National Institute For Communicable Diseases Research Articles

How paediatric HIV services weathered the COVID-19 storm in Tshwane District, South Africa.

The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released. This study describes COVID-19's impact on paediatric HIV services in Tshwane District, South Africa. A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children (< 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared. Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% - 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022.Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%. Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care.

Characterization of Salmonella enterica serovar Isangi from South Africa, 2020-2021.

We describe the genotypic characteristics and antimicrobial resistance (AMR) determinants of Salmonella enterica serovar Isangi (Salmonella Isangi) clinical isolates in South Africa from 2020 through 2021. During the years 2020 to 2021, the Centre for Enteric Diseases of the National Institute for Communicable Diseases, a national reference centre in South Africa for human infections resulting from enteric bacterial pathogens, investigated a total of 3549 clinical isolates of Salmonella species. Whole genome sequencing (WGS) was performed using Illumina NextSeq Technology. WGS data was analyzed using Centre for Genomic Epidemiology-based tools and EnteroBase web-based platform. Genotypic relatedness and cluster analysis was investigated based on core-genome multilocus sequence typing. Forty-nine isolates were confirmed to be Salmonella Isangi, with most submitted from Gauteng Province (24/49, 49%). The most prevalent sequence type was ST335 (48/49, 98%), and the remaining 1 isolate was ST216. All ST335 isolates were genotypically multidrug-resistant (MDR), with resistance to fluoroquinolones, chloramphenicol, trimethoprim-sulfamethoxazole and tetracycline; the ST216 isolate was resistant only to aminoglycosides. All ST335 isolates carried ESBL genes, the most common being blaCTX-M-15. Five clusters (consisting of isolates related within five allele differences) were detected, all being ST335. Most Salmonella Isangi isolates in South Africa are MDR and ESBL-positive. Ongoing monitoring of the epidemiology and AMR profile of this serovar is important for public health and treatment guidelines.

A COVID-19 epidemic model with periodicity in transmission and environmental dynamics

From the beginning of the outbreak of SARS-CoV-2 (COVID-19), South African data depicted seasonal transmission patterns, with infections rising in summer and winter every year. Seasonality, control measures, and the role of the environment are the most important factors in periodic epidemics. In this study, a deterministic model incorporating the influences of seasonality, vaccination, and the role of the environment is formulated to determine how these factors impact the epidemic. We analyzed the stability of the model, demonstrating that when R0 &amp;lt; 1, the disease-free equilibrium is globally symptomatically stable, whereas R0 &amp;gt; 1 indicates that the disease uniformly persists and at least one positive periodic solution exists. We demonstrate its application by using the data reported by the National Institute for Communicable Diseases. We fitted our mathematical model to the data from the third wave to the fifth wave and used a damping effect due to mandatory vaccination in the fifth wave. Our analytical and numerical results indicate that different efficacies for vaccination have a different influence on epidemic transmission at different seasonal periods. Our findings also indicate that as long as the coronavirus persists in the environment, the epidemic will continue to affect the human population and disease control should be geared toward the environment.

Covid-19 Disruptions in the Catholic Diocese of Bethlehem in the Free State, South Africa

Since the beginning of Christianity, pulpit or church sermons have been the primary mode of delivering sermons. The last decade has seen huge progress in technological advancement in Africa. Several pastors have now empowered themselves with the use of technology in their ministry and in delivering sermons. In 2019, Covid-19 swept across the globe and caused worldwide panic. In South Africa, the National Institute for Communicable Diseases reported the first case of Covid-19 in March 2020. To contain the spread of the coronavirus, the President of South Africa, Mr Cyril Ramaphosa, announced a lockdown for 21 days and alert level 5 was imposed on South Africans. That compelled all South Africans to stay at home, and all faith-based gatherings were prohibited. Thus, preaching the Word of God in churches was prohibited. During the pandemic, online sermons or the streaming of church services online became a popular way of hearing Sunday sermons. This article discusses the historical use of technology, for example, radio and television, which were the tools employed to reach out further. We will explore the recent use of online sermons and electronic communion in churches, particularly in the Catholic Church. Statistics will be scrutinised to examine the effects of online sermons and faith practices (electronic communion). In achieving the goal of this article, the study utilised desk research and oral interviews through a narrative analysis of aspects mentioned by church leaders and congregants considered to relate directly to online sermons and electronic communion. The following will be points of discussion: methodology, with a brief discussion of data collection and analysis; the Covid-19 crisis; the impact of coronavirus and leadership; alternative methods employed by the Diocese of Bethlehem; challenges with online sermons; successes; electronic communion; recommendations; and conclusion.

Upsurge of measles in South Africa: cause for alarming concern

Upsurge of measles in South Africa: cause for alarming concern

Enteric fever cluster identification in South Africa using genomic surveillance of Salmonella enterica serovar Typhi.

The National Institute for Communicable Diseases in South Africa participates in national laboratory-based surveillance for human isolates of Salmonella species. Laboratory analysis includes whole-genome sequencing (WGS) of isolates. We report on WGS-based surveillance of Salmonella enterica serovar Typhi (Salmonella Typhi) in South Africa from 2020 through 2021. We describe how WGS analysis identified clusters of enteric fever in the Western Cape Province of South Africa and describe the epidemiological investigations associated with these clusters. A total of 206 Salmonella Typhi isolates were received for analysis. Genomic DNA was isolated from bacteria and WGS was performed using Illumina NextSeq technology. WGS data were investigated using multiple bioinformatics tools, including those available at the Centre for Genomic Epidemiology, EnteroBase and Pathogenwatch. Core-genome multilocus sequence typing was used to investigate the phylogeny of isolates and identify clusters. Three major clusters of enteric fever were identified in the Western Cape Province; cluster one (n=11 isolates), cluster two (n=13 isolates), and cluster three (n=14 isolates). To date, no likely source has been identified for any of the clusters. All isolates associated with the clusters, showed the same genotype (4.3.1.1.EA1) and resistome (antimicrobial resistance genes: bla TEM-1B, catA1, sul1, sul2, dfrA7). The implementation of genomic surveillance of Salmonella Typhi in South Africa has enabled rapid detection of clusters indicative of possible outbreaks. Cluster identification allows for targeted epidemiological investigations and a timely, coordinated public health response.

Hyperendemic carbapenem-resistant Acinetobacter baumannii at a hospital in Botswana: Insights from whole-genome sequencing

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major cause of bloodstream infection among hospitalized patients in low- and middle-income countries (LMICs). CRAB infections can be difficult to treat and are devastating in neonates (~30% mortality). CRAB outbreaks are hypothesized to arise from reservoirs in the hospital environment, but outbreak investigations in LMICs seldom incorporate whole-genome sequencing (WGS). Methods: WGS (Illumina NextSeq) was performed at the National Institute for Communicable Diseases (South Africa) on 43 preserved A. baumannii isolates from a 530-bed referral hospital in Gaborone, Botswana, from March 2021–August 2022. This included 23 blood-culture isolates from 21 unique patients (aged 2 days–69 years) and 20 environmental isolates collected at the 36-bed neonatal unit in April–June 2021. Infections were considered healthcare-associated if the culture was obtained &gt;72 hours after hospital arrival (or sooner in inborn infants). Blood cultures were incubated using an automated system (BACT/ALERT, BioMérieux) and were identified using manual methods. Environmental isolates were identified using selective or differential chromogenic media (CHROMagarTM). Taxonomic assignment, multilocus sequence typing (MLST), antimicrobial resistance gene identification, and phylogenetic analyses were performed using publicly accessible analysis pipelines. Single-nucleotide polymorphism (SNP) matrices were used to assess clonal lineage. Results: All 23 blood isolates and 5 (25%) of 20 environmental isolates were confirmed as A. baumannii; thus, 28 A. baumannii isolates were included in the phylogenetic analysis. MLST revealed that 22 (79%) of 28 isolates were sequence type 1 (ST1), including all 19 healthcare-associated blood isolates and 3 (60%) of 5 environmental isolates. Genes encoding for carbapenemases (blaNDM-1, blaOXA-23) and biocide resistance (qacE) were present in all 22 ST1 isolates; colistin resistance genes were not identified. Phylogenetic analysis of the ST1 clade demonstrated spatial clustering by hospital unit. Related isolates spanned wide ranges in time (&gt;1 year), suggesting ongoing transmission from environmental sources (Fig. 1). An exclusively neonatal clade (0–2 SNPs) containing all 8 neonatal blood isolates was closely associated with 3 environmental isolates from the neonatal unit: a sink drain, bed rail, and a healthcare worker’s hand. Conclusions: WGS analysis of clinical and environmental A. baumannii revealed the presence of unit-specific CRAB clones, with evidence of ongoing transmission likely driven by persistent environmental reservoirs. This research highlights the potential of WGS to detect hospital outbreaks and reaffirms the importance of environmental sampling to identify and remediate reservoirs (eg, sinks) and vehicles (eg, hands and equipment) within the healthcare environment.Disclosures: None

Using generalized structured additive regression models to determine factors associated with and clusters for COVID-19 hospital deaths in South Africa

BackgroundThe first case of COVID-19 in South Africa was reported in March 2020 and the country has since recorded over 3.6 million laboratory-confirmed cases and 100 000 deaths as of March 2022. Transmission and infection of SARS-CoV-2 virus and deaths in general due to COVID-19 have been shown to be spatially associated but spatial patterns in in-hospital deaths have not fully been investigated in South Africa. This study uses national COVID-19 hospitalization data to investigate the spatial effects on hospital deaths after adjusting for known mortality risk factors.MethodsCOVID-19 hospitalization data and deaths were obtained from the National Institute for Communicable Diseases (NICD). Generalized structured additive logistic regression model was used to assess spatial effects on COVID-19 in-hospital deaths adjusting for demographic and clinical covariates. Continuous covariates were modelled by assuming second-order random walk priors, while spatial autocorrelation was specified with Markov random field prior and fixed effects with vague priors respectively. The inference was fully Bayesian.ResultsThe risk of COVID-19 in-hospital mortality increased with patient age, with admission to intensive care unit (ICU) (aOR = 4.16; 95% Credible Interval: 4.05–4.27), being on oxygen (aOR = 1.49; 95% Credible Interval: 1.46–1.51) and on invasive mechanical ventilation (aOR = 3.74; 95% Credible Interval: 3.61–3.87). Being admitted in a public hospital (aOR = 3.16; 95% Credible Interval: 3.10–3.21) was also significantly associated with mortality. Risk of in-hospital deaths increased in months following a surge in infections and dropped after months of successive low infections highlighting crest and troughs lagging the epidemic curve. After controlling for these factors, districts such as Vhembe, Capricorn and Mopani in Limpopo province, and Buffalo City, O.R. Tambo, Joe Gqabi and Chris Hani in Eastern Cape province remained with significantly higher odds of COVID-19 hospital deaths suggesting possible health systems challenges in those districts.ConclusionThe results show substantial COVID-19 in-hospital mortality variation across the 52 districts. Our analysis provides information that can be important for strengthening health policies and the public health system for the benefit of the whole South African population. Understanding differences in in-hospital COVID-19 mortality across space could guide interventions to achieve better health outcomes in affected districts.

COVID-19-related queries received by the National Health Laboratory Service and the National Institute for Communicable Diseases in South Africa: January to August 2020

The National Institute for Communicable Diseases − a division of the National Health Laboratory Service − launched a clinician and public hotline, adapted from an existing NICD clinicians’ hotline, to guide healthcare workers and members of the public on COVID-19-related queries. The hotlines received over 150 000 queries within eight months. We describe the queries so as to inform recommendations for tailoring clinician training, improving access to information, and guiding health promotion. A retrospective description of data from the NHLS-NICD clinician and public hotlines from January to August 2020 was performed. Queries were analysed by province, caller type and sector. A thematic analysis with a deductive and semantic approach was used to describe the reason for each query. From January to August 2020, 99.9% (152 766/152 985) of queries attended to on the hotlines were related to COVID-19, with most queries being made in April (n=53 471). The majority of queries were from members of the public (95.0%), and from the public sector (97.0%). Gauteng Province accounted for most queries (42.9%). General information on COVID-19, advice for testing and administrative/systems issues (related to nationwide announcements/events), together accounted for the largest proportion of COVID-19 queries, at 86.0%. The hotline provided general and clinical COVID-19 advice. Data from the hotline mirrored information gaps and distributions of concerns related to COVID-19, and could be used to guide clinician training and public informationsharing. A significant proportion of the queries did not fall within the NHLS-NICD scope of practice, indicating a need for targeted public engagement and education. Future outbreak hotline services could be planned on the basis of this experience to define the objectives of contact centres and establish these in awareness campaigns

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

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. 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. 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. 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.

The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant.

Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level.

Rabies on rise in Africa amid COVID and monkeypox: a global health concern.

Dear Editor, After Asia, Africa contributes to the greatest number of Rabies cases. Despite being vaccine-preventable, around 21 500 dog-mediated rabies deaths are reported from the continent each year.1 Recently, outbreaks of the disease have been reported in Kenya, where three deaths and several cases were reported across eight counties, maximum from the capital city of Nairobi.2 In South Africa, 6 probable, 11 confirmed human rabies cases, and 1 death were reported from the Eastern Cape, Limpono and KwaZuluNatal.3 The same 3 provinces were responsible for most of the 17 confirmed cases reported last year. The National Institute for Communicable Diseases (NICD) reported an increase in cases compared to previous years.4 In Ghana, the regional health directorate published a notice regarding a rise in rabies cases in the Ashanti region, recording four confirmed and one probable case, all resulting in death.5 Livestock and human mortality have also been reported from Zimbawe, and Morocco.6,7

S5.5a Standing up FungiNet: Genomic epidemiology and surveillance of fungal diseases

S5.5 Genomic Epidemiology of Fungal Infections, September 22, 2022, 3:00 PM - 4:30 PM ObjectivesWith the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing, the public health landscape for genomic epidemiology and surveillance has transformed for a variety of pathogens. For fungal diseases, the U.S. Centers for Disease Control and Prevention (CDC) is working with global partners to stand up FungiNet, a network that aims to equip scientists with laboratory, bioinformatics, and informatics resources to harness genomic data. FungiNet partners will use genomic and epidemiologic data to detect outbreaks, identify introductions, and characterize transmission of fungal infections. In 2022, FungiNet aims to onboard nine state and local health departments in the United States and two global partners, the Instituto Nacional de Salud in Colombia and the National Institute for Communicable Diseases in South Africa, with a focus on Candida auris.MethodsTo streamline the onboarding process, CDC generated standardized operating procedures (SOPs) specific to C. auris. For DNA extraction, SOPs were created for workflows using the Zymo Research Quick-DNA™ (ZR) Fungal/Bacterial Miniprep, Qiagen Dneasy Blood and Tissue, and Epicentre (Illumina) MasterPure Yeast DNA Purification kits. For library preparation and Illumina sequencing, PulseNet methods used for foodborne pathogens were validated for C. auris. For NCBI data submissions, required data elements were defined. For SNP and phylogenetic analyses, the bioinformatics workflow MycoSNP was adapted to use Nextflow software and the Terra platform. For visualization with epidemiologic data, guidance documents and tutorials for Microreact were created. Finally, for data reporting, processes are being designed in REDCap and in laboratory information management systems to rapidly share genomic-related data.ResultsTo date, 11 partners have committed to building capacity for C. auris genomic sequencing and analysis as a FungiNet partner. Of these, seven have validated methods for DNA extraction, and nine have generated high-quality sequencing data. Only one partner has installed and locally run MycoSNP, and none have submitted raw sequence data to NCBI.ConclusionsCurrently, 11 FungiNet partners are working to onboard C. auris genomic sequencing and bioinformatics analysis in 2022. This process is complex, requiring several laboratories, bioinformatics, and informatics workflows. For many partners, bioinformatics analysis and NCBI submission are the most challenging activities with the installation of MycoSNP and the ability to batch upload data to NCBI as the main barriers. Next steps will focus on the validation of informatics methods to link genomic and epidemiologic data.

A retrospective review of rabies post-exposure prophylaxis queries, South Africa, 2016-2019.

BackgroundThe National Institute for Communicable Diseases (NICDs) of South Africa (SA) provides technical support to healthcare workers (HCWs) with regard to infectious diseases through the NICD clinician hotline. Queries to the hotline are often about rabies prophylaxis. An analysis of these queries may help to identify knowledge gaps amongst HCWs regarding prevention of rabies in humans in SA.MethodsA retrospective descriptive review was conducted to analyse rabies post-exposure prophylaxis (PEP) queries received by the NICD from 01 January 2016 to 31 December 2019.ResultsA total of 4655 queries were received by the NICD clinician hotline for the study period, of which 2461 pertained to rabies PEP (52.87%). The largest number of calls were placed by HCWs (n = 2313/2437; 94.9%). Queries originated mainly from Gauteng (n = 912/2443; 37.3%) and KwaZulu-Natal (n = 875/2443; 35.8%) provinces. A total of 50 different types of animals were related to exposures involving humans. Dogs (67.7%) and cats (11.8%) were the animals most frequently reported and exposure category III was most common (88.6%). Approximately equal numbers of callers were advised active management of administering rabies PEP and conservative management of withholding PEP. This did not seem to be affected by the exposure category related to the call.ConclusionThis analysis shows the ongoing demand by HCWs for technical support regarding patient management following potential exposure to rabies. Gaps in HCWs rabies knowledge provide unique learning points on guiding training to achieve the goal of eliminating dog-mediated human rabies deaths by 2030.

Methods for early characterisation of the severity and dynamics of SARS-CoV-2 variants: a population-based time series analysis in South Africa

BackgroundAssessment of disease severity associated with a novel pathogen or variant provides crucial information needed by public health agencies and governments to develop appropriate responses. The SARS-CoV-2 omicron variant of concern (VOC) spread rapidly through populations worldwide before robust epidemiological and laboratory data were available to investigate its relative severity. Here we develop a set of methods that make use of non-linked, aggregate data to promptly estimate the severity of a novel variant, compare its characteristics with those of previous VOCs, and inform data-driven public health responses.MethodsUsing daily population-level surveillance data from the National Institute for Communicable Diseases in South Africa (March 2, 2020, to Jan 28, 2022), we determined lag intervals most consistent with time from case ascertainment to hospital admission and within-hospital death through optimisation of the distance correlation coefficient in a time series analysis. We then used these intervals to estimate and compare age-stratified case-hospitalisation and case-fatality ratios across the four epidemic waves that South Africa has faced, each dominated by a different variant.FindingsA total of 3 569 621 cases, 494 186 hospitalisations, and 99 954 deaths attributable to COVID-19 were included in the analyses. We found that lag intervals and disease severity were dependent on age and variant. At an aggregate level, fluctuations in cases were generally followed by a similar trend in hospitalisations within 7 days and deaths within 15 days. We noted a marked reduction in disease severity throughout the omicron period relative to previous waves (age-standardised case-fatality ratios were consistently reduced by >50%), most substantial for age strata with individuals 50 years or older.InterpretationThis population-level time series analysis method, which calculates an optimal lag interval that is then used to inform the numerator of severity metrics including the case-hospitalisation and case-fatality ratio, provides useful and timely estimates of the relative effects of novel SARS-CoV-2 VOCs, especially for application in settings where resources are limited.FundingNational Institute for Communicable Diseases of South Africa, South African National Government.

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

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. 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. 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). 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. National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. For the Zulu translation of the abstract see Supplementary Materials section.

The impact of COVID-19 on use of maternal and reproductive health services and maternal and perinatal mortality

South Africa experienced two waves of COVID-19 infection in the financial year 2020/21. This study examines the impact of these waves on maternal and perinatal mortality and their effect on the use of and access to maternal and reproductive health services. Data from the District Health Information System on maternal and perinatal deaths, births, antenatal visits, and use of contraceptive termination of pregnancy services were used, and the 2020/21 and 2019/20 financial years were compared in order to formulate national and provincial perspectives. Data on visits for initiating antenatal care, births, contraceptive prescriptions and termination-of-pregnancy services were used to assess utilisation of maternal and reproductive health services respectively; and the number and rates of maternal and perinatal deaths were examined to assess impact. A second descriptive analysis of pregnant women who had delivered after having contracted COVID-19 was performed using a separate database set up by the National Department of Health/South African Medical Research Council/University of Pretoria (NDoH/ SAMRC/UP), specifically to monitor the effects of COVID-19). The data suggest that there was a marked increase (of 40%) in maternal deaths (p&lt;0.00001), 10% in stillbirths (p&lt;0.00001), and 3% in (p=0.31) neonatal deaths when compared with the same period in 2019/20. There was a mean 28% increase in the institutional maternal mortality ratio in all provinces during the second wave compared with the first wave (p&lt;0.0001), except in the Western Cape which had a decrease of 1%. Data from the National Institute for Communicable Diseases showed that the case fatality rate for pregnant women with COVID-19 was high (4.5%), as was the perinatal mortality rate (70.6 per 1 000 births), while the institutional maternal mortality ratio for South Africa was 16.94/100 000 live births. An increase of 3.6% in in-facility births in 2020/21 compared with 2019/20 was observed, with increased movement of pregnant women to the more rural provinces and districts for delivery. Antenatal care services were maintained overall, but use of reproductive health services declined (contraceptive prescriptions by 5%, and termination of pregnancy by 17% overall). The effect of the COVID-19 epidemic on pregnant women and its collateral damage is severe. Strengthening the health system to maintain essential services during a pandemic and vaccination of healthcare workers and pregnant women are key to reducing maternal and perinatal mortality.

SARS-CoV-2 incidence, transmission, and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020–21

SummaryBackgroundBy August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa.MethodsWe conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members).Findings222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1–66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4–14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4–137). Of 662 RT-rtPCR-confirmed episodes (>14 days after the start of follow-up) with available data, 97 (14·7% [11·9–17·9]) were symptomatic with at least one symptom (in individuals aged <19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3–93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8–28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5–2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs >30) of the index case (OR 5·3 [2·3–12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4–8·2] and 10·4 [4·1–26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3–8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3–0·6]) compared with HIV-uninfected individuals.InterpretationIn this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up.FundingUS CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.

Cheryl Cohen—promoting evidence-based health policy

Cheryl Cohen—promoting evidence-based health policy

Understanding the differential impacts of COVID-19 among hospitalised patients in South Africa for equitable response.

There are limited in-depth analyses of COVID-19 differential impacts, especially in resource-limited settings such as South Africa (SA). To explore context-specific sociodemographic heterogeneities in order to understand the differential impacts of COVID-19. Descriptive epidemiological COVID-19 hospitalisation and mortality data were drawn from daily hospital surveillance data, National Institute for Communicable Diseases (NICD) update reports (6 March 2020 - 24 January 2021) and the Eastern Cape Daily Epidemiological Report (as of 24 March 2021). We examined hospitalisations and mortality by sociodemographics (age using 10-year age bands, sex and race) using absolute numbers, proportions and ratios. The data are presented using tables received from the NICD, and charts were created to show trends and patterns. Mortality rates (per 100 000 population) were calculated using population estimates as a denominator for standardisation. Associations were determined through relative risks (RRs), 95% confidence intervals (CIs) and p-values &lt;0.001. Black African females had a significantly higher rate of hospitalisation (8.7% (95% CI 8.5 - 8.9)) compared with coloureds, Indians and whites (6.7% (95% CI 6.0 - 7.4), 6.3% (95% CI 5.5 - 7.2) and 4% (95% CI 3.5 - 4.5), respectively). Similarly, black African females had the highest hospitalisation rates at a younger age category of 30 - 39 years (16.1%) compared with other race groups. Whites were hospitalised at older ages than other races, with a median age of 63 years. Black Africans were hospitalised at younger ages than other race groups, with a median age of 52 years. Whites were significantly more likely to die at older ages compared with black Africans (RR 1.07; 95% CI 1.06 - 1.08) or coloureds (RR 1.44; 95% CI 1.33 - 1.54); a similar pattern was found between Indians and whites (RR 1.59; 95% CI 1.47 - 1.73). Women died at older ages than men, although they were admitted to hospital at younger ages. Among black Africans and coloureds, females (50.9 deaths per 100 000 and 37 per 100000, respectively) had a higher COVID-19 death rate than males (41.2 per 100 000 and 41.5 per 100000, respectively). However, among Indians and whites, males had higher rates of deaths than females. The ratio of deaths to hospitalisations by race and gender increased with increasing age. In each age group, this ratio was highest among black Africans and lowest among whites. The study revealed the heterogeneous nature of COVID-19 impacts in SA. Existing socioeconomic inequalities appear to shape COVID-19 impacts, with a disproportionate effect on black Africans and marginalised and low socioeconomic groups. These differential impacts call for considered attention to mitigating the health disparities among black Africans.