Browsing by Author "Boom, W Henry"

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    Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda
    (BMC Infectious Diseases, 2014-06) Ma, Ningning; Zalwango, Sarah; Malone, LaShaunda L; Nsereko, Mary; Wampande, Eddie M; Thiel, Bonnie A; Okware, Brenda; Igo, Robert P; Joloba, Moses L; Mupere, Ezekiel; Mayanja-Kizza, Harriet; Boom, W Henry; Stein, Catherine M
    Background Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment. Methods During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed. Results When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009). Conclusions Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
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    A Single-Nucleotide-Polymorphism Real-Time PCR Assay for Genotyping of Mycobacterium tuberculosis complex in Peri-Urban Kampala
    (BMC Infectious Diseases, 2015-09) Wampande, Eddie M.; Hatzios, Stavroula K.; Achan, Beatrice; Mupere, Ezekiel; Nsereko, Mary; Mayanja, Harriet K.; Eisenach, Kathleen; Boom, W Henry; Gagneux, Sebastien; Joloba, Moses L.
    Background: Accurate and high-throughput genotyping of Mycobacterium tuberculosis complex (MTBC) may be important for understanding the epidemiology and pathogenesis of tuberculosis (TB). In this study, we report the development of a LightCycler® real-time PCR single-nucleotide-polymorphism (LRPS) assay for the rapid determination of MTBC lineages/sublineages in minimally processed sputum samples from TB patients. Method: Genotyping analysis of 70 MTBC strains was performed using the Long Sequence Polymorphism-PCR (LSP-PCR) technique and the LRPS assay in parallel. For targeted sequencing, 9 MTBC isolates (three isolates per MTBC lineage) were analyzed for lineage-specific single nucleotide polymorphisms (SNPs) in the following three genes to verify LRPS results: Rv004c for MTB Uganda family, Rv2962 for MTB lineage 4, and Rv0129c for MTB lineage3. The MTBC lineages present in 300 smear-positive sputum samples were then determined by the validated LRPS method without prior culturing. Results: The LSP-PCR and LRPS assays produced consistent genotyping data for all 70 MTBC strains; however, the LSP-PCR assay was 10-fold less sensitive than the LRPS method and required higher DNA concentrations to successfully characterize the MTBC lineage of certain samples. Targeted sequencing of genes containing lineage specific SNPs was 100 % concordant with the genotyping results and provided further validation of the LRPS assay. Of the 300 sputum samples analyzed, 58 % contained MTBC from the MTBC-Uganda family, 27 % from the MTBC lineage 4 (excluding MTBC Uganda family), 13 % from the MTBC lineage 3, and the remaining 2 % were of indeterminate lineage. Conclusion: The LRPS assay is a sensitive, high-throughput technique with potential application to routine genotyping of MTBC in sputum samples from TB patients
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    Tuberculosis Case Finding in First-Degree Relative Contacts Not Living With Index Tuberculosis Cases in Kampala, Uganda
    (Clinical Epidemiology, 2015-10) Chheng, Phalkun; Nsereko, Mary; Malone, L aShaunda L; Okware, Brenda; Zalwango, S arah; Joloba, Moses; Boom, W Henry; Mupere, Ezekiel; Stein, Catherine M
    Purpose: 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
    (BMC Infectious Diseases, 2014-01) Mupere, Ezekiel; Malone, LaShaunda; Zalwango, Sarah; Okwera, Alphonse; Nsereko, Mary; Tisch, Daniel J; Parraga, Isabel M; Stein, Catherine M; Mugerwa, Roy; Boom, W Henry; Mayanja, Harriet K; Whalen, Christopher C
    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.