Tuberculosis in children treated with second-line drugs under programmatic conditions in Lima, Peru.

OBJECTIVE: To characterise childhood tuberculosis (TB) treated with second-line drugs (SLDs) in Lima, Peru. DESIGN: Results for the age groups <5 and 5-14 years were compared and treatment outcomes were assessed in cases reported between 2011 and 2015 from six districts of Lima. RESULTS: Of 96 reported cases, 82 were evaluated. Among these, 59% were boys; the median age was 8 years and 32% were aged <5 years. Contact with a TB case was reported in 82% of cases; 90% were treatment-naïve, 98% had pulmonary localisation and 50% underwent the tuberculin skin test (purified protein derivative), with induration 10 mm in 88%. A positive smear was found in 40%, all in the 5-14 years age group, and 46% were culture-positive. Only 26% had confirmed multidrug-resistant TB, 90% of whom were in the 5-14 years age group. SLDs for confirmed or probable drug-resistant TB (DR-TB) were administered to all cases, with a high proportion of success (over 83%), no failures or deaths and a high proportion of loss to follow-up. CONCLUSION: The main indication for SLDs in childhood TB was the empirical treatment of DR-TB due to contact with one or more identified DR-TB patients. Bacteriological confirmation was limited; however, treatment success was adequate.

Programmatic management of patients with pre-extensively drug-resistant tuberculosis in Peru, 2011-2014.

BACKGROUND: In Peru, a treatment approach for extensively drug-resistant tuberculosis (XDR-TB) incorporating World Health Organization Group 5 drugs and patient-centred care has achieved 65% success. To extend this approach to pre-XDR-TB patients, we evaluated this population separately. OBJECTIVE: To assess programmatic management of pre-XDR-TB. METHOD: Retrospective study using the official national registry from 2011 to 2014. Cases were separately evaluated according to resistance to fluoroquinolones (FQs) (pre-XDR-F) or to second-line injectables (SLIs) (pre-XDR-I). RESULTS: Of 610 pre-XDR-TB patients, 120 (20%) had pre-XDR-F and 490 (80%) had pre-XDR-I. Pre-XDR-F cases were older (34 years vs. 28 years, P < 0.001) and a higher proportion had previously received two or more regimens (70% vs. 38%, P < 0.001). Among the 452 patients who started treatment in 2011-2013, treatment success was 43.3%, 26.5% were lost to follow-up, 12.1% died and 13.7% failed treatment. Success was higher in pre-XDR-I (48.5%) than pre-XDR-F (21.4%) patients. History of previous treatment (OR 2.23, 95%CI 1.52-3.38) and pre-XDR-F (OR 2.39, CI 1.18-4.83) were associated with unsuccessful outcomes. CONCLUSION: Programmatic management of pre-XDR-TB has not been successful, particularly in pre-XDR-F patients, with lower rates of success than those achieved in the same setting for XDR-TB. The strategy used for XDR-TB should be extended to pre-XDR-TB patients in Peru.

Rapid drug susceptibility testing and treatment outcomes for multidrug-resistant tuberculosis in Peru.

SETTING: The detection of multidrug-resistant tuberculosis (MDR-TB) using rapid drug susceptibility testing (DST) has increased steadily in recent years in Peru, from 9216 tests in 2010 to 27 021 tests in 2015. Research examining the impact of rapid DST on treatment outcomes is required. OBJECTIVE: To evaluate the association between rapid DST use (nitrate reductase assay, microscopic observation drug susceptibility assay [MODS] and GenoType® MTBDRplus) and treatment outcomes and mortality in MDR-TB patients in Peru. DESIGN: Retrospective cohort study of patients diagnosed with pulmonary MDR-TB between 2010 and 2013 (with treatment outcomes up to December 2015) using the electronic registry of the Peruvian National TB Programme. RESULTS: A total of 2671 MDR-TB patients were included; the median age was 27 years, 2.8% were co-infected with the human immunodeficiency virus. Use of rapid DST was associated with a 40% increase in the adjusted odds of treatment success (aOR 1.40, 95%CI 1.19-1.64) and a 54% reduction in mortality (aOR 0.46, 95%CI 0.33-0.64). Higher treatment success rates were driven by MODS and GenoType® MTBDRplus testing (aORs for unsuccessful outcomes respectively 0.68 and 0.66). CONCLUSION: The use of rapid DST (MODS and MTBDRplus) to diagnose MDR-TB was associated with a reduction in the odds of death and a substantial increase in the odds of treatment success.

Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru.

SETTING: Primary health care centres in Callao, Peru. OBJECTIVES: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). DESIGN: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. RESULTS: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P =30.003) was observed in the 2009 cohort. CONCLUSION: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru.

Language in tuberculosis services: can we change to patient-centred terminology and stop the paradigm of blaming the patients?

The words 'defaulter', 'suspect' and 'control' have been part of the language of tuberculosis (TB) services for many decades, and they continue to be used in international guidelines and in published literature. From a patient perspective, it is our opinion that these terms are at best inappropriate, coercive and disempowering, and at worst they could be perceived as judgmental and criminalising, tending to place the blame of the disease or responsibility for adverse treatment outcomes on one side-that of the patients. In this article, which brings together a wide range of authors and institutions from Africa, Asia, Latin America, Europe and the Pacific, we discuss the use of the words 'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue using them in the context of TB. We propose that 'defaulter' be replaced with 'person lost to follow-up'; that 'TB suspect' be replaced by 'person with presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' be replaced with 'prevention and care' or simply deleted. These terms are non-judgmental and patient-centred. We appeal to the global Stop TB Partnership to lead discussions on this issue and to make concrete steps towards changing the current paradigm.