01. Tuberculosis

Sumona Datta, Robert H. Gilman, Rosario Montoya, Luz Quevedo Cruz, Teresa Valencia, Doug Huff, Matthew J. Saunders and Carlton A. Evans.

Eur Respir J 2020; 56: 1900495

Background: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights he lack of evidence concerning tuberculosis-related quality of life (QOL).
Methods: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ⩾15 years for “patients” (n=1545) starting treatment for tuberculosis disease in health centres; “contacts” (n=3180) who shared a patient’s household for ⩾6 h·week−1; and randomly selected “controls” (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place.
Findings: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p⩽0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13 points had 4.2-fold (95% CI 2.3–7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001).
Conclusions: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.

Gwenyth O. Lee, Germán Comina, Gustavo Hernandez-Cordova, Nehal Naik, Oscar Gayoso, Eduardo Ticona, Jorge Coronel, Carlton A. Evans, Mirko Zimic, Valerie A. Paz-Soldan, Robert H. Gilman, Richard Oberhelman.

PLoS ONE 15(6): e0231167

Cough is a characteristic symptom of tuberculosis, is the main cause of transmission, and is
used to assess treatment response. We aimed to identify the best measure of cough severity
and characterize changes during initial tuberculosis therapy. We conducted a prospective
cohort of recently diagnosed ambulatory adult patients with pulmonary tuberculosis in two tertiary hospitals in Lima, Peru. Pre-treatment and five times during the first two months of treatment, a vibrometer was used to capture 4-hour recordings of involuntary cough. A total of 358
recordings from 69 participants were analyzed using a computer algorithm. Total time spent
coughing (seconds per hour) was a better predictor of microbiologic indicators of disease
severity and treatment response than the frequency of cough episodes or cough power.
Patients with prior tuberculosis tended to cough more than patients without prior tuberculosis,
and patients with tuberculosis and diabetes coughed more than patients without diabetes comorbidity. Cough characteristics were similar regardless of HIV co-infection and for drug-susceptible versus drug-resistant tuberculosis. Tuberculosis treatment response may be meaningfully assessed by objectively monitoring the time spent coughing. This measure demonstrated
that cough was increased in patients with TB recurrence or co-morbid diabetes, but not
because of drug resistance or HIV co-infection.

Matthew J Saunders, Tom Wingfield, Sumona Datta, Rosario Montoya, Eric Ramos, Matthew R Baldwin, Marco A Tovar, Benjamin E W Evans, Robert H Gilman, Carlton A Evans.

Lancet Infect Dis 2020; 20: 110–22

The epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis.

In this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty
towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone.

We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score.

Shibabaw A, Gelaw B, Kelley HV, Tesfaye E, Balada-Llasat JM, Evans CA, Torrelles JB, Wang SH, Tessema B.

Int J Infect Dis. 2019 Nov 2.

Appropriate-technology tests are needed for Mycobacterium tuberculosis drug-susceptibility testing (DST) in resource-constrained settings. We evaluated the MDR/XDRTB colour plate thin-layer agar test (TB-CX) for M. tuberculosis DST by directly testing sputum at University of Gondar Hospital.

The TB-CX was simple and rapid for M. tuberculosis DST. Discordant DST results may have resulted from sub-optimal storage and different isoniazid concentrations used in TB-CX versus the reference standard test.

Mekonnen B, Mihret A, Getahun M, Hailu T, Sidiki S, V Kelley H, Scordo JM, Hunt WG, Pan X, Balada-Llasat JM, Gebreyes W, Evans CA, Aseffa A, Torrelles JB, Wang SH, Abebe T.

PLoS One. 2019 May 28;14(5):e0215679.

Timely diagnosis of tuberculosis (TB) is limited in Ethiopia. We evaluated the performance of a low technology, thin layer agar, Mycobacterium tuberculosis (M.tb) culture color plate (TB-CX) test with concurrent drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) directly from sputum specimens. Patients undergoing examination for TB and multidrug-resistant (MDR)-TB were enrolled in Addis Ababa, Ethiopia from March 2016 to February 2017. All subjects received a GeneXpert MTB/RIF PCR test. TB-CX test results were compared to reference Löwenstein-Jensen (LJ) culture for M.tb detection and DST for susceptibility to INH and RIF. Kappa statistic was applied to test agreement between results for TB-CX test and the reference methods, a cut-off Kappa value of 0.75 was considered as high level of agreements. A total of 137 participants were analyzed: 88 (64%) were new TB cases, 49 (36%) were re-treatment cases. The TB-CX test detected M.tb and DST in an average of 13 days compared to 50 days for the conventional DST result. The sensitivity and specificity of the TB-CX test for detecting M.tb were 94% and 98%, respectively (concordance, 96%; kappa 0.91). The sensitivity of the TB-CX test to detect drug resistance to INH, RIF, and MDR-TB was 91%, 100%, and 90% respectively. The specificity of the TB-CX test for detecting INH, RIF, and MDR-TB was 94%, 40%, and 94% respectively. Overall agreement between TB-CX test and LJ DST for detection of MDR-TB was 93%. The TB-CX test showed strong agreement with the GeneXpert test for detecting M.tb (89%, kappa 0.76) but low agreement for the detection of RIF resistance (57%, kappa 0.28). The TB-CX test was found to be a good alternative method for screening of TB and selective drug resistant-TB in a timely and cost-efficient manner.

Sumona Datta, Keren Alvarado, Robert H. Gilman, Teresa Valencia, Christian Aparicio, Eric S. Ramos, Rosario Montoya, Carlton A. Evans.

PLoS One. 2019; 14(4): e0214131.

Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings.