October 2018 Newsletter

Recent News and Announcements


New publication! Nursing Guide for Managing Side Effects to Drug-resistant TB Treatment is a collaborative project between CITC and the International Council of Nurses (ICN). This guide was developed by nurses with experience in the clinical care and programmatic management of TB and DR-TB in both high- and low-resource settings.

The guide is designed as a reference and job aid so nurses can quickly:

  1. Identify symptoms that may indicate a side effect related to DR-TB treatment or antiretroviral medication;
  2. Assess for severity as well as other potential contributors; and
  3. Intervene appropriately in order to minimize patient discomfort, reduce side effect progression, and ultimately support successful treatment completion.

Access the full guide here.



1. Clinical trial research in focus: overcoming barriers in MDR-TB clinical trials.
Lancet Respir Med. 2017 Apr;5(4):247-248. doi: 10.1016/S2213-2600(17)30091-7.
Zumla A, Abubakar I.

ABSTRACT: The WHO 2016 annual report states “The TB epidemic is larger than previously estimated”. There were an estimated 480 000 new cases of multidrug-resistant tuberculosis (MDR-TB) and a substantial proportion of them remain undiagnosed and untreated. The current WHO-recommended MDR-TB treatment regimen is associated with poor treatment outcomes. The regimen is based on no trial evidence of efficacy and might not cover local, evolving tuberculosis drug resistance patterns. Many patients with MDR-TB who survive, suffer long-term lung damage and functional disability, and are unable to return to gainful employment.

Read free abstract here. Not open access.

2. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.
Lancet Respir Med. 2018 Apr;6(4):265-275. doi:https://doi.org/10.1016/S2213-2600(18)30078-X.
Fregonese F1, Ahuja SD2, Akkerman OW3, Arakaki-Sanchez D 4, Ayakaka I5, Baghaei P6, Bang D7, Bastos M8, Benedetti A9, Bonnet M10, Cattamanchi A11, Cegielski P12, Chien JY13, Cox H14, Dedicoat M15, Erkens C16, Escalante P17, Falzon D18, Garcia-Prats AJ19, Gegia M18, Gillespie SH20, Glynn JR21, Goldberg S22, Griffith D23, Jacobson KR24, Johnston JC25, Jones-López EC24, Khan A22, Koh WJ26, Kritski A27, Lan ZY9, Lee JH28, Li PZ1, Maciel EL29, Galliez RM30, Merle CSC31, Munang M15, Narendran G32, Nguyen VN33, Nunn A34, Ohkado A35, Park JS28, Phillips PPJ36, Ponnuraja C37, Reves R38, Romanowski K39, Seung K40, Schaaf HS19, Skrahina A41, Soolingen DV42, Tabarsi P6, Trajman A43, Trieu L2, Banurekha VV32, Viiklepp P44, Wang JY13, Yoshiyama T45, Menzies D46.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ.

METHODS: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1–3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology.

FINDINGS: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8–9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1–7·3), but no significant effect on mortality (aOR 0·7, 0·4–1·1) or acquired rifampicin resistance (aOR 0·1, 0·0–1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2–0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates.

INTERPRETATION: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis.

Read abstract here. Not open access.

3. Time to revise WHO-recommended definitions of MDR-TB treatment outcomes.
Lancet Respir Med. 2018 Apr;6(4):246-248. doi: 10.1016/S2213-2600(18)30104-8.
Lange C, van Leth F, Mitnick CD, Dheda K, Günther G.

ABSTRACT: According to the latest WHO global tuberculosis report, 10.4 million people worldwide developed tuberculosis in 2016. The number of people developing newly acquired tuberculosis has increased by 1.8 million (or 17%) during the past 5 years. Additionally, the emergence of multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis caused by bacteria resistant to the two first-line antituberculosis drugs rifampicin and isoniazid, is especially alarming. For the first time, in 2017, the leaders of the G20 nations recognised antimicrobial-resistant tuberculosis as a growing threat to public health and economic growth.

Read abstract here. Not open access.

4. Time to act on injectable-free regimens for children with multidrug-resistant tuberculosis.
Lancet Respir Med. 2018 Sep;6(9):662-664. doi: 10.1016/S2213-2600(18)30329-1.
Seddon JA, Schaaf HS, Marais BJ, McKenna L, Garcia-Prats AJ, Hesseling AC, Hughes J, Howell P, Detjen A, Amanullah F, Singh U, Master I, Perez-Velez CM, Misra N, Becerra MC, Furin JJ.

ABSTRACT: We read with interest the study by Kathryn Schnippel and colleagues, showing good efficacy and low toxicity associated with bedaquiline use in adults with rifampicin-resistant tuberculosis. An interim analysis from endTB, released on July 13, 2018, evaluating the use of bedaquiline and delamanid in more than 1000 patients, has also demonstrated the safety and efficacy of these new drugs. The tide appears to be turning, and in June, 2018, the South African Department of Health announced that bedaquiline will now replace second-line injectable agents in the routine treatment of all patients with rifampicin-resistant or multidrug-resistant (MDR) tuberculosis aged 12 years and older.

Read abstract here.  Not open access.