Children In Resource-limited Settings Research Articles

2165. Surveillance of Severe Viral Respiratory Infections among Children Presenting to Hôpital Saint Damien in Haiti

Abstract Background Learning the burden and seasonality of respiratory viral infections in children in resource-limited settings is critical for hospital infection care and prevention and national public health programs. We built a prospective surveillance program of severe acute respiratory illness (SARI) in hospitalized children at Hôpital Saint Damien - Nos Petits Frères et Soeurs to gather local evidence and support informed clinical and policy decision-making. The COVID-19 pandemic erupted as we were launching our project, requiring the use of available point-of-care diagnostics. Methods Children < 18 years of age with cough, history of fever ≥ 38 C°, of < 10 days evolution, and requiring hospitalization were included in the study. We obtained a nasopharyngeal swab and collected demographic and clinical data for eligible patients. Samples were tested using antigen test on-site for influenza A (Flu A) and B (Flu B), respiratory syncytial virus (RSV), and SARS-CoV-2. Afterwards, all specimens (both negative and positive) were stored and shipped for molecular studies. Results We obtained and tested 167 samples from patients since April 30, 2021, through January 31, 2022. Single isolates were detected in 88 samples (53%), multiple isolates in 20 samples (12%), and no isolates in 59 samples (35%). Positive cases for RSV, Flu A, and Flu B peaked between November and January. Rhinovirus 1A (RhV) was detected throughout the study period, with peaks around August-September and was the most often detected viral isolate (49, 38%), followed by RSV (37, 29%). Co-infections were seen with RSV, Flu A, RhV, and SARS-CoV-2. Molecular studies detected 7 isolates of Flu A not detected by rapid test, 1 isolate of Flu B, and 1 isolate of SARS-CoV-2. However, it failed to detect 2 isolates of Flu A detected by rapid test, 1 isolate of Flu B, and 1 isolate of SARS-CoV-2. Conclusion Our study captured circulating respiratory viruses in children with SARI in Haiti during the COVID-19 pandemic. Preliminary data suggest an increase in respiratory viruses between August and January. Improving point-of-care diagnostics can better inform providers of the local epidemiology of respiratory viruses and support clinical decision-making, such as good use of antibiotics. However, we confirmed the sensitivity of molecular testing. Disclosures All Authors: No reported disclosures.

Bilateral pallidotomy for acquired or heredodegenerative generalized dystonia in children.

Dystonias are relatively rare disorders characterized by sustained or intermittent muscle contractions causing abnormal movements or postures. Generalized dystonia is a therapeutic challenge because medications are unable to control dystonia adequately in most patients. These patients may be candidates for surgical therapy. The commonly used surgical procedures in these patients are pallidotomy and deep brain stimulation. Limited studies are available on the role of pallidotomy in children with acquired/heredodegenerative generalized dystonia. The objective of this study was to describe the authors' experience with bilateral pallidotomy in this group of patients. The authors retrospectively reviewed all pediatric patients (less than 18 years of age) with acquired/heredodegenerative generalized dystonia who underwent bilateral simultaneous pallidotomy at their center between January 2014 and January 2021. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores before and after surgery were recorded. Complications arising after the procedure were recorded as well. Ten patients (8 male and 2 female) with a mean (range) age of 11.1 (5-17) years were included in this study. The mean duration between disease onset and surgical intervention was 3.9 years. Two patients presented in status dystonicus. The mean ± SD (range) preoperative BFMDRS score of the patients without status dystonicus (n = 8) was 80 ± 18.9 (59.5-108). The mean ± SD BFMDRS score at the time of discharge from the hospital after surgery was 58.8 ± 37.9. Three patients had more than 20% change in BFMDRS score at the time of discharge from the hospital. The mean improvement was 25.5% at the end of 1 year. Of 5 surviving patients in the non-status dystonicus group, 3 patients had more than 40% change in BFMDRS score while the other 2 patients developed recurrence at the last follow-up (4.5 years). Status dystonicus abated after bilateral pallidotomy in both patients. Permanent bulbar complications were seen in 2 patients. Bilateral pallidotomy may result in clinically significant improvement in children with acquired/heredodegenerative generalized dystonia, although the benefits should be closely weighed against the risk of irreversible bulbar dysfunction. It is a viable option for children in resource-limited settings.

Development and design of the first structured clinic-based program in lower resource settings to transition emerging adults with type 1 diabetes from pediatric to adult care.

Type 1 diabetes (T1D) is increasing in young people worldwide and more children in resource limited settings are living into adulthood. There is a need for rigorous testing and reporting of evidence-based and stakeholder-informed strategies that transition individuals with T1D from pediatric to adult care. We present the development of and design of the first structured transition program in Delhi, India, to inform similar efforts in India and resource limited settings. The intervention development team included clinicians and researchers with expertise in T1D and the implementation context. To select intervention outcomes, establish intervention targets, and design session modules, we drew upon formative research conducted at prospective intervention implementation sites, consensus guidelines, and previous care transition and behavior change research conducted in developed settings. We used the Template for Intervention Description and Replication and GUIDance for the rEporting of intervention Development checklists to report the intervention and development process. The 15-month program ("PATHWAY") includes five quarterly ~30 minute sessions delivered predominantly by diabetes educators at pediatric and adult clinics, which coincide with routine care visits. Primary program components include educational and behavioral sessions that address psychosocial drivers of clinic attendance and self-management, diabetes educators as transition coordinators and counselors, and a one-year "overlap period" of alternating visits between pediatric and adult providers. We followed a systematic and transparent process to develop PATHWAY, which facilitated rich description of intervention context, guiding principles, targets, and components. Dependence on previously published program examples to design PATHWAY may have introduced challenges for program feasibility and effectiveness, underscoring the importance of input gathering from prospective intervention actors at multiple points in the development process. This detailed report in combination with future evaluations of PATHWAY support efforts to increase rigorous development and testing of strategies to improve outcomes among emerging adults with T1D.

Evidence of reduced academic performance among schoolchildren with helminth infection.

BackgroundSoil-transmitted helminths (STHs) pose a formidable health risk to school-age children in resource-limited settings. Unfortunately, mass deworming campaigns have been derailed since the onset of the coronavirus disease 2019 pandemic. The present study assessed the cross-sectional associations between STHs, nutritional status and academic performance of schoolchildren in the Banda District of Ghana.MethodsSchoolchildren (5–16 y of age; n=275) were recruited through both school and household visits by community health workers using a multistage cluster sampling technique. In addition to school microscopy, anthropometric records were also taken.ResultsThe prevalence of geohelminthiasis was 40.4% (95% confidence interval 34.6 to 46.2). STHs targeted for elimination by the World Health Organization and national programmes were detected among schoolchildren. Children with intestinal parasite infection (53.7 [standard deviation {SD} 11.5]) had lower mean academic scores compared with uninfected children (59.6 [SD 16.9]) (p=0.034). In multiple regression analysis, intestinal parasite infection status and z-scores for weight-for-age showed a collective significant effect on the academic score (F1117=8.169, p<0.001, R2=0.125).ConclusionsSchoolchildren with STHs had poorer academic performance compared with uninfected children, despite their nutritional status. In addition to school feeding programmes, school-based mass drug administration campaigns may be critical for improving learning outcomes in young schoolchildren.

Immunization of Rabbits with a Quadrivalent Shigella Bioconjugate Vaccine Induces Functional Antibodies Reactive with Shigella Isolates from Kenya.

ABSTRACTDiarrheal diseases are a leading cause of global morbidity and mortality, disproportionately affecting children in resource-limited settings. Although improvements in hygiene and access to clean water are helpful, vaccines are considered essential due to the low infectious dose of Shigella species and increasing antibiotic resistance. Building on achievements with conjugate vaccines, a safe and immunogenic novel bioconjugate vaccine linking Shigella O-antigen to Pseudomonas aeruginosa exoprotein A has been developed to induce immunity against Shigella flexneri 2a, 3a, and 6 and S. sonnei. This study evaluated the breadth of reactivity and functionality of pooled serum from rabbits immunized with monovalent and quadrivalent Shigella bioconjugates formulated with or without an adjuvant against Shigella serotypes isolated in Kenya. Rabbit sera were assayed by colony blot for reactivity with 67 isolates of Shigella serotypes targeted by the vaccine, S. flexneri (2a, 3a, and 6) and S. sonnei, and 42 isolates of Shigella serotypes not targeted by the vaccine, S. flexneri (1b, 2b, 4a, and 4b), S. boydii, and S. dysenteriae. Shigella isolates testing positive in the colony blot assay were then used to assess functional activity using a bactericidal assay. Of the 41 Shigella isolates targeted by the vaccine, 22 were reactive with the adjuvanted quadrivalent and the respective monovalent rabbit sera. The S. flexneri 2a and 3a monovalent rabbit serum cross-reacted with S. flexneri 3a, 2b, and 2a, respectively. Immunization with the adjuvanted quadrivalent vaccine also induced cross-reactivity with isolates of S. flexneri 2b, 4a, and 4b. Collectively, these results suggest that the Shigella quadrivalent vaccine may be more broadly protective than designed, offering a promising solution to Shigella infections.IMPORTANCE Diarrheal diseases are the third leading cause of death globally, disproportionally affecting low- to middle-income countries like Kenya, with Shigella species being the leading cause of bacterial diarrhea, especially in children. The low infectious dose and high antibiotic resistance levels complicate treatment, leading to long-term sequelae that necessitate control measures such as vaccines to reduce morbidity and mortality rates, especially among children under 5 years of age. A quadrivalent bioconjugate Shigella vaccine was recently developed to safely and effectively induce immunity against four important Shigella spp. This study demonstrates the breadth of reactivity and functionality of the parenterally administered bioconjugate vaccine by evaluating the ability of rabbit sera to bind and kill Shigella isolates recently collected in Kenya. These results suggest that the Shigella quadrivalent vaccine may be more broadly protective than designed and may offer a promising solution to the morbidity and mortality associated with Shigella infections.

Psychometric properties of the ASEBA Child Behaviour Checklist and Youth Self-Report in sub-Saharan Africa -A systematic review.

Behavioural screening tools may be used to identify at-risk children in resource-limited settings in sub-Saharan Africa. The ASEBA forms (Child Behaviour Checklist and Youth Self-Report) are frequently translated and adapted for use in sub-Saharan African populations, but little is known about their measurement properties in these contexts. We conducted a systematic review of all published journal articles that used the ASEBA forms with sub-Saharan African samples. We evaluated the reported psychometric properties, as well as the methodological quality of the psychometric evaluations, using COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) guidelines. Fifty-eight studies reported measurement properties of the ASEBA forms. Most studies came from Southern (n = 29, 50%) or East African (n = 25, 43%) countries. Forty-nine studies (84%) used translated versions of the tool, but details regarding the translation process, if available, were often sparse. Most studies (n = 47, 81%) only reported internal consistency (using coefficient alpha) for one or more subscale. The methodological quality of the psychometric evaluations ranged from 'very good' to 'inadequate' across all measurement properties, except for internal consistency. There is limited good quality psychometric evidence available for the ASEBA forms in sub-Saharan Africa. We recommend (i) implementing a standardised procedure for conducting and reporting translation processes and (ii) conducting more comprehensive psychometric evaluations of the translated versions of the tools.

Safety of Vasopressor Medications through Peripheral Line in Pediatric Patients in PICU in a Resource-Limited Setting.

Objective Central venous catheter (CVC) placement in children in resource-limited settings (RLSs) can be a difficult task. Timely administration of vasopressor medications (VMs) through peripheral intravenous line (PIV) can help overcome this limitation. We aim to determine the safety of administration of vasopressor medications through PIVs in children admitted to pediatric intensive care unit (PICU) in a RLS. Design Prospective observational study. Setting. An eight-bedded PICU of a tertiary care hospital. Patients. Children aged 1 month to 18 years admitted to the PICU. Intervention. None. Measurements and Main Results. All children (aged 1 month–18 years) who received VMs through PIV line from January 2019 to December 2019 were prospectively followed for the development of extravasation, conversion to CVC, duration of infusion, maximum dose of VMs used, maximum vasopressor inotropic score (VIS), and coadministration of vasopressor medication through PIV line. Results are presented as means with standard deviation and frequency with percentages. A total of 369 patients were included in the study, 221 (59.9%) were males, and the median age of the study population was 24 months (IQR; 6–96). Epinephrine was the most frequently used vasopressor medication (n = 279, 75.6%), followed by milrinone (n = 93, 25.2%), norepinephrine (n = 42, 11.4%), and dopamine (n = 32, 8.7%). The maximum dose of vasopressor medication was 0.25 µg/kg/min (epinephrine), 0.2 µg/kg/min (norepinephrine), 15 µg/kg/min (dopamine), and 0.8 µg/kg/min (milrinone). Extravasation was observed in 8 (2.2%) patients, while PIV line was converted to CVC in 127 (34.4%) children. Maximum dose of epinephrine, norepinephrine, VIS score, and PRISM Score was associated with conversion to CVC (p < 0.001), while none of them was associated with risk for extravasation. Conclusion Vasopressor medication through PIV line is a safe option in patients admitted to the PICU.

Clostridioides difficile colonization among very young children in resource-limited settings

ObjectivesTo describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings. MethodsWe tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth. ResultsThe prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02–1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39–2.16), and treated water (aRR: 1.24; 95% CI: 1.02–1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age. DiscussionC. difficile colonization among children ages 0–2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.

Clinical and Radiological Characteristics of Critically Ill Children with COVID-19 Disease Presenting to a Resources Limited Setting Paediatric Intensive Care Unit

BackgroundIn March 2020, WHO declared COVID-19 disease caused by SARS-nCOV-2 as a pandemic. COVID-19 is characterized by a spectrum of disease syndrome commonly affecting respiratory system. Progression to severe and critical disease is seen in 20% of confirmed cases. Childhood clinical presentation and radiological features children in resource limited settings including Africa has been less described in literature. Study aimed to describe common clinical characteristics and radiological features of childhood covid-19 disease with critical illness.&#x0D; Methods&#x0D; Electronic records of paediatric patients aged 2 months to 14 years admitted to PICU of KATH between the period of 1st February - 31st August 2021 were respective reviewed. Clinical features were collected using a case record form and radiological features reviewed by radiologist.&#x0D; ResultsPICU admitted 78 patients during the study, 8 covid-19 cases (10%); 7 confirmed and 1 probable. The median age 4 years (0-14 years), 6 males. The most common presenting features include; altered level of consciousness, breathlessness, and fever. The respiratory system was the most common site of presentation followed by circulatory system. Associated co morbid condition on admission includes sickle cell disease and road traffic accident. Six out of 7 had CXR showing abnormal features; 4 had ground glass appearance, 3 with consolidations, reticulo-nodular and pleural effusion respectively, and peri-bronchial thickening 2. Three (37.5%) presented as ARDS with severe hypoxaemia4. Echocardiography in 2 patients showed abnormalities: myocardial dysfunction, pericardial effusion and right ventricular failure. Seven (87%) received mechanical ventilation and 2 (25%) received inotrope support. PICU survival was 75% about half of the overall outcome reported on the continent2.&#x0D; ConclusionThis study shows that COVID-19 and radiological features suggest severity of illness requiring critical care services including mechanical ventilation and inotrope therapy(Please rephrase sentence). Early identification and referral to centres with PICU capacity are needed for management.

Continuous positive airway pressure for children in resource-limited settings, effect on mortality and adverse events: systematic review and meta-analysis

ObjectiveDetermine non-invasive ventilation with continuous positive airway pressure (CPAP) outcomes for paediatric respiratory distress in low-income and middle-income countries (LMICs).DesignSystematic review and meta-analysis.SettingLMIC hospitals.PatientsOne month to 15 year olds with...

Evolution of a Bidirectional Pediatric Critical Care Educational Partnership in a Resource-Limited Setting.

Introduction: Children in resource-limited settings are disproportionately affected by common childhood illnesses, resulting in high rates of mortality. A major barrier to improving child health in such regions is limited pediatric-specific training, particularly in the care of children with critical illness. While global health rotations for trainees from North America and Europe have become commonplace, residency and fellowship programs struggle to ensure that these rotations are mutually beneficial and do not place an undue burden on host countries. We created a bidirectional, multimodal educational program between trainees in Manila, Philippines, and Baltimore, Maryland, United States, to improve the longitudinal educational experience for all participants.Program Components: Based on stakeholder input and a needs assessment, we established a global health training program in which pediatricians from the Philippines traveled to the United States for observerships, and pediatric residents from a tertiary care center in Baltimore traveled to Manila. Additionally, we created and implemented a contextualized simulation-based shock curriculum for pediatric trainees in Manila that can be disseminated locally. This bidirectional program was adapted to include telemedicine and regularly scheduled “virtual rounds” and educational case conferences during the COVID-19 pandemic. Providers from the two institutions have collaborated on educational and clinical research projects, offering opportunities for resource sharing, bidirectional professional development, and institutional improvements.Conclusion: Although creating a mutually beneficial global health partnership requires careful planning and investment over time, establishment of a successful bidirectional educational and professional development program in a limited-resource setting is feasible and benefits learners in both countries.

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

BackgroundMeningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire® FilmArray® Meningitis/Encephalitis multiplex PCR panel (BioFire ME) in HIV-infected adults and HIV-infected and uninfected children presenting with suspected meningitis in Uganda. MethodsWe tested cerebrospinal fluid (CSF) using a stepwise meningitis diagnostic algorithm including BioFire ME. We determined the diagnostic performance of BioFire ME for cryptococcal meningitis, using cryptococcal antigen (CrAg) and CSF culture as reference standards, and assessed other central nervous system (CNS) pathogens identified by the panel. ResultsWe evaluated 328 adult and 42 pediatric CSF specimens using BioFire ME. Of the adult CSF samples tested, 258 were obtained at baseline, and 70 were obtained from repeat lumbar punctures in cryptococcal meningitis. For Cryptococcus, sensitivity was 82%, specificity was 98%, PPV was 98%, and NPV was 79% in baseline specimens using CSF CrAg as the reference standard. Among follow-up specimens, a negative BioFire ME for Cryptococcus predicted CSF culture sterility with 84% NPV. Overall sensitivity was decreased at low fungal burdens: 29% for 0–99 Cryptococcus CFU/mL compared to 94% for ≥100 CFU/mL in baseline specimens. Other pathogens detected included E. Coli, H. influenzae, S. pneumoniae, CMV, enterovirus, HSV, HHV-6, and VZV. Two specimens tested positive for S. pneumoniae and one for Cryptococcus in the pediatric population. ConclusionsMultiplex PCR is a promising rapid diagnostic test for meningitis in adults and children in resource-limited settings. Cryptococcus at low fungal burdens in CSF may be missed by BioFire ME.

Overview of Langerhans Cell Histiocytosis among Children

Aim: To analyze clinical manifestations, course and outcome of Langerhans Cell Histiocytosis in children in resource limited settings lacking salvage therapy. Study design: Observational retrospective study Place and duration of study: Department of Haematology/Oncology, The Children’s Hospital, Lahore Pakistan from 1st January 2011 to 31st December 2018. Methodology: Sixty-five patients with age range from&lt;1 to 8 years included analysing their age, gender, clinical classification, course of therapy and outcome. The major treatment was composed of either prednisolone and vinblastine or cytarabine pulses. Results: There were 59% males and 41% females. Forty-seven (72%) patients presented with multi system-LCH with 49% Risk Organ involvement. Most of them 42 (65%) had bone lesions while 15patients (23%) presented with central nervous system involvement. Forty patients (61%) have completed treatment, 11(17%) left against medical advice and 12(18%)patients expired due to progressive disease and worsening infection. Only 2 patients were put on palliation with progressive brain parenchyma disease. 22 patients (34%) had reactivations of disease requiring therapy for more than one-year (p-value=0.06), while 15 (23%) patients received two cycles of initiation therapy before continuation therapy started. The treatment initiated &gt;6 months after the onset of symptoms in 48 (74%) patients. Conclusion: Early diagnosis and timely initiation of therapy are of utmost importance to reduce mortality and morbidity. There is a dire need of social support to reduce treatment abandonment in low-middle-income countries LMIC. Keywords: Paediatric Langerhans cell histiocytosis, Resource-limited settings, Delayed diagnosis, Abandonment

The utility of a modified W.H.O. TB screening tool among children at a Botswana child welfare clinic

Background: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment.&#x0D; Objective: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a “Well Child” Clinic (CWC).&#x0D; Methods: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status.&#x0D; Results: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19).&#x0D; Conclusion: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detec- tion and treatment of TB in HIV exposed children in resource limited settings.&#x0D; Keywords: Childhood TB screening; HIV Exposure screening; TB/HIV integration.

The utility of a modified WHO TB screening tool among children at a Botswana child welfare clinic.

In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a "Well Child" Clinic (CWC). Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detection and treatment of TB in HIV exposed children in resource limited settings.

Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load

BackgroundMany HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there’s limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).MethodsHIV-infected Ugandan children aged 1–12 years from HIV-care programs with > 1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and > 400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression.ResultsAt baseline all children (n = 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5–9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p = 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p = 0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p = 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p = 0.15). Longer duration of a child’s ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p < .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL.ConclusionWith increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.Trial registrationClinicalTrials.gov NCT04489953, 28 Jul 2020. Retrospectively registered. (https://register.clinicaltrials.gov).

Sensitive and Feasible Specimen Collection and Testing Strategies for Diagnosing Tuberculosis in Young Children

Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.

Thymus size and its correlates among children admitted with severe acute malnutrition: a cross-sectional study in Uganda

BackgroundMalnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM.MethodsThis cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM.ResultsAmong 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm2, p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01).ConclusionThe thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Pediatric Emergency and Critical Care Resources and Infrastructure in Resource-Limited Settings: A Multicountry Survey.

To describe the infrastructure and resources for pediatric emergency and critical care delivery in resource-limited settings worldwide. Cross-sectional survey with survey items developed through literature review and revised following piloting. The electronic survey was disseminated internationally in November 2019 via e-mail directories of pediatric intensive care societies and networks and using social media. Healthcare providers who self-identified as working in resource-limited settings. None. Results were summarized using descriptive statistics and resource availability was compared across World Bank country income groups. We received 328 responses (238 hospitals, 60 countries), predominantly in Latin America and Sub-Saharan Africa (n = 161, 67.4%). Hospitals were in low-income (28, 11.7%), middle-income (166, 69.5%), and high-income (44, 18.4%) countries. Across 174 PICU and adult ICU admitting children, there were statistically significant differences in the proportion of hospitals reporting consistent resource availability ("often" or "always") between country income groups (p < 0·05). Resources with limited availability in lower income countries included advanced ventilatory support, invasive and noninvasive monitoring, central venous access, renal replacement therapy, advanced imaging, microbiology, biochemistry, blood products, antibiotics, parenteral nutrition, and analgesic/sedative drugs. Seventy-seven ICUs (52.7%) were staffed 24/7 by a pediatric intensivist or anesthetist. The nurse-to-patient ratio was less than 1:2 in 71 ICUs (49.7%). Contemporary data demonstrate significant disparity in the availability of essential and advanced human and material resources for the care of critically ill children in resource-limited settings. Minimum standards for essential pediatric emergency and critical care in resource-limited settings are needed.

Long-Term Outcomes and Risk Factors for Mortality in a Cohort of HIV-Infected Children Receiving Antiretroviral Therapy in Vietnam.

BackgroundManagement of HIV-infected children on a long-term basis is a challenge in resource-limited countries. The aim of this study is to evaluate the long-term outcome and identify the risk factors for mortality in a cohort of children with antiretroviral therapy (ART) in Vietnam.Patients and MethodsA retrospective cohort study was conducted in children aged 0–15 years, seen at the outpatient clinic of the Women and Children Hospital of An Giang, Vietnam, from August 2006 to May 2019. Cox proportional-hazard models were used to determine factors associated with mortality.ResultsA total of 266 HIV-infected children were on ART. During 1545 child-years of follow-up (median follow-up was 5.8 years), 28 (10.5%) children died yielding a mortality rate of 1.8 death per 100 child-years. By multivariate analysis, World Health Organization clinical stage 3 or 4 (AHR; 7.86, 95% CI; 1.02–60.3, P= 0.047), tuberculosis (TB) co-infection (AHR; 6.26, 95% CI; 2.50–15.64, P= 0.001) and having severe immunosuppression before ART (AHR; 11.73, 95% CI; 1.52–90.4, P= 0.018) were independent factors for mortality in these children.ConclusionAntiretroviral therapy has reduced mortality in HIV-infected children in resource-limited settings. Independent risk factors for mortality were advanced clinical stage (3 or 4), TB co-infection and severe immunosuppression. Early investigation and treatment of TB co-infection allow early ART initiation which may improve outcomes in our settings.