The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children’s rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population

Fostering reciprocity in global health partnerships through a structured, hands-on experience for visiting postgraduate medical trainees

BACKGROUND: Global health programs that allow international experiences for US learners should also enable reciprocal learning experiences for international learners, particularly if that is a need identified by the partner institution. METHODS: A partnership between Indiana University and Moi University, Kenya, has successfully hosted 41 visiting Kenyan internal medicine and pediatrics registrars at Indiana University since 2006. The program's logistics, curriculum, and evaluation are described. RESULTS: The registrars rotated through nephrology, cardiology, hematology and oncology, infectious diseases, and intensive care, as well as related ambulatory experiences, functioning on a level comparable to fourth-year medical students. They showed significant improvement in pretest and posttest scores on a standardized National Board of Medical Examiners examination (P  =  .048). International learners experienced culture shock, yet they felt the Indiana University elective was helpful and would recommend it to future participants. CONCLUSIONS: Global health programs can reciprocate the benefits derived for US students and residents by offering learning experiences to international learners if that is an expressed need from the international partner. Barriers to those experiences can be overcome, and the hands-on, elective experience has the potential to positively affect the knowledge and attitudes of participants as well as the home nation

Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children

BACKGROUND: Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure. METHODS: In a population of HIV-infected Kenyan children on antiretroviral therapy including nevirapine (NVP), we used a one-compartment model with previously established PK parameters and Medication Event Monitoring Systems (MEMS®)-recorded dosing times to estimate the mean plasma concentration of NVP (Cp) in individual patients during 1 month of follow-up. Intended NVP concentration (Cp') was calculated under a perfectly followed dosing regimen and frequency. The ratio between the two (R = Cp/Cp') characterized the patient's NVP exposure as compared to intended level. Smaller R values indicated poorer adherence. We validated R by evaluating its association with MEMS®-defined adherence, CD4%, and spot-check NVP plasma concentrations assessed at 1 month. RESULTS: In data from 152 children (82 female), children were mean age 7.7 years (range 1.5-14.9) and on NVP an average of 2.2 years. Mean MEMS® adherence was 79%. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS® adherence (p < 0.0001), and lower-than-median R values were significantly associated with lower NVP drug concentrations (p = 0.0018) and lower CD4% (p = 0.0178), confirming a smaller R value showed poorer adherence. CONCLUSION: The proposed adherence measures, R, captured patient drug-taking behaviours and PK properties

Early Childhood Development in Children Born to HIV-Infected Mothers: Perspectives From Kenyan Clinical Providers and Caregivers

Objective. To understand the perspectives of clinical providers and caregivers regarding early childhood development (ECD) in children born to HIV-infected mothers in Kenya. Methods. This was a qualitative study of provider and caregiver perspectives on ECD at 5 Kenyan HIV clinics, using semistructured interviews and focus group discussions. Constant comparison and triangulation methods were employed to elucidate the concepts of ECD. Results. Twenty-five providers and 67 caregivers participated. While providers understood ECD in terms of milestones, caregivers strongly equated ECD with physical growth. Factors affecting ECD, such as nutrition, perinatal effects, and illness, were perceived differently by providers and caregivers. Both groups generally believed that HIV-infected children would have typical ECD if adherent to their HIV treatment. Conclusions. Important considerations regarding ECD in this population were uncovered. Understanding provider and caregiver perspectives’ on ECD in HIV-exposed children is critical for promoting ECD in this community

Growth of young HIV-infected and HIV-exposed children in western Kenya: A retrospective chart review

Introduction The objective of this study was to determine the growth patterns, rates of malnutrition, and factors associated with malnutrition in children born to HIV-infected mothers in western Kenya using data from an electronic medical record system. Methods This study was a retrospective chart review of HIV-infected (HIV+) and–exposed (HEU) children (<5 years) using data collected prospectively in the course of routine clinical care and stored in the electronic medical record system in western Kenya between January 2011 and August 2016. Demographics and anthropometrics were described, with Chi-square testing to compare proportions. Multiple variable logistic regression analysis was used to identify correlates of children being stunted, underweight, and wasted. We also examined growth curves, using a resampling method to compare the areas under the fitted growth curves to compare males/females and HIV+/HEU. Results Data from 15,428 children were analyzed. The children were 51.6% (n = 7,955) female, 5.2% (n = 809) orphans, 83.3% (n = 12,851) were HEU, and 16.7% (n = 2,577) were HIV+. For HIV+ children assessed at 24 months, 50.9% (n = 217) were stunted, 26.5% (n = 145) were underweight, and 13.6% (n = 58) were wasted, while 45.0% (n = 577) of HEU children were stunted, 14.8% (n = 255) were underweight, and 5.1% (n = 65) were wasted. When comparing mean z-scores, HIV+ children tended to have larger and earlier dips in z-scores compared to HIV-exposed children, with significant differences found between the two groups (p<0.001). Factors associated with an increased risk of malnutrition included being male, HIV+, and attending an urban clinic. Maternal antiretroviral treatment during pregnancy and mixed feeding at 3 months of age decreased the risk of malnutrition. Conclusions HIV+ and HEU children differ in their anthropometrics, with HIV+ children having overall lower z-scores. Continued efforts to develop and implement sustainable and effective interventions for malnutrition are needed for children born to HIV+ mothers

Comprehensive evaluation of caregiver-reported antiretroviral therapy adherence for HIV-infected children

For HIV-infected children, adherence to antiretroviral therapy (ART) is often assessed by caregiver report but there are few data on their validity. We conducted prospective evaluations with 191 children ages 0-14 years and their caregivers over 6 months in western Kenya to identify questionnaire items that best predicted adherence to ART. Medication Event Monitoring Systems(®) (MEMS, MWV/AARDEX Ltd., Switzerland) electronic dose monitors were used as external criterion for adherence. We employed a novel variable selection tool using the LASSO technique with logistic regression to identify items best correlated with dichotomized MEMS adherence (≥90 or <90 % doses taken). Nine of 48 adherence items were identified as the best predictors of adherence, including missed or late doses in the past 7 days, problems giving the child medicines, and caregiver-level factors like not being present at medication taking. These items could be included in adherence assessment tools for pediatric patients

Nutritional Status of Orphaned and Separated Children and Adolescents Living in Community and Institutional Environments in Uasin Gishu County, Kenya

Objective: To describe the nutritional status of orphaned and separated children and adolescents (OSCA) living in households in the community (HH), on the street, and those in institutional environments in western Kenya. Methods: The study enrolled OSCA from 300 randomly selected households (HH), 19 Charitable Children’s Institutions(CCIs), and 100 street-involved children. Measures of malnutrition were standardized with Z-scores using World Health Organization criteria; Z-scores #-2 standard deviations (sd) were moderate-severe malnutrition. Data were analyzed using multivariable logistic regression adjusting for child age, sex, HIV status, whether the child had been hospitalized in theprevious year, time living with current guardian, and intra- household clustering for adequacy of diet and moderate-severe malnutrition. Results: Included are data from 2862 participants (1337 in CCI’s, 1425 in HH’s, and 100 street youth). The population was 46% female with median age at enrolment of 11.1 years. Only 4.4% of households and institutions reported household food security; 93% of children in HH reported an adequate diet vs. 95% in CCI’s and 99% among street youth. After adjustment, OSCA in HH were less likely to have an adequate diet compared to those in CCI’s (AOR 0.4, 95% CI 0.2–1.0). After adjustment, there were no differences between the categories of children on weight-for-age, weight-for-height, or BMI-for-age. Children living in HH (AOR 2.6, 95% CI: 2.0–3.4) and street youth (AOR: 5.9, 95% CI: 3.6–9.5) were more likely than children in CCI’s to be low height-for-age. Conclusion: OSCA in HH are less likely to have an adequate diet compared to children in CCI’s. They and street children are more likely to be moderately-severely low height-for-age compared to children in CCI’s, suggesting chronic malnutrition among them

Adherence to antiretroviral therapy in a clinical cohort of HIV-infected children in East Africa

Objective To describe antiretroviral therapy (ART) adherence and associated factors for a large HIVinfected pediatric cohort followed by sites of the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium. Methods This study utilized prospectively collected clinical data from HIV-infected children less than 13 years of age who initiated ART within 4 clinical care programs (with 26 clinical sites) in Kenya, Uganda, and Tanzania and were followed for up to 6 years. Programs used one of 3 adherence measures, including 7-day quantitative recall, 7-day categorical recall, and clinician pill assessments. We fit a hierarchical, three-level, logistic-regression model to examine adherence, with observations nested within patient, and patients within the 26 sites providing pediatric HIV data to this analysis. Results In East Africa, 3,304 children, 52.0% male, were enrolled in care and were subsequently observed for a median of 92 weeks (inter-quartile range [IQR] 50.3±145.0 weeks). Median age at ART initiation was 5.5 years ([IQR] 3.0±8.5 years). ªGoodº adherence, as reported by each clinic\u27s measures, was extremely high, remaining on average above 90% throughout all years of follow-up. Longer time on ART was associated with higher adherence (adjusted Odds Ratio±aOR±per log-transformed week on ART: 1.095, 95% Confidence Interval±CI± [1.052±1.150].) Patients enrolled in higher-volume programs exhibited higher rates of clinician- assessed adherence (aOR per log-500 patients: 1.174, 95% CI [1.108±1.245]).Significant site-level variability in reported adherence was observed (0.28), with even higher variability among patients (0.71). In a sub-analysis, being an orphan at the start of ART was strongly associated with lower ART adherence rates (aOR: 0.919, 95% CI [0.864±0.976]). Conclusions Self-reported adherence remained high over a median of 1.8 years in HIV care, but varied according to patient-level and site-level factors. Consistent adherence monitoring with validated measures and attention to vulnerable groups is recommended

Preventive Health Service Coverage Among Infants and Children at Six Maternal-Child Health Clinics in Western Kenya: A Cross-Sectional Assessment

Objectives Despite the substantial reduction of child mortality in recent decades, Kenya still strives to provide universal healthcare access and to meet other international benchmarks for child health. This study aimed to describe child health service coverage among children visiting six maternal and child health (MCH) clinics in western Kenya. Methods In a cross-sectional study of Kenyan children who are under the age of 5 years presenting to MCH clinics, child health records were reviewed to determine coverage of immunizations, growth monitoring, vitamin A supplementation, and deworming. Among 78 children and their caregivers, nearly 70% of children were fully vaccinated for their age. Results We found a significant disparity in full vaccination coverage by gender (p = 0.017), as males had 3.5 × higher odds of being fully vaccinated compared to females. Further, full vaccination coverage also varied across MCH clinic sites ranging from 43.8 to 92.9%. Conclusions for Practice Health service coverage for Kenyan children in this study is consistent with national and sub-national findings; however, our study found a significant gender equity gap in coverage at these six clinics that warrants further investigation to ensure that all children receive critical preventative services