A double-blind randomized trial in South Africa documented poor efficacy of two doses of the ChAdOx1 nCoV-19 vaccine against the B.1.351 variant of SARS-CoV-2 that emerged in South Africa. Infections ...occurred in 3.2% of placebo recipients and in 2.5% of vaccine recipients. Thirty-nine of the 42 virus isolates were the B.1.351 variant. None of the cases led to hospitalization or death.
Summary Background The most important risk factor for early-onset (babies younger than 7 days) invasive group B streptococcal disease is rectovaginal colonisation of the mother at delivery. We aimed ...to assess whether differences in colonisation drive regional differences in the incidence of early-onset invasive disease. Methods We did a systematic review of maternal group B streptococcus colonisation studies by searching MEDLINE, Embase, Pascal Biomed, WHOLIS, and African Index Medicus databases for studies published between January, 1997, and March 31, 2015, that reported the prevalence of group B streptococcus colonisation in pregnant women. We also reviewed reference lists of selected studies and contacted experts to identify additional studies. Prospective studies in which swabs were collected from pregnant women according to US Centers for Disease Control and Prevention guidelines that used selective culture methods were included in the analyses. We calculated mean prevalence estimates (with 95% CIs) of maternal colonisation across studies, by WHO region. We assessed heterogeneity using the I2 statistic and the Cochran Q test. Findings 221 full-text articles were assessed, of which 78 studies that included 73 791 pregnant women across 37 countries met prespecified inclusion criteria. The estimated mean prevalence of rectovaginal group B streptococcus colonisation was 17·9% (95% CI 16·2–19·7) overall and was highest in Africa (22·4, 18·1–26·7) followed by the Americas (19·7, 16·7–22·7) and Europe (19·0, 16·1–22·0). Studies from southeast Asia had the lowest estimated mean prevalence (11·1%, 95% CI 6·8–15·3). Significant heterogeneity was noted across and within regions (all p≤0·005). Differences in the timing of specimen collection in pregnancy, selective culture methods, and study sample size did not explain the heterogeneity. Interpretation The country and regional heterogeneity in maternal group B streptococcus colonisation is unlikely to completely explain geographical variation in early-onset invasive disease incidence. The contribution of sociodemographic, clinical risk factor, and population differences in natural immunity need further investigation to understand these regional differences in group B streptococcus maternal colonisation and early-onset disease. Funding None.
Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to ...intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable use of efficient clinical trial designs for vaccine development and licensure, without needing to undertake efficacy trials in prohibitively large number of mother-infant dyads. The association of maternal naturally acquired serotype-specific anti-capsular antibodies (IgG) against serotype-specific IGbsD in their infants has been studied in case-control studies. The statistical models used so far to estimate IGbsD risk from these case-control studies assumed that the antibody concentrations measured sharing the same disease status are sampled from the same population, not allowing for differences between mothers colonised by GBS and mothers also potentially infected (e.g urinary tract infection or chorioamnionitis) by GBS during pregnancy. This distinction is relevant as infants born from infected mothers with occult medical illness may be exposed to GBS prior to the mother developing antibodies measured in maternal or infant sera.
Unsupervised mixture model averaging (MMA) is proposed and applied here to accurately estimate infant IGbsD risk from case-control study data in presence or absence of antibody concentration subgroups potentially associated to maternal GBS carriage or infection. MMA estimators are compared to non-parametric disease risk estimators in simulation studies and by analysis of two published GBS case-control studies.
MMA provides more accurate relative risk estimates under a broad range of data simulation scenarios and more accurate absolute disease risk estimates when the proportion of IGbsD cases with high antibody levels is not ignorable. MMA estimates of the relative and absolute disease risk curves are more amenable to clinical interpretation compared to non-parametric estimates with no detectable overfitting of the data. Antibody concentration thresholds predictive of protection from infant IGbsD estimated by MMA from maternal and infant sera are consistent with non-parametric estimates.
MMA is a flexible and robust method for design, accurate analysis and clinical interpretation of case-control studies estimating relative and absolute IGbsD risk from antibody concentrations measured at or after birth.
By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the ...dynamics of SARS-CoV-2 exposure in Malawi.
We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant.
A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20-49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% 7/9) than the beta variant (22% 2/9), while more second wave sera showed neutralisation activity against the beta variant (75% 12/16) than the original variant (63% 10/16).
The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.
Maternal recto-vaginal colonization with Group B Streptococcus (GBS) and consequent vertical transmission to the newborn predisposes neonates to early-onset invasive GBS disease. This study aimed to ...determine the acquisition and loss of serotype-specific recto-vaginal GBS colonization from 20-37+ weeks of gestational age.
Vaginal and rectal swabs were collected from HIV-uninfected women at 20-25 weeks of gestation age and at 5-6 weekly intervals thereafter. Swabs were cultured for GBS and isolates were serotyped by latex agglutination. Serologically non-typable isolates and pilus islands were characterized by PCR.
The prevalence of recto-vaginal GBS colonization was 33.0%, 32.7%, 28.7% and 28.4% at 20-25 weeks, 26-30 weeks, 31-35 weeks and 37+ weeks of gestational age, respectively. The most common identified serotypes were Ia (39.2%), III (32.8%) and V (12.4%). Of 507 participants who completed all four study visits, the cumulative overall recto-vaginal acquisition rate of new serotypes during the study was 27.9%, including 11.2%, 8.2% and 4.3% for serotypes Ia, III and V, respectively. Comparing the common colonizing serotypes, serotype III was more likely to be associated with persistent colonization throughout the study (29%) than Ia (18%; p = 0.045) or V (6%; p = 0.002). The median duration of recto-vaginal GBS colonization for serotype III was 6.35 weeks, which was longer than other serotypes. Pilus island proteins were detected in all GBS isolates and their subtype distribution was associated with specific serotypes.
South African pregnant women have a high prevalence of GBS recto-vaginal colonization from 20 weeks of gestational age onwards, including high GBS acquisition rates in the last pregnancy-trimesters. There are differences in specific-serotype colonization patterns during pregnancy.
Abstract SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated ...SARS-CoV-2-specific T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4 + and CD8 + T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV-2-specific T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4 + and CD8 + T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity.
Streptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human ...hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon colonizing the reproductive tract, the bacterial cell is presented with numerous nutritional challenges imposed by the host. One strategy employed by the host innate immune system is intoxication of bacterial invaders with certain transition metals such as zinc.
Previous work has demonstrated that GBS must employ elegant strategies to circumnavigate zinc stress in order to survive in the vertebrate host. We assessed 30 strains of GBS from diverse isolation sources, capsular serotypes, and sequence types for susceptibility or resistance to zinc intoxication.
Invasive strains, such as those isolated from early onset disease manifestations of GBS infection were significantly less susceptible to zinc toxicity than colonizing strains isolated from rectovaginal swabs of pregnant patients. Additionally, capsular type III (cpsIII) strains and the ST-17 and ST-19 strains exhibited the greatest resilience to zinc stress, whereas ST-1 and ST-12 strains as well as those possessing capsular type Ib (cpsIb) were more sensitive to zinc intoxication. Thus, this study demonstrates that the transition metal zinc possesses antimicrobial properties against a wide range of GBS strains, with isolation source, capsular serotype, and sequence type contributing to susceptibility or resistance to zinc stress.
Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are ...emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination.
Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Šídák's or Holm-Šídák's test.
We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30-60 days vs. 210-270 days; Log ID
6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants.
These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.
There is a paucity of longitudinal data on the serotype-specific burden of invasive group B Streptococcus (GBS) disease from low-middle income countries, which could inform selection of vaccine ...epitopes.
From 2005 to 2014, infants less than 90 days of age with invasive GBS disease were identified through sentinel laboratory and hospital admission surveillance at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa.
We identified 820 cases of invasive GBS disease, including 55% among newborns <7 days age (i.e. early-onset disease; EOD). The overall incidence (per 1,000 live births) of invasive GBS disease was 2.59 (95% CI: 2.42-2.77), including 1.41 (95% CI: 1.28-1.55) for EOD and 1.18 (95% CI: 1.06-1.30) in infants 7-89 days age (late-onset disease). Year-on-year, from 2005 to 2014, we observed a 9.4% increase in incidence of serotype Ia invasive disease (RR: 1.09; 95% CI: 1.04-1.15; p<0.001), and a 7.4% decline in serotype III invasive disease (RR: 0.93; 95% CI: 0.90-0.96; p<0.001). Overall, serotypes Ia (28.2%), III (55.4%) and V (7.9%) were the commonest disease causing serotypes.
The incidence of invasive GBS disease has remained persistently high in our setting, with some changes in serotype distribution, albeit mainly involving the same group of dominant serotypes.
Invasive group B streptococcal (GBS) disease is the commonest perinatally-acquired bacterial infection in newborns; the burden is higher in African countries where intrapartum antibiotic prophylaxis ...strategies are not feasible. In sub-Saharan Africa, almost one in four newborns with GBS early-onset disease will demise, and one in ten survivors have moderate or severe neurodevelopmental impairment. A maternal GBS vaccine to prevent invasive GBS disease in infancy is a pragmatic and cost-effective preventative strategy for Africa. Hexavalent polysaccharide protein conjugate and Alpha family surface protein vaccines are undergoing phase II clinical trials. Vaccine licensure may be facilitated by demonstrating safety and immunological correlates/thresholds suggestive of protection against invasive GBS disease. This will then be followed by phase IV effectiveness studies to assess the burden of GBS vaccine preventable disease, including the effect on all-cause neonatal infections, neonatal deaths and stillbirths.
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