Seasonality of childhood tuberculosis cases in Kampala, Uganda, 2010-2015.

BackgroundSeasonality in tuberculosis (TB) has been described, especially in children. However, few studies have assessed seasonality of TB in the equatorial region, and none in children.ObjectivesTo assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses.MethodsWe retrospectively analyzed demographic and clinical data of children (under 15 years) diagnosed with TB at a pediatric TB clinic in Kampala, Uganda from 2010 to 2015. We performed decomposition analysis of the monthly case time series to assess seasonality. We compared monthly mean plots and performed Poisson regression to assess any association between TB diagnoses and temperature, rainfall, and influenza.ResultsOf the 713 childhood TB cases diagnosed at the clinic, 609 (85%) were clinically diagnosed and 492 (69%) were pulmonary cases. There were minimal monthly variations in TB cases, with a trough in December and peaks in July and October, but there was no significant seasonality. Temperature variations did not show a clear pattern with TB diagnoses. Rainfall alternated with TB diagnoses in the first half of the year, but then overlapped in the second half and was significantly associated with TB diagnoses. Influenza cases were significantly related to TB diagnoses with (β = 0.05, 95% CI 0.01 to 0.09, p = 0.01) or without (β = 0.06, 95% CI 0.01 to 0.1, p = 0.01) rainfall, and had particular overlap with pulmonary TB cases.ConclusionsSeasonal variations in childhood TB diagnoses were non-significant. Temperature did not have a clear pattern with TB diagnoses, but rainfall and influenza cases correlated with the primarily clinically diagnosed childhood TB cases

Mean corpuscular volume as a marker for adherence to antiretroviral therapy among HIV infected children and adolescents in Uganda

Mean corpuscular volume, which is an inexpensive and widely available measure to assess, increases in HIV infected individuals receiving zidovudine and stavudine raising the hypothesis that it could be used as a surrogate for adherence. The aim of this study was to examine the association between mean corpuscular volume and adherence to antiretroviral therapy among HIV infected children and adolescents aged 0–19 years in Uganda as well as the extent to which changes in mean corpuscular volume predict adherence as determined by virologic suppression. The investigator retrospectively reviewed and analyzed secondary data of 158 HIV infected children and adolescents aged 0–19 years who initiated antiretroviral therapy under an observational cohort at the Baylor College of Medicine Children\u27s Foundation - Uganda. Viral suppression was used as the gold standard for monitoring adherence and defined as viral load of \u3c 400 copies/ml at 24 and 48 weeks. Patients were at least 48 weeks on therapy, age 0.2–18.4 years, 54.4% female, 82.3% on zidovudine based regimen, 92% WHO stage III at initiation of therapy, median pre therapy MCV 80.6 fl (70.3–98.3 fl), median CD4% 10.2% (0.3%–28.0%), and mean pre therapy viral load 407,712.9 ± 270,413.9 copies/ml. For both 24 and 48 weeks of antiretroviral therapy, patients with viral suppression had a greater mean percentage change in mean corpuscular volume (15.1% ± 8.4 vs. 11.1% ± 7.8 and 2.3% ± 13.2 vs. -2.7% ± 10.5 respectively). The mean percentage change in mean corpuscular volume was greater in the first 24 weeks of therapy for patients with and without viral suppression (15.1% ± 8.4 vs. 2.3% ± 13.2 and 11.1% ± 7.8 vs. -2.7% ± 10.5 respectively). In the multivariate logistic regression model, percentage change in mean corpuscular volume ≥ 20% was significantly associated with viral suppression (adjusted OR 4.0; CI 1.2–13.3; p value 0.02). The ability of percentage changes in MCV to correctly identify children and adolescents with viral suppression was higher at a cut off of ≥ 20% (90.7%; sensitivity, 31.7%) than at ≥ 9% (82.9%; sensitivity, 78.9%). Negative predictive value was lower at ≥ 20% change (25%; specificity, 84.8%) than at ≥ 9% change (33.3%; specificity, 39.4%). Mean corpuscular volume is a useful marker of adherence among children and adolescents with viral suppression

Outcomes of empiric treatment for pediatric tuberculosis, Kampala, Uganda, 2010–2015

Abstract Background Childhood tuberculosis (TB) diagnoses often lack microbiologic confirmation and require empiric treatment. Barriers to empiric treatment include concern for poor outcomes and adverse effects. We thus determined the outcomes of empiric TB treatment from a retrospective cohort of children at a national referral hospital in Kampala, Uganda from 2010 to 2015. Methods Children were diagnosed clinically and followed through treatment. Demographics, clinical data, outcome and any adverse events were extracted from patient charts. A favorable outcome was defined as a child completing treatment with clinical improvement. We performed logistic regression to assess factors associated with loss to follow up and death. Results Of 516 children, median age was 36 months (IQR 15–73), 55% (95% CI 51–60%) were male, and HIV prevalence was 6% (95% CI 4–9%). The majority (n = 422, 82, 95% CI 78–85%) had a favorable outcome, with no adverse events that required treatment discontinuation. The most common unfavorable outcomes were loss to follow-up (57/94, 61%) and death (35/94, 37%; overall mortality 7%). In regression analysis, loss to follow up was associated with age 10–14 years (OR 2.38, 95% CI 1.15–4.93, p = 0.02), HIV positivity (OR 3.35, 95% CI 1.41–7.92, p = 0.01), hospitalization (OR 4.14, 95% CI 2.08–8.25, p < 0.001), and living outside of Kampala (OR 2.64, 95% CI 1.47–4.71, p = 0.001). Death was associated with hospitalization (OR 4.57, 95% CI 2.0–10.46, p < 0.001), severe malnutrition (OR 2.98, 95% CI 1.07–8.27, p = 0.04), baseline hepatomegaly (OR 4.11, 95% CI 2.09–8.09, p < 0.001), and living outside of Kampala (OR 2.41, 95% CI 1.17–4.96, p = 0.02). Conclusions Empiric treatment of child TB was effective and safe, but treatment success remained below the 90% target. Addressing co-morbidities and improving retention in care may reduce unfavorable outcomes

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

A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation

Abstract Background Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed by researchers at Baylor College of Medicine (Houston, Texas, USA) for TB bacteriological confirmation with promising results in pilot studies. Methods The study will take place in high TB/HIV burden countries (Mozambique, Eswatini and Uganda) where we will enroll, over a period of 30 months, 650 PLHIV (> 15) and 1295 children under 8 years of age (irrespective of HIV status) presenting pressumptive TB. At baseline, all participants will provide clinical history, complete a physical assessment, and undergo thoracic chest X-ray imaging. To obtain bacteriological confirmation, participants will provide respiratory samples (1 for adults, 2 in children) and 1 stool sample for Xpert Ultra MTB/RIF (Cepheid, Sunnyvale, CA, USA). Mycobacterium tuberculosis (M.tb) liquid culture will only be performed in respiratory samples and lateral flow lipoarabinomannan (LF-LAM) in urine following WHO recommendations. Participants will complete 2 months follow-up if they are not diagnosed with TB, and 6 months if they are. For analytical purposes, the participants in the pediatric cohort will be classified into “confirmed tuberculosis”, “unconfirmed tuberculosis” and “unlikely tuberculosis”. Participants of the adult cohort will be classified as “bacteriologically confirmed TB”, “clinically diagnosed TB” or “not TB”. We will assess accuracy of the novel qPCR test compared to bacteriological confirmation and Tb diagnosis irrespective of laboratory results. Longitudinal qPCR results will be analyzed to assess its use as treatment response monitoring. Discussion The proposed stool-based qPCR is an innovation because both the strategy of using a non-sputum based sample and a technique specially designed to detect M.tb DNA in stool. Protocol registration details ClinicalTrials.gov Identifier: NCT05047315

Priority Activities in Child and Adolescent Tuberculosis to Close the Policy-Practice Gap in Low- and Middle-Income Countries

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality—over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy–practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors