Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species 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 paenibacilliosis versus clinical sepsis due to other causes. RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of 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 (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

High burden of wasting among children under-five with hydrocephalus receiving care at CURE children's hospital in Uganda: a cross-sectional study.

BACKGROUND: Hydrocephalus is one of the most common neurological disabilities presenting in children. Although there are limited studies on its association with wasting, neurological comorbidities such as dysphagia have been associated with an increased risk of wasting in children. In this study, we aimed to determine the prevalence and factors associated with wasting in children less than five years with hydrocephalus. METHODS: We conducted a cross-sectional study at various satellite clinics of CURE Children's Hospital in Uganda between September and November 2021. Children with hydrocephalus were identified at the outpatient departments of the satellite clinics of the Cure Children's Hospital and these include Mbale, Gulu, Lira, Jinja and Katalemwa. A structured questionnaire was used to collect information on several variables including (1) for the mother: socio-demographic characteristics, partner support, and wealth index (2) for the child: socio-demographic characteristics, clinical symptoms, feeding difficulties and neural comorbidity. Anthropometric measurements were also taken and these included the mid-upper arm circumference. Data were analysed using Stata version 14. We estimated adjusted odds ratios and their corresponding 95% confidence intervals while relying on multivariable logistic regression models. RESULTS: The prevalence of wasting among children with hydrocephalus was 23.2% (n = 89/384) (95%CI: 19 - 27.7%). Their mean age was 19.5 months (SD 16.8). Most of the children were below 12 months (47.9%) and were male (57.5%). The factors associated with wasting among children with hydrocephalus included: having; difficulty in chewing and swallowing (AOR = 2.6, (95%CI:1.05-3.94), a poor appetite (AOR = 1.74, (95%CI: 1.31-2.32), difficulty in breathing (AOR = 1.9, (95%CI: 1.18-3.16), chocking on food (AOR = 1.42, (95%CI:1.1-1.9) and attending the Mbale satellite clinic (AOR = 2.1 (95% CI 1.19-3.7). Children under 5 years of age with hydrocephalus that were born to women whose highest level of education was 7 to 10 years of formal schooling (AOR = 0.32, 95%CI: (0.12-0.87) were less likely to be wasted. CONCLUSIONS AND RECOMMENDATIONS: The prevalence of wasting among children with hydrocephalus was high. The factors associated with wasting were mainly feeding challenges. We recommend that children with hydrocephalus should be given greater attention regarding their nutrition especially those with various forms of feeding difficulties. The caregivers of children with hydrocephalus should receive counseling on nutrition and on the best modalities to rely on while feeding their children.