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Background: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus., Methods: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort., Findings: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered., Interpretation: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality., Funding: National Institutes of Health and Boston Children's Hospital Office of Faculty Development., Competing Interests: Declaration of interests KB is Principal Investigator on a Joint Global Health Trials grant from the UK Medical Research Council and has received travel grants and honoraria for speaking at Hot Topics in Neonatology. JEE has received honoraria for participation on the Data Safety Monitoring Board of AbbVie. BCW has received honoraria for participation on the Data Safety Monitoring Board for the Endoscopic versus Shunt Treatment of Hydrocephalus in Infants trial of the Hydrocephalus Clinical Research Network and is the Chairman of Neurokids. JNP has been employed by Genentech and N-Power Medicine; has held stocks and holds and is planning patents at Genentech and N-Power Medicine; has received honoraria for speaking at the International Human Microbiome Consortia meeting; and has received travel support from Genentech. All other authors declare no competing interests. The National Institutes of Health (NIH) Director's Pioneer Award 5DP1HD086071 and NIH Director's Transformative Award 1R01AI145057 has been given to SJS, and the Boston Children's Hospital Office of Faculty Development Career Development Award to SUM. No authors are employed by the NIH., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Over two million stillbirths and neonatal deaths occur in sub-Saharan Africa (sSA) annually. Despite multilateral efforts, reducing perinatal mortality has been slow. Although targeted pathologic investigation can often determine the cause of perinatal death, in resource-limited settings, stillbirths, early neonatal deaths, and placentas are rarely examined pathologically. However, the placenta is a key source of diagnostic information and is the main determinant of fetal growth and development in utero , influencing child health outcomes., Methods: In 2016, our collaborative intercontinental group began investigating infectious perinatal death and adverse child health outcomes in Uganda. We developed and initiated a 4-day combined didactic/practical curriculum to train health workers in placental collection, gross placental examination, and tissue sampling for histology. We also trained a local technician to perform immunohistochemistry staining., Results: Overall, we trained 12 health workers who performed gross placental assessment for > 1,000 placentas, obtaining > 5,000 formalin-fixed tissue samples for research diagnostic use. Median placental weights ranged from 425 to 456 g, and 33.3% of placentas were < 10th percentile in weight, corrected for gestational age. Acute chorioamnionitis (32.3%) and maternal vascular malperfusion (25.4%) were common diagnoses., Discussion: Through a targeted training program, we built capacity at a university-affiliated hospital in sSA to independently perform placental collection, gross pathologic examination, and placental tissue processing for histology and special stains. Our training model can be applied to other collaborative research endeavors in diverse resource-limited settings to improve research and clinical capacity and competency for diagnostics and management of stillbirth, neonatal death, and child health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bebell, Ngonzi, Meier, Carreon, Birungi, Kerry, Atwine and Roberts.)

Objectives: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda., Design and Methods: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV., Results: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001)., Conclusions: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)