Browsing by Author "Swindells, Susan"

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    Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial
    (BMC (part of Springer Nature), 2021-02-24) Demers, Anne-Marie; Kim, Soyeon; McCallum, Sara; Eisenach, Kathleen; Hughes, Michael; Naini, Linda; Mendoza-Ticona, Alberto; Pradhan, Neeta; Narunsky, Kim; Poongulali, Selvamuthu; Badal-Faesen, Sharlaa; Upton, Caryn; Smith, Elizabeth; Shah, N. S.; Churchyard, Gavin; Gupta, Amita; Hesseling, Anneke; Swindells, Susan
    Background: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.
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    Feasibility of identifying household contacts of rifampin-and multidrug-resistant tuberculosis cases at high risk of progression to tuberculosis disease
    (Oxford University Press, 2020-01) Gupta, Amita; Swindells, Susan; Kim, Soyeon; Hughes, Michael D.; Naini, Linda; Wu, Xingye; Dawson, Rodney; Mave, Vidya; Sanchez, Jorge; Mendoza, Alberto; Gonzales, Pedro; Kumarasamy, Nagalingeswaran; Comins, Kyla; Conradie, Francesca; Shenje, Justin; Fontain, Sandy Nerette; Garcia-Prats, Anthony; Asmelash, Aida; Nedsuwan, Supalert; Mohapi, Lerato; Lalloo, Umesh G.; Ferreira, Ana Cristina Garcia; Mugah, Christopher; Harrington, Mark; Jones, Lynne; Cox, Samyra R.; Smith, Betsy; Shah, N Sarita; Hesseling, Anneke C.; Churchyard, Gavin
    Background: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. Results: From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions: The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.
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    Willingness to take multidrug-resistant tuberculosis (MDR-TB) preventive therapy among adult and adolescent household contacts of MDR-TB index cases : an international multisite cross-sectional study
    (Oxford University Press, 2020-02) Suryavanshi, Nishi; Murrill, Matthew; Gupta, Amita; Hughes, Michael; Hesseling, Anneke; Kim, Soyeon; Naini, Linda; Jones, Lynne; Smith, Betsy; Gupte, Nikhil; Dawson, Rodney; Mave, Vidya; Meshram, Sushant; Mendoza-Ticona, Alberto; Sanchez, Jorge; Kumarasamy, Nagalingeswaran; Comins, Kyla; Conradie, Francesca; Shenje, Justin; Fontain, Sandy Nerette; Garcia-Prats, Anthony; Asmelash, Aida; Nedsuwan, Supalert; Mohapi, Lerato; Lalloo, Umesh; Ferreira, Ana Cristina Garcia; Okeyo, Elisha; Swindells, Susan; Churchyard, Gavin; Shah, N. Sarita
    Background. Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. Methods. In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. Results. From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). Conclusions. The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.