Uninformed Origins: Should We Be Advising Parents on the Source of Medicines and Therapies?

Respecting patient autonomy through the process of soliciting informed consent is a cornerstone of clinical ethics. In pediatrics, until a child becomes an adult or legally emancipated, that ethical tenet takes the form of respect for parental decision-making authority. In instances of respecting religious beliefs, doing so is not always apparent and sometimes the challenge lies not only in the healthcare provider's familiarity of religious restrictions but also their knowledge of medical interventions themselves which might conflict with those restrictions. We examine a case of a newborn receiving animal-derived surfactant, a common scenario in neonatology, and present considerations for providers to weigh when confronting when such an intervention might conflict with parent's religious beliefs. We end with strategizing ways to address this issue as a medical community.

Optimizing DNA Extraction from Pediatric Stool for Diagnosis of Tuberculosis and Use in Next-Generation Sequencing Applications.

The WHO has endorsed the use of stool samples for diagnosis of tuberculosis (TB) in children, and targeted next-generation sequencing (tNGS) of stool has been shown to support diagnosis and provide information about drug susceptibility (DS). Optimizing extraction of DNA from stool for sequencing is critical to ensure high diagnostic sensitivity and accurate DS information. Human stool samples were spiked with various concentrations of Mycobacterium bovis bacillus Calmette-Guérin (BCG), and DNA was extracted from the samples using four different DNA extraction kits. Each sample was subjected to quantitative PCR for identifying Mycobacterium tuberculosis complex bacteria and underwent further analysis to assess the overall DNA yield, fragment length, and purity. This same process was performed with 10 pediatric participants diagnosed with pulmonary TB, and the samples underwent tNGS. The FastDNA spin kit for soil showed the best results on model samples spiked with known quantities of BCG, compared to the other extraction methods evaluated. For clinical samples, the FastDNA and PowerFecal Pro DNA (PowerFecal) kits both showed an increase in the overall DNA quantity, M. tuberculosis-specific DNA quantity, and successful targeted sequencing when testing was performed on stool samples, compared to the two other kits. Three samples extracted via PowerFecal and three samples extracted via FastDNA (from different patients) provided successful sequencing data, with an average depth of coverage of the rpoB region for FastDNA of 298 (range, 107 to 550) and for PowerFecal of 310 (range, 182 to 474), results that were comparable to one another (P = 0.946). The PowerFecal Pro and FastDNA spin kits were superior for extracting DNA from pediatric stool samples for tNGS. IMPORTANCE This is the first study to compare Mycobacterium tuberculosis DNA extraction techniques from pediatric stool samples for use with sequencing technologies. It provides an important starting point for other researchers to isolate quality DNA for this purpose to further the field and to continue to optimize protocols and approaches.

Pediatric Eosinophilia: A Review and Multiyear Investigation into Etiologies.

OBJECTIVES: To identify the etiology of peripheral eosinophilia in a large pediatric population and to develop a diagnostic algorithm to help guide diagnosis and management of peripheral eosinophilia in the outpatient pediatric population. STUDY DESIGN: We performed a retrospective chart review of children presenting to Texas Children's Hospital in Houston with peripheral eosinophilia between January 1, 2011 and December 31, 2019. Eosinophilia was classified as mild (absolute eosinophil count [AEC] >500 and <1500 cells/µL), moderate (AEC >1500 and <4500 cells/µL), or severe (AEC >4500 cells/µL). Demographic information and diagnostic workup data were collected. RESULTS: A total of 771 patients aged <18 years were evaluated. The most common cause of eosinophilia was allergy (n = 357; 46%), with atopy (n = 296) and drug reaction (n = 54) the most common subcauses. This was followed by unknown etiology (n = 274; 36%), infectious causes (n = 72; 9%), and eosinophilic disorders (n = 47; 6%). Many patients with an unknown cause (n = 202; 74%) had limited or no follow-up testing. CONCLUSIONS: More information on the etiology of pediatric eosinophilia and workup data could help identify the causes. This study provides important information on the evaluation of eosinophilia in the US pediatric population, including a diagnostic algorithm to guide primary care pediatricians.

High Throughput Sequencing for Clinical Tuberculosis: An Overview.

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field.

How I Approach Leishmaniasis: Diagnosis and Treatment in the United States.

Leishmaniasis is a vector-borne disease caused by over 20 species of obligate intracellular protozoa belonging to the genus Leishmania. Leishmaniasis has a global distribution, including in the United States, and can cause a spectrum of clinical syndromes, including cutaneous, mucosal, and visceral diseases depending on host factors and the infecting Leishmania spp. Accurate diagnosis, including Leishmania species identification, is an important step to guide the most appropriate therapeutic intervention. Antileishmanial therapy is dependent on the Leishmania spp. identified, the clinical syndrome, and the child's immune system. However, many treatment regimens for children have been extrapolated from adult clinical trials, which may lead to underdosing and subsequent poor outcomes in infected children. Additional research is urgently needed to help guide therapy for children and determine appropriate antileishmanial agents, doses, and treatment courses for children with leishmaniasis.

Impact of using creative arts programming to support HIV treatment in adolescents and young adults in Eswatini.

BACKGROUND: In 2018, approximately 1.6 million adolescents (aged 10-19) were living with HIV worldwide, with the highest HIV prevalence found in Eswatini. Adolescents and young adults living with HIV are a vulnerable population due to unique psychosocial challenges that come with having a stigmatizing disease. This group struggles more than other age-groups with medication adherence and requires novel approaches to supporting treatment, including peer-group encouragement, and self-expression. METHODS: We piloted a theater camp for a group of adolescents and young adults enrolled at our HIV clinic in Mbabane, Eswatini, to determine the impact of having an outlet for creative expression and peer support on treatment and feelings of stigma. Pre- and post-camp surveys were administered to the participants to assess perceived stigma and impact of the camp. The results were analyzed using a Wilcoxon-signed rank test. RESULTS: Twenty individuals (ages 12-23) living with HIV participated in the camp concurrently with standard treatment. 25% showed a substantial decrease in viral load within six months of completing the camp (> 0.1 log10 change) while only 10% showed a substantial increase. Those who completed the survey felt the camp helped them with confidence, teamwork, and friendships. A comparison of pre- and post- surveys showed an overall decrease in personalized stigma. Quotes from participants reinforced these results. CONCLUSIONS: Adolescents and young adults living with HIV are an important population for further program development. Our study showed creative arts programming has beneficial psychosocial effects, aids in community building, and potentially enhances the effectiveness of medical treatment. Further programs and studies should continue to investigate creative arts as an avenue for self-expression and community building among vulnerable populations.

Evaluating antibiotic use and developing a tool to optimize prescribing in a family-centered HIV clinic in Eswatini.

In a human immunodeficiency virus (HIV) clinic for children and their families in Eswatini, we sought to understand the use of antibiotics and identify specific areas for improvement. We performed a retrospective patient chart review as part of a quality improvement (QI) initiative to assess antimicrobial use before and after implementation of a standardized antimicrobial guide. For each prescribing period, 100 random patient encounters were selected for review if the indication for antibiotics, duration, and dose were consistent with World Health Organization (WHO) guidelines. Two physicians reviewed each encounter using a structured abstraction tool, with a third resolving discrepancies. Results were analyzed using a chi-square test of proportions and a structured survey was performed to assess perceptions of the guide. After the implementation of an antimicrobial guide, there was a significant decrease in the proportion of clinic visits with an antibiotic prescribed (p < 0.001). Incorrect indication for antimicrobial use decreased from 20.4% in the initial period to 10.31% and 10.2% but did not reach significance (p = .0621) in the subsequent periods after implementation. Incorrect dose/duration decreased from 10.47% in the initial period to 7.37% and 3.1% in the subsequent periods, but this was also was not significant (p = 0.139). All prescribers who completed the survey felt that it positively impacted their prescribing. Our study found that an antimicrobial guide reduced and improved the prescription of antimicrobials, demonstrating practical solutions can have a lasting impact on prescribing in low resource settings.

Maternal Hookworm Infection and Its Effects on Maternal Health: A Systematic Review and Meta-Analysis.

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely to have anemia (combined odds ratio [cOR] 2.55 [2.20, 2.96], P < 0.001). In addition, pregnant woman with hookworm were more likely to have malaria coinfection (cOR 1.60 [1.38, 1.86], P < 0.001). Other effects on maternal and child health were investigated and summarized without systematic review or meta-analysis because of the limited study numbers. Despite current deworming recommendations in pregnant women, heavy hookworm burden, coinfection with malaria, and subsequent anemia persist. Although this is likely due, in part, to a lack of implementation of preventive chemotherapy, additional interventions such as health education, proper waste management, or linking malaria and soil-transmitted helminth treatment and prevention programs may also be needed. Further investigations on maternal-child outcomes as a result of hookworm infection during pregnancy will highlight public health interventional targets to reduce morbidity in pregnant women and children globally.

Point-of-Care Testing to Guide Treatment and Estimate Risk Factors for Sexually Transmitted Infections in Adolescents and Young People With Human Immunodeficiency Virus in Eswatini.

BACKGROUND: The World Health Organization (WHO) estimates 127 million new cases of Chlamydia trachomatis (CT), 87 million new cases of Neisseria gonorrhea (NG), and 156 million new cases of Trichomonas vaginalis (TV) each year, which corresponds to 355 (219-606), 303 (216-468), and 243 (97.6-425) thousand disability-adjusted life-years. In low-resource settings, however, sexually transmitted infections (STIs) are treated syndromically and many individuals with asymptomatic infection may be missed, especially adolescents and young adults with human immunodeficiency virus (HIV). METHODS: We enrolled patients aged 15-24 with HIV (N = 300) attending a family-centered HIV clinic in Mbabane, Eswatini. Participants completed a sexual history questionnaire and provided urine as well as oropharyngeal and/or vaginal swabs, if sexually active, for testing with Xpert CT/NG and TV tests. Analysis included bivariate and multivariate odds ratios and test sensitivity and specificity. RESULTS: Sexually transmitted infection rates were highest (25.0%; 95% confidence interval [CI], 15.2-37.3) in females ages 20-24 who were ever sexually active. In patients with confirmed STIs, NG (15 of 32, 47%) was more common than CT (9 of 32, 28%) and TV (8 of 32, 25%). Syndromic screening alone had a sensitivity of 32.0% (95% CI, 14.9-53.3) and specificity of 86.0% (95% CI, 79.0-91.4) but varied by gender. The presence of an STI was associated with reporting new sexual partner(s) (OR = 2.6; 95% CI, 1.1-6.4), sometimes to never using condoms (OR = 4.2; 95% CI, 1.7-10.2), most recent sexual partner >25 years old (OR = 3.2; 95% CI, 1.3-7.9), and HIV diagnosis at age ≥15 years (OR = 3.4; 95% CI, 1.4-8.2). CONCLUSIONS: Syndromic screening alone performed poorly. Routine diagnostic testing significantly increases STI detection and should be considered in high-risk populations, such as adolescents and young adults with HIV.

Infantile Pyknocytosis: An Uncommon Cause of Newborn Hemolytic Anemia.

Infantile pyknocytosis is a rare cause of neonatal hemolytic anemia, which presents in the first few weeks of life. We report a classic case of infantile pyknocytosis that presented to our institution with rebound hyperbilirubinemia after receiving phototherapy. The infant was found to have a hemoglobin of 5.8 g/dL, requiring a total of 15 mL/kg of red blood cells (in 2 separate transfusions) before discharge. The diagnosis was ultimately made by a review of the peripheral blood smear. We review the literature and suggest pediatricians consider infantile pyknocytosis on their differential when hemolytic anemia presents in the newborn period.

Using an Innovative Telehealth Model to Support Community Providers Who Deliver Perinatal HIV Care.

Mountain West AETC (AIDS Education and Training Center) ECHO (Extension for Community Healthcare Outcomes), a longitudinal HIV telemen-toring program, connects community providers and a multidisciplinary specialist team at the University of Washington. The program employs focused lectures and real-time case discussions to educate and support providers in low-resource and rural settings. We assessed the impact of the program on management of perinatal HIV through surveying community providers who participate, and reviewing cases presented by providers for consultation. One hundred percent of providers who presented a perinatal HIV case for ECHO consultation reported that presentation "very much" impacted management of the case, and 93% of survey respondents reported that ECHO participation helped them stay up to date on national perinatal HIV guidelines. All 13 cases had the successful outcome of prevention of mother-to-child transmission of HIV. The ECHO model can effectively support and educate community providers who care for HIV-infected pregnant women.