Search

Euwallacea fornicatus (polyphagous shot hole borer, PSHB) is an invasive ambrosia beetle that infests hundreds of tree species worldwide. Damage occurs due to colonization of host sapwood with both the beetle and its fungal symbiont, Fusarium euwallaceae, which leads to Fusarium dieback disease in highly susceptible hosts. Except for almond (Prunus dulcis), and despite the name of the disease, the pathogenicity of F. euwallaceae towards stone fruit tree species have not been demonstrated. Here we set out to determine the pathogenicity of F. euwallaceae towards nectarine (P. persica) and plum (P. domestica) following its detection on various Prunus species in South Africa. Trees were inoculated with multiple isolates of F. euwallaceae, lesion development was characterised, and the causal agents were re-isolated to fulfil Koch's postulates. The influence of factors such as branch diameter, cultivar, host species, inoculum load and isolate identity on lesion development was also assessed. We confirm that F. euwallaceae is a pathogen to nectarine and plum and that the susceptibility of nectarine to F. euwallaceae was higher than for plum. Lesion development did not differ between the two plum cultivars. Branch diameter and an increase in inoculum load did not influence the rate of lesion development. We confirm that PSHB can breed in many Prunus species in gardens, including almond, nectarine, apricot, cherry plum and black plum. [ABSTRACT FROM AUTHOR]

Background: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W, and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021., Methods: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico., Results: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%), and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9, or penA14., Conclusions: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008; however, peni was higher than previously reported, and occurred in a variety of lineages., Competing Interests: Potential conflicts of interest. S. M. has participated in an advisory board for GSK for meningococcal B vaccine use in South Africa (no payment or honoraria received); and gave an educational presentation for Sanofi Pasteur at an industry-sponsored symposium at the PASA Conference on Meningitis, South Africa (travel expenses but no honoraria or payment received). K. J. reports a Wellcome Trust Biomedical Resource Grant for PubMLST, paid to the University of Oxford; and database royalties from GSK. L. H. attends scientific advisory boards for Pfizer, Merk, and GSK (no fees paid); and participates on the data safety monitoring board for experimental pneumococcal vaccine for Merck. V. Q. attended the MSD Pediatric Vaccines Symposium, 29–30 September 2023, Warsaw, Poland (no payment received). C. C. has received funding from US Centers for Disease Control and Prevention, Bill and Melinda Gates Foundation, Wellcome Trust, South African Medical Research Council, Sanofi Pasteur, and PATH. A. v. G. is the chairperson of the National Advisory Group for Immunisation, South Africa. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Surveillance programmes for influenza and other respiratory pathogens are important to generate vaccine effectiveness (VE) estimates and to inform vaccine composition. We aimed to explore the feasibility and acceptability of home-based testing., Methods: In three out of nine provinces in South Africa, we established a self-referral system for individuals aged ≥ 18 years with respiratory symptoms of ≤ 10 days duration. Following consent, swab collection material was delivered to participants who also completed a questionnaire including self-reported vaccination status. Swabs were tested by PCR for influenza, respiratory syncytial virus (RSV) and SARS-CoV-2. A test-negative methodology was used to estimate influenza VE., Results: Of 1456 samples collected between 19 November 2021 and 3 September 2022, 73 (5%) tested positive for influenza, 38 (3%) tested positive for RSV and 394 (27%) for SARS-CoV-2. We subtyped 55% (40/73) of the influenza positive specimens; 16/40 (40%) were influenza A(H1N1)pdm09; 10/40 (25%)A(H3N2)) and all 14/40(35%) influenza B were B/Victoria. Only 20% (279/1451) of participants reported influenza-like illness case definition symptoms of fever and cough. Influenza vaccine coverage was 11% (157/1454). The overall influenza VE was 26% (95% confidence interval: -73%, 69%). Of the completed acceptability questionnaires, 123/127 (97%) participants would make use of the service again; 90% (1306) were recruited via the COVID-19 testing centre (call in, social media, webpage), and 7% (99/1306) through CoughWatchSA., Conclusions: Home-based swabbing was feasible and acceptable. We were able to calculate an influenza VE, although a larger sample size and verification of vaccine status may improve the VE estimates in the future., (© 2024 The Author(s). Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations., (© 2024. The Author(s).)

Background: In South Africa, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and 13-valent PCV (PCV13) was introduced in 2011, both in a two plus one schedule. We evaluated the ongoing effects of PCV on the prevention of invasive pneumococcal disease (IPD) over 15 years of sustained surveillance in South Africa before the COVID-19 pandemic., Methods: We conducted national, active, laboratory-based surveillance for IPD among all ages in South Africa, including isolate serotyping and susceptibility testing. We fitted linear regression models with vaccine covariates to imputed IPD case counts each year by serotype and age to compare expected and actual IPD cases in 2019, which was the main outcome. Vaccine effects were set to zero to identify expected incidence after the introduction of PCV7 and PCV13., Findings: From Jan 1, 2005, to Dec 31, 2019, surveillance identified 52 957 IPD cases. Among the 50 705 individuals with age data available, 9398 (18·5%) were infants aged younger than 2 years. Compared with expected case numbers (no vaccination) predicted using all available data, overall IPD rates among children younger than 2 years declined by 76·0% (percentage risk difference; 95% CI -79·0 to -72·8%) in 2019; notably, PCV7 and additional PCV13 serotype IPD rates declined by 95·5% (-97·0 to -93·4%) and 93·8% (-96·2 to-90·5%), respectively, whereas non-vaccine serotypes (NVTs) did not change significantly. Among adults aged 25-44 years, overall IPD declined by 50·4% (-54·2 to -46·3%), and PCV7 and additional PCV13 serotype IPD rates declined by 86·1% (-88·7 to -83·1%) and 77·2% (-80·9 to -73·0%), respectively, whereas NVTs increased by 78·5% (56·8 to 103·4%). Individuals aged older than 64 years also benefited from declines in IPD (-30·2%; -41·9 to -16·2%), but NVTs increased (234·9%; 138·1 to 379·4%)., Interpretation: We documented sustained direct and indirect benefits of PCV across age groups, and NVT increases in adults older than 24 years. Higher valency PCVs would have the added benefit of preventing this residual disease., Funding: National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa) and US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests SAM has received grant funds from MSD, Pfizer, GSK, and the Bill and Melinda Gates Foundation; and honoraria from GSK, related to this work. CvM declares grant funds from Pfizer. CvM and VC declare honoraria from MSD and Pfizer. CC declares grant funds from Sanofi and the Bill and Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 vaccine effectiveness (VE) studies leveraging systematic surveillance in sub-Saharan Africa are limited. We assessed the effectiveness of two vaccines (Pfizer BNT162b2 and Johnson & Johnson Ad26.COV2.S) against SARS-CoV-2-associated hospitalization in South African adults aged ≥18 years., Methods: We conducted a test-negative case-control study using pneumonia surveillance data in South Africa. Inpatients with physician-diagnosed lower respiratory tract infection or suspected COVID-19, testing SARS-CoV-2 positive or negative from June 2021-March 2022, were cases or controls, respectively. Fully vaccinated individuals received one Ad26.COV2.S dose or two BNT162b2 doses ≥14-days before enrollment. VE was estimated using multivariable logistic regression for Delta- and Omicron BA.1/BA.2-predominant periods, stratified by age and HIV status., Results: The study included 925 cases and 1890 controls; 38 (4%) cases and 186 (10%) controls were fully vaccinated with BNT162b2, and 30 (3%) cases and 94 (5%) controls with Ad26.COV2.S. The vaccine effectiveness of BNT162b2 against SARS-CoV-2-associated hospitalization over Delta and Omicron BA.1/BA.2 periods was 91% (95% CI: 52%, 98%) and 33% (-16%, 86%), respectively. The vaccine effectiveness of Ad26.COV2.S against hospitalization over Delta and Omicron BA.1/BA.2 periods was 72% (-36% ,94%), and -19% (-130%, 39%), respectively. The vaccine effectiveness of BNT162b2 against hospitalization over the Delta period was 94% (50%, 99%) and 89% (27%, 98%) among adults aged ≥60 years and HIV-uninfected, respectively., Conclusions: The BNT162b2 vaccine was effective against SARS-CoV-2-associated hospitalization during the Delta period for adults aged ≥18 years, ≥60 years and those HIV-uninfected. VE for Ad26.COV2.S was inconclusive, potentially due to limited sample size or residual confounding. These findings highlight the utility of sentinel surveillance for estimating VE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location 1,2 . The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient., (© 2024. The Author(s).)

Background: Identifying children at risk for severe COVID-19 disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may guide future mitigation interventions. Using sentinel surveillance data, we aimed to identify risk factors for SARS-CoV-2-associated hospitalisation among patients aged ≤ 18 years with respiratory illness., Methods: From April 2020 to March 2022, patients meeting study case definitions were enrolled at four outpatient influenza-like illness (ILI) and five inpatient severe respiratory infection (SRI) surveillance sites and tested for SARS-CoV-2 infection using polymerase chain reaction (PCR). Each ILI clinic shared a catchment area with its corresponding SRI hospital. Potential risk factors for SARS-CoV-2-associated hospitalisation were analysed using multivariable logistic regression by comparing inpatient versus outpatient SARS-CoV-2 cases., Results: Of 4688 participants aged ≤ 18 years, 4556 (97%) with complete PCR and HIV data were included in the analysis. Among patients with ILI and SRI, 92/1145 (8%) and 154/3411 (5%) tested SARS-CoV-2 positive, respectively. Compared to outpatients, hospitalised SARS-CoV-2 cases were associated with age < 6 months ([adjusted odds ratio (aOR) 8.0, 95% confidence interval (CI) 2.7-24.0] versus 1-4 years); underlying medical condition other than HIV [aOR 5.8, 95% CI 2.3-14.6]; laboratory-confirmed Omicron BA.1/BA.2 or Delta variant ([aOR 4.9, 95% CI 1.7-14.2] or [aOR 2.8, 95% CI 1.1-7.3] compared to ancestral SARS-CoV-2); and respiratory syncytial virus coinfection [aOR 6.2, 95% CI 1.0-38.5]., Conclusion: Aligning with previous research, we identified age < 6 months or having an underlying condition as risk factors for SARS-CoV-2-associated SRI hospitalisation and demonstrated the potential of sentinel surveillance to monitor COVID-19 in children., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa., Methods: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant., Results: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35)., Conclusions: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness., (© 2024. The Author(s).)

Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32 Bordetella pertussis isolates sourced from three different surveillance programmes in South Africa between 2015 and 2019. Genome sequences were characterized using multilocus sequence typing, vaccine antigen genes ( ptxP , ptxA , ptxB , prn and fimH ) and overall genome structure. All isolates were sequence type 2 and harboured the pertussis toxin promoter allele ptxP3 . The dominant genotype was ptxP 3 -ptxA 1 -ptxB2-prn 2 -fimH 2 (31/32, 96.9 %), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Amongst 21 isolates yielding closed genome assemblies, eight distinct genome structures were detected, with 61.9 % (13/21) of the isolates exhibiting three predominant structures. Increases in case numbers are probably not due to evolutionary changes in the genome but possibly due to other factors such as the cyclical nature of B. pertussis disease, waning immunity due to the use of acellular vaccines and/or population immunity gaps.

Objectives: To describe the prevalence of pediatric acute respiratory distress syndrome (pARDS) and the characteristics of children with pARDS in South African PICUs., Design: Observational multicenter, cross-sectional point-prevalence study., Setting: Eight PICUs in four South African provinces., Patients: All children beyond the neonatal period and under 18 years of age admitted to participating PICUs., Interventions: None., Measurements and Main Results: Clinical and demographic data were prospectively collected on a single day of each month, from February to July 2022, using a centralized database. Cases with or at risk of pARDS were identified using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria. Prevalence was calculated as the number of children meeting pARDS criteria/the total number of children admitted to PICU at the same time points. Three hundred ten patients were present in the PICU on study days: 166 (53.5%) male, median (interquartile range [IQR]) age 9.8 (3.1-32.9) months, and 195 (62.9%) invasively mechanically ventilated. Seventy-one (22.9%) patients were classified as being "at risk" of pARDS and 95 patients (prevalence 30.6%; 95% CI, 24.7-37.5%) fulfilled pARDS case criteria, with severity classified as mild (58.2%), moderate (25.3%), and severe (17.6%). Median (IQR) admission Pediatric Index of Mortality 3 risk of mortality in patients with and without pARDS was 5.6 (3.4-12.1) % versus 3.9 (1.0-8.2) % ( p = 0.002). Diagnostic categories differed between pARDS and non-pARDS groups ( p = 0.002), with no difference in age, sex, or presence of comorbidities. On multivariable logistic regression, increasing admission risk of mortality (adjusted odds ratio [aOR] 1.02; 95% CI, 1.00-1.04; p = 0.04) and being admitted with a respiratory condition (aOR 2.64; 95% CI, 1.27-5.48; p = 0.01) were independently associated with an increased likelihood of having pARDS., Conclusions: The 30.6% prevalence of pARDS in South Africa is substantially higher than reports from other sociogeographical regions, highlighting the need for further research in this setting., Competing Interests: Dr. Morrow’s institution received funding from the Society of Critical Care Medicine, the National Research Foundation of South Africa, and the Critical Care Society of Southern Africa; she received funding from the European Cystic Fibrosis Society and Brazilian Physiotherapy Association. Drs. Solomon and Khan received funding from the Critical Care Society of Southern Africa. Dr. Solomon received funding from ANN LAKE Publications. Dr. Naidoo received funding from Mbuso Medical, Fresenius Kabi, and Nutricia. Dr. Argent received funding for travel, accommodation, and registration to attend a number of conferences as an invited guest speaker and for providing expert witness evidence to a number of medicolegal cases. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Introduction: Culturally relevant developmental screening is one of the best ways to appropriately identify developmental delays and disabilities in children as early as possible across diverse cultural backgrounds. This study aimed to adapt the Parents' Evaluation of Developmental Status (PEDS) tools for a low-income community in South Africa by using a detailed multiphased cultural and contextual adaption process., Method and Results: A three-phase mixed-method design relying on triangulation of data was used. Data were collected at an immunization clinic in a low-income community in Mamelodi, South Africa. Phase 1 was a focus group discussion with 11 community participants. The topics explored the possible changes to the PEDS tools to make them more relevant to the community. Phase 1 informed Phase 2 where 12 early childhood development experts achieved consensus through a two-round survey on a modified Delphi method. In Phase 3, a draft of the PEDS tools-SA was presented to the authors of the PEDS tools for final approval. Of 55 questions that were adapted for the PEDS tools-SA, two original questions (3.6%), 14 questions from the expert suggestions (25.4%) and 39 from the community participant's suggestions (71%) were included. A final version of the PEDS tools-SA was created., Conclusion: This study used a systematic method to adapt the PEDS tools to create the culturally appropriate PEDS tool-SA for a low-income community in South Africa, informed by community stakeholders' views from the first step. This resulted in a high-quality adaptation process that is more likely to result in a tool that is more acceptable to caregivers from a low-income South African community., (© 2022 John Wiley & Sons Ltd.)

We conducted 3 prospective cohort studies (2016-2018), enrolling persons from 2 communities in South Africa. Nasopharyngeal swab specimens were collected twice a week from participants. Factors associated with Bordetella pertussis incidence, episode duration, and household transmission were determined by using Poisson regression, Weibull accelerated time-failure, and logistic regression hierarchical models, respectively. Among 1,684 participants, 118 episodes of infection were detected in 107 participants (incidence 0.21, 95% CI 0.17-0.25 infections/100 person-weeks). Children <5 years of age who had incomplete vaccination were more likely to have pertussis infection. Episode duration was longer for participants who had higher bacterial loads. Transmission was more likely to occur from male index case-patients and persons who had >7 days infection duration. In both communities, there was high incidence of B. pertussis infection and most cases were colonized.

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. Here, we use the presence/absence of the S-gene target as a proxy for SARS-CoV-2 variant/lineage for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We link national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assess severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR 1.24, 95% CI 0.98-1.55) and severe outcome (aOR 0.72, 95% CI 0.41-1.26) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 showed similar severity to the BA.1 lineage and continued to show reduced clinical severity compared to the Delta variant., (© 2022. The Author(s).)

Objectives: We describe the use of a multipathogen platform, TaqMan array card (TAC) real-time polymerase chain reaction, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI)., Methods: Prospective hospital-based syndromic surveillance for acute and chronic SRI was carried out at two sentinel sites in South Africa between January and December 2017. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-square test., Results: During 2017, 956 patients of all ages were enrolled in the SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 naso- and oro-pharyngeal swabs, and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected included Haemophilus influenzae (225/637; 35%), Streptococcus pneumoniae (224/637; 35%), rhinovirus (144/637; 23%), Staphylococcus aureus (129/637; 20%), Klebseilla pneumoniae (85/637; 13%), Mycobacterium tuberculosis (75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were codetected in 57% (364/637) of patients., Conclusion: Although the use of a multi-pathogen platform improved pathogen yield, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.

Background: We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding duration and magnitude among persons living with human immunodeficiency virus (HIV, PLHIV)., Methods: From May through December 2020, we conducted a prospective cohort study at 20 hospitals in South Africa. Adults hospitalized with symptomatic coronavirus disease 2019 (COVID-19) were enrolled and followed every 2 days with nasopharyngeal/oropharyngeal (NP/OP) swabs until documentation of cessation of SARS-CoV-2 shedding (2 consecutive negative NP/OP swabs). Real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2 was performed, and cycle-threshold (Ct) values < 30 were considered a proxy for high SARS-CoV-2 viral load. Factors associated with prolonged shedding were assessed using accelerated time-failure Weibull regression models., Results: Of 2175 COVID-19 patients screened, 300 were enrolled, and 257 individuals (155 HIV-uninfected and 102 PLHIV) had > 1 swabbing visit (median 5 visits [range 2-21]). Median time to cessation of shedding was 13 days (interquartile range [IQR] 6-25) and did not differ significantly by HIV infection. Among a subset of 94 patients (41 PLHIV and 53 HIV-uninfected) with initial respiratory sample Ct-value < 30, median time of shedding at high SARS-CoV-2 viral load was 8 days (IQR 4-17). This was significantly longer in PLHIV with CD4 count < 200 cells/µL, compared to HIV-uninfected persons (median 27 days [IQR 8-43] vs 7 days [IQR 4-13]; adjusted hazard ratio [aHR] 0.14, 95% confidence interval [CI] .07-.28, P < .001), as well as in unsuppressed-HIV versus HIV-uninfected persons., Conclusions: Although SARS-CoV-2 shedding duration did not differ significantly by HIV infection, among a subset with high initial SARS-CoV-2 viral loads, immunocompromised PLHIV shed SARS-CoV-2 at high viral loads for longer than HIV-uninfected persons. Better HIV control may potentially decrease transmission time of SARS-CoV-2., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Despite the undeniable diagnostic benefits of urodynamic studies (UDS), their adoption into clinical practice in Africa has been slow. This study aimed to review the use of invasive UDS in children at a tertiary paediatric hospital in South Africa., Methods: A retrospective analysis of 1108 UDS was conducted. Patient demographic characteristics, primary diagnosis, indication and urodynamic outcomes were reviewed. Presence of urodynamic high-risk features were documented, and a comparison was made between the first study and follow-up study., Results: This study revealed increasing trends in the use of UDS from 2015. Referrals were from Urology (37.7%), Spinal defects clinic (34.4%), Nephrology (20.8%) and other departments (7.0%). The most common reason for referral was review of medical treatment (36.5%). Spinal dysraphism (58.3%) accounted for the majority of conditions seen. Majority (59.1%) of the patients were receiving more than one type of bladder treatment at the time of their first study, with clean intermittent catheterisation (46.5%) being the most common form of bladder management. 97.5% of studies were performed using transurethral bladder catheterization. Urodynamic diagnosis was neurogenic in 74.0%, anatomical (12.2%), functional (8.8%) and normal (5.0%). There was statistically significant improvement in bladder compliance, detrusor leak point pressure and detrusor sphincter dyssynergia between the first study and a subsequent study following therapeutic intervention., Conclusions: The unique ability of UDS to demonstrate changes in detrusor pressures, which is a common reason for therapy failure, makes UDS an invaluable tool in the diagnosis and management of children with lower urinary tract dysfunction., (© 2022. The Author(s).)

Background: By 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., Methods: We 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)., Findings: 222 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., Interpretation: In 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., Funding: US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust., Competing Interests: Declaration of interests CC has received grant support from Sanofi Pasteur, the US Centers for Disease Control and Prevention (CDC), Wellcome Trust, the Programme for Applied Technologies in Health (PATH), Bill & Melinda Gates Foundation, and the South African Medical Research Council (SA-MRC). AvG has received grant support from the US CDC, the African Society for Laboratory Medicine and Africa Centres for Disease Control and Prevention, the SA-MRC, WHO Regional Office for Africa, the Fleming Fund, WHO, and Wellcome Trust. NW reports grants from Sanofi Pasteur and the Bill & Melinda Gates Foundation. NAM has received a grant to his institution from Pfizer to conduct research in patients with pneumonia. JM has received grant support from Sanofi Pasteur and PATH. JB has received grant funds from the European and Developing Countries Clinical Trials Partnership, the Fleming Fund, and the SA-MRC. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.

Background: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy., Methods: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021., Findings: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1-0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3-1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2-0·5), after controlling for factors associated with disease severity., Interpretation: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity., Funding: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund., Competing Interests: Declaration of interests CC has received grant support from the South African Medical Research Council, the UK Foreign, Commonwealth and Development Office, the Wellcome Trust, the US Centers for Disease Control and Prevention, and Sanofi Pasteur. NW and MdP have received grant support from Sanofi Pasteur and the Bill & Melinda Gates Foundation. AvG has received grant support from Sanofi Pasteur, the US Centers for Disease Control and Prevention, the South African Medical Research Council, the Bill & Melinda Gates Foundation, WHO, the Fleming Fund, and the Wellcome Trust. RW declares personal shareholding in Adcock Ingram Holdings, Dischem Pharmacies, Discovery, Netcare, and Aspen Pharmacare Holdings. WS has received grant support from the South African Medical Research Council, with funds received from the Department of Science and Innovation, and the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high human immunodeficiency virus (HIV) prevalence and routine pertussis vaccination for 6 decades including the acellular vaccine since 2009., Methods: Hospitalized patients of all ages were enrolled at 5 sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by polymerase chain reaction (PCR) for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013-2016, and multivariable logistic regression performed to identify factors associated with pertussis., Results: Over the 6-year period 19 429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100 000 population, with the highest incidence in children <1 year of age (228 per 100 000). Age-adjusted incidence was 65.9 per 100 000 in HIV-infected individuals compared to 8.5 per 100 000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval: 23.0-40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults., Conclusions: Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

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.

Background: Invasive meningococcal disease clusters occur among university students and may reflect higher carriage prevalence among this population. We aimed to measure meningococcal carriage prevalence, acquisition, and risk factors among first-year university students in South Africa., Methods: In summer-autumn 2017, after consenting to participate, we collected oropharyngeal swabs and questionnaires on carriage risk factors and tested students for HIV at 2 universities, during registration week (survey 1) and 6-8 weeks later (survey 2). Meningococci were detected by culture and polymerase chain reaction., Results: We enrolled 2120 students at registration. Mean age was 18.5 years, 59% (1252/2120) were female and 0.8% (16/1984) had HIV. Seventy-eight percent of students returned for survey 2 (1655/2120). Among the cohort, carriage prevalence was 4.7% (77/1655) at registration, increasing to 7.9% (130/1655) at survey 2: 5.0% (83) acquired new carriage, 2.8% (47) had persistent carriage, 1.8% (30) cleared the initial carriage, and 90.3% (1495) remained carriage free. At both surveys, nongenogroupable meningococci predominated, followed by genogroups Y, B, W, and C. On multinomial analysis, risk factors for carriage acquisition included attending nightclubs (adjusted relative risk ratio [aRRR], 2.1; 95% CI, 1.1-4.0), having intimate kissing partners (aRRR, 1.8; 95% CI, 1.1-2.9) and HIV (aRRR, 5.0; 95% CI, 1.1-24.4)., Conclusions: Meningococcal carriage among first-year university students increased after 2 months. Sociobehavioral risk factors were associated with increased carriage for all analyses. HIV was associated with carriage acquisition. Until vaccination programs become mandatory in South African universities, data suggest that students with HIV could benefit most from meningococcal vaccination., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes., Design: Prospective observational study., Setting: PICU and trauma unit at a tertiary-care university hospital in South Africa., Patients: Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017., Interventions: None., Measurements and Main Results: We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02)., Conclusions: Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes., Competing Interests: Dr. Morrow’s institution received funding from National Research Foundation, and she received funding from University of Cape Town and Imperial College Press (royalties). Dr. Argent received funding from N. Kelly Attorneys and from various conferences as an invited speaker. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes ( tet , erm , cat ) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.

Objectives: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions., Methods: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model., Results: We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage., Conclusions: The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Most pneumococci express a polysaccharide capsule, a key virulence factor and target for pneumococcal vaccines. However, pneumococci showing no serological evidence of capsule expression [nontypeable pneumococci (NTPn)] are more frequently isolated from carriage studies than in invasive disease. Limited data exist about the population structure of carriage NTPn from the African continent. We aimed to characterize carriage NTPn and compare them to previously described invasive NTPn. Carriage and invasive NTPn isolates were obtained from South African cross-sectional studies (2009 and 2012) and laboratory-based surveillance for invasive pneumococcal disease (2003-2013), respectively. Isolates were characterized by capsular locus sequence analysis, multilocus sequence typing, antimicrobial non-susceptibility patterns and phylogenetic analysis. NTPn represented 3.7 % (137/3721) of carriage isolates compared to 0.1 % (39/32 824) of invasive isolates ( P <0.001), and 24 % (33/137) of individuals were co-colonized with encapsulated pneumococci. Non-susceptibility to cotrimoxazole [84 % (112/133) vs 44 % (17/39)], penicillin [77 % (102/133) vs 36 % (14/39)], erythromycin [53 % (70/133) vs 31 % (12/39)] and clindamycin [36 % (48/133) vs 18 % (7/39)] was higher ( P =0.03) among carriage than invasive NTPn. Ninety-one per cent (124/137) of carriage NTPn had complete deletion of the capsular locus and 9 % (13/137) had capsule genes, compared to 44 % (17/39) and 56 % (22/39) of invasive NTPn, respectively. Carriage NTPn were slightly less diverse [Simpson's diversity index (D)=0.92] compared to invasive NTPn [D=0.97]. Sixty-seven per cent (92/137) of carriage NTPn belonged to a lineage exclusive to NTPn strains compared to 23 % (9/39) of invasive NTPn. We identified 293 and 275 genes that were significantly associated with carriage and invasive NTPn, respectively. NTPn isolates detected in carriage differed from those causing invasive disease, which may explain their success in colonisation or in causing invasive disease.

Background: Bacterial meningitis is a major cause of morbidity and mortality in sub-Saharan Africa. We analyzed data from the World Health Organization's (WHO) Invasive Bacterial Vaccine-preventable Diseases Surveillance Network (2011-2016) to describe the epidemiology of laboratory-confirmed Streptococcus pneumoniae (Spn), Neisseria meningitidis, and Haemophilus influenzae meningitis within the WHO African Region. We also evaluated declines in vaccine-type pneumococcal meningitis following pneumococcal conjugate vaccine (PCV) introduction., Methods: Reports of meningitis in children <5 years old from sentinel surveillance hospitals in 26 countries were classified as suspected, probable, or confirmed. Confirmed meningitis cases were analyzed by age group and subregion (South-East and West-Central). We described case fatality ratios (CFRs), pathogen distribution, and annual changes in serotype and serogroup, including changes in vaccine-type Spn meningitis following PCV introduction., Results: Among 49 844 reported meningitis cases, 1670 (3.3%) were laboratory-confirmed. Spn (1007/1670 [60.3%]) was the most commonly detected pathogen; vaccine-type Spn meningitis cases declined over time. CFR was the highest for Spn meningitis: 12.9% (46/357) in the South-East subregion and 30.9% (89/288) in the West-Central subregion. Meningitis caused by N. meningitidis was more common in West-Central than South-East Africa (321/954 [33.6%] vs 110/716 [15.4%]; P < .0001). Haemophilus influenzae (232/1670 [13.9%]) was the least prevalent organism., Conclusions: Spn was the most common cause of pediatric bacterial meningitis in the African region even after reported cases declined following PCV introduction. Sustaining robust surveillance is essential to monitor changes in pathogen distribution and to inform and guide vaccination policies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Invasive meningococcal disease (IMD) is endemic to South Africa, where vaccine use is negligible. We describe the epidemiology of IMD in South Africa., Methods: IMD cases were identified through a national, laboratory-based surveillance program, GERMS-SA, from 2003-2016. Clinical data on outcomes and human immunodeficiency virus (HIV) statuses were available from 26 sentinel hospital sites. We conducted space-time analyses to detect clusters of serogroup-specific IMD cases., Results: Over 14 years, 5249 IMD cases were identified. The incidence was 0.97 cases per 100 000 persons in 2003, peaked at 1.4 cases per 100 000 persons in 2006, and declined to 0.23 cases per 100 000 persons in 2016. Serogroups were confirmed in 3917 (75%) cases: serogroup A was present in 4.7% of cases, B in 23.3%, C in 9.4%; W in 49.5%; Y in 12.3%, X in 0.3%; Z in 0.1% and 0.4% of cases were non-groupable. We identified 8 serogroup-specific, geo-temporal clusters of disease. Isolate susceptibility was 100% to ceftriaxone, 95% to penicillin, and 99.9% to ciprofloxacin. The in-hospital case-fatality rate was 17% (247/1479). Of those tested, 36% (337/947) of IMD cases were HIV-coinfected. The IMD incidence in HIV-infected persons was higher for all age categories, with an age-adjusted relative risk ratio (aRRR) of 2.5 (95% confidence interval [CI] 2.2-2.8; P < .001) from 2012-2016. No patients reported previous meningococcal vaccine exposure. Patients with serogroup W were 3 times more likely to present with severe disease than those with serogroup B (aRRR 2.7, 95% CI 1.1-6.3); HIV coinfection was twice as common with W and Y diseases (aRRR W = 1.8, 95% CI 1.1-2.9; aRRR Y = 1.9, 95% CI 1.0-3.4)., Conclusions: In the absence of significant vaccine use, IMD in South Africa decreased by 76% from 2003-2016. HIV was associated with an increased risk of IMD, especially for serogroup W and Y diseases., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The association of rhinovirus (RV) detection to illness is poorly understood., Methods: We enrolled case patients hospitalized with severe respiratory illness (SRI) at 2 hospitals and outpatients with influenza-like illness (ILI) and asymptomatic individuals (controls) from 2 affiliated clinics during 2013-2015. We compared the RV prevalence among ILI and SRI cases to those of controls stratified by human immunodeficiency virus (HIV) serostatus using penalized logistic regression. The attributable fraction (AF) was calculated., Results: During 2013-2015, RV was detected in 17.4% (368/2120), 26.8% (979/3654), and 23.0% (1003/4360) of controls, ILI cases, and SRI cases, respectively. The RV AF (95% confidence interval) was statistically significant among children aged <5 years (ILI: 44.6% [30.7%-55.7%] and SRI: 50.3% [38.6%-59.9%]; P < .001) and individuals aged ≥5 years (ILI: 62.9% [54.4%-69.8%] and SRI: 51.3% [38.7%-61.3%]; P < .001) as well as among HIV-infected (ILI: 59.9% [45.8%-70.3%] and SRI: 39.8% [22.3%-53.3%]; P < .001) and HIV-uninfected (ILI: 53.6% [44.7%-61.1%] and SRI: 55.3% [45.6%-63.2%]; P < .001) individuals., Conclusions: Although RV detection was common among controls, it was also associated with a substantial proportion of clinical illness across age groups, irrespective of HIV status., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls., Methods: Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (C t ) value cut-offs, IS481 positive cases were classified as confirmed (C t  < 35) or possible (C t 35-39) pertussis disease., Results: Among 12,922 samples, 146 (1.1%) were IS481 positive of which 62% (90/146) were classified as confirmed. The attributable fraction (AF) was 92.2% (95% CI, 65.6 to 98.2%) and 90.5% (95% CI, 57.5 to 97.9%) amongst SRI and ILI PCR-confirmed pertussis cases, respectively. Amongst possible pertussis cases, AF was 36.9% (95% CI, - 142.3 to 83.6%) and 67.5% (95% CI, - 30.6 to 91.9%) in the SRI and ILI groups, respectively., Conclusion: All IS481 positive specimens could be considered as B. pertussis infection, and potentially pertussis disease with supportive clinical information.

Peritoneal dialysis and kidney transplantation remain the preferred choices for renal replacement therapy in young children. These options, however, are not always feasible, and hemodialysis (HD) is therefore an accepted alternative. In small children presenting with end-stage renal disease, HD presents several challenges and is often unavailable in lower- and middle-income countries. To assess these challenges and outcomes of maintenance HD in young children, we performed an audit of children below 20 kg with end-stage renal disease, receiving HD for ≥4 weeks, from 1 January 2008 to 31 July 2016 at the Red Cross War Memorial Children's Hospital. We identified 15 children weighing 6.8-18.5 kg (mean 12.9 kg ±3.5 SD) and aged 11.5-105 months (mean 52.2 months±4.2 SD) at HD initiation. Mean duration of HD was 11.8 months (range 1-61.5 months ± 16.9 SD). Seven children underwent successful transplantation, two patients died, and four currently still receive HD. Two patients, while on HD, relocated to other centers. An average of 2.6 (range 1-5) different vascular accesses was required per patient. Technical difficulties were the most common cause of central-line removal (81%), while catheter-associated bacteremia was 1.1/1000 catheter days. Frequent problems were intradialytic hypotension, growth stunting, and interdialytic hypertension. HD in lower- and middle-income countries is feasible in small children but presents with certain challenges. Advocacy with lobbying for funding and development of "child-friendly" dialysis equipment and specialized centers with highly skilled personnel are the cornerstones of successful pediatric HD programs in less-resourced centers., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

During 2012-2015, we tested respiratory specimens from patients with severe respiratory illness (SRI), patients with influenza-like illness (ILI), and controls in South Africa by real-time PCR for Mycoplasma pneumoniae, followed by culture and molecular characterization of positive samples. M. pneumoniae prevalence was 1.6% among SRI patients, 0.7% among ILI patients, and 0.2% among controls (p<0.001). Age <5 years (adjusted odd ratio 7.1; 95% CI 1.7-28.7) and HIV infection (adjusted odds ratio 23.8; 95% CI 4.1-138.2) among M. pneumonia-positive persons were associated with severe disease. The detection rate attributable to illness was 93.9% (95% CI 74.4%-98.5%) in SRI patients and 80.7% (95% CI 16.7%-95.6%) in ILI patients. The hospitalization rate was 28 cases/100,000 population. We observed the macrolide-susceptible M. pneumoniae genotype in all cases and found P1 types 1, 2, and a type 2 variant with multilocus variable number tandem repeat types 3/6/6/2, 3/5/6/2, and 4/5/7/2.

There are at least 98 known pneumococcal serotypes. Invasive pneumococcal disease (IPD) is usually caused by a single serotype, and dual-serotype IPD is rare. To assess factors associated with dual-serotype IPD, patient information obtained through laboratory-based surveillance for IPD from 2005 through 2014 in South Africa was reviewed. Genomes of isolate pairs from coinfected individuals were sequenced to determine their molecular characteristics. For 30 (91%) of 33 patients with dual serotypes, one or both isolates were a pneumococcal conjugate vaccine (PCV13) serotype. Dual-serotype IPD was associated with children <5 years of age (adjusted odds ratio [aOR], 4.7; 95% confidence interval [95% CI], 1.8 to 11.7), underlying illness (other than HIV) (aOR, 2.8; 95% CI, 1.1 to 6.6) and death (aOR, 2.5; 95% CI, 1.08 to 6.09). For each coinfecting pair, isolates were genotypically unrelated, and their genotypes were common among isolates of the same serotype in South Africa. Of 701 accessory genes identified among dual-serotype IPD isolates, four were common between isolate pairs. Coinfecting isolate pairs had different genotypic backgrounds. The association of dual serotypes with death warrants increased awareness of IPD coinfection caused by two or more serotypes., (Copyright © 2017 American Society for Microbiology.)

Background: The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear. We identified four invasive cnl meningococci through laboratory-based surveillance in South Africa from 2003 through 2013, which we aimed to characterize using whole genome data., Results: One isolate [NG: P1.7-2,30: F1-2: ST-53 (cc53)] contained cnl allele 12, and caused empyema in an adult male with bronchiectasis from tuberculosis, diabetes mellitus and a smoking history. Three isolates were NG: P1.18-11,42-2: FΔ: ST-192 (cc192) and contained cnl allele 2. One patient was an adolescent male with meningitis. The remaining two isolates were from recurrent disease episodes (8 months apart) in a male child with deficiency of the sixth complement component, and with the exception of two single nucleotide polymorphisms, contained identical core genomes. The ST-53 (cc53) isolate possessed alleles for NHBA peptide 191 and fHbp variant 2; whilst the ST-192 (cc192) isolates contained NHBA peptide 704 and fHbp variant 3. All four isolates lacked nadA. Comparison of the South African genomes to 61 additional cnl genomes on the PubMLST Neisseria database ( http://pubmlst.org/neisseria/ ), determined that most putative virulence genes could be found in both invasive and carriage phenotypes., Conclusions: Although rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.

Objectives: Neisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000-2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution., Methods: Representatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks., Results: MenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the 'Hajj outbreak' strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct., Conclusions: High resolution 'genomic' multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Objective: Fluid resuscitation is integral to resuscitation guidelines and critical care. However, fluid overload (FO) yields increased morbidity., Methods: Prospective observational study of Red Cross War Memorial Children's Hospital pediatric intensive care unit admissions (February to March 2013). FO % = (fluid in minus fluid out) [liters]/weight [kg] × 100%., Primary Outcomes: FO ≥ 10%, 28 day mortality., Results: Median [interquartile range (IQR)] age: 9.5 (2.0-39.0) months, median (IQR) admission weight: 7.9 (3.6-13.7) kg. Median (IQR) FO with admission weight: 3.5 (2.1-4.9)%; three patients had FO ≥ 10%. The 28 day mortality was 10% (n = 10). Patients who died had higher mean (IQR) FO using admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-4.8)%; p = 0.04]., Conclusions: Low FO ≥ 10% prevalence with 28 day mortality 10%. Higher FO% with admission weight associated with mortality (p = 0.04). We advocate further investigation of FO% as a simple bedside tool., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs)., Methods: In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae., Results: Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and ≥5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2)., Conclusions: Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Infections in broilers and broiler breeders by Enterococcus cecorum, causing clinical disease, have increasingly been described in various countries in the Northern Hemisphere over the past decade. This case report describes an outbreak of enterococcal-associated vertebral osteoarthritis (EVOA) in male broiler breeders in several flocks in South Africa. Male birds aged 4 and 9 weeks displayed the common presentation of lameness, paresis or complete paralysis. Autopsies of culled birds revealed masses on caudal thoracic vertebrae T5-T7, with vertebral osteomyelitis and spondylitis. Microbiological assays identified E. cecorum cultured from spondylitic lesions. Affected flocks were treated with amoxycillin at 25 mg/kg in the drinking water for 5 days, resulting in decreased numbers of lame birds and culls. The origin and pathogenesis of EVOA are poorly understood, which limits prevention to environmental factors that may inhibit systemic access by the enteric bacteria. Skeletal growth trends of male birds are thought to increase their susceptibility to bacterial colonisation at sites of skeletal strain, resulting in abscesses and lesions. Evidence points to the emergence of E. cecorum strains with increased pathogenicity; this highlights the need for greater understanding of the origins, treatment and prevention of EVOA to minimise its economic impact on poultry operations.

We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD) prior to routine use of pneumococcal conjugate vaccines (PCV) in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60%) from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ≥5 years) was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC) 217, 98% of all serotype 1] and 14 [CC230, 43%)]), some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]). In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively). Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12) and 64% (9/14) of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction.

Recent advances in the molecular identification and serotyping of Streptococcus pneumoniae are useful for culture-negative samples; however, there are limitations associated with these methods. We aimed to assess the value of molecular assays for invasive pneumococcal disease (IPD) surveillance in South Africa from 2010 through 2012. Nonviable isolates and culture-negative clinical specimens were tested for the lytA gene and, if positive, were serotyped, using real-time PCRs. Multinomial regression analysis was used to determine the maximum lytA cycle threshold (CT) value useful for predicting the ability to detect a serotype for the sample. The χ(2) test was used to compare the prevalence of serotypes between viable/nonviable isolates and culture-negative clinical specimens. Of 11,224 IPD cases reported, 1,091 (10%) were culture-negative samples and 981 (90%) of these were lytA positive. Samples with a lytA CT value of ≥35 were significantly less likely to be serotyped. A serotype/group was determined for 87% (737/844) of samples with a lytA CT value of <35, of which 60% (443/737) were identified as individual serotypes. The serotype prevalence did not differ significantly between isolates and culture-negative specimens. Although molecular serotyping added 7% (737/11,224) serotyping data, the inability to resolve 40% of samples to single serotypes remains a challenge for serotype-specific data analysis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Purpose: To determine the outcomes of sutured scleral fixation of posterior chamber intraocular lenses (PC IOLs) after trauma in an African population., Setting: State hospital and affiliated district hospital, Cape Town, South Africa., Design: Case series., Methods: A retrospective review was performed of the medical records of patients in whom a sutured PC IOL had been implanted for traumatic aphakia in the preceding 5 years., Results: Eighty-five percent of the 59 patients had a significant improvement in uncorrected distance visual acuity (UDVA) at the final visit. Two-thirds of patients achieved an UDVA of 6/18 or better. Those not improving had severe preexisting macular or corneal pathology. A significant number of patients (28%) with angle recession developed ocular hypertension during the postoperative period., Conclusion: After careful preoperative selection, sutured PC IOLs were effective in the visual rehabilitation of eyes with traumatic subluxated cataract in which the capsular bag could not be retained., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: Increased pneumococcal loads are associated with severe outcomes. We determined the prevalence of pneumococcal DNA in blood specimens from patients hospitalized with acute lower respiratory tract infection and identified factors associated with invasive pneumococcal pneumonia, bacterial loads, and death., Methods: A total of 8523 patients were enrolled as part of prospective hospital-based surveillance. Blood was collected for quantitative pneumococcal (lytA) detection, and nasopharyngeal specimens were collected for detection of influenza virus and other respiratory viruses by real-time polymerase chain reaction., Results: Of 6396 cases (75%) with lytA results, 422 (7%) were positive for pneumococcal DNA. The prevalences of human immunodeficiency virus (HIV) and influenza virus were 51% (2965/5855) and 8% (485/6358), respectively. On multivariable analysis, HIV infection (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.6-3.6), influenza virus coinfection (aOR, 1.4; 95% CI, 1.2-2.1), oxygen therapy during admission (aOR, 1.6; 95% CI, 1.1-2.3) and in-hospital death (aOR, 2.1; 95% CI, 1.1-4.0) were significantly associated with increased pneumococcal load. Among lytA-positive patients, after adjustment for length of hospitalization, duration of symptoms, and oxygen therapy during admission, pneumococcal loads ≥10,000 DNA copies/mL (aOR, 3.6; 95% CI, 1.8-7.2) were associated with increased risk of death., Conclusions: HIV and influenza virus infections were associated with elevated pneumococcal loads, which, in turn, were associated with increased risk of death.

From August 1999 through July 2002, hyperinvasive Neisseria meningitidis serogroup B (MenB) clonal complexes (CCs), namely, ST-32/ET-5 (CC32) and ST-41/44/lineage 3 (CC41/44), were predominant in the Western Cape Province of South Africa. This study analyzed MenB invasive isolates from a national laboratory-based surveillance system that were collected from January 2002 through December 2006. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) (n = 302), and multilocus sequence typing (MLST) and PorA and FetA typing were performed on randomly selected isolates (34/302, 11%). In total, 2,400 cases were reported, with the highest numbers from Gauteng Province (1,307/2,400, 54%) and Western Cape Province (393/2,400, 16%); 67% (1,617/2,400) had viable isolates and 19% (307/1,617) were identified as serogroup B. MenB incidence remained stable over time (P = 0.77) (average incidence, 0.13/100,000 population [range, 0.10 to 0.16/100,000 population]). PFGE (302/307, 98%) divided isolates (206/302, 68%) into 13 clusters and 96 outliers. The largest cluster, B1, accounted for 25% of isolates (76/302) over the study period; its prevalence decreased from 43% (20/47) in 2002 to 13% (8/62) in 2006 (P < 0.001), and it was common in the Western Cape (58/76, 76%). Clusters B2 and B3 accounted for 10% (31/302) and 6% (19/302), respectively, and showed no significant change over time and were predominant in Gauteng. Randomly selected isolates from clusters B1, B2, and B3 belonged to CC32, CC41/44, and the new CC4240/6688, respectively. Overall, 15 PorA and 12 FetA types were identified. MenB isolates were mostly diverse with no single dominant clone; however, CC32 and CC41/44 accounted for 35% and the new CC4240/6688 was the third most prevalent clone.

In South Africa, serogroup B meningococcal disease is sporadic. The aim of this study was to characterize serogroup B strains causing invasive meningococcal disease (IMD) in South Africa from 2005 to 2008. Isolates, collected through a national, laboratory-based surveillance program for IMD, were characterized by multilocus sequence typing (MLST). Two thousand two hundred thirty-four cases were reported, of which 1,447 had viable isolates. Intermediate resistance to penicillin was observed in 2.8% (41/1,447) of all strains. Serogroup B was the second most common serogroup (17%, 251/1,447) and increased from 14% (58/414) in 2005 to 25% (72/290) in 2008 (P < 0.001); however, incidence remained stable during the study period (average incidence, 0.13/100,000 population) (P = 0.54). Serogroup B was predominantly characterized by three clonal complexes, namely, ST-41/44/lineage 3, ST-32/ET-5, and the new complex ST-4240/6688, which accounted for 27% (65/242), 23% (55/242), and 16% (38/242) of isolates, respectively. ST-4240/6688 was more prevalent among young children (<5 years) than other clonal complexes (27/37 [73%] versus 108/196 [55%]; P = 0.04). In the most densely populated province of South Africa, Gauteng, the prevalence of ST-32/ET-5 increased from 8% (2/24) in 2005 to 38% (9/24) in 2008 (P = 0.04). Capsular switching was observed in 8/242 (3%) strains. The newly assigned clonal complex ST-4240/6688 was more common in young children.

Factor H binding protein (fHBP) is currently under investigation as a potential vaccine antigen for protection against meningococcal serogroup B (MenB) disease. This study describes the distribution of genotypes among all (n=58) MenB, and a total of 80 representative non-MenB (serogroups A, C, Y and W135) isolates causing invasive disease in South Africa in 2005 using fHBP sequence analysis, PorA, FetA and multilocus sequence typing. There was less fHBP diversity among non-MenB isolates compared to MenB isolates. fHBP subfamily variant A32 was the most common fHBP variant among MenB isolates and was represented by 17% (10/58) of the isolates, while fHBP variant B16 was the most prevalent variant among non-MenB strains and was represented by 40% (32/80) of isolates. Overall, subfamily B domain N6 (modular group I) was most prevalent (57%, 79/138). Twenty PorA and 16 FetA types were identified among MenB isolates whereas non-MenB serogroups were largely associated with specific serosubtypes. The most common MenB clonal complex (ST-41/44/lineage 3) was represented by 29% (17/58) of the MenB isolates, while each of the non-MenB serogroups had a major clone represented by at least 75% of the isolates within the serorogroup. Our data highlight that non-MenB meningococcal isolates also harbor fHBP., (Copyright © 2010 Elsevier Ltd. All rights reserved.)