Detection of pathogens associated with early-onset neonatal sepsis in cord blood at birth using quantitative PCR

Background: Early onset neonatal sepsis (EONS) typically begins prior to, during or soon after birth and may be rapidly fatal. There is paucity of data on the aetiology of EONS in sub-Saharan Africa due to limited diagnostic capacity in this region, despite the associated significant mortality and long-term neurological impairment. Methods: We compared pathogens detected in cord blood samples between neonates admitted to hospital with possible serious bacterial infection (pSBI) in the first 48 hours of life (cases) and neonates remaining well (controls). Cord blood was systematically collected at Kilifi County Hospital (KCH) from 2011-2016, and later tested for 21 bacterial, viral and protozoal targets using multiplex PCR via TaqMan Array Cards (TAC). Results: Among 603 cases (101 [17%] of whom died), 179 (30%) tested positive for ≥1 target and 37 (6.1%) tested positive for multiple targets. Klebsiella oxytoca, Escherichia coli/Shigella spp., Pseudomonas aeruginosa, and Streptococcus pyogenes were commonest. Among 300 controls, 79 (26%) tested positive for ≥1 target, 11 (3.7%) were positive for multiple targets, and K. oxytoca and P. aeruginosa were most common. Cumulative odds ratios across controls: cases (survived): cases (died) were E. coli/Shigella spp. 2.6 (95%CI 1.6-4.4); E. faecalis 4.0 (95%CI 1.1-15); S. agalactiae 4.5 (95%CI 1.6-13); Ureaplasma spp. 2.9 (95%CI 1.3-6.4); Enterovirus 9.1 (95%CI 2.3-37); and Plasmodium spp. 2.9 (95%CI 1.4-6.2). Excluding K. oxytoca and P. aeruginosa as likely contaminants, aetiology was attributed in 9.4% (95%CI 5.1-13) cases using TAC. Leading pathogen attributions by TAC were E. coli/Shigella spp. (3.5% (95%CI 1.7-5.3)) and Ureaplasma spp. (1.7% (95%CI 0.5-3.0)). Conclusions: Cord blood sample may be useful in describing EONS pathogens at birth, but more specific tests are needed for individual diagnosis. Careful sampling of cord blood using aseptic techniques is crucial to minimize contamination. In addition to culturable bacteria, Ureaplasma and Enterovirus were causes of EONS.</p

Congenital microcephaly unrelated to flavivirus exposure in coastal Kenya

Background: Zika virus (ZIKV) was first discovered in East Africa in 1947.  ZIKV has caused microcephaly in the Americas, but it is not known whether ZIKV is a cause of microcephaly in East Africa.Methods: We used surveillance data from 11,061 live births at Kilifi County Hospital in coastal Kenya between January 2012 and October 2016 to identify microcephaly cases and conducted a nested case-control study to determine risk factors for microcephaly. Gestational age at birth was estimated based on antenatal ultrasound scanning (‘Scanned cohort’) or last menstrual period (‘LMP cohort’, including births ≥37 weeks’ gestation only). Controls were newborns with head circumference Z scores between &gt;-2 and ≤2 SD that were compared to microcephaly cases in relation to ZIKV exposure and other maternal and newborn factors.Results: Of the 11,061 newborns, 214 (1.9%, 95%CI 1.69, 2.21) had microcephaly. Microcephaly prevalence was 1.0% (95%CI 0.64, 1.70, n=1529) and 2.1% (95%CI 1.81, 2.38, n=9532) in the scanned and LMP cohorts, respectively. After excluding babies &lt;2500 g (n=1199) in the LMP cohort the prevalence was 1.1% (95%CI 0.93, 1.39). Microcephaly showed an association with being born small for gestational age (p&lt;0.001) but not with ZIKV neutralising antibodies (p=0.6) or anti-ZIKV NS1 IgM response (p=0.9). No samples had a ZIKV neutralising antibody titre that was at least fourfold higher than the corresponding dengue virus (DENV) titre. No ZIKV or other flavivirus RNA was detected in cord blood from cases or controls.Conclusions: Microcephaly was prevalent in coastal Kenya, but does not appear to be related to ZIKV exposure; the ZIKV response observed in our study population was largely due to cross-reactive responses to DENV or other related flaviviruses. Further research into potential causes and the clinical consequences of microcephaly in this population is urgently needed

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

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 colonization (7,967 women), stillbirth and neonatal disease. Whole-genome sequencing was used to determine serotypes, sequence types and phylogeny. We found low maternal GBS colonization prevalence (934/7,967, 12%), but comparatively high incidence of GBS-associated stillbirth and early onset neonatal disease (EOD) in hospital (0.91 (0.25-2.3)/1,000 births and 0.76 (0.25-1.77)/1,000 live births, respectively). However, using a population denominator, EOD incidence was considerably reduced (0.13 (0.07-0.21)/1,000 live births). Treated cases of EOD had very high case fatality (17/36, 47%), especially within 24 h of birth, making under-ascertainment of community-born cases highly likely, both here and in similar facility-based studies. Maternal GBS colonization was less common in women with low socio-economic status, HIV infection and undernutrition, but when GBS-colonized, they were more probably colonized by the most virulent clone, CC17. CC17 accounted for 267/915 (29%) of maternal colonizing (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

Replication Data for: Congenital Microcephaly Unrelated to Flavivirus Exposure in Coastal Kenya

This dataset contains demographic information, anthropometric measures and results of lab assays for 11,061 live births at Kilifi County Hospital in coastal Kenya between January 2012 and October 2016. The variables in the dataset were used in the analysis presented in the related manuscript published at Wellcome Open Researc