Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in Africa.

Hepatitis B virus (HBV) is a significant public health issue that has not been adequately addressed, especially in the high-prevalence region of Africa. Despite the incorporation of HBV vaccines into the Expanded Program on Immunization, children continue to be infected with HBV through maternal-to-child transmission (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the Western Pacific region but not yet in Africa. Even better protection against HBV MTCT can be achieved by treatment of pregnant women with high HBV viral loads with tenofovir. Tenofovir is already widely used in prevention of HIV MTCT (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded to deliver care for HBV-infected pregnant women. With appropriate adoption of birth-dose vaccination policies and expansion of PMTCT programs, elimination of HBV MTCT in Africa is achievable.

New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations.

It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.

Tris(4-chlorophenyl)methane and tris(4-chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos.

OBJECTIVES: Tris(4-chlorophenyl) methane (TCPM) and tris(4-chlorophenyl)methanol (TCPMOH) are anthropogenic environmental contaminants believed to be manufacturing byproducts of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) due to environmental co-occurrence. TCPM and TCPMOH are persistent, bioaccumulate in the environment, and are detected in human breast milk and adipose tissues. DDT exposures have been previously shown to disrupt insulin signaling and glucoregulation, increasing risk for diabetes. We have previously shown that embryonic exposures organochlorines such as polychlorinated biphenyls disrupted pancreatic development and early embryonic glucoregulatory networks. Here, we determined the impacts of the similar compounds TCPM and TCPMOH on zebrafish pancreatic growth and gene expression following developmental exposures. METHODS: Zebrafish embryos were exposed to 50 nM TCPM or TCPMOH beginning at 24 hr postfertilization (hpf) and exposures were refreshed daily. At 96 hpf, pancreatic growth and islet area were directly visualized in Tg(ptf1a::GFP) and Tg(insulin::GFP) embryos, respectively, using microscopy. Gene expression was assessed at 100 hpf with RNA sequencing. RESULTS: Islet and total pancreas area were reduced by 20.8% and 13% in embryos exposed to 50 nM TCPMOH compared to controls. TCPM did not induce significant morphological changes to the developing pancreas, indicating TCPMOH, but not TCPM, impairs pancreatic development despite similarity in molecular responses. Transcriptomic responses to TCPM and TCPMOH were correlated (R2  = .903), and pathway analysis found downregulation of processes including retinol metabolism, circadian rhythm, and steroid biosynthesis. CONCLUSION: Overall, our data suggest that TCPM and TCPMOH may be hazardous to embryonic growth and development.

The ecotoxicological contaminant tris(4-chlorophenyl)methanol (TCPMOH) impacts embryonic development in zebrafish (Danio rerio).

Tris(4-chlorophenyl)methanol (TCPMOH) is a water contaminant with unknown etiology, but is believed to be a byproduct of DDT manufacturing. It is highly persistent in the environment, and bioaccumulates in marine species. TCPMOH has also been measured in human breast milk, which poses a risk for developing infants. However, almost no toxicity data is currently available. In this study, we investigate the hazard posed by developmental TCPMOH exposures using the zebrafish model (Danio rerio). Zebrafish (Danio rerio) embryos were exposed to 0, 0.1, 0.5, 1, or 5 µM TCPMOH beginning at 24 h post fertilization (hpf). Embryonic mortality and incidence of morphological deformities increased in a concentration-dependent manner with TCPMOH exposure. RNA sequencing assessed changes in gene expression associated with acute (4 hour) exposures to 50 nM TCPMOH. Developmental exposure to TCPMOH decreased expression of ahr2, as well as metabolic enzymes cyp1a1, cyp1b1, cyp1c1, cyp1c2, and cyp2y3 (p<0.05). These findings were concordant with decreased Cyp1a1 induction measured by the ethoxyresorufin-O-deethylase (EROD) assay (p<0.05). Pathways associated with xenobiotic metabolism, lipid metabolism, and transcriptional and translational regulation were decreased. Pathways involved in DNA replication and repair, carbohydrate metabolism, and endocrine function were upregulated. Overall, this study demonstrates that TCPMOH is acutely toxic to zebrafish embryos at elevated concentrations.

Missed hepatitis B birth dose vaccine is a risk factor for incomplete vaccination at 18 and 24 months.

OBJECTIVES: To determine whether missing the HepB birth dose vaccine is a risk factor for incomplete vaccination later in childhood. METHODS: This was a retrospective cohort study of infants born over one year at an academic medical center. The "not vaccinated at birth" group consisted of all infants who did not receive the HepB birth dose vaccine by seven days of life, while the "vaccinated at birth" group included infants who did receive the birth dose. The primary outcome was vaccination status at 18 months of age, determined from the state vaccination registry. RESULTS: Infants "not vaccinated at birth" had lower vaccination rates. At 18 months, 44% of the "vaccinated at birth" group received all recommended vaccines, compared with 23% of the "not vaccinated at birth" group (p < 0.001); at 24 months, rates were 65% and 45%, respectively (p < 0.001). Over 80% of the variability in vaccination completions were related to a single latent variable, which is most likely vaccine hesitancy/refusal. CONCLUSIONS: Infants who miss the HepB birth dose vaccine are at risk for under-immunization by 18 and 24 months of age. This suggests that parents likely form opinions about vaccines long before the birth of their child; therefore, efforts to influence attitudes must begin earlier.

Retrospective review of the patient cases at a major trauma center in Nairobi, Kenya and implications for emergency care development.

INTRODUCTION: Low- and middle-income countries (LMICs) are continuing to experience a "triple burden" of disease - traumatic injury, non-communicable diseases (NCDs), and communicable disease with maternal and neonatal conditions (CD&Ms). The epidemiology of this triad is not well characterised and poses significant challenges to resource allocations, administration, and education of emergency care providers. The data collected in this study provide a comprehensive description of the emergency centre at Kenya's largest public tertiary care hospital. METHODS: This study is a retrospective chart review conducted at Kenyatta National Hospital of all patient encounters over a four-month period. Data were collected from financial and emergency centre triage records along with admission and mortality logbooks. Chief complaints and discharge diagnoses collected by specially trained research assistants were manually converted to standardised diagnoses using International Classification of Disease 10 (ICD-10) codes. ICD-10 codes were categorised into groups based on the ICD-10 classification system for presentation. RESULTS: A total of 23,941 patients presented to the emergency centre during the study period for an estimated annual census of 71,823. The majority of patients were aged 18-64 years (58%) with 50% of patients being male and only 3% of unknown sex. The majority of patients (61%) were treated in the emergency centre, observed, and discharged home. Admission was the next most common disposition (33%) followed by death (6%). Head injury was the overall most common diagnosis (11%) associated with admission. CONCLUSIONS: Trends toward NCDs and traumatic diseases have been described by this study and merit further investigation in both the urban and rural setting. Specifically, the significance of head injury on healthcare cost, utilisation, and patient death and disability points to the growing need of additional resources at Kenyatta National Hospital for acute care. It further demonstrates the mounting impact of trauma in Kenya and throughout the developing world.

Persistent Gaps in Appropriate Use of Empiric Acyclovir in Neonates.

The use of empiric acyclovir for suspected neonatal herpes simplex virus (HSV) infection has been debated for years. To identify the gap in the decision to initiate empiric acyclovir, we performed a retrospective chart review and administered a survey to pediatricians to assess current practices regarding evaluation for possible HSV infection. Seventy infants received empiric acyclovir over a 1-year period; of these, 3 infants (4.3%) had positive HSV testing. Fourteen infants were identified as "high-risk" for HSV infection; of these, 13 infants had incomplete testing. Survey results revealed uncertainty in the decision to initiate acyclovir and in the composition of complete diagnostic testing. This study confirmed the clinical uncertainty in the decision to initiate empiric acyclovir. Using this chart review and survey as a baseline, future efforts will focus on a quality improvement project to reduce empiric acyclovir use in low-risk infants and to ensure complete diagnostic evaluation in high-risk infants.

Screening for Spinal Dysraphisms in Newborns With Sacral Dimples.

Sacral dimples are common physical examination findings among newborns and are rarely associated with spinal dysraphism. Screening ultrasonography for simple sacral dimples in the absence of other physical findings leads to unnecessary health care costs and undue stress on families. This study was a retrospective chart review of infants with a sacral dimple on examination who underwent spinal ultrasonography in the first week of life. The documented indication for ultrasonography was compared to standard guidelines. Among 151 infants in the study, 80% had a normal spinal ultrasound. Of infants with abnormal ultrasonography, 7 (5%) had abnormal spinal magnetic resonance imaging and 2 infants (1%) required neurosurgical intervention. Our study revealed that nearly one-third of infants who underwent spinal ultrasonography had a simple sacral dimple and low likelihood of spinal dysraphism according to existing guidelines. Among patients who underwent spinal ultrasonography in accordance with guidelines, only a small percentage required neurosurgical intervention indicating that guidelines may need to be revised. Larger studies involving multiple centers are necessary to assess this need.