Mignon du Plessis

Background: Community-acquired pneumonia (CAP) is a leading cause of death in adults, but recent data in people with HIV (PWH) are lacking. We studied South African adults hospitalized with CAP to describe mortality and risk factors. Methods: We prospectively enrolled consenting adults aged ≥18 years hospitalized with CAP, as defined by symptoms, signs, and chest x-ray, from March 2019 to October 2021 in 3 South African hospitals. Blood, sputum, nasopharyngeal/oropharyngeal swabs, and urine were tested for HIV, tuberculosis, SARS-CoV-2, influenza, respiratory syncytial virus, and Streptococcus pneumoniae. Participants were followed for 1 year. Causes of death were defined following record review. Timing and risk factors for death were evaluated by Kaplan-Meier and Cox analyses. Results: Of 2000 adults (median age, 46 years), 1079 (54.0%) were PWH. Among 994 with HIV viral load results, 289 (29.1%) were virally suppressed, and among 1556 tested for SARS-CoV-2, 700 (45.0%) were positive. There were 569 (28.5%) deaths, and the majority died early: 47.7% during hospitalization and 10.6% ≤30 days postdischarge. Leading underlying causes of death were COVID-19 (23.0%), tuberculosis (16.9%), and advanced HIV (13.2%). Age ≥45 years (hazard ratio, 2.7; 95% CI, 1.5–4.6), active tuberculosis (1.6, 1.2–2.0), unsuppressed HIV viral load (1.4, 1.0–1.9), anemia (1.3, 1.0–1.6), underweight (1.3, 1.0–1.7), and low admission oxygen saturation (<94% on room air; 1.3, 1.0–1.6) were associated with mortality. Mortality was higher in PWH (18.2 vs 11.7 per 100 person-years) but similar between PWH who were virally suppressed and unsuppressed (21.3 vs 24.7 per 100 person-years). Conclusions: In-hospital and postdischarge CAP mortality remains high, particularly among PWH, regardless of virologic status, warranting urgent investigation of mitigation strategies.

Streptococcus pneumoniae is highly diverse, comprising over 100 serotypes and hundreds of genomic lineages amid widespread vaccination. While it can cause invasive pneumococcal disease (IPD) which exhibits pronounced seasonal spikes, the interplay between pneumococcal diversity and environmental drivers remains unexplored. Here we analysed 59,017 IPD cases over 19 years from South Africa, incorporating 4,350 genome-sequenced isolates, using Bayesian spatiotemporal models to link environmental exposure and pneumococcal diversity. Cumulatively, across an 8-week period, moderate relative humidity (33–49%) and cold minimum temperatures (4–10 °C) increased IPD risk by 5% and 4%, respectively. Conversely, warm maximum temperatures (27–38 °C) were associated with up to a 10% increased risk within a week of exposure. There was a positive association between air pollution (PM _2.5 ) and IPD, although it varied by age, disease presentation, and most notably serotype and lineage. Specifically, the lag time between PM _2.5 exposure and disease onset varied by serotype, with only serotypes 4, 8 and 23F conferring an immediate IPD risk. High prevalence of GPSC21 lineage (serotype 19F) also modified the pollution response, shifting the lag structure to produce immediate risk of disease following high PM _2.5 exposure. Our results demonstrate that pneumococcal population structure shapes air quality risk which in turn can shape the fitness landscape of microbial populations. Integration of these data may inform public health policy.

Background: Accurate detection of RSV infections is important to understand epidemiology. We estimated symptomatic fraction and shedding duration of reverse‐transcription polymerase chain reaction (RT‐PCR)‐confirmed cases and compared RSV detection through molecular and serologic techniques. Methods: We enrolled healthy children aged 6–23 months in a prospective cohort study, from May to October 2022, collecting thrice‐weekly mid‐turbinate nasal swabs for RSV RT‐PCR testing. We collected serum at baseline and end of follow‐up and detected anti‐RSV IgG using enzyme‐linked immunosorbent assay (ELISA) and multipathogen bead‐based immunoassay (MIA). We ascertained symptoms by twice‐weekly nurse visits, and daily caregiver symptom diaries. We calculated sensitivity, specificity, and positive (PPV) and negative (NPV) predictive value of RT‐PCR, ELISA, and MIA compared to a standard (two or more assays‐positive) among children with paired sera and baseline blood preceding an RT‐PCR–confirmed episode. Results: The RSV season started mid‐February 2022. We enrolled 93 participants; 87 (94%) followed to the final study visit. Forty individuals had one or more RT‐PCR–confirmed RSV infection, and six of them had a repeat episode. One‐or‐more symptom was reported from 54% (25/46) of RT‐PCR–confirmed episodes, fever in 26% (12/46), and cough in 37% (17/46). Median RNA shedding duration was 7 days (IQR = 4–11 days). Among 80 children meeting criteria, ELISA and MIA each had > 92% sensitivity, specificity, PPV, and NPV while RT‐PCR had 78% (95% CI = 61%–90%) sensitivity, 98% (95% CI = 88–100%) specificity, 97% (95% CI = 82%–100%) PPV, and 84% (95% CI = 71%–93%) NPV. Discussion: Approximately half of RSV episodes were symptomatic. Serology had a high sensitivity and specificity for infection identification.

Background . Serotype 8 has emerged as a common non-vaccine serotype causing invasive pneumococcal disease (IPD) in children and adults globally after the introduction of pneumococcal conjugate vaccines (PCV). We aimed to determine serotype 8 incidence and genomic epidemiology in South Africa. Methods . From national, laboratory-based surveillance for IPD in South Africa, we calculated the incidence of serotype 8 and global pneumococcal sequence cluster 3 (GPSC3) before and after PCV introduction. We performed phylodynamic analysis of genomes from clonal complex (CC) 53 and described South African isolates in the context of a global collection of serotype 8 and GPSC3 genomes. Results. Compared to the pre-PCV period, serotype 8 incidence increased in the late-PCV13 period among children 64 years (2.8, 1.1–8.3). Similarly, GPSC3 rates increased among children Conclusion. Serotype 8 invasive disease incidence increased in South Africa after PCV introduction. Predictions showed sustained increases over time. Since South Africa switched to a lower-valency PCV10 (Pneumosil, Serum Institute of India) that does not include serotype 8 in 2024, continued surveillance will be crucial to inform PCV policy-making.

Streptococcus pneumoniae (pneumococcus) remains a major global cause of invasive human disease with seasonal variation suggesting that environmental factors may drive transmission. The pneumococcus includes >100 serotypes and lineages with different disease patterns. Potential interactions between microbial diversity, environmental factors, and invasive pneumococcal disease (IPD) have not been explored. We examined effects of air pollution and meteorological factors on 59,017 IPD cases over 15 years, including 4,350 genome-sequenced isolates, using Bayesian spatio-temporal hierarchical models linking environmental exposures to bacterial diversity. Humidity and air pollution were important environmental drivers. Humidity (33-49%) conferred a 5% disease risk, while high humidity was protective. Weekly PM _2.5 exposure (50 μg/m³) was associated with a 4% increase in disease risk, was greatest in adults > 65, and varied by disease type. Quantifying these relationships may refine vaccine-impact models and inform air pollution policy targets.

Routine use of pneumococcal conjugate vaccines (PCV) in South Africa caused a decline in vaccine-associated invasive pneumococcal disease (IPD), followed by the emergence of non-PCV serotypes, driven mainly by pre-existing lineages. We determined the molecular epidemiology of isolates causing IPD among adults in South Africa from 2020 to 2025 before and following the implementation of PCV in 2009. We performed whole-genome sequencing on randomly selected isolates causing IPD among adults aged ≥18 years ( N =1 581) during the four vaccine periods [pre-PCV (2005–2008), PCV7 (2009–2010), early-PCV13 (2011–2014) and late-PCV13 (2015–2020)]. We assigned in silico serotype, multi-locus sequence type, clonal complex (CC) and global pneumococcal sequence cluster (GPSC) and determined antimicrobial non-susceptibility profiles in silico . Poisson regression was used to calculate incidence rate ratios of imputed individual GPSC lineages using IPD incidence rate estimated per year for the three vaccine periods (PCV7, early-PCV13 and late-PCV13), compared to the pre-PCV period. Overall, our dataset represented 3.7% ( n =270), 3.4% ( n =128), 4.9% ( n =287) and 13.5% ( n =896) of adult pneumococcal isolates received during the four periods, respectively. We identified 135 GPSCs with the majority of isolates [68.7%(1 086/1 581)] clustering into 1 of 23 dominant GPSCs defined as GPSCs that comprised ≥20 genomes in the dataset. Compared to the pre-PCV7 period, a decrease in incidence of vaccine type lineages normally associated with vaccine serotypes was observed during the late-PCV13 period. GPSC2 (serotype 1) declined from 1.4 to 0.039/100,000 population ( P P n =3) expressed serotype 14; however, during the late-PCV13 period, nearly all (88.2%, 15/17) were serotype 15A. The emergence among non-PCV13 serotypes, of lineages usually associated with PCV13 serotypes (such as GPSC5/CC172 and GPSC9/CC63), warrants continued genomic surveillance in South Africa, more so as PCV10 (Pneumosil) replaced PCV13 in South Africa in 2024.

Background: Pertussis is vaccine preventable, and surveillance can guide interventions. Assessing the performance of syndromic surveillance and the World Health Organization (WHO) pertussis case definitions can identify improvements to enhance detection and monitoring of Bordetella pertussis. Methods: We analyzed respiratory illness sentinel surveillance data among children aged <5 years from January 2017 through December 2023. Participants were enrolled for surveillance as outpatients with influenza-like illness (ILI) or in-patients with severe respiratory illness (SRI). Nasopharyngeal swabs were tested for B pertussis via polymerase chain reaction (PCR). Sensitivity and specificity, and performance indicators of case definitions were evaluated against PCR results. Results: Of 23 642 participants with PCR results, B pertussis was detected in 0.7% from ILI and 1.6% from SRI. When compared with the WHO pertussis case definition, a modified definition (including apnea, omitting cough duration) improved sensitivity (ILI, 30.0% vs 43.3%; SRI, 55.7% vs 60.2%) but reduced specificity (ILI, 90.5% vs 75.8%; SRI, 88.3% vs 80.9%). WHO and modified pertussis case definitions missed a large proportion of true pertussis cases (ILI, 70.0% vs 56.7%; SRI, 44.3% vs 39.8%). Conclusions: Current pertussis case definitions likely underestimate disease burden. Revising the WHO pertussis case definition and integrating pertussis into syndromic surveillance could improve detection while leveraging existing resources.

A review of epidemiologic and isolate characteristics from reported C. diphtheriae infections in South Africa over a 9-year period reveals a heterogeneous population of toxigenic and nontoxigenic strains causing diphtheria, cutaneous diphtheria, and infective endocarditis.

Background: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development. Methods: Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020. Phenotypic serotyping and antimicrobial susceptibility testing were conducted, followed by whole-genome sequencing for analysis of population structure and surface protein and resistance genes. Results: In total, 1748 invasive GBS cases were reported. Of these, 661 isolates underwent characterization, with 658 yielding both phenotypic and genotypic results. Isolates (n = 658) belonged to 5 clonal complexes (CC1, CC8/10, CC17, CC19, and CC23) and 6 serotypes were detected: III (42.8%), Ia (27.9%), V (11.9%), II (8.4%), Ib (6.7%), and IV (2.3%). Phenotypically, only 1 isolate exhibited reduced penicillin susceptibility (minimum inhibitory concentration 0.25 µg/mL). Phenotypic resistance to erythromycin, clindamycin, and tetracycline was observed in 16.1%, 3.8%, and 91.5% of isolates, respectively. ermTR (34.9%) and mefA/E (30.1%) genes were most common among erythromycin-resistant isolates, while ermB predominated in clindamycin-resistant isolates (32.0%). tetM accounted for 95.8% of tetracycline resistance. All isolates carried at least 1 of the 3 pilus gene clusters, 1 of the 4 homologous alpha/Rib family determinants, and 98% harbored 1 of the serine-rich repeat protein genes. hvgA was found exclusively in CC17 isolates. Conclusions: In our setting, β-lactam antibiotics remain appropriate for GBS treatment and polysaccharide and protein-based vaccines under development are expected to provide good coverage.