Risk Factors for Severe COVID-19 Among Children and Adolescents Enrolled in Acute Respiratory Infection Sentinel Surveillance in South Africa, 2020-2022.

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.

Genomic characterization of Bordetella pertussis in South Africa, 2015-2019.

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 ptxP3-ptxA1-ptxB2-prn2-fimH2 (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.

International Pediatric COVID-19 Severity Over the Course of the Pandemic.

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Bronchiolitis versus bronchopneumonia: navigating antibiotic use within the LRTI spectrum.

Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.

Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020-2022.

BACKGROUND: South Africa experienced four waves of SARS-CoV-2 infection, dominated by Wuhan-Hu, Beta, Delta, and Omicron (BA.1/BA.2). We describe the trends in SARS-CoV-2 testing, cases, admissions, and deaths among children and adolescents in South Africa over successive waves. METHODS: We analyzed national SARS-CoV-2 testing, case, and admissions data from March 2020 to February 2022 and estimated cumulative rates by age group for each endpoint. The severity in the third versus the fourth wave was assessed using multivariable logistic regression. RESULTS: Individuals ≤18 years comprised 35% (21,008,060/60,142,978) of the population but only 12% (424,394/3,593,644) of cases and 6% (26,176/451,753) of admissions. Among individuals ≤18 years, infants had the highest admission (505/100,000) rates. Testing, case, and admission rates generally increased successively in the second (Beta) and third (Delta) waves among all age groups. In the fourth (Omicron BA.1/BA.2) wave, the case rate dropped among individuals ≥1 year but increased among those <1 year. Weekly admission rates for children <1 year (169/100,000) exceeded rates in adults (124/100,000) in the fourth wave. The odds of severe COVID-19 in all admitted cases were lower in the fourth wave versus the third wave in each age group, but they were twice as high in admitted cases with at least one comorbidity than those without. CONCLUSIONS: The admission rate for children <5 years was higher in the fourth wave than in previous waves, but the overall outcomes were less severe. However, children with at least one comorbidity had increased odds of severe disease, warranting consideration of prioritizing this group for vaccination.

Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020-March 2022: Data From Sentinel Surveillance.

Background: Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization and mortality in high human immunodeficiency virus (HIV) prevalence settings are limited. Methods: Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalization and mortality. Results: From April 2020 through March 2022, severe acute respiratory syndrome coronavirus 2 was detected in 24.0% (660 of 2746) of outpatient and 32.5% (2282 of 7025) of inpatient cases. Factors associated with COVID-19-associated hospitalization included the following: older age (25-44 [adjusted odds ratio {aOR}= 1.8, 95% confidence interval (CI) = 1.1-2.9], 45-64 [aOR = 6.8, 95% CI = 4.2-11.0] and ≥65 years [aOR = 26.6, 95% CI = 14.4-49.1] vs 15-24 years); black race (aOR, 3.3; 95% CI, 2.2-5.0); obesity (aOR, 2.3; 95% CI, 1.4-3.9); asthma (aOR, 3.5; 95% CI, 1.4-8.9); diabetes mellitus (aOR, 5.3; 95% CI, 3.1-9.3); HIV with CD4 ≥200/mm3 (aOR, 1.5; 95% CI, 1.1-2.2) and CD4 <200/mm3 (aOR, 10.5; 95% CI, 5.1-21.6) or tuberculosis (aOR, 12.8; 95% CI, 2.8-58.5). Infection with Beta (aOR, 0.5; 95% CI, .3-.7) vs Delta variant and being fully vaccinated (aOR, 0.1; 95% CI, .1-.3) were less associated with COVID-19 hospitalization. In-hospital mortality was increased in older age (45-64 years [aOR, 2.2; 95% CI, 1.6-3.2] and ≥65 years [aOR, 4.0; 95% CI, 2.8-5.8] vs 25-44 years) and male sex (aOR, 1.3; 95% CI, 1.0-1.6) and was lower in Omicron-infected (aOR, 0.3; 95% CI, .2-.6) vs Delta-infected individuals. Conclusions: Active syndromic surveillance encompassing clinical, laboratory, and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly people with tuberculosis or people with HIV, especially severely immunosuppressed, should be prioritized for vaccination.

Effectiveness of Influenza Vaccination of Pregnant Women for Prevention of Maternal and Early Infant Influenza-Associated Hospitalizations in South Africa: A Prospective Test-Negative Study.

Background: Influenza vaccination during pregnancy reduces influenza-associated illness in the women and their infants, but effectiveness estimates against influenza-associated hospitalization are limited and lacking from settings with high human immunodeficiency virus (HIV) infection prevalence. We assessed the effect of maternal vaccination in HIV-uninfected women and women with HIV in preventing influenza-associated hospitalizations in infants and the women. Methods: During 2015-2018, influenza vaccination campaigns targeting pregnant women were augmented at selected antenatal clinics; these were coupled with prospective hospital-based surveillance for acute respiratory or febrile illness in infants aged <6 months and cardiorespiratory illness among pregnant or postpartum women. Vaccine effectiveness (VE) was assessed using a test-negative case-control study. Results: Overall, 71 influenza-positive and 371 influenza-negative infants were included in the analysis; mothers of 26.8% of influenza-positive infants were vaccinated during pregnancy compared with 35.6% of influenza-negative infants, corresponding to an adjusted VE (aVE) of 29.0% (95% confidence interval [CI], -33.6% to 62.3%). When limited to vaccine-matched strains, aVE was 65.2% (95% CI, 11.7%-86.3%). For maternal hospitalizations, 56 influenza-positive and 345 influenza-negative women were included in the analysis, with 28.6% of influenza-positive women being vaccinated compared with 38.3% of influenza-negatives, for an aVE of 46.9% (95% CI, -2.8% to 72.5%). Analysis restricted to HIV-uninfected women resulted in 82.8% (95% CI, 40.7%-95.0%) aVE. No significant aVE (-32.5% [95% CI, -208.7% to 43.1%]) was detected among women with HIV. Conclusions: Influenza vaccination during pregnancy prevented influenza-associated hospitalizations among young infants when infected with vaccine strains and among HIV-uninfected women.

Impact of the COVID-19 pandemic on TB services at ART programmes in low- and middle-income countries: a multi-cohort survey.

INTRODUCTION: COVID-19 stretched healthcare systems to their limits, particularly in settings with a pre-existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID-19 on TB services at antiretroviral therapy (ART) clinics in low- and middle-income countries. METHODS: We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia-Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site-level data using standardized questionnaires. RESULTS: Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia-Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia-Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow-up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia-Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (-8%) but not in the Asia-Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage. CONCLUSIONS: The COVID-19 pandemic led to staff shortages, reduced access to TB care and delays in follow-up visits for people with TB across IeDEA sites in Africa and the Asia-Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts.

Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020.

OBJECTIVES: Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to "defeating meningitis by 2030". METHODS: From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed. RESULTS: Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae, and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae, and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility. CONCLUSION: BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk.

Integrating services for HIV and multidrug-resistant tuberculosis: A global cross-sectional survey among ART clinics in low- and middle-income countries.

Tuberculosis (TB) is the leading cause of death among PLHIV and multidrug-resistant-TB (MDR-TB) is associated with high mortality. We examined the management for adult PLHIV coinfected with MDR-TB at ART clinics in lower income countries. Between 2019 and 2020, we conducted a cross-sectional survey at 29 ART clinics in high TB burden countries within the global IeDEA network. We used structured questionnaires to collect clinic-level data on the TB and HIV services and the availability of diagnostic tools and treatment for MDR-TB. Of 29 ART clinics, 25 (86%) were in urban areas and 19 (66%) were tertiary care clinics. Integrated HIV-TB services were reported at 25 (86%) ART clinics for pan-susceptible TB, and 14 (48%) clinics reported full MDR-TB services on-site, i.e. drug susceptibility testing [DST] and MDR-TB treatment. Some form of DST was available on-site at 22 (76%) clinics, while the remainder referred testing off-site. On-site DST for second-line drugs was available at 9 (31%) clinics. MDR-TB treatment was delivered on-site at 15 (52%) clinics, with 10 individualizing treatment based on DST results and five using standardized regimens alone. Bedaquiline was routinely available at 5 (17%) clinics and delamanid at 3 (10%) clinics. Although most ART clinics reported having integrated HIV and TB services, few had fully integrated MDR-TB services. There is a continued need for increased access to diagnostic and treatment options for MDR-TB patients and better integration of MDR-TB services into the HIV care continuum.

Detection of Victoria lineage influenza B viruses with K162 and N163 deletions in the hemagglutinin gene, South Africa, 2018.

BACKGROUND: A group of Victoria lineage influenza B viruses with a two amino acid deletion in the hemagglutinin (HA) at residues K162 and N163, was detected during the 2016 to 2017 Northern Hemisphere influenza season and continues to spread geographically. We describe the first identification of viruses with these deletions from South Africa in 2018. METHODS: Nasopharyngeal samples were obtained from the syndromic surveillance programs. Real-time reverse transcription-polymerase chain reaction was used for virus detection and lineage determination. Influenza genetic characterization was done using next-generation sequencing on the MiSeq platform. The duration of virus circulation was determined using thresholds calculated using the Moving Epidemic Method; duration was used as an indicator of disease transmissibility and impact. RESULTS: In 2018, 42% (426/1015) of influenza-positive specimens were influenza B viruses. Of 426 influenza B-positive samples, 376 (88%) had the lineage determined of which 75% (283/376) were Victoria lineage. The transmissibility of the 2018 South African influenza season was high for a few weeks, although the severity remained moderate through most of the season. The sequenced 2018 South African Victoria lineage influenza B viruses clustered in sub-clade V1A.1 with the 162-163 deletions. CONCLUSIONS: We report the first detection of the 162-163 deletion variant of influenza B/Victoria viruses from South Africa in 2018, and suggest that this deletion variant replaced the previous circulating influenza B/Victoria viruses. These deletions putatively affect the antigenic properties of the viruses because they border an immune-dominant region at the tip of the HA. Therefore, close monitoring of these newly emerging viruses is essential.

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

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

Trends in RPR Seropositivity among Children Younger than 2 Years in South Africa, 2010-2019.

A positive rapid plasma reagin (RPR) result in children under the age of 2 years indicates either passive transplacental transfer of maternal antibodies or active infection with syphilis (possible congenital syphilis). We describe trends in RPR seropositivity in this population using centralized laboratory data. A secondary analysis of laboratory data collected through the National Health Laboratory Service, Corporate Data Warehouse from 2010 to 2019 was conducted. Of the 127 150 children <2 years included in the analysis, 10 969 [8.6%; 95% confidence interval (95% CI) 85-88]) were RPR seropositive. RPR seropositivity increased from 6.5% to 13.0% between 2010 and 2019. Overall, the annual rate of RPR seropositivity was relatively stable between 2010 and 2018 with a range of 89-127/100 000 live births, increasing sharply to 165/100 000 livebirths in 2019. KwaZulu-Natal and North West provinces recorded the largest increases in annual seropositivity rate, while Eastern Cape and Western Cape had the most significant declines. Although this analysis is limited to laboratory results, in the absence of major changes in testing practices, there may be a rise in the burden of antenatal syphilis exposure in utero indicating an increase in maternal syphilis and syphilis transmission in the general population. South Africa needs to intensify Mother-to-Child Transmission of syphilis elimination efforts to reach the WHO target of ≤50 cases per 100 live births by 2030.

South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline.

Clostridioides difficile infection (CDI) is a problem in both developed and developing countries and is a common hospital-acquired infection. This guideline provides evidence-based practical recommendations for South Africa and other developing countries. The scope of the guideline includes CDI diagnostic approaches; adult, paediatric and special populations treatment options; and surveillance and infection prevention and control recommendations.

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa: 2003-2008.

BACKGROUND: Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009. METHODS: Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database. Clinical and laboratory characteristics of IPD among neonates (0-27 days old) was compared with IPD among young children (≥ 28 days ≤ 2 years). Early-onset IPD (0-6 days old) was compared with late-onset IPD (≥ 7-27 days old). Isolates were serotyped using the Quellung reaction. RESULTS: Overall 27,630 IPD cases were reported. Of the 26,277 (95%) with known ages, 6583 (25%) were ≤ 2 years of age, of which 4.5% (294/6583) were neonates. The estimated annual incidence of neonatal IPD in 2008 was 5 per 100,000 live births. Fifty-one percent of neonates with IPD presented with early-onset IPD. Case fatality ratios (CFRs) were high in both groups, 31% (28/89) in neonatal IPD versus 26% (614/2383) in non-neonatal IPD (P = 0.18). Among neonates, the meningitis cases (15/37, 41%) were associated with the highest CFR. The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes accounted for 69% (134/194) of neonatal IPD isolates. CONCLUSIONS: Pneumococcal neonatal disease in South Africa was not uncommon before PCV introduction and is associated with a high CFR. The indirect effect on neonatal IPD of PCV rollout requires further evaluation.

Declining Incidence of Invasive Meningococcal Disease in South Africa: 2003-2016.

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.

Congenital Rubella Syndrome Surveillance in South Africa Using a Sentinel Site Approach: A Cross-sectional Study.

BACKGROUND: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. METHODS: This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. RESULTS: There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). CONCLUSION: Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14-30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.

Molecular Detection of Mycobacterium tuberculosis from Stools in Young Children by Use of a Novel Centrifugation-Free Processing Method.

The microbiological diagnosis of tuberculosis (TB) in children is challenging, as it relies on the collection of relatively invasive specimens by trained health care workers, which is not feasible in many settings. Mycobacterium tuberculosis is detectable from the stools of children using molecular methods, but processing stool specimens is resource intensive. We evaluated a novel, simple, centrifugation-free processing method for stool specimens for use on the Xpert MTB/RIF assay (Xpert), using two different stool masses: 0.6 g and a swab sample. Two hundred eighty children (median age, 15.5 months; 35 [12.5%] HIV infected) with suspected intrathoracic TB were enrolled from two sites in South Africa. Compared to a single Xpert test on respiratory specimens, the sensitivity of Xpert on stools using the 0.6-g and swab samples was 44.4% (95% confidence interval [CI], 13.7 to 78.8%) for both methods, with a specificity of >99%. The combined sensitivities of two stool tests versus the first respiratory Xpert were 70.0% (95% CI, 34.8 to 93.3) and 50.0% (95% CI, 18.7 to 81.3) for the 0.6-g and swab sample, respectively. Retesting stool specimens with nondeterminate Xpert results improved nondeterminate rates from 9.3% to 3.9% and from 8.6% to 4.3% for 0.6-g and swab samples, respectively. Overall, stool Xpert detected 14/94 (14.9%) children who initiated antituberculosis treatment, while respiratory specimens detected 23/94 (24.5%). This stool processing method is well suited for settings with low capacity for respiratory specimen collection. However, the overall sensitivity to detect confirmed and clinical TB was lower than that of respiratory specimens. More sensitive rapid molecular assays are needed to improve the utility of stools for the diagnosis of intrathoracic TB in children from resource-limited settings.