• Demanding an end to tuberculosis: treatment of tuberculosis infection among persons living with and without HIV

      Fargher, J; Reuter, A; Furin, J (Lippincott, Williams & Wilkins, 2019-01-01)
      More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention.
    • Field Evaluation of Near Point of Care Cepheid GeneXpert HIV-1 Qual for Early Infant Diagnosis

      Opollo, VS; Nikuze, A; Ben-Farhat, J; Anyango, E; Humwa, F; Oyaro, B; Wanjala, S; Omwoyo, W; Majiwa, M; Akelo, V; Zeh, C; Maman, D (Public Library of Science, 2018-12-27)
      Access to point-of-care HIV testing shortens turn-around times, time to diagnosis and reduces loss to follow-up hence minimizing barriers to early linkage to care and treatment among HIV infected infants. Currently samples for early infant HIV diagnosis are sent to centralized testing facilities which are few and located only at specific regions in Kenya. However, there are Point of Care (POC) early infant diagnosis [EID] technologies elsewhere such as SAMBA and ALERE-Q that are yet to be evaluated in Kenya despite the urgent need for data to inform policy formulation regarding EID. The Cepheid GeneXpert HIV-1 Qual (GeneXpert) technology for POC EID offers a great opportunity to minimize HIV associated morbidity, mortality and loss to follow-up through decentralization of early infant HIV testing to the clinics. This technology also allows for same-day results thus facilitating prompt linkage to care.
    • 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; Bonnet, M (BMJ, 2018-12-06)
      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.
    • Beyond 'cure' and 'treatment success': quality of life of patients with multidrug-resistant tuberculosis

      Laxmeshwar, C; Stewart, A G; Dalal, A; Kumar, A M V; Kalaiselvi, S; Das, M; Gawde, N; Thi, S S; Isaakidis, P (International Union Against Tuberculosis and Lung Disease, 2019-01-01)
      Two drug-resistant tuberculosis (DR-TB) sites (MSF Clinic, Jupiter Hospital) in Mumbai, India.
    • High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

      Ndjeka, N; Schnippel, K; Master, I; Meintjes, G; Maartens, G; Romero, R; Padanilam, X; Enwerem, M; Chotoo, S; Singh, N; Hughes, J; Variava, E; Ferreira, H; Te Riele, J; Ismail, N; Mohr, E; Bantubani, N; Conradie, F (European Respiratory Society, 2018-10-25)
      Background: South African patients with rifampicin-resistant tuberculosis and resistance to fluoroquinolones and/or injectables (pre/XDR-TB) were granted access to bedaquiline through a Clinical Access Programme with strict inclusion and exclusion criteria.Methods: Pre/XDR-TB and XDR-TB patients were treated with 24 weeks bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed.Results: 200 patients were enrolled: 87 (43.9%) with XDR-TB, 99 (49.3%) were female, median age 34 years (IQR 27, 42). 134 (67.0%) were living with HIV; median CD4+ 281 (IQR 130; 467) and all on antiretroviral therapy.16/200 patients (8.0%) did not complete 6 months of bedaquiline of which 8 were lost to follow up, 6 died, 1 stopped for side effects and 1 patient was diagnosed with drug-sensitive TB.146/200 (73.0%) patients had favourable outcomes: 139/200 were cured (69.5%) and 7 completed treatment (3.5%). 25 died (12.5%), were lost from treatment (10.0%), 9 had treatment failure (4.5%).22 adverse events were attributed to bedaquiline: including QTcF >500 ms (n=5), QTcF increase >50 ms from baseline (n=11), paroxysmal atrial flutter (n=1).Conclusion: Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this MDR-TB and XDR-TB cohort.
    • Model of care and risk factors for poor outcomes in patients on multi-drug resistant tuberculosis treatment at two facilities in eSwatini (formerly Swaziland), 2011–2013

      Verdecchia, M; Keus, K; Blankley, S; Vambe, D; Ssonko, C; Piening, T; Casas, EC (Public Library of Science, 2018-10-17)
    • Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis: a systematic literature review

      Ioos, V; Cordel, H; Bonnet, M (BMJ Journals, 2018-08-20)
      Diagnosis of intrathoracic tuberculosis (ITB) is limited in children partly by their difficulty to produce sputum specimen.
    • "Life continues": Patient, health care and community care workers perspectives on self-administered treatment for rifampicin-resistant tuberculosis in Khayelitsha, South Africa

      Mohr, E; Snyman, L; Mbakaz, Z; Caldwell, J; DeAzevedo, V; Kock, Y; Trivino Duran, L; Venables, E (Public Library of Science, 2018-09-14)
      Self-administered treatment (SAT), a differentiated model of care for rifampicin-resistant tuberculosis (RR-TB), might address adherence challenges faced by patients and health care systems. This study explored patient, health-care worker (HCW) and community care worker (CCW) perspectives on a SAT pilot programme in South Africa, in which patients were given medication to take at home with the optional support of a CCW.
    • Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis

      Harausz, EP; Garcia-Prats, AJ; Law, S; Schaaf, HS; Kredo, T; Seddon, JA; Menzies, D; Turkova, A; Achar, J; Amanullah, F; Barry, P; Becerra, M; Chan, ED; Chan, PC; Ioana Chiotan, D; Crossa, A; Drobac, PC; Fairlie, L; Falzon, D; Flood, J; Gegia, M; Hicks, RM; Isaakidis, P; Kadri, SM; Kampmann, B; Madhi, SA; Marais, E; Mariandyshev, A; Méndez-Echevarría, A; Moore, BK; Nargiza, P; Ozere, I; Padayatchi, N; Ur-Rehman, S; Rybak, N; Santiago-Garcia, B; Shah, NS; Sharma, S; Shim, TS; Skrahina, A; Soriano-Arandes, A; van den Boom, M; van der Werf, MJ; van der Werf, TS; Williams, B; Yablokova, E; Yim, J; Furin, J; Hesseling, AC (Public Library of Science, 2018-07-11)
      An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children.
    • Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study

      Schnippel, K; Ndjeka, N; Maartens, G; Meintjes, G; Master, I; Ismail, N; Hughes, J; Ferreira, H; Padanilam, X; Romero, R; Te Riele, J; Conradie, F (Elsevier, 2018-07-09)
      Addition of bedaquiline to treatment for multidrug-resistant tuberculosis was associated with an increased risk of death in a phase 2b clinical trial, resulting in caution from WHO. Following a compassionate access programme and local regulatory approval, the South African National Tuberculosis Programme began widespread use of bedaquiline in March, 2015, especially among patients with extensively drug resistant tuberculosis for whom no other effective treatment options were available. We aimed to compare mortality in patients on standard regimens with that of patients on regimens including bedaquiline.
    • Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia

      Hewison, C; Bastard, M; Khachatryan, N; Kotrikadze, T; Hayrapetyan, A; Avaliani, Z; Kiria, N; Yegiazaryan, L; Chumburidze, N; Kirakosyan, O; Atshemyan, H; Qayyum, S; Lachenal, N; Varaine, F; Huerga, H (International Union Against Tuberculosis and Lung Disease, 2018-07-01)
      Bedaquiline (BDQ) was initially only available through compassionate use programmes.
    • Tuberculosis in Visceral Leishmaniasis-Human Immunodeficiency Virus Coinfection: An Evidence Gap in Improving Patient Outcomes?

      van Griensven, J; Mohammed, R; Ritmeijer, K; Burza, S; Diro, E (Oxford University Press, 2018-04)
      Visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection remains a major problem in Ethiopia, India, and Brazil. Tuberculosis (TB), a treatable factor, could contribute to high mortality (up to 25%) in VL-HIV coinfection. However, the current evidence on the prevalence and clinical impact of TB in VL-HIV coinfection is very limited. In previous reports on routine care, TB prevalence ranged from 5.7% to 29.7%, but information on how and when TB was diagnosed was lacking.
    • The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?

      Reuter, A; Tisile, P; von Delft, D; Cox, H; Cox, V; Ditiu, L; Garcia-Prats, A; Koenig, S; Lessem, E; Nathavitharana, R; Seddon, JA; Stillo, J; von Delft, A; Furin, J (International Union Against Tuberculosis and Lung Disease, 2017-11-01)
      For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care. We conclude that there is limited evidence of the efficacy of IAs, clear evidence of the risks of these drugs, and that persons living with MDR-TB should be informed about these risks and provided with access to alternative therapeutic options.
    • Impact of pyrazinamide resistance on multidrug-resistant tuberculosis in Karakalpakstan, Uzbekistan

      Kuhlin, J; Smith, C; Khaemraev, A; Tigay, Z; Parpieva, N; Tillyashaykhov, M; Achar, J; Hajek, J; Greig, J; du Cros, P; Moore, D (International Union Against Tuberculosis and Lung Disease, 2018-05-01)
      The World Health Organization (WHO) recommends the inclusion of pyrazinamide (PZA) in treatment regimens for multidrug-resistant tuberculosis (MDR-TB) unless resistance has been confirmed.
    • Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: Multicenter cohort study

      Bastard, M; Sanchez-Padilla, E; du Cros, P; Khamraev, AK; Parpieva, N; Tillyashaykov, M; Hayrapetyan, A; Kimenye, K; Khurkhumal, S; Dlamini, T; Perez, SF; Telnov, A; Hewison, C; Varaine, F; Bonnet, M (Public Library of Science, 2018-03-08)
      The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance.
    • Multidisease testing for HIV and TB using the GeneXpert platform: A feasibility study in rural Zimbabwe

      Ndlovu, Z; Fajardo, E; Mbofana, E; Maparo, T; Garone, D; Metcalf, C; Bygrave, H; Kao, K; Zinyowera, S (Public Library of Science, 2018-03-02)
      HIV Viral Load and Early Infant Diagnosis technologies in many high burden settings are restricted to centralized laboratory testing, leading to long result turnaround times and patient attrition. GeneXpert (Cepheid, CA, USA) is a polyvalent near point-of-care platform and is widely implemented for Xpert MTB/RIF diagnosis. This study sought to evaluate the operational feasibility of integrated HIV VL, EID and MTB/RIF testing in new GeneXpert platforms.
    • Global programmatic use of bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis

      Cox, V; Brigden, G; Crespo, RH; Lessem, E; Lynch, S; Rich, ML; Waning, B; Furin, J (International Union Against Tuberculosis and Lung Disease, 2018-04-01)
      The World Health Organization recommended two new drugs, bedaquiline (BDQ) and delamanid (DLM), for the treatment of multidrug-resistant tuberculosis (MDR-TB) in 2013 and 2014, respectively. An estimated one third of patients with MDR-TB would benefit from the inclusion of these drugs in their treatment regimens.
    • Precision medicine for drug-resistant tuberculosis in high-burden countries: is individualised treatment desirable and feasible?

      Cox, H; Hughes, J; Black, J; Nicol, MP (Elsevier, 2018-03-13)
      Treatment for drug-resistant tuberculosis is largely delivered through standardised, empirical combination regimens in low-resource, high-burden settings. However, individualised treatment, guided by detailed drug susceptibility testing, probably results in improved individual outcomes and is the standard of care in well-resourced settings. Driven by the urgent need to scale up treatment provision, new tuberculosis drugs, incorporated into standardised regimens, are being tested. Although standardised regimens are expected to improve access to treatment in high-burden settings, they are also likely to contribute to the emergence of resistance, even with good clinical management. We argue that a balance is required between the need to improve treatment access and the imperative to minimise resistance amplification and provide the highest standard of care, through a precision medicine approach. In tuberculosis, as in other diseases, we should aim to reduce the entrenched inequalities that manifest as different standards of care in different settings.
    • Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high HIV and tuberculosis burden countries: a systematic review

      Atwine, D; Bonnet, M; Taburet, AM (Wiley-Blackwell, 2018-04-06)
      Efavirenz (EFV) and Rifampicin-Isoniazid (RH) are cornerstone drugs in HIV-tuberculosis (TB) co-infection treatment but with complex drug interactions, efficacy and safety challenges. We reviewed recent data on EFV and RH interaction in TB/HIV high-burden countries.