Linda de Gouveia

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

Background: Mozambique introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 using a three-dose primary series with no booster dose (3p+0) and later switched to the PCV13 using a schedule of two primary doses with one booster (2p+1). We aimed to describe the burden and serotype distribution of pneumococcal meningitis in children under 5 years of age in Mozambique over an eleven-year period starting with the year of PCV10 introduction, and assess the impact of the PCV vaccine and schedule changes. Methods: We analysed meningitis surveillance data in Mozambique from March 2013 through to December 2023. Cerebrospinal fluid (CSF) samples were collected from eligible children in three referral hospitals (Maputo Central Hospital [south], Beira Central Hospital [central], and Nampula Central Hospital [north]). Culture and polymerase chain reaction assay (qPCR) were performed on each sample. S. pneumoniae-positive samples were subsequently serotyped using multiplex assay. We estimated annual incidence rates for pneumococcal meningitis in children under 5 years old following the PCVs’ introduction (2013–2023). The impact of the product switch and schedule change from PCV10/3p+0 to PCV13/2p+1 on the burden and serotype distribution of pneumococcal meningitis was assessed. Results: Of the 4075 CSF samples tested, 7.4% (301/4075) were positive for S. pneumoniae, 2.5% (103/4075) for H. influenzae, and 1.0% (42/4075) for N. meningitidis. Pneumococcal meningitis incidence in children under five reduced from 44.7 cases per 100,000 in 2013 to 4.6 cases per 100,000 in 2023, an 89.7% reduction. In the PCV13/2p+1 period (2020–2023), pneumococcal meningitis incidence was 51.2% lower than the PCV10/3p+0 period (2013–2017) (IRR 0.49, 95% CI 0.4–0.6; p < 0.001). PCV10-serotype pneumococcal meningitis incidence among children under five decreased by 65.6% in the PCV13/2p+1 period (IRR 0.34, 95% CI 0.2–0.6; p < 0.001). We detected zero cases of pneumococcal meningitis due to the PCV13-serotype in 2020–2023, whereas non-PCV10/13-serotypes increased by 76% (IRR 1.76, 95% CI 1.2–2.6; p = 0.004). The case–fatality proportion decreased by 71.9% (95% CI 62.9–84.8%) in the PCV13/2p+1 period. Conclusions: Since the introduction of PCVs in Mozambique, the burden of pneumococcal meningitis and deaths in children under 5 years of age has substantially decreased, as well as the prevalence of PCV13-serotypes. Higher valency PCVs are needed due to the increased prevalence of non-PCV10/13-serotypes. Funding: Gavi, The Vaccine Alliance, reference number: MOZ-HSS-2-INS; WHO Reference: 2014405143-0, creation DFC to support HIB & Surveillance System.

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

Background In Mozambique, the introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) using a two plus one schedule began in September 2019. However, the replacement of serotypes with non-PCV types remains a concern worldwide following widespread vaccination. We aim to describe the epidemiology of non-PCV13 types among children under 5 years of age with pneumococcal meningitis four years after PCV13 introduction in Mozambique. Methods Between January 2020 and December 2023, a total of 2,014 cerebrospinal fluid (CSF) samples were collected from eligible children as part of the meningitis surveillance system in Mozambique, 103 (5.1%) of which tested positive for S. pneumoniae after triplex qPCR. Among these, 86 (83.5%) samples met the quality criteria for serotyping and were subsequently analysed using sequential quadriplex qPCR. Results Among children under 2 years of age, 84.8% of the S. pneumoniae- positive samples belonged to non-PCV13 serotypes, with serotype 15B/C (31.0%) being the most prevalent, followed by 12F/12A/12B/44/46 (12.1%), 38B (10.6%), and 8 (7.6%). Serotypes 15B/C, 12F/12A/12B/44/46, 38, 8, and 1 were predominant in the northern region of the country (Nampula), whereas serotypes 15B/C and 12F/12A/12B/44/46 were most common in the central region (Sofala). The serotypes coverage of the PCV13, PCV15 and PCV20 vaccine formulations were 20.0%, 26.3% and 75.8%, respectively. Conclusion PCV13 vaccines save many lives in Mozambique. However, they do not seem to be adequate in addresing some of the highly prevailing non-PCV13 serotypes (15B/C and 12F/12A/12B/44/46). Therefore, we suggest that the country's National Immunization Technical Advisory Group (NITAG) review new data and advice on switching to extended valency vaccines such as PCV20.

(1) Background: Laboratories supporting the invasive bacteria preventable disease (IB-VPD) network are expected to demonstrate the capacity to identify the main etiological agents of pediatric bacterial meningitis (PBM) (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) on Gram stains and in phenotypic identification. Individual reports of sentinel site (SSL), national (NL) and regional reference (RRL) laboratories participating in the World Health Organization (WHO)-coordinated external quality assessment, distributed by the United Kingdom National External Quality Assessment (EQA) Services (UK NEQAS) for Microbiology between 2014 and 2019 were analyzed. (2) Methods: The panels consisted of (1) unstained bacterial smears for Gram staining, (2) viable isolates for identification and serotyping/serogrouping (ST/SG) and (3) simulated cerebral spinal fluid (CSF) samples for species detection and ST/SG using polymerase chain reaction (PCR). SSLs and NLs tested for Gram staining and species identification (partial panel). RRLs, plus any SSLs and NLs (optionally) also analyzed the simulated CSF samples (full panel). The passing score was ≥75% for NLs and SSLs, and ≥90% for RRLs and NLs/SSLs testing the full panel. (3) Results: Overall, 63% (5/8) of the SSLs and NLs were able to correctly identify the targeted pathogens, in 2019; but there were challenges to identify Haemophilus influenzae either on Gram stains (35% of the labs failed 2014), or in culture. Individual performance showed inconsistent capacity, with only 39% (13/33) of the SSLs/NLs passing the EQA exercise throughout all surveys in which they participated. RRLs performed well over the study period, but one of the two failed to reach the minimal passing score in 2016 and 2018; while the SSLs/NLs that optionally tested the full panel scored between 75% and 90% (intermediate pass category). (4) Conclusions: We identified a need for implementing a robust quality management system for timely identification of the gaps and then implementing corrective and preventive actions, in addition to continuous refresher training in the SSLs and NLs supporting the IB-VPD surveillance in the World Health Organization, Regional Office for Africa (WHO AFRO).

Background In South Africa 19% of the adult population aged 15-49 years are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available. Methods We performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR), duration of SARS-CoV-2 positivity (at cycle threshold valueResults We recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [50/83] in cases LWH vs 58% [173/293] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and ≥60 years: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts’ age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to 35 years were more likely to transmit, and individuals aged 13-34 to acquire SARS-CoV-2 in the household. Health services must maintain HIV testing with initiation of antiretroviral therapy for those HIV-infected. Summary In this case-ascertained, prospective household transmission study, household cumulative infection risk was 59% from symptomatic SARS-CoV-2 index cases, not differing based on index HIV status. Index cases living with HIV were positive for SARS-CoV-2 for longer at higher viral loads.

Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction. During the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W. There was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy.

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.