Browsing by Author "Boom, Henry W."

Now showing 1 - 5 of 5
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    Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease
    (BMC Infectious Diseases, 2013) Wampande, Eddie M.; Mupere, Ezekiel; Debanne, SaraM; Asiimwe, Benon B.; Nsereko, Mary; Mayanja, Harriet; Eisenach, Kathleen; Kaplan, Gilla; Boom, Henry W.; Gagneux, Sebastien; Joloba, Moses L.
    Previous studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala. A total of 1,746 MTB clinical isolates collected from1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes.
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    Tuberculin Skin Test Reversion following Isoniazid Preventive Therapy Reflects Diversity of Immune Response to Primary Mycobacterium tuberculosis Infection
    (Katalin Andrea Wilkinson, 2014) Johnson, Denise F.; Malone, LaShaunda L.; Zalwango, Sarah; Oketcho, Joy Mukisa; Chervenak, Keith A.; Thiel, Bonnie; Mayanja-Kizza, Harriet; Stein, Catherine M.; Boom, Henry W.; Lancioni, Christina L.
    Rationale: Healthy household contacts (HHC) of individuals with Tuberculosis (TB) with Tuberculin Skin Test (TST) conversions are considered to harbor latent Mycobacterium tuberculosis (Mtb), and at risk for TB. The immunologic, clinical, and public health implications of TST reversions that occur following Isoniazid preventive therapy (IPT) remain controversial. Objectives: To measure frequency of TST reversion following IPT, and variation in interferon-gamma (IFN-c) responses to Mtb, in healthy Ugandan TB HHC with primary Mtb infection evidenced by TST conversion. Methods: Prospective cohort study of healthy, HIV-uninfected, TST-negative TB HHC with TST conversions. Repeat TST was performed 12 months following conversion (3 months following completion of 9 month IPT course) to assess for stable conversion vs. reversion. Whole blood IFN-c responses to Mtb antigen 85B (MtbA85B) and whole Mtb bacilli (wMtb) were measured in a subset (n = 27 and n = 42, respectively) at enrollment and TST conversion, prior to initiation of IPT. Results: Of 122 subjects, TST reversion was noted in 25 (20.5%). There were no significant differences in demographic, clinical, or exposure variables between reverters and stable converters. At conversion, reverters had significantly smaller TST compared to stable converters (13.7 mm vs 16.4 mm, respectively; p = 0.003). At enrollment, there were no significant differences in IFN-c responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated significant increases in IFN-c responses to Ag85B and wMtb compared to enrollment (p = 0.001, p,0.001, respectively), while there were no significant changes among reverters. Conclusions: TST reversion following IPT is common following primary Mtb infection and associated with unique patterns of Mtb-induced IFN-c production. We have demonstrated that immune responses to primary Mtb infection are heterogeneous, and submit that prospective longitudinal studies of cell mediated immune responses to Mtb infection be prioritized to identify immune phenotypes protective against development of TB disease.
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    Tuberculosis case finding in first-degree relative contacts not living with index tuberculosis cases in Kampala, Uganda
    (Dove Medical Press Limited,, 2015) Chheng, Phalkun; Nsereko, Mary; Malone, LaShaunda L.; Okware, Brenda; Zalwango, Sarah; Joloba, Moses; Boom, Henry W.; Mupere, Ezekiel; Stein, Catherine M.
    To assess the prevalence of pulmonary tuberculosis among first-degree relative (FDR) contacts not living with tuberculosis (TB) cases. Methods: A cross-sectional analysis of household contacts living with an index TB case and FDR contacts living outside of households in Kampala, Uganda, is presented.Results: A total of 177 contacts (52 FDRs and 125 index household contacts) of 31 TB cases were examined. Compared with index household contacts, FDR contacts were older, more likely to be TB symptomatic (50% vs 33%), had a higher percentage of abnormal chest X-rays (19% vs 11%), sputum smear positive (15% vs 5%), and many similar epidemiologic risk factors, including HIV infection (13% vs 10%). Contact groups had similar pulmonary tuberculosis prevalence: 9.6% in FDR vs 10.4% in index household contacts and similar Mycobacterium tuberculosis infection: 62% in FDR vs 61% in index households.Conclusion: TB is common among FDR contacts. High TB prevalence justifies targeting FDRs during household contact investigations. Combining TB active-case finding among FDR contacts with household contact investigation in low-income setting is feasible. This should be part of national TB control program strategies for increasing TB case-detection rates and reducing community TB transmission and death.
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    Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study
    (Bio med central, 2014) Malone, LaShaunda; Zalwango, Sarah; Okwera, Alphonse; Nsereko, Mary; Tisch, Daniel J; Parraga, Isabel M; Stein, Catherine M.; Mugerwa, Roy; Boom, Henry W.; Mayanja, Harriet K; Whalen, Christopher C; Mupere, Ezekiel
    Background: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. Methods: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. Results: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. Conclusion: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment
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    Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda
    (Plos one, 2008) Lewinsohn, Deborah A.; Zalwango, Sarah.; Stein, Catherine M.; Mayanja-Kizza, Harriet.; Okwera, Alphonse.; Boom, Henry W.; Mugerwa, Roy D.; Whalen, Christopher C.
    Background: Due to immunologic immaturity, IFN-c-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-c responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-c production in response to mycobacterial antigens between children and adults in Uganda. Methodology/Principal Findings: We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-c production in response to Mtb culturefiltrate antigens was measured by ELISA and compared between infants (,2 years old, n = 80), young children (2 ,5 years old, n = 216), older children (5 ,15 years old, n = 443) and adults ($15 years old, n = 528). We evaluated the relationship between IFN-c responses and the tuberculin skin test (TST), and between IFN-c responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-c responses. Young household contacts demonstrated robust IFN-c responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-c response. Conclusions/Significance: Young children in a TB endemic setting can mount robust IFN-c responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors forMtb infection.