Browsing by Author "Eisenach, Kathleen"

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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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    Drug Tolerance in Mycobacterium tuberculosis
    (Antimicrobial agents and chemotherapy, 1999) Wallis, Robert S.; Patil, Shripad; Cheon, Seon-Hee; Edmonds, Kay; Phillips, Manijeh; Perkins, Mark D.; Joloba, Moses; Namale, Alice; Johnson, John L.; Teixeira, Lucileia; Dietze, Reynaldo; Siddiqi, Salman; Mugerwa, Roy D.; Eisenach, Kathleen; Ellner, Jerrold J.
    Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between mycobacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human immunodeficiency virus-uninfected subjects with pulmonary tuberculosis in Brazil and Uganda. The rate of killing in vitro was determined by monitoring the growth index (GI) in BACTEC 12B medium after addition of drug to established cultures and was measured as the number of days required for 99% sterilization. Drugs differed significantly in bactericidal activity, in the following order from greatest to least, rifampin > isoniazid-ethambutol > ethambutol (P < 0.001). Isolates from subjects who had relapses (n 5 2) or in whom persistence was prolonged (n 5 1) were significantly more tolerant of isoniazidethambutol and rifampin than isolates from other subjects (P < 0.01).
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    Induction of the Antigen 85 Complex of Mycobacterium tuberculosis in Sputum: A Determinant of Outcome in Pulmonary Tuberculosis Treatment
    (The Journal of infectious diseases, 1998) Wallis, Robert S.; Perkins, Mark; Phillips, Manijeh; Joloba, Moses; Demchuk, Barbara; Namale, Alice; Johnson, John L.; Williams, Donna; Wolski, Kathy; Dietze, Reynaldo; Mugerwa, Roy D.; Eisenach, Kathleen; Ellner, Jerrold J.
    Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90–180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values 60 pg/mL responded rapidly to treatment and were cured. Of those with values 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy
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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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    Secondary Attack Rate of Tuberculosis in Urban Households in Kampala, Uganda
    (PLoS ONE, 2011) Whalen, Christopher C.; Zalwango, Sarah; Chiunda, Allan; Malone, LaShaunda; Eisenach, Kathleen; Joloba, Moses; Boom, W. Henry; Mugerwa, Roy
    Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case. Methods: In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection. The ratio of these rates is the likelihood of progressive primary disease after recent household infection. Results: The secondary attack rate for tuberculosis disease was 3.0% (95% confidence interval: 2.2, 3.8). The overall secondary attack rate for tuberculosis infection was 47.4 (95% confidence interval: 44.3, 50.6) and did not vary widely with age, HIV status or BCG vaccination. The risk for progressive primary disease was highest among the young or HIV infected and was reduced by BCG vaccination. Conclusions: Early case detection and treatment may limit household transmission of M. tuberculosis. Household members at high risk for disease should be protected through vaccination or treatment of latent tuberculosis infection.