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  • MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

    Battista Migliori, G; Tiberi, S; Zumla, A; Petersen, E; Muhwa Chakaya, J; Wejse, C; Muñoz Torrico, M; Duarte, R; Alffenaar, JW; Schaaf, HS; et al. (Elsevier, 2020-02-04)
    The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.
  • Cost-effectiveness of diagnostic algorithms including lateral-flow urine lipoarabinomannan for HIV-positive patients with symptoms of tuberculosis

    Yakhelef, N; Audibert, M; Ferlazzo, G; Sitienei, J; Wanjala, S; Varaine, F; Bonnet, M; Huerga, H (Public Library of Science, 2020-01-30)
    BACKGROUND: Tuberculosis (TB) is the leading cause of death among HIV-positive patients. We assessed the cost-effectiveness of including lateral-flow urine lipoarabinomannan (LF-LAM) in TB diagnostic algorithms for severely ill or immunosuppressed HIV-positive patients with symptoms of TB in Kenya. METHODS: From a decision-analysis tree, ten diagnostic algorithms were elaborated and compared. All algorithms included clinical exam. The costs of each algorithm were calculated using a 'micro-costing' method. The efficacy was estimated through a prospective study that included severely ill or immunosuppressed (CD4<200cells/μL) HIV-positive adults with symptoms of TB. The cost-effectiveness analysis was performed using the disability-adjusted life year (DALY) averted as effectiveness outcome. A 4% discount rate was applied. RESULTS: The algorithm that added LF-LAM alone to the clinical exam lead to the least average cost per TB case detected (€47) and was the most cost-effective with a cost/DALY averted of €4.6. The algorithms including LF-LAM, microscopy and X-ray, and LF-LAM and Xpert in sputum, detected a high number of TB cases with a cost/DALY averted of €6.1 for each of them. In the comparisons of the algorithms two by two, using LF-LAM instead of microscopy (clinic&LAM vs clinic&microscopy) and using LF-LAM along with GeneXpert in sputum instead of GeneXpert in urine along with GeneXpert in sputum, (clinic&LAM&Xpert_sputum vs clinic&Xpert_sputum&Xpert_urine) led to the highest increase in the cost-effectiveness ratios (ICERs): €-7.2 and €-12.6 respectively. In these two comparisons, using LF-LAM increased the number of TB patients detected while reducing costs. Adding LF-LAM to smear microscopy alone or to smear microscopy and Xray led to the highest increase in the additional number of TB cases detected (31 and 25 respectively) with an incremental efficiency estimated at 134 and 344 DALYs respectively. The ICERs were €22.0 and €8.6 respectively. CONCLUSION: Including LF-LAM in TB diagnostic algorithms is cost-effective for severely ill or immunosuppressed HIV-positive patients.
  • Non-disclosure of tuberculosis diagnosis by patients to their household members in south western Uganda

    Nyangoma, M; Bajunirwe, F; Atwine, D (Public Library of Science, 2020-01-24)
    BACKGROUND: Tuberculosis (TB) non-disclosure by adult patients to all household members is a setback to TB control efforts. It reduces the likelihood that household contacts will seek early TB screening, initiation on preventive or curative treatment, but also hinders the implementation of infection controls and home-based directly observed treatment. Therefore, the purpose of this study was to determine the level of TB non-disclosure, its predictors and the effects of disclosure among adult TB patients in Uganda. METHODS: We conducted a cross-sectional study at a large regional referral hospital in Mbarara, south-western Uganda. Questionnaires were administered to collect patients' sociodemographic and their TB disclosure data. Non-disclosure was considered if a patient did not reveal their TB diagnosis to all household members within 2 weeks post-treatment initiation. Univariate and multivariate logistic regression models were fitted for predictors of non-disclosure. RESULTS: We enrolled 62 patients, 74% males, mean age of 32 years, and median of five people per household. Non-disclosure rate was 30.6%. Post-disclosure experiences were positive in 98.3% of patients, while negative experiences suggestive of severe stigma occurred in 12.3% of patients. Being female (OR 6.5, 95% CI: 1.4-29.3) and belonging to Muslim faith (OR 12.4, 95% CI: 1.42-109.1) were significantly associated with TB non-disclosure to household members. CONCLUSIONS: There is a high rate of TB non-disclosure to all household members by adult patients in rural Uganda, particularly among women and muslim patients. Interventions enhancing TB disclosure at household level while minimizing negative effects of stigma should be developed and prioritized.
  • Systematic, Point-of-Care Urine Lipoarabinomannan (Alere TB-LAM) Assay for Diagnosing Tuberculosis in Severely Immunocompromised HIV-Positive Ambulatory Patients

    Huerga, H; Cossa, L; Manhica, I; Bastard, M; Telnov, A; Molfino, L; Sanchez-Padilla, E (American Society of Tropical Medicine and Hygiene, 2020-01-20)
    Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (aOR:4.48, 95% CI: 1.24-16.23, P = 0.022). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.
  • Tuberculosis-HIV Co-Infection: Progress and Challenges After Two Decades of Global Antiretroviral Treatment Roll-Out.

    Letang, E; Ellis, J; Naidoo, K; Casas, EC; Sanchez, P; Hassan-Moosa, R; Cresswell, F; Miro, JM; Garcia-Basteiro, AL (Elsevier, 2020-01-10)
    Despite wide antiretroviral scale-up during the past two decades resulting in declining new infections and mortality globally, HIV-associated tuberculosis remains as a major public health concern. Tuberculosis is the leading HIV-associated opportunistic infection and the main cause of death globally and, particularly, in resource-limited settings. Several challenges exist regarding diagnosis, global implementation of latent tuberculosis treatment, management of active tuberculosis, delivery of optimal patient-centered TB and HIV prevention and care in high burden countries. In this article we review the advances on pathogenesis, diagnosis, and treatment after nearly two decades of global roll-out of antiretroviral therapy and discuss the current challenges for the global control of tuberculosis-HIV co-infection.
  • 'SILVAMP TB LAM' rapid urine tuberculosis test predicts mortality in hospitalized HIV patients in South Africa.

    Sossen, B; Broger, T; Kerkhoff, AD; Schutz, C; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Wilkinson, RJ; et al. (Oxford University Press, 2020-01-09)
    Reducing diagnostic delay is key towards decreasing tuberculosis-associated deaths in people living with HIV. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.
  • New opportunities in tuberculosis prevention: implications for people living with HIV.

    Gonzalez Fernandez, L; Casas, EC; Singh, S; Churchyard, GJ; Brigden, G; Gotuzzo, E; Vandevelde, W; Sahu, S; Ahmedov, S; Kamarulzaman, A; et al. (Wiley Open Access, 2020-01-01)
    INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
  • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India

    Isaakidis, P; Ferlazzo, G; Das, M; Pasupuleti, D; Sloan, S; Hossain, F; Kalon, S; Mansoor, H; Rao, S (MDPI AG, 2019-12-21)
    Abstract: Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
  • Barriers and solutions to finding rifampicin-resistant tuberculosis cases in older children and adolescents

    Mohr-Holland, E; Apolisi, I; Reuter, A; de Azevedo, V; Hill, J; Matthee, S; Seddon, JA; Isaakidis, P; Furin, J; Trivino-Duran, L (International Union Against Tuberculosis and Lung Disease, 2019-12-21)
    Little is known about the barriers to post-exposure management of rifampicin-resistant tuberculosis (RR-TB) in older children and adolescents. We report on implementation lessons from a pilot programme targeting household-exposed individuals aged 6–18 years in Khayelitsha, South Africa. Barriers included misperceptions regarding risk of exposure, multiple research and implementation stakeholders, additional workload for an overburdened healthcare system, logistical issues faced by families, and insufficient human and financial resources. Solutions to these barriers are possible, but creativity and persistence are required. Our experience can guide others looking to roll-out care for children and adolescents exposed to RR-TB.
  • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

    Das, M; Pasupuleti, D; Rao, S; Sloan, S; Mansoor, H; Kalon, S; Hossain, F; Ferlazzo, G; Isaakidis, P (MDPI AG, 2019-12-21)
    Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
  • Standardised shorter regimens versus individualised longer regimens for multidrug-resistant TB

    Abidi, S; Achar, J; Neino, M; Bang, D; Benedetti, A; Brode, S; Campbell, J; Casas, E; Conradie, F; Dravniece, G; et al. (European Respiratory Society (ERS), 2019-12-20)
    We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: a standardised regimen of 9-12 months (the "shorter regimen"), and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up.We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD, -0.15 95%CI: -0.17 to -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: -0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
  • 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)
  • Culture conversion at six months in patients receiving delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis.

    Seung, KJ; Khan, P; Franke, MF; Ahmed, S; Aiylchiev, S; Alam, M; Putri, FA; Bastard, M; Docteur, W; Gottlieb, G; et al. (Oxford University Press, 2019-11-02)
    Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
  • 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.

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