Maternal colonization with Streptococcus agalactiae and associated stillbirth and neonatal disease in coastal Kenya

Abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) causes neonatal disease and stillbirth, but its burden in sub-Saharan Africa is uncertain. We assessed maternal recto-vaginal GBS colonisation (7967 women), stillbirth and neonatal disease. Whole genome sequencing was used to determine serotypes, sequence types (ST), and phylogeny. We found low maternal GBS colonisation prevalence (934/7967, 12%), but comparatively high incidence of GBS-associated stillbirth and early onset neonatal disease (EOD) in hospital (0.91(0.25-2.3)/1000 births; 0.76(0.25-1.77)/1000 live-births respectively). However, using a population denominator, EOD incidence was considerably reduced (0.13(0.07-0.21)/1000 live-births). Treated cases of EOD had very high case fatality (17/36, 47%), especially within 24 hours of birth, making under-ascertainment of community-born cases highly likely, both here and in similar facility-based studies. Maternal GBS colonisation was less common in women with low socio-economic status, HIV infection and undernutrition, but when GBS-colonised, they were more likely colonised by the most virulent clone, CC17. CC17 accounted for 267/915(29%) of maternal colonising (265/267(99%) serotype III, 2/267(0.7%) serotype IV), and 51/73(70%) of neonatal disease cases (all serotype III). Trivalent (Ia/II/III) and pentavalent (Ia/Ib/II/III/V) vaccines would cover 71/73(97%) and 72/73(99%) of disease-causing serotypes respectively. Serotype IV should be considered for inclusion, with evidence of capsular switching in CC17 strains.

Increased Risk of Group B Streptococcus Invasive Infection in HIV-Exposed but Uninfected Infants: A Review of the Evidence and Possible Mechanisms

“…Correlates of protection remain to be established to further validate the impact of this vaccine in the protection of HEU infants against GBS diseases. However, more studies are needed to assess whether or not HIV-infected pregnant women are colonized by specific strains (29, 32), which would impact vaccine policy. Evidence suggests that HEU infants are more likely to suffer from LOD (4, 13, 14); therefore, IAP that results in significant reductions in EOD will not contribute to a substantial decrease of GBS burden in this population (9).…”

“…The increased colonization rate in HIV-infected women with high CD4 cell count might be biased by the presence of other risk factors for GBS colonization like diabetes or obesity (23), which are expected to be found more often in women with higher CD4 cell counts (26) and were not taken into account. On the other hand, HIV-infected women with low CD4 cell count are known to have increased prevalence of bacterial vaginosis that could compete with GBS and are more likely to take cotrimoxazole prophylaxis resulting in lower GBS carriage rates (27–29). In the Cutland et al’s study, CD4 cell count was only available in a limited proportion of HIV-infected women but the majority had a CD4 count >350/mm 3 (24).…”

“…In a recently published study performed in Kenya, while HIV infection was associated with lower risk of GBS colonization rate, HIV-infected women had higher risk of being colonized with the hypervirulent clone CC17. This risk was even higher for those taking co-trimoxazole prophylaxis (29). This predominance of serotype III in HIV-infected women could explain the higher incidence of GBS LOD in HIV-exposed infants (4, 13, 14) but needs confirmation in larger cohorts.…”

An empirical Bayes method for serotype case-carrier ratios, with an application to Group B streptococcus

“…The rare occurrence of certain GBS serotypes in maternal carriage and neonatal disease, however, makes it difficult to estimate these quantities with certainty, even in large samples. 20,21 While randomeffects meta-analysis of data from multiple epidemiologic studies may thus present an attractive analysis strategy, 22 investigators remain likely to encounter challenges when generating pooled risk ratios or odds ratios in the presence of zero-valued counts within studies. Common ad-hoc workarounds, such as "continuity corrections" adding a fixed value to cells [23][24][25] and simple summing or averaging of values across studies, 13 risk introducing bias in both point estimates and measures of uncertainty.…”

Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation

“…and Kenya,Seale et al, 2016), Canadian, American[Flores et al, 2015], Dutch and animal-derived strains using Roary, (ver. 3.8.0;Page et al, 2015).…”