Predictors of loss to follow-up among children attending HIV clinic in a hospital in rural Kenya

Introduction: African studies have reported high rates of loss to follow up (LTFU) among children in HIV care and treatment centres. Factors associated with LTFU may vary across populations. Few studies have been conducted among HIV infected children in care in rural areas of Kenya. Methods: this involved children aged less than 15 years on follow up at Kangundo Level 4 Hospital HIV clinic from January 2010 to December 2015. We obtained sociodemographic and clinical information from patient files and electronic databases. Univariate and multivariate regression analyses were conducted to identify factors predictive of LTFU. Results: a total of 261 HIV-infected children were followed up. The mean age was 10.0 years (IQR, 7-13) and median CD4 count of 582cells/ul (IQR 314-984). By December 2015, 171 children (65.5%) remained in active care, 32 (12.3%) transferred out, 13 (5%) died, while 45 (17.2%) were classified as LTFU. Out of the 45 children presumed as LTFU, we traced 44 out of the 45 children (98%) and found that their actual current status was as follows: 33 of the 44 children (75.0%) had dropped out of care (true LTFU). Factors strongly predictive of LTFU included low caregiver level of education (HR 2.3, 1.9-3.9, P = 0.001), WHO stage I and II at enrolment (HR 1.6, 1.4-2.1, P = 0.05). Conclusion: LTFU of HIV infected children was common with an incidence of 32.9 per 1000 child years and occurred early in treatment and risk factors included poverty, low caregiver education, male child and early HIV disease stage

Risk Factors for Hypoxia and Tachypnea Among Adolescents With Vertically-acquired HIV in Nairobi

Background: Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. Methods: We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99th percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics, and HIV severity estimated odds ratios for risk of hypoxia and tachypnea associated with potential risk factors. Results: Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV [adjusted odds ratio (aOR): 2.41] and low CD4 (aOR: 1.74) were associated with greater hypoxia risk, but confidence intervals (CIs) were wide and included the null (95% CI: 0.93–6.23 and 0.69–4.39, respectively). Low CD4 (aOR: 2.45, 95% CI: 1.39–4.32), current antiretroviral therapy use (aOR: 0.48, 95% CI: 0.27–0.86) and stunted growth (aOR: 3.46, 95% CI: 1.94–6.18) were associated with altered tachypnea risk. Conclusions: Hypoxia and tachypnea are common among adolescents with vertically-acquired HIV. There was a suggestion that advanced HIV and low CD4 were associated with greater hypoxia risk. Low CD4, lack of antiretroviral therapy use and stunted growth are risk factors for tachypnea. Our findings highlight the chronic lung disease burden in this population and may inform diagnostic algorithms

Coronavirus disease 2019 (COVID-19) pharmacologic treatments for children : research priorities and approach to pediatric studies

CITATION: Garcia-Prats, A. J. et al. 2021. Coronavirus Disease 2019 (COVID-19) Pharmacologic Treatments for Children: Research Priorities and Approach to Pediatric Studies. Clinical infectious diseases, 72(6):1067–1073. doi:10.1093/cid/ciaa885The original publication is available at https://academic.oup.com/cid/Clinical trials of pharmacologic treatments of coronavirus disease 2019 (COVID-19) are being rapidly designed and implemented in adults. Children are often not considered during development of novel treatments for infectious diseases until very late. Although children appear to have a lower risk compared with adults of severe COVID-19 disease, a substantial number of children globally will benefit from pharmacologic treatments. It will be reasonable to extrapolate efficacy of most treatments from adult trials to children. Pediatric trials should focus on characterizing a treatment’s pharmacokinetics, optimal dose, and safety across the age spectrum. These trials should use an adaptive design to efficiently add or remove arms in what will be a rapidly evolving treatment landscape, and should involve a large number of sites across the globe in a collaborative effort to facilitate efficient implementation. All stakeholders must commit to equitable access to any effective, safe treatment for children everywhere.https://academic.oup.com/cid/article/72/6/1067/5864500?login=truePublishers versio

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

<p>Abstract</p> <p>Background</p> <p>In resource-limited settings, such as Kenya, access to CD4 testing is limited. Therefore, evaluation of less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children.</p> <p>Objectives</p> <p>To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected children.</p> <p>Methods</p> <p>This was a hospital based retrospective study conducted in three HIV clinics in Kisumu and Nairobi in Kenya. TLC, CD4 count and CD4 percent data were abstracted from hospital records of 487 antiretroviral-naïve HIV-infected children aged 1 month - 12 years.</p> <p>Results</p> <p>TLC and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest correlation seen in children with severe immuno-suppression (r = 0.72, p < 0.001) and children >59 months of age (r = 0.68, p < 0.001). Children were considered to have severe immuno-suppression if they met the following WHO set CD4 count thresholds: age below 12 months (CD4 counts < 1500 cells/mm³), age 12-35 months (CD4 count < 750 cells/mm3), age 36-59 months (CD4 count < 350 cells/mm³, and age above 59 months (CD4 count < 200 cells/mm³). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm³for age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%, 33% and 62% respectively in predicting severe immuno-suppression using CD4 count as gold standard. Raising TLC thresholds to 7000, 6000, 4500 and 3000 cells/mm³for each of the stated age categories increased sensitivity to 71%, 64%, 56% and 86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but reduced specificity to 73%, 62%, 54% and 68% with negative predictive values of 54%, 65%, 71% and 87% respectively.</p> <p>Conclusion</p> <p>TLC is positively correlated with absolute CD4 count in children but current WHO age-specific thresholds had low sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity and therefore utility of TLC to identify immuno-suppressed children may be improved by raising the TLC cut off levels across the various age categories.</p

Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study

BACKGROUND: Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. METHODS: We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. RESULTS: The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9-5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%-51%) and specificity of 79% (95% CI, 71%-86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. CONCLUSIONS: Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable

Stakeholder perspectives for optimization of tuberculosis contact investigation in a high-burden setting.

INTRODUCTION:Optimal tuberculosis contact investigation impacts TB prevention, timely case finding and linkage to care, however data on routine implementation in high burden contexts is limited. MATERIALS AND METHODS:In a multi-method qualitative study based on individual interviews with TB patients, facility observations and focus group discussions with health workers (HWs) in 13 public health facilities, and key informant interviews with governmental and non-governmental experts, we describe TB contact investigation in the context of an urban setting in Kenya and identify opportunities for optimization. RESULTS:Invitation of TB patients to bring close contacts by HWs was key for all patient decisions that led to contact screening in addition to patients' understanding of TB transmission and desire to avoid contacts suffering from TB. Sub-optimal HW enquiry of TB patients and contacts presenting at the facility were missed opportunities which stemmed from lack of standardized operational procedures, documentation tools and HW training. Stakeholders proposed provision of fast tracked and holistic health packages for contacts seeking TB screening, and sustainable government led funding for the requisite infrastructure and workforce. CONCLUSION:TB contact invitation by HWs leading to contact screening occurs in this context. Stakeholder perspectives inform the design of an operational framework for optimized delivery

HIV-Associated Tuberculosis in Children and Adolescents: Evolving Epidemiology, Screening, Prevention and Management Strategies

Children and adolescents living with HIV continue to be impacted disproportionately by tuberculosis as compared to peers without HIV. HIV can impact TB screening and diagnosis by altering screening and diagnostic test performance and can complicate prevention and treatment strategies due to drug&ndash;drug interactions. Post-tuberculosis lung disease is an underappreciated phenomenon in children and adolescents, but is more commonly observed in children and adolescents with HIV-associated tuberculosis. This review presents new data related to HIV-associated TB in children and adolescents. Data on the epidemiology of HIV-associated TB suggests that an elevated risk of TB in children and adolescents with HIV persists even with broad implementation of ART. Recent guidance also indicates the need for new screening strategies for HIV-associated TB. There have been major advances in the availability of new antiretroviral medications and also TB prevention options for children, but these advances have come with additional questions surrounding drug&ndash;drug interactions and dosing in younger age groups. Finally, we review new approaches to manage post-TB lung disease in children living with HIV. Collectively, we present data on the rapidly evolving field of HIV-associated child tuberculosis. This evolution offers new management opportunities for children and adolescents living with HIV while also generating new questions for additional research

HIV-exposed uninfected infants: elevated cord blood Interleukin 8 (IL-8) is significantly associated with maternal HIV infection and systemic IL-8 in a Kenyan cohort

Abstract Background In low and middle income countries, human immunodeficiency virus (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and mortality than their unexposed counterparts. To determine possible immune correlates of this effect, we investigated the impact of in utero HIV exposure on the uninfected neonatal immune milieu and maternal factors mediating these abnormalities in a cohort of vaginally delivered mother-infants. Samples of delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while 19 Kenyan HIV-uninfected (HU) women and their infants were selected from a control cohort. Results Compared to HU cord plasma, HEU cord plasma contained significantly higher levels of pro-inflammatory cytokines interleukins (IL)-6 and -8 (both p < 0.001) and significantly lower levels of CXC motif chemokine 11 (CXC11) (p < 0.001). Mediation analysis demonstrated that maternal HIV infection status was a significant determinant of infant IL-8 responses: HEU status was associated with a ninefold higher infant:mother (cord:delivery) plasma levels of IL-8 (p < 0.005), whereas maternal viral load was negatively associated with HEU IL-8 levels (p = 0.04) and not associated with HEU IL-6 levels. Conclusions Exposure to maternal HIV infection drives an increase in prenatal IL-8 that is partially mediated by maternal cytokine levels. Differences between maternal and infant cytokine levels strongly suggest independent modulation in utero, consistent with prenatal immune activation. Elevated pro-inflammatory signals at birth may interfere with T cell responses at birth and subsequently influence immune maturation and the risk of morbidity and mortality in HEU infants