Browsing by Author "Nsereko, Mary"

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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
    (BioMed Central, 2014) Ma, Ningning; Zalwango, Sarah; Malone, LaShaunda L; Nsereko, Mary; Wampande, Eddie M; Thiel, Bonnie A; Okware, Brenda; Igo Jr., Robert P; Joloba3, Moses L.; Mupere, Ezekiel; Mayanja-Kizza, Harriet; Boom, 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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    Comparison of MGIT and Myco/F Lytic Liquid-Based Blood Culture Systems for Recovery of Mycobacterium tuberculosis from Pleural Fluid
    (Journal of clinical microbiology, 2015) Harausz, Elizabeth; Kafuluma Lusiba, John; Nsereko, Mary; Johnson, John L.; Toossi, Zahra; Ogwang, Sam; Boom, Henry; Joloba, Moses L.
    Tuberculosis (TB) is the most frequent cause of exudative pleural effusions in areas of high TB incidence. Studies have shown that Mycobacterium tuberculosis is the causative agent in up to 44% of HIV-seronegative people hospitalized with a pleural effusion (1–3), and the percentage is higher in HIV-seropositive people (4). Pleural TB is a paucibacillary disease. The pathogenesis of a tuberculous pleural effusion is likely due to a delayed hypersensitivity reaction to M. tuberculosis proteins (for a review, see reference 5) and not to a large burden of organisms. The scarcity of organisms makes it difficult to isolate M. tuberculosis from pleural fluid samples, leading to low rates of culture confirmation. Rich culture media are generally more sensitive in detecting M. tuberculosis in sputum and other clinical samples (6). Few studies have compared different liquid media and examined their potential role in combination with solid media for the diagnosis of tuberculous pleurisy. In this study, we compared the Bactec 9120 Myco/F lytic blood culture system (Myco/F lytic) to the Bactec mycobacterial growth indicator tube (MGIT) 960 system (Becton Dickinson, Sparks, MD) (with each liquid system used in conjunction with locally prepared Middlebrook 7H11 solid medium) with respect to time to positivity (TTP), sensitivity, specificity, and percent culture yield of M. tuberculosis isolates from pleural fluid.
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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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    Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results
    (Clinical Infectious Diseases, 2021) Sutherland, Jayne S.; Spuy, Gian van der; Gindeh, Awa; Thuong, Nguyen Thuy; Namuganga, AnnRitah; Owolabi, Olumuyiwa; Mayanja-Kizza, Harriet; Nsereko, Mary; Thwaites, Guy; Winter, Jill; Dockrell, Hazel M.; Scriba, Thomas J.; Geluk, Annemieke; Corstjens, Paul; Stanley, Kim; Richardson, Tracy; Shaw, Jane A.; Smith, Bronwyn; Walzl, Gerhard
    The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert-MTB-Host Response (HR)-Prototype), which generates a ‘TB score’ based on mRNA expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype.
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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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    Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study
    (Elsevier Inc., 2011) Baker, Allison R.; Zalwango, Sarah; Malone, LaShaunda L.; Igo Jr, Robert P.; Qiu, Feiyou; Nsereko, Mary; Adams, Mark D.; Supelak, Pamela
    Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), causes 9 million new cases worldwide and 2 million deaths annually. Genetic linkage and association analyses have suggested several chromosomal regions and candidate genes involved in TB susceptibility. This study examines the association of TB disease susceptibility with a selection of biologically relevant genes on regions on chromosomes 7 (IL6 and CARD11) and 20 (CTSZ and MC3R) and fine mapping of the chromosome 7p22–p21 region identified through our genome scan. We analyzed 565 individuals from Kampala, Uganda, who were previously included in our genome-wide linkage scan. Association analyses were conducted for 1,417 single-nucleotide polymorphisms (SNP) that passed quality control. None of the candidate gene or fine mapping SNPs was significantly associated with TB susceptibility (p 0.10). When we restricted the analysis to HIV-negative individuals, 2 SNPs on chromosome 7 were significantly associated with TB susceptibility (p 0.05). Haplotype analyses identified a significant risk haplotype in cathepsin X (CTSZ; p 0.0281, odds ratio 1.5493, 95% confidence interval [1.039, 2.320]).
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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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    Long-term Stability of Resistance to Latent Mycobacterium tuberculosis Infection in Highly Exposed Tuberculosis Household Contacts in Kampala, Uganda
    (Clinical Infectious Diseases, 2019) Stein, Catherine M.; Nsereko, Mary; Malone, LaShaunda L.; Okware, Brenda; Kisingo, Hussein; Nalukwago, Sophie; Chervenak, Keith; Mayanja-Kizza, Harriet; Hawn, Thomas R.; Boom, W. Henry
    Resistance to latent Mycobacterium tuberculosis (M.tb) infection, identified by persistently negative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA), after close contact with pulmonary tuberculosis (TB) patients has not been extensively characterized. Stability of this “resistance” beyond 2 years from exposure is unknown. Methods. 407 of 657 eligible human immunodeficiency virus (HIV)-negative adults from a TB household contact study with persistently negative TST (PTST−) or with stable latent M.tb infection (LTBI) were retraced 9.5 years (standard deviation = 3.2) later. Asymptomatic retraced contacts underwent 3 IGRAs and follow-up TST, and their M.tb infection status classified as definite/ possible/probable. Results. Among PTST− with a definite classification, 82.7% were concordantly TST−/ quantiferon-TB Gold− (QFT−), and 16.3% converted to TST+/QFT+ LTBI. Among original LTBI contacts, 83.6% remained LTBI, and 3.9% reverted their TST and were QFT−. Although TST and QFT concordance was high (κ = 0.78), 1.0% of PTST and 12.5% of original LTBI contacts could not be classified due to discordant TST and QFT results. Epidemiological variables did not differ between retraced PTST− and LTBI contacts. Conclusion. Resistance to LTBI, defined by repeatedly negative TST and IGRA, in adults who have had close contact with pulmonary TB patients living in TB-endemic areas, is a stable outcome of M.tb exposure. Repeated longitudinal measurements with 2 different immune assays and extended follow-up provide enhanced discriminatory power to identify this resister phenotype and avoid misclassification. Resisters may use immune mechanisms to control aerosolized M.tb that differ from those used by persons who develop “classic” LTBI.
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    Mycobacterium tuberculosis Specific CD8+ T Cells Rapidly Decline with Antituberculosis Treatment
    (PLoS One, 2013) Nyendak, Melissa R.; Park, Byung; Null, Megan D.; Baseke, Joy; Swarbrick, Gwendolyn; Mayanja-Kizza4, Harriet; Nsereko, Mary; Johnson, Denise F.; Gitta, Phineas; Okwera, Alphonse; Goldberg, Stefan; Bozeman, Lorna; Johnson, John L.; Boom, W. Henry; Lewinsohn, Deborah A.; Lewinsohn, David M.; the Tuberculosis Research Unit and the Tuberculosis Trials Consortium
    Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8+ T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. We sought to determine the relationship of Mtb specific CD4+ T cells and CD8+ T cells with duration of antituberculosis treatment. We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4+ and CD8+ T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24.There was a significant difference in the Mtb specific CD8+ T response, but not the CD4+ T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8+ T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4+ T cell during the treatment. The Mtb specific CD4+ T cell response, but not the CD8+ response, was negatively impacted by the body mass index.Our data provide evidence that the Mtb specific CD8+ T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8+ T cell response can detect early treatment failure, relapse, or to predict disease progression.
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    Mycobacterium tuberculosis Specific CD8+ T Cells Rapidly Decline with Antituberculosis Treatment
    (PLoS ONE, 2013) Nyendak, Melissa R.; Byung, Park; Null, Megan D.; Baseke, Joy; Swarbrick, Gwendolyn; Mayanja-Kizza, Harriet; Nsereko, Mary; Johnson, Denise F.; Gitta, Phineas; Okwera, Alphonse; Goldberg, Stefan; Bozeman, Lorna; Johnson, John L.; Boom, W. Henry
    Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8+ T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. Objectives: We sought to determine the relationship of Mtb specific CD4+ T cells and CD8+ T cells with duration of antituberculosis treatment. Materials and Methods: We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4+ and CD8+ T cell responses to ESAT-6 and CFP-10 were measured by IFN-c ELISPOT at enrollment, week 8 and 24. Results: There was a significant difference in the Mtb specific CD8+ T response, but not the CD4+ T cell response, over 24 weeks of antituberculosis treatment (p,0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8+ T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4+ T cell during the treatment. The Mtb specific CD4+ T cell response, but not the CD8+ response, was negatively impacted by the body mass index. Conclusions: Our data provide evidence that the Mtb specific CD8+ T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8+ T cell response can detect early treatment failure, relapse, or to predict disease progression.
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    Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans
    (Frontiers in Immunology, 2020) Swarbrick, Gwendolyn M.; Gela, Anele; Cansler, Meghan E.; Null, Megan D.; Duncan, Rowan B.; Nemes, Elisa; Shey, Muki; Nsereko, Mary; Mayanja-Kizza, Harriet; Kiguli, Sarah; Koh, Jeffrey; Hanekom, Willem A.; Hatherill, Mark; Lancioni, Christina; Lewinsohn, David M.; Scriba, Thomas J.; Lewinsohn, Deborah A.
    MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR a-chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-RU tetramer labeling and of the TRAV1-2+ MAIT cells defined by expression of TRAV1-2 and high expression of CD26 and CD161 (TRAV1-2+CD161++CD26++ cells). We analyzed postnatal expansion, maturation, and functionality of peripheral blood MR1-5-OP-RU tetramer+ MR1T cells in cohorts from three different geographic settings with different tuberculosis (TB) vaccination practices, levels of exposure to and infection with M. tuberculosis. Early after birth, frequencies of MR1-5-OP-RU tetramer+ MR1T cells increased rapidly by several fold. This coincided with the transition from a predominantly CD4+ and TRAV1-2− population in neonates, to a predominantly TRAV1-2+CD161++CD26++ CD8+ population. We also observed that tetramer+ MR1T cells that expressed TNF upon mycobacterial stimulation were very low in neonates, but increased ∼10-fold in the first year of life. These functional MR1T cells in all age groups were MR1-5-OP-RU tetramer+TRAV1-2+ and highly expressed CD161 and CD26, markers that appeared to signal phenotypic and functional maturation of this cell subset. This age-associated maturation was also marked by the loss of naïve T cell markers on tetramer+ TRAV1-2+ MR1T cells more rapidly than tetramer+TRAV1-2− MR1T cells and non-MR1T cells. These data suggest that neonates have infrequent populations of MR1T cells with diverse phenotypic attributes; and that exposure to the environment rapidly and preferentially expands the MR1-5-OP-RU tetramer+TRAV1-2+ population of MR1T cells, which becomes the predominant population of functional MR1T cells early during childhood.
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    Resistance and Susceptibility to Mycobacterium tuberculosis Infection and Disease in Tuberculosis Households in Kampala, Uganda
    (Oxford University Press, 2017) Stein, Catherine M.; Zalwango, Sarah; Malone, LaShaunda L.; Thiel, Bonnie; Mupere, Ezekiel; Nsereko, Mary; Okware, Brenda; Kisingo, Hussein; Lancioni, Christina L.; Bark, Charles M.; Whalen, Christopher C.; Joloba, Moses L.; Boom, W. Henry; Mayanja-Kizza, Harriet
    Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002–2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men.
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    Resistance to TST/IGRA conversion in Uganda: Heritability and Genome-Wide 2 Association Study
    (EBioMedicine, 2021) McHenry, Michael L.; Benchek, Penelope; Malone, LaShaunda; Nsereko, Mary; Mayanja-Kizza, Harriet; Boom, W. Henry; Williams, Scott M.; Hawn, Thomas R.; Stein, Catherine M.
    Pulmonary tuberculosis (TB) is one of the most deadly pathogens on earth. However, the majority of people have resistance to active disease. Further, some individuals, termed resisters (RSTRs), do not develop traditional latent tuberculosis (LTBI). The RSTR phenotype is important for understanding pathogenesis and preventing TB. The host genetic underpinnings of RSTR are largely understudied. Methods: In a cohort of 908 Ugandan subjects with genome-wide data on single nucleotide polymorphisms, we assessed the heritability of the RSTR phenotype and other TB phenotypes using restricted maximum likelihood estimation (REML). We then used a subset of 263 RSTR and LTBI subjects with high quality phenotyping and long-term follow-up to identify DNA variants genome-wide associated with the RSTR phenotype relative to LTBI subjects in a case- control GWAS design, and annotated and enriched these variants to better understand their role in TB pathogenesis. Results: The heritability of the TB outcomes was very high, at 55% for TB vs. LTBI and 50.4% for RSTR vs. LTBI among HIV- subjects, controlling for age and sex. We identified 27 loci associated with the RSTR phenotype (P<5e-05) and our annotation and enrichment analyses suggest an important regulatory role for many of them. Interpretation: The heritability results show that the genetic contribution to variation in TB outcomes is very high and our GWAS results highlight variants that may play an important role in resistance to infection as well as TB pathogenesis as a whole.
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    Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis
    (Antimicrob Agents Chemother, 2015) Ogwang, Sam; Good, Caryn E.; Okware, Brenda; Nsereko, Mary; Jacobs, Michael R.; Boom, W. Henry; Bark, Charles M.
    Alternative drugs are urgently needed to treat multidrug-resistant (MDR) tuberculosis (TB). Given the difficulties of new drug development, repurposing currently licensed antibiotics is practical and efficient. Trimethoprim-sulfamethoxazole (SXT) is a fixed-dose drug combination used worldwide as treatment and prophylaxis for multiple infections. Sulfamethoxazole (SMX) is in the sulfonamide class of antibiotics, which were explored as an anti-TB treatment in the mid-20th century with early studies showing potential value for the treatment of pulmonary and miliary TB (1–5). More recently, Forgacs et al. reported defervescence of a patient with pulmonary TB who was initially treated with SXT alone and also demonstrated in vitro susceptibility to SXT in 43 of 44 Mycobacterium tuberculosis isolates (6). These drug susceptibility results were independently confirmed in laboratory strains (7, 8) and in patient isolates demonstrating SMX to be the active agent with MICs within achievable serum levels (9, 10). In addition, Alsaad and colleagues reported the use of SXT as part of a combination regimen used to treat 10 patients with MDR-TB in the Netherlands (11). They also reported M. tuberculosis susceptibility to SXT in 17 of 18 patients with TB-HIV coinfection; however, only 1 was taking SXT prior to TB diagnosis (12). Given the development of drug resistance when active TB is treated with a single drug, there is concern for resistance to SMX among TBHIV- coinfected patients taking SXT prophylaxis. To address this concern, we performed drug susceptibility testing (DST) on M. tuberculosis isolates obtained from pretreatment sputum specimens of HIV-infected patients taking SXT prophylaxis at the time of diagnosis of active TB. Sputum isolates used for
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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