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

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. Methods: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Findings: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. Interpretation: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. Funding: WHO, US National Institutes of Health

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

Trend and outcome of notified children with tuberculosis during 2011-2015 in Kampala, Uganda

Abstract Background The road map for childhood tuberculosis launched in 2013 provided strong renewed efforts focused towards zero deaths due to tuberculosis in children. From 2010, there were efforts to improve childhood tuberculosis diagnosis in Kampala and this study aimed to document the trend and outcome of tuberculosis in children over the period. Methods This was a retrospective study of tuberculosis data for Kampala city for the period 2011–2015. We extracted data from the unit TB registers in the 52 Diagnostic and treatment units (DTUs) in the Kampala. We report on data for children 0 to 14 years. Results We accessed 33,221 TB patient records of which 2333 (7.0% 95% CI 6.7 to 7.3) were children. The proportion of children with pulmonary TB was 80% (1870/2333) (95% CI 76.7 to 83.7 and extra-pulmonary TB accounted for 20% (463/2333) (CI 18.3 to 21.5). Among pulmonary TB cases, the clinically diagnosed were 82% (1530/1870) (95% CI 80.0 to 83.5) while the bacteriologically confirmed were 18% (340/1870) (95% CI 16.5 to 20.0). Among the bacteriologically confirmed, 45% (154/340) (95% CI 40.1 to 50.6) were smear positive. During the study period 2011 through 2015, the childhood TB notification rate declined as follows; 105, 76, 72, 88, and 74 per 100,000 respectively. The treatment success rate increased from 78% in 2011 to 83% in 2015. Conclusions The TB notification rate among children in Kampala city showed a large decline during the period 2011 to 2015. There was a slight improvement in the treatment success rate among the children

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

Integration of COVID-19 and TB screening in Kampala, Uganda: healthcare provider perspectives

Abstract Background Following the first wave of the COVID-19 outbreak, Uganda experienced a 40% drop in tuberculosis (TB) screening by June 2020. We sought to identify barriers to and facilitators of integrated COVID-19 and TB screening from the perspective of healthcare providers (HCPs) at a National Referral Hospital in Kampala, Uganda. Design/methods We conducted a cross-sectional study using in-depth interviews with 12 HCPs involved in TB activities in the outpatient and emergency departments at Kiruddu National Referral Hospital, Kampala, Uganda. We explored the HCP experiences at work in the setting of COVID-19, HCP perceived effect of COVID-19 on TB screening activities at the hospital, and perceptions about social and contextual factors that might influence the willingness of HCP to integrate screening of COVID-19 and TB. We analyzed the data using an inductive thematic approach and we denoted the emergent themes as barriers to and facilitators of COVID-19/TB integrated screening. We then mapped the themes to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Results The facilitators to integrated COVID-19 and TB screening included the availability of TB focal persons and already existing training forums at the hospital that could be utilized to strengthen the capacity of HCP to integrate COVID-19 and TB screening. The barriers included HCP’s inadequate knowledge on how to integrate screening of COVID-19 and TB, the absence of simple easy-to-use standard operating procedures and data collection tools for integrated screening, inconsistent supply of personal protective equipment (PPE), understaffing, and fear of contracting COVID-19 infection. The identified intervention functions to address the facilitators or barriers included education, persuasion, enablement, and training. Conclusions These findings provided a basis for designing contextually appropriate interventions targeting factors that are likely to influence HCP decisions and willingness to conduct TB screening in the context of COVID-19. Future studies should evaluate the effect of addressing these barriers to the integration of COVID-19 and TB as well as the effect of this on TB case finding in high-burden TB settings

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: An individual participant data meta-analysis

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. Methods: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model\u27s generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Findings: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. Interpretation: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. Funding: WHO, US National Institutes of Healt