The Microbial Spectrum of Neonatal Sepsis in Uganda: Recovery of Culturable Bacteria in Mother-Infant Pairs

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections

Economic burden of neonatal sepsis in sub-Saharan Africa

Background and significance The third Sustainable Development Goal for child health, which aims to end preventable deaths of newborns and children less than 5 years of age by 2030, cannot be met without substantial reduction of infection-specific neonatal mortality in the developing world. Neonatal infections are estimated to account for 26% of annual neonatal deaths, with mortality rates highest in sub-Saharan Africa (SSA). Reliable and comprehensive estimates of the incidence and aetiology surrounding neonatal sepsis in SSA remain incompletely available. We estimate the economic burden of neonatal sepsis in SSA. Methods: Data available through global health agencies and in the medical literature were used to determine population demographics in SSA, as well as to determine the incidence, disease burden, mortality and resulting disabilities associated with neonatal sepsis. The disability-adjusted life years (DALY) associated with successful treatment or prevention of neonatal sepsis in SSA for 1 year were calculated. The value of a statistical life (VSL) methodology was estimated to evaluate the economic burden of untreated neonatal sepsis in SSA. Results: We conservatively estimate that 5.29–8.73 million DALYs are lost annually in SSA due to neonatal sepsis. Corresponding VSL estimates predict an annual economic burden ranging from $10 billion to$469 billion. Conclusions: Our results highlight and quantify the scope of the public health and economic burden posed by neonatal sepsis in SSA. We quantify the substantial potential impact of more successful treatment and prevention strategies, and we highlight the need for greater investment in strategies to characterise, diagnose, prevent and manage neonatal sepsis and its long-term sequelae in SSA

Risk factors of sudden death in young adult patients with myelomeningocele

Object Although survival for patients with myelomeningocele has dramatically improved in recent decades, the occasional occurrence of sudden, unexplained death in young adult patients with myelomeningocele has been noted by the authors. This study was undertaken to determine risk factors for sudden death in this population. Methods The authors performed a retrospective chart review of patients born between 1978 and 1990 who received care at Children's Hospital Boston. The relationship between sudden death and patient demographics, presence of CSF shunt and history of shunt revisions, midbrain length as a marker for severity of hindbrain malformation, seizures, pulmonary and ventilatory dysfunction, body mass index, scoliosis, renal dysfunction, and cardiac disease was evaluated using the t-test, Fisher exact test, and logistic regression analysis. Results The age range for 106 patients in the study cohort was 19–30 years, with 58 (54.7%) women and 48 (45.3%) men. Six patients, all of whom were young women, experienced sudden death. In multivariate analysis, female sex, sleep apnea, and midbrain elongation ≥ 15 mm on MR imaging remained significantly associated with a higher risk of sudden death. These risk factors were cumulative, and female patients with sleep apnea and midbrain length ≥ 15 mm had the greatest risk (adjusted risk ratio 24.0, 95% CI 7.3–79.0; p < 0.05). No other comorbidities were found to significantly increase the risk of sudden death. Conclusions Young adult women with myelomeningocele are at significantly increased risk of sudden death in the setting of midbrain elongation and sleep apnea. Further investigation is needed to determine the benefit of routine screening to identify at-risk patients for closer cardiopulmonary monitoring and treatment