Leonardo Martinez1, Juliet N Sekandi1,2, María E Castellanos1, Sarah Zalwango3, Christopher C Whalen1. 1. 1 Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia. 2. 2 School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda; and. 3. 3 Uganda-CWRU Research Collaboration, Makerere University and Mulago Hospital, Kampala, Uganda.
Abstract
RATIONALE: Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa. OBJECTIVES: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship. METHODS: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed. MEASUREMENTS AND MAIN RESULTS: Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction). CONCLUSIONS: This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV-seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings.
RATIONALE: Policy recommendations on contact investigation of HIV-seropositivepatients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa. OBJECTIVES: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship. METHODS: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed. MEASUREMENTS AND MAIN RESULTS: Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction). CONCLUSIONS: This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV-seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings.
Authors: Leonardo Martinez; Alyssa Arman; Nathan Haveman; Ashley Lundgren; Lilia Cabrera; Carlton A Evans; Tom F Pelly; Mayuko Saito; David Callacondo; Richard Oberhelman; Gisela Collazo; Andrés M Carnero; Robert H Gilman Journal: Am J Trop Med Hyg Date: 2013-07-22 Impact factor: 2.345
Authors: A C Carvalho; K DeRiemer; Z B Nunes; M Martins; M Comelli; A Marinoni; A L Kritski Journal: Am J Respir Crit Care Med Date: 2001-12-15 Impact factor: 21.405
Authors: Anthony D Harries; Rony Zachariah; Elizabeth L Corbett; Stephen D Lawn; Ezio T Santos-Filho; Rhehab Chimzizi; Mark Harrington; Dermot Maher; Brian G Williams; Kevin M De Cock Journal: Lancet Date: 2010-05-18 Impact factor: 79.321
Authors: M A Espinal; E N Peréz; J Baéz; L Hénriquez; K Fernández; M Lopez; P Olivo; A L Reingold Journal: Lancet Date: 2000-01-22 Impact factor: 79.321
Authors: Per Gustafson; Ida Lisse; Victor Gomes; Cesaltina S Vieira; Christian Lienhardt; Anders Nauclér; Henrik Jensen; Peter Aaby Journal: Epidemiology Date: 2007-05 Impact factor: 4.822
Authors: Catherine M Stein; Sarah Zalwango; LaShaunda L Malone; Bonnie Thiel; Ezekiel Mupere; Mary Nsereko; Brenda Okware; Hussein Kisingo; Christina L Lancioni; Charles M Bark; Christopher C Whalen; Moses L Joloba; W Henry Boom; Harriet Mayanja-Kizza Journal: Am J Epidemiol Date: 2018-07-01 Impact factor: 4.897
Authors: Leonardo Martinez; Ye Shen; Andreas Handel; Srijita Chakraburty; Catherine M Stein; LaShaunda L Malone; W Henry Boom; Frederick D Quinn; Moses L Joloba; Christopher C Whalen; Sarah Zalwango Journal: Lancet Respir Med Date: 2017-12-19 Impact factor: 30.700
Authors: Leonardo Martinez; Andreas Handel; Ye Shen; Srijita Chakraburty; Frederick D Quinn; Catherine M Stein; LaShaunda L Malone; Sarah Zalwango; Christopher C Whalen Journal: Am J Respir Crit Care Med Date: 2018-05-01 Impact factor: 21.405
Authors: Julian S Peters; Jason R Andrews; Mark Hatherill; Sabine Hermans; Leonardo Martinez; Erwin Schurr; Yuri van der Heijden; Robin Wood; Roxana Rustomjee; Bavesh D Kana Journal: Lancet Infect Dis Date: 2018-12-13 Impact factor: 25.071
Authors: Palwasha Y Khan; Tom A Yates; Muhammad Osman; Robin M Warren; Yuri van der Heijden; Nesri Padayatchi; Edward A Nardell; David Moore; Barun Mathema; Neel Gandhi; Vegard Eldholm; Keertan Dheda; Anneke C Hesseling; Valerie Mizrahi; Roxana Rustomjee; Alexander Pym Journal: Lancet Infect Dis Date: 2018-12-13 Impact factor: 25.071
Authors: Leonardo Martinez; Renu Verma; Julio Croda; C Robert Horsburgh; Katharine S Walter; Nicholas Degner; Keren Middelkoop; Anastasia Koch; Sabine Hermans; Digby F Warner; Robin Wood; Frank Cobelens; Jason R Andrews Journal: Eur Respir J Date: 2019-06-27 Impact factor: 16.671
Authors: P Fernandes; Y Ma; M Gaeddert; T Tsacogianis; P Marques-Rodrigues; G Fregona; A Loomans; E C Jones-López; R Dietze; J J Ellner; L F White; N S Hochberg Journal: Epidemiol Infect Date: 2018-06-08 Impact factor: 4.434
Authors: Leonardo Martinez; Limei Zhu; Maria E Castellanos; Qiao Liu; Cheng Chen; Benjamin D Hallowell; Christopher C Whalen Journal: Clin Infect Dis Date: 2017-11-29 Impact factor: 9.079