The use of rats to detect drug-resistant TB.

Although detection of drug-susceptible TB by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling-trained African giant pouched rats has been known for more than a decade, the detection of drug-resistant TB (DR-TB) using rats has never been explored before. We present what we believe to be the first report on rifampicin-resistant TB (RR-TB) detected using Xpert® MTB/RIF Ultra, comparably identified by rats sniffing sputum samples from presumptive TB patients: 88% of RR-TB detected using Ultra were identified by the rats. Further evaluation of the usefulness of rats for large-scale DR-TB contact triage testing is needed, especially in low- and middle-income countries, where resources are limited.

Bien que la détection de la TB pharmacosensible par des rats géants de Gambie dressés par APOPO (Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling) soit connue depuis plus d'une décennie, la détection de la TB pharmacorésistante (DR-TB) à l'aide de rats n'a jamais été explorée auparavant. Nous présentons ce que nous pensons être le premier rapport sur la TB résistante à la rifampicine (RR-TB) détectée par test Xpert® MTB/RIF Ultra, identifiée de manière comparable par des rats reniflant des échantillons d'expectorations de patients avec une TB présumée : 88% des RR-TB détectées par test Ultra ont été identifiées par les rats. L'évaluation de l'utilité des rats dans le cadre de tests de triage des contacts de cas de DR-TB à grande échelle doit être poursuivie, en particulier dans les pays à revenu faible ou intermédiaire, où les ressources sont limitées.

Contribution of Xpert® MTB/RIF to tuberculosis case finding among pregnant women in Botswana.

SETTING: Seven health facilities with antenatal care (ANC) clinics in two districts near Gaborone, Botswana. OBJECTIVES: To determine 1) the prevalence of tuberculosis (TB) and HIV-TB co-infection in pregnancy, and 2) the sensitivities of symptomatic TB screening and Xpert testing against gold standard culture. DESIGN: This was a cross-sectional study. Pregnant women were randomly enrolled and screened using TB symptoms. HIV status was determined from ANC clinics' client records. Two sputum specimens were collected from all clients and each was tested using Xpert® and culture for Mycobacterium tuberculosis. RESULTS: Of 407 cases, eight had one or more TB symptoms, and all tested negative with Xpert® and culture. Another two (0.5%, 95%CI 0.08-1.96) asymptomatic clients tested positive with both tests. The adjusted TB prevalence was higher than that of the general population (0.6% vs. 0.24%; P < 0.001). The prevalence of TB among HIV-positive and HIV-negative clients was 1/69 (1.45%, 95%CI 0.29-2.61) and 1/336 (0.3%, 95%CI 0.23-0.83), respectively (Fisher's exact test P = 0.312). Xpert® demonstrated a 100% sensitivity and 100% specificity, while symptom screening had 0.0% sensitivity and 98% specificity. CONCLUSIONS: TB prevalence among pregnant women was high and TB symptom screening had limited ability to detect TB. An alternative TB screening algorithm for pregnant women is urgently needed irrespective of TB symptoms.

OBJECTIFS: Déterminer 1) la prévalence de la tuberculose (TB) et de la co-infection VIH-TB pendant la grossesse, et 2) la sensibilité du dépistage de la TB basé sur les symptômes et de l'Xpert® MTB/RIF par rapport à l'étalon or de la culture. SCHÉMA: Ceci est une étude transversale. Des femmes enceintes venant de sept centres de santé ont été enrôlées de façon aléatoire et dépistées en fonction des symptômes de TB. Deux échantillons de crachats ont été recueillis chez toutes les femmes et chacune a eu un test Xpert® et une culture. Le statut VIH a été déterminé grâce aux dossiers de consultation prénatale. RÉSULTATS: Sur 407 femmes enrôlées et analysées, huit (2,0% IC95% 0,62­3,32) avaient un ou plusieurs symptômes de TB et toutes ont été négatives pour l'Xpert® et la culture. Deux autres femmes (0,5% ; IC95% 0,08­1,96) asymptomatiques ont été positives pour les deux tests. La prévalence ajustée de TB est plus élevée que dans la population générale (0,6% contre 0,24% ; P < 0,001). La prévalence de TB parmi les femmes positives au VIH et non infectées a été respectivement de 1/69 (1,45% ; IC95% 0,29­2,61) et 1/336 (0,3% ; IC95% 0,23­0,83) (test exact de Fisher, P = 0,312). L'Xpert® a démontré une sensibilité de 100% et une spécificité de 100,0% alors que le dépistage sur les symptômes a eu une sensibilité de 0,0% mais une spécificité de 98%. CONCLUSION: La prévalence de la TB chez les femmes enceintes est élevée et le dépistage sur les symptômes a une capacité limitée de détection de la TB. Il y a un besoin urgent d'un algorithme alternatif de dépistage de la TB pour les femmes enceintes quels que soient leurs symptômes de TB.

Tuberculosis preventive treatment opportunities at antiretroviral therapy initiation and follow-up visits.

SETTING: Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%. OBJECTIVES: To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV. DESIGN: A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the Xpert® MTB/RIF Package Rollout Evaluation Study between 2012 and 2015. RESULTS: Of 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4 <200 cells/mm3 (aOR = 1.4, P = 0.030); anemia (aOR = 2.39, P < 0.001); cough (aOR = 11.21, P < 0.001); fever (aOR = 2.15, P = 0.001); and weight loss (aOR = 2.60, P = 0.002). CONCLUSION: Eligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana.

MARCO DE REFERENCIA: Veintidós consultorios que prestan atención y tratamiento relacionados con la infección por el virus de la inmunodeficiencia humana (VIH) en Botswana, donde la comorbilidad por tuberculosis (TB) e infección por el VIH puede alcanzar 49%. OBJETIVOS: Evaluar los criterios para recibir el tratamiento preventivo de la TB (TPT) durante las consultas de iniciación y seguimiento del tratamiento antirretrovírico (TAR) y describir la prevalencia de TB y los factores asociados en el momento del inicio y el rendimiento del diagnóstico de TB en cada cita de seguimiento del TAR. MÉTODO: Fue este un estudio prospectivo de los datos obtenidos sistemáticamente en las personas con infección por el VIH (PLHIV), inscritas en la atención para el estudio de evaluación del despliegue de la prueba Xpert® MTB/RIF del 2012 al 2015. RESULTADOS: De los 6041 PLHIV que iniciaron el TAR, 69% (4177/6041) cumplía los criterios para recibir el TPT al comienzo; 93% (5408/5815) en la primera consulta de seguimiento; 95% (5234/5514) en la segunda; 96% (4869/5079) en la tercera; y 97% (3925/4075) en la cuarta cita de seguimiento. La prevalencia inicial de TB fue 11% y durante el seguimiento fue 2%, 3%, 3% y 6%, respectivamente. Al comienzo del TAR, los factores de riesgo independientes de diagnóstico de TB fueron una cifra de linfocitos CD4 <200 células/mm3 (aOR 1,4; P = 0,030), la anemia (aOR 2,39; P < 0,001), la tos (aOR 11,21; P = <0,001), la fiebre (aOR 2,15; P = 0,001) y la pérdida de peso (aOR 2,60; P = 0,002). CONCLUSIÓN: Los pacientes cumplen las condiciones para recibir el TPT con mayor frecuencia en las consultas posteriores al comienzo del TAR, pero la mayoría de los casos de TB activa se detecta al iniciarlo. Las oportunidades desaprovechadas para detectar casos de TB dificultan aún más el control de esta enfermedad en las PLHIV en Botswana.

Improving sputum collection processes to increase tuberculosis case finding among HIV-positive persons in Botswana.

SETTING: Twenty-two human immunodeficiency virus (HIV) clinics in Botswana. OBJECTIVE: To compare sputum collection rates, sputum quality and volume, and tuberculosis (TB) diagnosis rates before and after field efforts to improve sputum collection among individuals newly diagnosed with HIV with TB symptoms. DESIGN: Newly diagnosed individuals living with HIV attending 22 HIV clinics in Botswana were screened for TB from August 2012 to March 2014. Starting in May 2013, a field intervention composed of the introduction of a tracking log for presumed TB patients, and patient instructions and sputum induction to improve sputum collection rates was implemented. RESULTS: Prior to the intervention, sputum collection rates were 44.1% (384/870). Subsequently, sputum collection increased to 58.3% (579/993) (P < 0.001). Sputum quality and volume also improved. Although rates of TB diagnosis increased from 9.7% (84/870) to 12.5% (120/993), this difference was not significant (P = 0.143). CONCLUSION: Sputum collection rates among presumptive TB cases, as well as sputum quality and volume improved after implementation of the field intervention. To improve sputum collection rates, efforts at the program level should be ongoing.

Treatment outcomes, diagnostic and therapeutic impact: Xpert vs. smear. A systematic review and meta-analysis.

BACKGROUND: Compared with smear microscopy, Xpert® MTB/RIF has the potential to reduce delays in tuberculosis (TB) diagnosis and treatment initiation, and improve treatment outcomes. We reviewed publications comparing treatment outcomes of drug-susceptible TB patients diagnosed using Xpert vs. smear. METHODS: Citations (2000-2016) reporting treatment outcomes of patients diagnosed using Xpert compared with smear were selected from PubMed, Scopus and conference abstracts. We conducted a systematic review and meta-analysis. Favorable (cured, completed) and unfavorable (failure, death, loss to follow-up) outcomes were pooled for meta-analysis; we also reviewed the number of TB cases diagnosed, time to treatment and empiric treatment. The Mantel-Haenszel method with a fixed-effect model was used; I² was calculated to measure heterogeneity. RESULTS: From 13 citations, 43 594 TB patients were included and 4825 were with known TB treatment outcome. From the pooled analysis, an unfavorable outcomes among those diagnosed using Xpert compared with smear was 20.2%, 541/2675 vs. 21.9%, 470/2150 (risk ratio 0.92, 95%CI 0.82-1.02). Statistical heterogeneity was low (I² = 0.0%, P = 0.910). Compared with smear, Xpert was reported to be superior in increasing the number of TB patients diagnosed (2/9 citations), increasing bacteriologically confirmed TB (7/9 citations), reducing empiric treatment (3/5 citations), reducing time to diagnosis (2/3 citations), and reducing time to treatment initiation (1/5 citations). CONCLUSIONS: Xpert implementation showed no discernible impact on treatment outcomes compared with conventional smear despite reduced time to diagnosis, time to treatment or reduced level of empiric treatment. Further research is required to learn more about gaps in the existing health system.

Anti-tuberculosis treatment outcomes in HIV-infected adults exposed to isoniazid preventive therapy in Botswana.

SETTING: Eight public health clinics in Gaborone and Francistown, Botswana. OBJECTIVES: To describe the characteristics and outcomes of incident tuberculosis (TB) cases in human immunodeficiency virus (HIV) infected adults exposed to isoniazid preventive therapy (IPT) with access to antiretroviral and anti-tuberculosis treatment. DESIGN: In 1995 HIV-infected adults, TB disease was excluded before commencing IPT. During and after receipt of 6 or 36 months of IPT, symptomatic participants were evaluated using chest radiographs, sputum microscopy, cultures and drug susceptibility testing (DST). Incident TB cases received ≥6 months of anti-tuberculosis treatment. RESULTS: Seventy-five incident TB cases were identified among 619 symptomatic participants. The median duration of IPT in these cases was 6 months (range 1-35), and the median time to initiation of anti-tuberculosis treatment was 12 months after IPT cessation. Antiretroviral therapy (ART) was initiated before anti-tuberculosis treatment in 37 cases. Culture was positive in 43/58 (74%) TB cultures. DST was available for 38 cases, of which six (16%) were resistant to isoniazid (INH); 67/75 (89%) cases, including four with INH-monoresistant TB, completed anti-tuberculosis treatment or were cured. CONCLUSIONS: With prompt initiation of anti-tuberculosis treatment and access to ART, excellent outcomes were achieved in a public health setting in HIV-infected adults who developed TB disease.

Association of chest radiographic abnormalities with tuberculosis disease in asymptomatic HIV-infected adults.

SETTING: Francistown and Gaborone, Botswana. OBJECTIVE: Chest radiography is used to screen for tuberculosis (TB) in asymptomatic persons living with the human immunodeficiency virus (PLWH) seeking isoniazid preventive therapy (IPT). We describe radiographic features in PLWH in a TB-endemic setting and identify features associated with TB disease. DESIGN: Asymptomatic PLWH seeking IPT under program conditions for a clinical trial between 2004 and 2006 received chest radiographs (CXRs) that were read using the standardized Chest Radiograph Reading and Recording System (CRRS). Clinical characteristics, including TB disease, were compared with the radiographic findings. RESULTS: From 2732 screening CXRs, 183 had one or more abnormalities and were scored using CRRS, with 42% having infiltrates (36% upper lobes), 35% parenchymal fibrosis and 32% adenopathy. TB disease status was determined in 129 (70%) PLWH, of whom 22 (17%) had TB disease. TB disease was associated with upper lobe infiltrates (relative risk [RR] 3.0, 95%CI 1.5-6.2) and mediastinal adenopathy (RR 3.9, 95%CI 1.8-8.4). The sensitivity and specificity of either upper lobe infiltrates or mediastinal lymphadenopathy for TB disease were respectively 64% and 82%. CONCLUSION: A combination of CXR features was useful for predicting TB disease in asymptomatic PLWH. CRRS should be used more frequently in similar studies.

Tuberculosis in asymptomatic HIV-infected adults with abnormal chest radiographs screened for tuberculosis prevention.

BACKGROUND: Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in people living with HIV (human immunodeficiency virus, PLWH). Symptom screening without chest radiographs (CXRs) was established as the strategy for excluding TB disease among PLWH seeking IPT in Botswana's 2001 pilot project. This strategy was evaluated in 2004-2006 among candidates screened for an IPT clinical trial. METHODS: PLWH referred from clinics and HIV testing centers were screened for TB symptoms. All asymptomatic candidates received CXRs; those with abnormal CXRs were investigated further. RESULTS: Among 2732 asymptomatic candidates screened, 302 (11%) had abnormal CXRs potentially compatible with TB; TB disease was diagnosed in 43 of these 302 (14%), or 43 (1.6%) of the 2732 asymptomatic candidates. While not associated with CD4 lymphocyte counts < 200 cells/mm(3), TB was associated with a positive tuberculin skin test (relative risk 2.1, 95%CI 1.1-4.0). IPT was initiated in 113 (62%) of 182 asymptomatic PLWH with abnormal CXRs; 8/113 (7%) subsequently developed TB, and 7/8 (88%) successfully completed anti-tuberculosis treatment. CONCLUSIONS: The prevalences of abnormal CXRs and TB were respectively 2.6- and 8.9-fold higher among asymptomatic PLWH screened for the trial than in the pilot. A cost-effectiveness analysis is needed to determine whether the benefits of symptom screening alone are offset by the risk of inducing INH resistance by excluding CXRs during screening.