in their mental health.

Combined Medical and Surgical Management of Hepatic Mucormycosis in an Adult with Acute Myeloid Leukemia: Case Report and Review of the Literature.

Hepatic mucormycosis is a disease caused by a ubiquitous fungus which is especially important in patients with hematologic malignancies. We present a case of an adult patient with acute myeloid leukemia who developed the infection after undergoing chemotherapy. His successful management was an integrated approach of a minimally invasive surgical resection with anti-fungal therapy. We describe the management of this patient and a review of the literature.

High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Does Disseminated Nontuberculous Mycobacterial Disease Cause False-Positive Determine TB-LAM Lateral Flow Assay Results? A Retrospective Review.

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.

Staphylococcus aureus bacteraemia cases at Helen Joseph Hospital.

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.

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections.

INTRODUCTION: Stroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. METHODS: This cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. RESULTS: 77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. CONCLUSION: Almost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Review: Emergomycosis.

Purpose of Review In this review, we provide an overview of emergomycosis from a clinical perspective and discuss the taxonomy and classification of the pathogens, epidemiology, pathophysiology of infection and mechanisms of pathogenesis, immunology, clinical manifestations, laboratory culture and diagnosis, molecular characterisation, therapy and prognosis. Recent Findings While Emergomyces pasteurianus is the most geographically-widespread species, Emergomyces africanus is endemic to Southern Africa and causes disseminated disease with cutaneous involvement primarily among patients with advanced human immunodeficiency virus (HIV) disease. Summary Emergomycosis, a disseminated clinical disease resulting from infection with dimorphic fungi in the genus Emergomyces, occurs primarily among immunocompromised patients. Further knowledge is needed on the pathophysiology, diagnosis and management of emergomycosis.

COVID-19 in-hospital mortality during the first two pandemic waves, at Helen Joseph Hospital, South Africa.

Introduction: there has been significant global variation in Coronavirus Disease (COVID-19) mortality at different time points in the pandemic. Contributing factors include population demographics, comorbidities, health system capacity, prior infection with COVID-19, vaccinations, and viral variants. The study aims to describe COVID-19-related mortality of inpatients at Helen Joseph Hospital (HJH), over 12 months, during the first two waves of the COVID-19 pandemic in South Africa. The primary objectives were to describe the socio-demographic details, clinical characteristics, and hospital outcomes during the first and second waves of COVID-19. This included an assessment of the in-hospital case fatality ratio (CFR) of patients admitted with COVID-19. The secondary objectives were to compare the socio-demographic details, clinical characteristics, and outcomes between the two waves, and to determine risk factors associated with COVID-19-related mortality. Methods: this is a retrospective cohort study of all inpatient laboratory-confirmed COVID-19 cases at HJH from 1st May 2020 to 31st April 2021. Data were collected by the National Institute for Communicable Diseases (NICD). Bivariate analysis was performed to describe and compare the socio-demographic characteristics, clinical characteristics, and hospital admission outcomes between the two waves. Multivariate logistic regression was used to determine risk factors for COVID-19-related mortality. Results: overall, 1359 patients were admitted, 595 in wave one, and 764 in wave two. Patients were predominantly male (52.4%), of Black African race (75.1%) with a mean age of 54.6 (standard deviation 15.4) years. The median length of stay was 8 days (interquartile range 5-14 days). In total, 73.2% (995) of patients required oxygen, 5.2% (71) of patients received mechanical ventilation, and 7.1% (96) were admitted to the high care and Intensive Care Unit (ICU). The most common comorbid illnesses were hypertension (36.7%, n=499), diabetes mellitus (26.6%, n=362), Human Immunodeficiency Virus (HIV) (10.8%, n=147), and obesity (11.0%, n=149). The in-hospital CFR during the first wave was 30.4% (181/595) and 25.5% (195/764) (p<0.001) in the second wave, and overall, in-hospital CFR was 27.7% (376/1359). The adjusted odds of death were 79% higher among patients admitted during wave one compared to wave two (aOR=1.79; 95% CI: 1.35-2.38). A one-year increase in age increased the odds of death by 4% (aOR=1.04; 95% CI: 1.03-1.05). The need for oxygen (aOR=2.17, 95%CI: 1.56-3.01) and ventilation (aOR=7.23, 95% CI: 4.02-13.01) were significant risk factors for mortality. Conclusion: prior to the availability of vaccines, COVID-19-related mortality was high and risk factors for mortality were consistent with national and international findings. This study reflects the impact of the pandemic on the South African public sector with limited resources and minimal ICU capacity.

A cohort study of post-COVID-19 condition across the Beta, Delta, and Omicron waves in South Africa: 6-month follow-up of hospitalized and nonhospitalized participants.

OBJECTIVES: The study aimed to describe the prevalence of and risk factors for post-COVID-19 condition (PCC). METHODS: This was a prospective, longitudinal observational cohort study. Hospitalized and nonhospitalized adults were randomly selected to undergo telephone assessment at 1, 3, and 6 months. Participants were assessed using a standardized questionnaire for the evaluation of symptoms and health-related quality of life. We used negative binomial regression models to determine factors associated with the presence of ≥1 symptoms at 6 months. RESULTS: A total of 46.7% of hospitalized and 18.5% of nonhospitalized participants experienced ≥1 symptoms at 6 months (P ≤0.001). Among hospitalized people living with HIV, 40.4% had persistent symptoms compared with 47.1% among participants without HIV (P = 0.108). The risk factors for PCC included older age, female sex, non-Black race, presence of a comorbidity, greater number of acute COVID-19 symptoms, hospitalization/COVID-19 severity, and wave period (lower risk of persistent symptoms for the Omicron compared with the Beta wave). There were no associations between self-reported vaccination status with persistent symptoms. CONCLUSION: The study revealed a high prevalence of persistent symptoms among South African participants at 6 months but decreased risk for PCC among participants infected during the Omicron BA.1 wave. These findings have serious implications for countries with resource-constrained health care systems.

A Severe Case of Molluscum Contagiosum Immune Reconstitution Inflammatory Syndrome in a Patient with Human Immunodeficiency Virus.

Paradoxical immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-positive patients initiating antiretroviral treatment (ART) is caused by restored immunity to specific antigens, resulting in worsening of a pre-existing infection. Molluscum contagiosum (MC) is commonly noted in HIV-positive individuals but ART alone is usually sufficient to bring about resolution. We present a rare case of severe MC-IRIS that worsened despite immune reconstitution. LEARNING POINTS: Molluscum contagiosum is a common opportunistic infection which can have severe manifestations in immunocompromised individuals.Antiretroviral treatment alone is usually sufficient to clear the infection, however refractory cases can persist despite immune reconstitution.Failure to improve or worsening immune reconstitution inflammatory syndrome should raise suspicion for additional immunological dysfunction.Surgery, cytodestructive therapies and chemotherapeutic agents can be considered in extensive, persistent disease.

Erratum: Southern African HIV Clinicians Society 2022 guideline for the management of sexually transmitted infections: Moving towards best practice.

[This corrects the article DOI: 10.4102/sajhivmed.v23i1.1450.].

Post-COVID-19 condition 3 months after hospitalisation with SARS-CoV-2 in South Africa: a prospective cohort study.

BACKGROUND: Post COVID-19 condition (PCC), as defined by WHO, refers to a wide range of new, returning, or ongoing health problems in people who have had COVID-19, and it represents a rapidly emerging public health priority. We aimed to establish how this developing condition has affected patients in South Africa and which population groups are at risk. METHODS: In this prospective cohort study, we used the DATCOV national hospital surveillance system to identify participants aged 18 years or older who had been hospitalised with laboratory-confirmed SARS-CoV-2 infection in South Africa. Participants underwent telephone follow-up assessment at 1 month and 3 months after hospital discharge. Participants were assessed using a standardised questionnaire for the evaluation of symptoms, functional status, health-related quality of life, and occupational status. We used negative binomial regression models to determine factors associated with PCC. FINDINGS: Of 241 159 COVID-19 admissions reported to DATCOV between Dec 1, 2020, and Aug 23, 2021, 8309 were randomly selected for enrolment. Of the 3094 patients that we were able to contact, 2410 (77·9%) consented to participate in the study at 1 month after discharge. Of these, 1873 (77·7%) were followed up at 3 months after hospital discharge. Participants had a median age of 52 years (IQR 41-62) and 960 (51·3%) were women. At 3 months of follow-up, 1249 (66·7%) of 1873 participants reported new or persistent COVID-19-related symptoms, compared with 1978 (82·1%) of 2410 at 1 month after hospital discharge. The most common symptoms reported at 3 months were fatigue (50·3%), shortness of breath (23·4%), confusion or lack of concentration (17·5%), headaches (13·8%), and problems seeing or blurred vision (10·1%). On multivariable analysis, the factors associated with persistent symptoms after acute COVID-19 were being female (adjusted incident rate ratio 1·20, 95% CI 1·04-1·38) and admission to an intensive care unit (1·17, 1·01-1·37). INTERPRETATION: Most participants in this cohort of individuals previously hospitalised with COVID-19 reported persistent symptoms 3 months after hospital discharge and a significant impact of PCC on their functional and occupational status. The large burden of PCC symptoms identified in this study emphasises the need for a national health strategy. This should include the development of clinical guidelines and training of health-care workers for identifying, assessing, and caring for patients affected by PCC; establishment of multidisciplinary health services; and provision of information and support to people who have PCC. FUNDING: Bill & Melinda Gates Foundation, UK Foreign, Commonwealth & Development Office, and Wellcome.

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study.

BACKGROUND: Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. METHODS: In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. FINDINGS: From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010). INTERPRETATION: In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. FUNDING: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. TRANSLATION: For the Zulu translation of the abstract see Supplementary Materials section.