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Background The etiology of neonatal sepsis is often not identified. Molecular methods can identify pathogens that culture-based methods miss. Most cases of neonatal sepsis globally are treated empirically per WHO guidelines with intravenous ampicillin and gentamicin, which may not be the best regimen for all pathogens. Methods We prospectively enrolled 800 neonates presenting with signs of sepsis to two Ugandan hospitals. Blood and cerebrospinal fluid were subjected to 16S rRNA sequencing, which identified Paenibacillus thiaminolyticus in 33/800 (4%) neonates. We confirmed the presence of P. thiaminolyticus by quantitative polymerase chain reaction (PCR). We describe neonatal and birth characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis. We performed antibiotic susceptibility testing and genomic analyses on three clinical isolates successfully grown in the laboratory. Results Neonates presented at a median age of 3 (1, 7) days. Fever (86%), irritability (78%) and seizures (52%) were common presenting signs (Figure). Most neonates were born vaginally (73%) at a medical facility (79%). Twelve (36%) had an adverse outcome: 5 (15%) neonates died; 4 (14%) survivors developed postinfectious hydrocephalus and three (9%) additional survivors had neurodevelopmental impairment. All three isolates were resistant to vancomycin, two were resistant to penicillin and ampicillin and one was unlikely to be sensitive to ceftriaxone; all were susceptible to gentamicin and meropenem. The genomes of all three strains contained multiple beta-lactamase genes and a cluster of genes that encodes a type IV pilus. Clinical signs at presentation for neonates with good and poor outcomes followng paenibacillosis Conclusion Molecular methods such as 16S rRNA sequencing and PCR can be used to improve the identification of pathogens causing neonatal sepsis. Paenibacillosis is an important emerging cause of neonatal sepsis in Uganda and is likely an underrecognized cause of postinfectious hydrocephalus in the region and possibly elsewhere. Antibiotics commonly used for neonatal sepsis may be inadequate for the treatment of paenibacillosis. Additional studies to understand the pathophysiology and optimal treatment of this novel infection are urgently needed to prevent neonatal mortality and morbidity including postinfectious hydrocephalus. Disclosures Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant Abhaya Kulkarni, MD, MSc, PhD, Medtronic: Advisor/Consultant.

Paenibacillus thiaminolyticusmay be an underdiagnosed cause of neonatal sepsis. We prospectively enrolled a cohort of 800 neonates presenting with a clinical diagnosis of sepsis at two Ugandan hospitals. Quantitative polymerase chain reaction specific toP. thiaminolyticusand to thePaenibacillusgenus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with virus detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis vs. clinical sepsis. Median age at presentation was 3 (interquartile range 1, 7) days. Fever (92%), irritability (84%) and seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus and one (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda.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.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 age25 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, p0.0001).Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Background: Congenital and postnatal cytomegalovirus (CMV) infections in Uganda is prevalent and may compromise the health of Ugandan children. The objective of this study is to estimate the prevalence of CMV infections in newborns, neonates with sepsis, and infants with hydrocephalus in Uganda. Methods: Three populations: (1) newborn-mother pairs, (2) neonates with sepsis, and (3) infants (≤ 3 months) with non-postinfectious (NPIH) or postinfectious (PIH) hydrocephalus, were evaluated over four years (2016-2019) for CMV infection at three medical centers – two in the Eastern (Mbale) and one in Western (Mbarara) Uganda. To characterize the prevalence of CMV we used quantitative PCR (qPCR) analysis. In newborn-mother pairs maternal blood (n=99) and a subset of matching cord blood (n=92), placental tissue (n=99), and vaginal specimens (n=99) were tested for CMV. In neonates and infants aged 3 months or less, peripheral blood (751 with sepsis, 399 with hydrocephalus) and cerebrospinal fluid samples (560 with sepsis, 399 with hydrocephalus (205 PIH, 194 NPIH) were also tested for CMV. Findings: The overall CMV prevalence across all groups was 9%. In newborn-mother pairs, a 3% (n=3/92; 95% CI, 1-9%) prevalence of cord blood positivity and 33% (n=33/99; 95% CI, 24-44%) prevalence of maternal vaginal shedding of CMV was estimated. In neonates with clinical sepsis, a 2% (n=17/751; 95% CI, 1-4%) CMV prevalence was estimated. Maternal HIV seropositivity (adjusted odds ratio [aOR], 21.09; 95% CI, 4-109; p= 0.0002), residence in Eastern Uganda (aOR, 11.10; 95% CI, 3-77; p=0 .003), maternal age < 25 years (aOR, 4.91; 95% CI, 2-20; p=0.012), and older neonatal age (9 days vs. 5 days; p= 0.006) were associated with CMV in neonates with clinical sepsis. In infants with PIH, the prevalence in blood was 24% (n=50/205; 95% CI, 19-31%) and in infants with NPIH it was 20% (n=39/194; 95% CI, 15-26%; p=0.34). CMV was present in the CSF of 13% (n=26/205; 95% CI, 8-18%) of infants with PIH compared to 0.5% of infants with NPIH (n=1/194; 95% CI, 0-3%, p

Object Despite lower failure and infection rates compared with shunt placement, it has not been known whether endoscopic third ventriculostomy/choroid plexus cauterization (ETV/CPC) might be inferior in regard to neurocognitive development. This study is the first to describe neurocognitive outcome and ventricle volume in infants with hydrocephalus due to myelomeningocele that was treated primarily by ETV/CPC. Methods The modified Bayley Scales of Infant Development (BSID-III) test was administered to 93 children with spina bifida who were 5–52 months of age. Fifty-five of these children had been treated by ETV/CPC, 19 received ventriculoperitoneal (VP) shunts, and 19 had required no treatment for hydrocephalus. Raw scores were converted to scaled scores for comparison with age-corrected norms. Ventricular volume was assessed by frontal/occipital horn ratio (FOR) calculated from late postoperative CT scans. The mean values between and among groups of patients were compared using independent samples t-test and ANOVA. The comparison of mean values to population normal means was performed using the single-sample t-test. Linear regression analyses were performed using BSID scores as the dependent variables, with treatment group and ventricular size (FOR) as the independent variables. Probability values < 0.05 were considered significant. Results . There was no significant difference in mean age at assessment among groups (p = 0.8). The mean scale scores for untreated patients were no different from normal (all p > 0.27) in all portions of the BSID (excluding gross motor), and were generally significantly better than those for both VP shunt–treated and ETV/CPC groups. The ETV/ CPC-treated patients had nonsignificantly better mean scores than patients treated with VP shunts in all portions of the BSID (all p > 0.06), except receptive communication, which was significantly better for the ETV/CPC group (p = 0.02). The mean FOR was similar among groups, with no significant difference between the untreated group and either the VP shunt or ETV/CPC groups. The FOR did not correlate with performance. Conclusions The ETV/CPC and VP shunt groups had similar neurocognitive outcomes. Neurocognitive outcomes for infants not requiring treatment for hydrocephalus were normal and significantly better than in those requiring treatment. The mean ventricular volume was similar among all 3 groups, and significantly larger than normal. There was no association between FOR and performance. Stable mild-to-moderate ventriculomegaly alone should not trigger intervention in asymptomatic infants with spina bifida.

Despite lower failure and infection rates compared with shunt placement, it has not been known whether endoscopic third ventriculostomy/choroid plexus cauterization (ETV/CPC) might be inferior in regard to neurocognitive development. This study is the first to describe neurocognitive outcome and ventricle volume in infants with hydrocephalus due to myelomeningocele that was treated primarily by ETV/CPC.The modified Bayley Scales of Infant Development (BSID-III) test was administered to 93 children with spina bifida who were 5-52 months of age. Fifty-five of these children had been treated by ETV/CPC, 19 received ventriculoperitoneal (VP) shunts, and 19 had required no treatment for hydrocephalus. Raw scores were converted to scaled scores for comparison with age-corrected norms. Ventricular volume was assessed by frontal/occipital horn ratio (FOR) calculated from late postoperative CT scans. The mean values between and among groups of patients were compared using independent samples t-test and ANOVA. The comparison of mean values to population normal means was performed using the single-sample t-test. Linear regression analyses were performed using BSID scores as the dependent variables, with treatment group and ventricular size (FOR) as the independent variables. Probability values0.05 were considered significant.There was no significant difference in mean age at assessment among groups (p = 0.8). The mean scale scores for untreated patients were no different from normal (all p0.27) in all portions of the BSID (excluding gross motor), and were generally significantly better than those for both VP shunt-treated and ETV/CPC groups. The ETV/ CPC-treated patients had nonsignificantly better mean scores than patients treated with VP shunts in all portions of the BSID (all p0.06), except receptive communication, which was significantly better for the ETV/CPC group (p = 0.02). The mean FOR was similar among groups, with no significant difference between the untreated group and either the VP shunt or ETV/CPC groups. The FOR did not correlate with performance.The ETV/CPC and VP shunt groups had similar neurocognitive outcomes. Neurocognitive outcomes for infants not requiring treatment for hydrocephalus were normal and significantly better than in those requiring treatment. The mean ventricular volume was similar among all 3 groups, and significantly larger than normal. There was no association between FOR and performance. Stable mild-to-moderate ventriculomegaly alone should not trigger intervention in asymptomatic infants with spina bifida.