1. MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis.
PLoS One. 2017 Mar 8;12(3):e0172748. doi: 10.1371/journal.pone.0172748. eCollection 2017.
Kendall EA(1), Azman AS(2), Cobelens FG(3), Dowdy DW(2).
BACKGROUND: In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality.
METHODS: We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. RESULTS: Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4-52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6-55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20-74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025.
CONCLUSIONS: Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected to significantly decrease MDR-TB incidence at the population level. Focusing MDR diagnostic efforts on previously-treated cases is an efficient first-step approach.
2. Outcomes from the first multidrug-resistant tuberculosis programme in Kenya.
Int J Tuberc Lung Dis. 2017 Mar 1;21(3):314-319. doi: 10.5588/ijtld.16.0661.
Huerga H(1), Bastard M(1), Kamene M(2), Wanjala S(3), Arnold A(4), Oucho N(5), Chikwanha I(6), Varaine F(6).
SETTING: In March 2006, the first multidrug-resistant tuberculosis (MDR-TB) treatment programme was implemented in Kenya.
OBJECTIVE: To describe patients’ treatment outcomes and adverse events.
DESIGN: A retrospective case note review of patients started on MDR-TB treatment at two Médecins Sans Frontières-supported sites and the national referral hospital of Kenya was undertaken. Sites operated an ambulatory model of care. Patients were treated for a minimum of 24 months with at least 4-5 drugs for the intensive phase of treatment, including an injectable agent.
RESULTS: Of 169 patients, 25.6% were human immunodeficiency virus (HIV) positive and 89.3% were culture-positive at baseline. Adverse events occurred in 67.4% of patients: 45.9% had nausea/vomiting, 43.9% electrolyte disturbance, 41.8% dyspepsia and 31.6% hypothyroidism. The median time to culture conversion was 2 months. Treatment outcomes were as follows: 76.6% success, 14.5% deaths, 8.3% lost to follow-up and 0.7% treatment failure. HIV-positive individuals (adjusted odds ratio [aOR] 3.51, 95% confidence interval [CI] 1.12-11.03) and women (aOR 2.73, 95%CI 1.01-7.39) had a higher risk of unfavourable outcomes, while the risk was lower in those with culture conversion at 6 months (aOR 0.11, 95%CI 0.04-0.32).
CONCLUSION: In Kenya, where an ambulatory model of care is used for MDR-TBtreatment, treatment success was high, despite high rates of HIV. Almost half of the patients experienced electrolyte disturbance and one third had hypothyroidism; this supports the view that systematic regular biochemical monitoring is needed in Kenya.
3. Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.
Int J Tuberc Lung Dis. 2017 Mar 1;21(3):297-302. doi: 10.5588/ijtld.16.0576.
Fox GJ(1), Anh NT(1), Nhung NV(2), Loi NT(1), Hoa NB(3), Ngoc Anh LT(4), Cuong NK(5), Buu TN(6), Marks GB(7), Menzies D(8).
BACKGROUND: Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB(MDR-TB) and drug-susceptible TB are not well understood.
OBJECTIVE: To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB (‘new TB‘).
DESIGN: Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm.
RESULTS: A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0).
CONCLUSION: Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.
4. The risk of global epidemic replacement with drug-resistant Mycobacterium tuberculosis strains.
Int J Infect Dis. 2017 Mar;56:14-20. doi: 10.1016/j.ijid.2017.01.031. Epub 2017 Feb 2.
McBryde ES(1), Meehan MT(2), Doan TN(3), Ragonnet R(4), Marais BJ(5), Guernier V(2), Trauer JM(6).
OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (TB) control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model.
METHODS: This model considers two TB strains, one with and one without an MDR phenotype. It was considered that intrinsic transmissibility may be different between the two strains, as may the control response including the detection, treatment failure, and default rates. The outcomes were explored in terms of the incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain.
RESULTS AND CONCLUSIONS: The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain; however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as the DS-TB strain). This model suggests that it may take decades or more for strain replacement to occur. It was also found that while the amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission.