Browsing by Author "Jaganath, Devan"

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    Contact Investigation for Active Tuberculosis Among Child Contacts in Uganda
    (Oxford University Press, 2013) Jaganath, Devan; Zalwango, Sarah; Okware, Brenda; Nsereko, Mary; Kisingo, Hussein; Malone, LaShaunda; Lancioni, Christina; Okwera, Alphonse; Joloba, Moses; Mayanja-Kizza, Harriet; Boom, Henry; Stein, Catherine; Mupere, Ezekiel
    Background. Tuberculosis is a large source of morbidity and mortality among children. However, limited studies characterize childhood tuberculosis disease, and contact investigation is rarely implemented in high-burden settings. In one of the largest pediatric tuberculosis contact investigation studies in a resource-limited setting, we assessed the yield of contact tracing on childhood tuberculosis and indicators for disease progression in Uganda. Methods. Child contacts aged <15 years in Kampala, Uganda, were enrolled from July 2002 to June 2009 and evaluated for tuberculosis disease via clinical, radiographic, and laboratory methods for up to 24 months. Results. Seven hundred sixty-one child contacts were included in the analysis. Prevalence of tuberculosis in our child population was 10%, of which 71% were culture-confirmed positive. There were no cases of disseminated tuberculosis, and 483 of 490 children (99%) started on isoniazid preventative therapy did not develop disease. Multivariable testing suggested risk factors including human immunodeficiency virus (HIV) status (odds ratio [OR], 7.90; P < .001), and baseline positive tuberculin skin test (OR, 2.21; P = .03); BCG vaccination was particularly protective, especially among children aged ≤5 years (OR, 0.23; P < .001). Adult index characteristics such as sex, HIV status, and extent or severity of disease were not associated with childhood disease. Conclusions. Contact tracing for children in high-burden settings is able to identify a large percentage of culture-confirmed positive tuberculosis cases before dissemination of disease, while suggesting factors for disease progression to identify who may benefit from targeted screening.
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    Distribution and transmission of Mycobacterium tuberculosis complex lineages among children in peri-urban Kampala, Uganda
    (BMC pediatrics, 2015) Wampande, Eddie M.; Mupere, Ezekiel; Jaganath, Devan; Nsereko, Mary; Mayanja, Harriet K.; Eisenach, Kathleen; Boom, W. Henry; Gagneu, Sebastien; Joloba, Moses L.
    To gain insight into the transmission of tuberculosis (TB) in peri-urban Kampala-Uganda, we performed a household contact study using children as a surrogate for recent transmission of Mycobacterium tuberculosis (MTB). Using this approach, we sought to understand M. tuberculosis complex (MTBC) lineage diversity, distribution and how these relate to TB transmission to exposed children. Method: MTBC isolates from children aged ≤ 15 years, collected from 2002 to 2010 in a household-contact study, were analyzed using a LightCycler RT-PCR SNP genotyping assay (LRPS). The resultant genotypic data was used to determine associations between MTBC lineage and the children’s clinical and epidemiological characteristics. Results and discussion: Of the 761 children surveyed, 9 % (69/761) had culture-positive TB an estimate in the range of global childhood TB; of these 71 % (49/69) were infected with an MTBC strain of the “Uganda family”, 17 % (12/69) infected with MTBC lineage 4 strains other than MTBC Uganda family and 12 % (8/69) infected with MTBC lineage 3, thereby disproportionately causing TB in the study area. Overall the data showed no correlation between the MTBC lineages studied and transmission (OR = 0.304; P-value = 0.251; CI: 95 %; 0.039-2.326) using children a proxy for TB transmission. Conclusions: Our findings indicate that MTBC Uganda family strains are the main cause of TB in children in peri-urban Kampala. Furthermore, MTBC lineages did not differ in their transmissibility to children.
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    Outcomes of empiric treatment for pediatric tuberculosis, Kampala, Uganda, 2010–2015
    (BMC public health, 2019) Wobudeya, Eric; Jaganath, Devan; Sekadde, Moorine P.; Nsangi, Betty; Haq, Heather; Cattamanchi, Adithya
    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.
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    A Prospective Evaluation of Xpert MTB/RIF Ultra for Childhood Pulmonary Tuberculosis in Uganda
    (Journal of the Pediatric Infectious Diseases Society, 2021) Jaganath, Devan; Wambi, Peter; Reza, Tania F.; Nakafeero, Jascent; Aben, Ernest O.; Kiconco, Emma; Nannyonga, Gertrude; Nsereko, Moses; Sekadde, Moorine P.; Mudiope, Mary; Kato-Maeda, Midori; Starke, Jeffrey; Andama, Alfred; Mohanty, Swomitra; Wobudeya, Eric; Cattamanchi, Adithya
    Xpert MTB/RIF Ultra (Xpert Ultra) has improved the sensitivity to detect pulmonary tuberculosis (TB) in adults. However, there have been limited prospective evaluations of its diagnostic accuracy in children. Methods. We enrolled children undergoing assessment for pulmonary TB in Kampala, Uganda, over a 12-month period. Children received a complete TB evaluation and were classified as Confirmed, Unconfirmed, or Unlikely TB. We calculated the sensitivity and specificity of Xpert Ultra among children with Confirmed vs Unlikely TB. We also determined the diagnostic accuracy with clinical, microbiological, and extended microbiological reference standards (MRSs). Results. Of the 213 children included, 23 (10.8%) had Confirmed TB, 88 (41.3%) had Unconfirmed TB, and 102 (47.9%) had Unlikely TB. The median age was 3.9 years, 13% were HIV-positive, and 61.5% were underweight. Xpert Ultra sensitivity was 69.6% (95% confidence interval [CI]: 47.1-86.8) among children with Confirmed TB and decreased to 23.4% (95% CI: 15.9-32.4) with the clinical reference standard. Specificity was 100% (95% CI: 96.4-100) among children with Unlikely TB and decreased to 94.7% (95% CI: 90.5-97.4) with a MRS. Sensitivity was 52.9% (95% CI: 35.1-70.2) and specificity 95.5% (95% CI: 91.4-98.1) with the extended MRS. Of the 26 positive Xpert Ultra results, 6 (23.1%) were “Trace-positive,” with most (5/6) occurring in children with Unconfirmed TB. Conclusions. Xpert Ultra is a useful tool for diagnosing pulmonary TB in children, but there remains a need for more sensitive tests to detect culture-negative TB.
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    Seasonality of childhood tuberculosis cases in Kampala, Uganda, 2010-2015
    (PloS one, 2019) Jaganath, Devan; Wobudeya, Eric; Sekadde, Moorine P.; Nsangi, Betty; Haq, Heather; Cattamanchi, Adithya
    Seasonality 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. Objectives To assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses. Methods We 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. Results Of 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.
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    Social Determinants of Adherence to Treatment for Tuberculosis Infection and Disease Among Children, Adolescents, and Young Adults: A Narrative Review
    (Journal of the Pediatric Infectious Diseases Society, 2022) Leddy, Anna M.; Jaganath, Devan; Triasih, Rina; Wobudeya, Eric; Bellotti de Oliveira, Marcia C.; Sheremeta, Yana; Becerra, Mercedes C.; Chiang, Silvia S.
    Global efforts to eliminate tuberculosis (TB) must address the unique barriers that children (ages 0 through 9 years) and adolescents/ young adults (AYA; ages 10 through 24 years) face in adhering to treatment for TB infection and disease. We conducted a narrative review to summarize current knowledge on the social determinants of treatment adherence among these age groups to guide efforts and policy to address their unique needs. Our findings revealed that research on TB treatment adherence among children and AYA is still in its nascent stage. The current literature revealed structural/community-, health system-, household-, and individual-level factors that influence treatment adherence and varied with developmental stage. There is a need to develop multilevel interventions to address the unique challenges that children and AYA face in adhering to TB treatment