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  • Diagnostic sensitivity of SILVAMP TB-LAM (FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV

    Kerkhoff, AD; Sossen, B; Schutz, C; Reipold, EI; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Nicol, MP; et al. (European Respiratory Society, 2019-11-07)
  • Evaluation of OMNIgene® SPUTUM and ethanol reagent for preservation of sputum prior to Xpert and culture testing in Uganda.

    Ardizzoni, E; Orikiriza, P; Ssuuna, C; Nyehangane, D; Gumsboga, M; Taremwa, IM; Turyashemererwa, E; Mwanga-Amumpaire, J; Langendorf, C; Bonnet, M (American Society for Microbiology, 2019-10-16)
    Background: Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low resource countries. We aimed to assess the effect of OMNIgene® SPUTUM (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacteria growth indicator tube (MGIT) testing over a period of 15 and 8 days respectively. Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days. Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8. Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
  • Should urine-LAM tests be used in TB symptomatic HIV-positive patients when no CD4 count is available? A prospective observational cohort study from Malawi

    Huerga, H; Mathabire, SR; Bastard, M; Dimba, A; Kamba, C; Amoros, I; Szumilin, E (Lippincott, Williams & Wilkins, 2019-10-16)
    Background: Current eligibility criteria for urine lateral-flow-lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002). Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.
  • Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study.

    Mathabire Rucker, SC; Cossa, L; Harrison, RE; Mpunga, J; Lobo, S; Kisaka Kimupelenge, P; Mandar Kol'Ampwe, F; Amoros Quiles, I; Molfino, L; Szumilin, E; et al. (Taylor & Francis, 2019-10-15)
    Background: Determine TB-LAM is a urine-based point-of-care assay for diagnosis of tuberculosis (TB). Objective: To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings. Methods: We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM. Results: The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing. Conclusion: It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.
  • What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

    Bastard, M; Sanchez-Padilla, E; Hayrapetyan, A; Kimenye, K; Khurkhumal, S; Dlamini, T; Fadul Perez, S; Telnov, A; Hewison, C; Varaine, F; et al. (International Union Against Tuberculosis and Lung Disease, 2019-10-01)
    INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration. METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted. RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1–95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains. CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.
  • A misleading appearance of a common disease: tuberculosis with generalized lymphadenopathy—a case report

    Bottineau, MC; Kouevi, KA; Chauvet, E; Garcia, DM; Galetto-Lacour, A; Wagner, N (Oxford University Press, 2019-09-28)
    Introduction: Tuberculosis is a common illness for vulnerable populations in resource-limited settings. Lymph nodes in tuberculosis represent the most frequent extra-pulmonary form of tuberculosis in children, but lymph nodes are rarely generalized and large. We report an atypical pediatric case of tuberculosis with lymphadenopathy. Patient concerns and findings: A two-year-old child with severe acute malnutrition presented with painless, generalized, and excessively large nodes which were not compressive and were without fistula. Main diagnoses, interventions, outcomes: Fine needle aspiration was performed and led to the detection of lymph node granulomatous lymphadenitis suggestive of tuberculosis. Conclusion: The child was immediately initiated on anti-tuberculosis therapy with a very successful outcome. Clinicians should be aware of atypical manifestations such as the one we describe in the interest of swift diagnosis and initiation of treatment.
  • A retrospective study of tuberculosis outcomes in Gulf Province, Papua New Guinea

    Moses, I; Main, S; Commons, RJ; Robertson, B; Mek, A; Gale, M (International Union Against Tuberculosis and Lung Disease, 2019-09-21)
    Setting: Gulf Province, a rural area of mainland Papua New Guinea, is known to have one of the highest burdens of tuberculosis (TB) in the country. Objectives: To describe the characteristics and outcomes of TB patients registered for first-line treatment in Kerema General Hospital in Gulf Province between January and December 2016. Design: This was a retrospective cohort study using routinely collected programme data. Results: Of 347 cases with a recorded TB site, 54% were male and 32% were aged <15 years. No human immunodeficiency virus (HIV) status was recorded for 51% of cases. TB was bacteriologically confirmed in 23% of cases. Among the cohort, there were 145 extrapulmonary TB cases (42%); the site of disease was unknown in 56% of these cases. Of the 297 cases with treatment outcome evaluated, 56% had a favourable outcome and 26% were lost to follow-up. On multivariable analysis, extrapulmonary TB (adjusted OR [aOR] 0.51, 95%CI 0.30–0.88, P = 0.02) and bacteriologically confirmed TB (aOR 0.40, 95%CI 0.21–0.77, P < 0.01) were associated with decreased odds of an unfavourable treatment outcome. Conclusion: The study findings highlight the need to improve TB diagnosis, access to HIV testing, treatment adherence, patient support and the quality of TB programme data in Gulf Province.
  • Detecting tuberculosis: rapid tools but slow progress

    England, K; Masini, T; Rajardo, E (International Union Against Tuberculosis and Lung Disease, 2019-09-21)
    The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.
  • Challenges and controversies in childhood tuberculosis

    Reuter, A; Hughes, J; Furin, J (Elsevier, 2019-09-14)
    Children bear a substantial burden of suffering when it comes to tuberculosis. Ironically, they are often left out of the scientific and public health advances that have led to important improvements in tuberculosis diagnosis, treatment, and prevention over the past decade. This Series paper describes some of the challenges and controversies in paediatric tuberculosis, including the epidemiology and treatment of tuberculosis in children. Two areas in which substantial challenges and controversies exist (ie, diagnosis and prevention) are explored in more detail. This Series paper also offers possible solutions for including children in all efforts to end tuberculosis, with a focus on ensuring that the proper financial and human resources are in place to best serve children exposed to, infected with, and sick from all forms of tuberculosis.
  • Adverse events among people on delamanid for rifampicin-resistant tuberculosis in a high HIV prevalence setting

    Hughes, J; Reuter, A; Chabalala, B; Isaakidis, P; Cox, H; Mohr, E (International Union Against Tuberculosis and Lung Disease, 2019-09-01)
    SETTING: Patients with rifampicin-resistant tuberculosis (RR-TB) in the township of Khayelitsha, South Africa, were offered delamanid (DLM) within a decentralised RR-TB treatment programme. OBJECTIVE: To describe adverse events (AEs) among HIV-positive and negative people receiving DLM for RR-TB in a programmatic setting. DESIGN: Patients were followed up monthly for blood, electrocardiography and clinical monitoring and AEs were assessed for severity grade, seriousness and relationship to DLM. RESULTS: Fifty-eight patients (55% male; median age 35 years, interquartile range [IQR] 28–42) started DLM; 46 (79%) were HIV-positive, median CD4 count 173 cells/mm3 (IQR 70–294). Fifty (86%) patients experienced ≥1 new or worsening AE after starting DLM, most commonly vomiting, QTcB >450 ms and/or myalgia. Serious and/or severe AEs were experienced by 22 (38%) patients; three HIV-positive patients died (not related to DLM). HIV status was not significantly associated with number (P = 0.089) or severity/seriousness (P = 0.11) of AEs during exposure to DLM. Two (3%) patients had DLM withdrawn due to AEs. CONCLUSION: AEs during RR-TB treatment, both before and during DLM exposure, were common, with relatively few serious/severe AEs considered related to DLM and no significant association with HIV status. Clinical and electrocardiography monitoring should be prioritised in the first two months after starting DLM.
  • The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens.

    Khan, U; Huerga, H; Khan, AJ; Mitnick, CD; Hewison, C; Varaine, F; Bastard, M; Rich, M; Franke, MF; Atwood, S; et al. (BioMed Central, 2019-08-20)
    BACKGROUND: At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. METHODS: This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. DISCUSSION: The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments.
  • High Activation of γδ T Cells and the γδ2 T-Cell Subset Is Associated With the Onset of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome, ANRS 12153 CAPRI NK.

    Polidy, P; Nouhin, J; Ratana, M; Madec, Y; Borand, L; Marcy, O; Laureillard, D; Fernandez, M; Barre-Sionussi, F; Weiss, L; et al. (Frontiers Media, 2019-08-09)
    Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS. Methods: Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV-/TB- (HD, n = 11), HIV+/TB- (n = 26), and HIV-/TB+ (n = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of anti-tuberculosis treatment for HIV-/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry. Results: Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδpos T and iNKT cells. HLA-DR on γδpos T cells and δ2posγδpos T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (p < 0.0001). NKG2D expression on γδpos T cells and the δ2posγδpos T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδpos T cells was higher in TB-IRIS than non-IRIS (p = 0.02), HIV+/TB-, and HIV-/TB- patients. Conclusion: The higher activation of γδposT cells and the γδ2posγδpos T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.
  • Successful expansion of community-based drug-resistant TB care in rural Eswatini - a retrospective cohort study.

    Kerschberger, B; Telnov, A; Yano, N; Cox, H; Zabsonre, I; Kabore, SM; Vambe, D; Ngwenya, S; Rusch, B; Luce, TM; et al. (Wiley-Blackwell, 2019-08-07)
    OBJECTIVES: Provision of drug-resistant tuberculosis (DR-TB) treatment is scarce in resource-limited settings. We assessed the feasibility of ambulatory DR-TB care for treatment expansion in rural Eswatini. METHODS: Retrospective patient-level data were used to evaluate ambulatory DR-TB treatment provision in rural Shiselweni (Eswatini), from 2008 to 2016. DR-TB care was either clinic-based led by nurses or community-based at the patient's home with involvement of community treatment supporters for provision of treatment to patients with difficulties in accessing facilities. We describe programmatic outcomes and used multivariate flexible parametric survival models to assess time to adverse outcomes. Both care models were costed in supplementary analyses. RESULTS: Of 698 patients initiated on DR-TB treatment, 57% were women and 84% were HIV-positive. Treatment initiations increased from 27 in 2008 to 127 in 2011 and decreased thereafter to 51 in 2016. Proportionally, community-based care increased from 19% in 2009 to 77% in 2016. Treatment success was higher for community-based care (79%) than clinic-based care (68%, P = 0.002). After adjustment for covariate factors among adults (n = 552), the risk of adverse outcomes (death, loss to follow-up, treatment failure) in community-based care was reduced by 41% (adjusted hazard ratio 0.59, 95% CI: 0.39-0.91). Findings were supported by sensitivity analyses. The care provider's per-patient costs for community-based (USD13 345) and clinic-based (USD12 990) care were similar. CONCLUSIONS: Ambulatory treatment outcomes were good, and community-based care achieved better treatment outcomes than clinic-based care at comparable costs. Contextualised DR-TB care programmes are feasible and can support treatment expansion in rural settings.
  • Multidrug-resistant tuberculosis.

    Nyang'wa, BT; Berry, C; Fielding, K; Nunn, AJ (Elsevier, 2019-07-27)
  • Tuberculosis control activities in the private and public health sectors of Kenya from 2013 to 2017: how do they compare?

    Mailu, EW; Owiti, P; Ade, S; Harries, AD; Manzi, M; Omesa, E; Kiende, P; Macharia, S; Mbithi, I; Kamene, M (Oxford University Press, 2019-07-23)
    BACKGROUND: Large numbers of tuberculosis (TB) patients seek care from private for-profit providers. This study aimed to assess and compare TB control activities in the private for-profit and public sectors in Kenya between 2013 and 2017. METHODS: We conducted a retrospective cross-sectional study using routinely collected data from the National Tuberculosis, Leprosy and Lung Disease Program. RESULTS: Of 421 409 patients registered and treated between 2013 and 2017, 86 894 (21%) were from the private sector. Data collection was less complete in the private sector for nutritional assessment and follow-up sputum smear examinations (p<0.001). The private sector notified less bacteriologically confirmed TB (43.1% vs 52.6%; p<0.001) and had less malnutrition (body mass index <18.5 kg/m2; 36.4% vs 43.3%; p<0.001) than the public sector. Rates of human immunodeficiency virus (HIV) testing and antiretroviral therapy initiation were >95% and >90%, respectively, in both sectors, but more patients were HIV positive in the private sector (39.6% vs 31.6%; p<0.001). For bacteriologically confirmed pulmonary TB, cure rates were lower in the private sector, especially for HIV-negative patients (p<0.001). The private sector had an overall treatment success of 86.3% as compared with the public sector at 85.7% (p<0.001). CONCLUSIONS: The private sector is performing well in Kenya although there are programmatic challenges that need to be addressed.
  • High prevalence of infection and low incidence of disease in child contacts of patients with drug-resistant tuberculosis: a prospective cohort study

    Huerga, H; Sanchez-Padilla, E; Melikyan, N; Atshemyan, H; Hayrapetyan, A; Ulumyan, A; Bastard, M; Khachatryan, N; Hewison, C; Varaine, F; et al. (The BMJ, 2019-07)
    Objective We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence. Design and setting This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment. Main outcome measures Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI. Results At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities. Conclusions Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
  • Bedaquiline overdose: A case report

    Telnov, O; Alvarez, V; Graglia, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-07)
    We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
  • Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis

    Mbuagbaw, L; Guglielmetti, L; Hewison, C; Bakare, N; Bastard, M; Caumes, E; Frechet-Jachym, M; Robert, J; Veziris, N; Khachatryan, N; et al. (Centers for Disease Control and Prevention, 2019-05-01)
    Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%-81.9%), and the treatment success rate was 65.8% (95% CI 59.9%-71.3%). Death rate was 11.7% (95% CI 7.0%-19.1%). Up to 91.1% (95% CI 82.2%-95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%-23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.
  • Bedaquiline and delamanid in combination for treatment of drug-resistant tuberculosis

    Mohr, E; Ferlazzo, G; Hewison, C; De Azevedo, V; Isaakidis, P (Elsevier, 2019-05-01)
    Here we report on the final outcomes for the cohort of 28 patients from Armenia, India, and South Africa who initiated regimens containing the combination of bedaquiline and delamanid from January to August, 2016, for the treatment of multidrug-resistant tuberculosis in our cohort study.1 The median duration on combination treatment was 12 months (interquartile range [IQR] 5·9–20·0); 17 (61%) of 28 patients received the combination for more than 6 months.

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