Congenital microcephaly unrelated to flavivirus exposure in coastal Kenya

Barsosio, Hellen C.; Gitonga, John N.; Karanja, Henry; Nyamwaya, Doris K.; Omuoyo, Donwilliams O.; Kamau, Everlyn; Hamaluba, Mainga; Nyiro, Joyce U.; Kitsao, Barnes; Nyaguara, Amek; Mwakio, Stella; Newton, Charles R.; Sang, Rosemary; Wright, Daniel; Sanders, Eduard J.; Seale, Anna C.; Agoti, Charles N.; Berkley, James A.; Bejon, Philip; Warimwe, George M.

doi:10.12688/wellcomeopenres.15568.1

Cited by 11 publications

(18 citation statements)

References 29 publications

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“…3296). Our approach was to screen all stored CSF for CHIKV and link these data to demographic surveillance (KHDSS) for incidence estimation as part of a larger program of work aimed at estimating the case burden of arboviral illnesses in coastal Kenya [ 14 , 24 ]. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline ( S1 STROBE Checklist ).…”

Section: Methodsmentioning

confidence: 99%

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

et al. 2022

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Background Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness. Methods and findings We estimated the incidence of CHIKV infection among children hospitalized with neurological disease in Kilifi County, coastal Kenya. We used reverse transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalized with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. There were 18,341 pediatric admissions for any reason during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures, and coma (47%, 22%, and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. Case fatality among CHIKV-positive children was 1.4% (95% CI 0.4, 3.2). The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. Because of incomplete case ascertainment due to children not presenting to hospital, or not having CSF collected, these are likely minimum estimates. Study limitations include reliance on hospital-based surveillance and limited CSF sampling in children in coma or other contraindications to lumbar puncture, both of which lead to under-ascertainment of incidence and of case fatality. Conclusions In this study, we observed that CHIKV infections are relatively more common than cerebral malaria and bacterial meningitis among children hospitalized with neurological disease in coastal Kenya. Given the wide distribution of CHIKV mosquito vectors, studies to determine the geographic extent of CHIKV-associated neurological disease in Africa are essential.

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Section: Methodsmentioning

confidence: 99%

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

et al. 2022

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“…Plates were washed with water and left to dry before being scored by eye. Focus reduction neutralizing test (FRNT): This was carried out as previously described (Barsosio et al, 2019) with some alterations. Briefly, serum was diluted in 2-fold steps in triplicate from a starting dilution of 1:20.…”

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confidence: 99%

Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein

et al. 2020

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Summary Rift Valley fever (RVF) is a viral hemorrhagic disease first discovered in Kenya in 1930. Numerous animal studies have demonstrated that protective immunity is acquired following RVF virus (RVFV) infection and that this correlates with acquisition of virus-neutralizing antibodies (nAbs) that target the viral envelope glycoproteins. However, naturally acquired immunity to RVF in humans is poorly described. Here, we characterized the immune response to the viral envelope glycoproteins, Gn and Gc, in RVFV-exposed Kenyan adults. Long-lived IgG (dominated by IgG1 subclass) and T cell responses were detected against both Gn and Gc. However, antigen-specific antibody depletion experiments showed that Gn-specific antibodies dominate the RVFV nAb response. IgG avidity against Gn, but not Gc, correlated with nAb titers. These data are consistent with the greater level of immune accessibility of Gn on the viral envelope surface and confirm the importance of Gn as an integral component for RVF vaccine development.

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“…Careful aseptic techniques and training of clinical staff are imperative to optimize sample collection and may improve the validity of results. Aseptic techniques were used during cord blood sample collection to minimise sample contamination, since identification of pathogens associated with adverse maternal and perinatal outcomes was planned 36 , including a recently published study on the association of flavivirus exposure with congenital microcephaly 55 . In addition, cord blood analysis using PCR has mostly focused on vertically transmitted viruses [56][57][58] , and more research on cord blood testing using molecular diagnostics is needed to better understand the clinical significance of detected organisms.…”

Section: Discussionmentioning

confidence: 99%

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

Obiero¹,

Gumbi²,

Mwakio³

et al. 2022

Wellcome Open Res

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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.

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Congenital microcephaly unrelated to flavivirus exposure in coastal Kenya

Cited by 11 publications

References 29 publications

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein

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

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