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.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Impact of rapid drug susceptibility testing for tuberculosis: program experience in Lima, Peru.

SETTING: Programmatic implementation of decentralized rapid drug susceptibility testing (DST) in Lima, Peru. OBJECTIVE: Pre-post analysis compared time to diagnosis, treatment outcome and survival among patients tested with direct nitrate reductase assay (NRA) vs. indirect conventional methods. DESIGN: From 2005 to 2009, we prospectively followed all patients referred for DST before (control) and after (intervention) NRA implementation. Among those referred for DST, NRA was used for smear-positive samples of patients with no prior history of multidrug resistance or treatment for multidrug-resistant tuberculosis (TB). Data were abstracted from patient charts and laboratory registers. Endpoints were favorable outcomes, time to result and time to death. RESULTS: Of those patients who met the criteria for NRA, 740 underwent NRA and 621 underwent conventional DST. NRA yielded test results for 78.4% of cases vs. 68.8% for conventional DST (P < 0.0001); the median time to result was 44 vs. 133 days, respectively (adjusted HR 0.64, 95%CI 0.56-0.73). Among individuals without previous anti-tuberculosis treatment, NRA was associated with a favorable treatment outcome (adjusted OR 1.39, 95%CI 1.01-1.90) and prolonged survival (adjusted HR 0.53, 95%CI 0.31-0.90). CONCLUSION: Direct NRA significantly shortened time to test result and improved treatment outcomes and survival in certain groups.

Tuberculosis in household contacts of multidrug-resistant tuberculosis patients.

SETTING: The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting interventions. DESIGN: This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients in 358 households. RESULTS: Of 2112 household contacts in 80 households (22% of households), 108 (5%) developed TB disease during the study, giving an incidence rate of 2360 per 100 000 contact follow-up years for each of the first 3 years after exposure. Drug susceptibility tests (DST) were available for 50 diseased contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were available, among which the contact had an identical or less resistant phenotype than the index case in 27 pairs. Multivariate Cox regression demonstrated that male contacts (hazard ratio [HR] 2.8, P < 0.05), with previous TB disease (HR 20.7, P < 0.001) and with associated (non-human immunodeficiency virus) comorbidities (HR 11.2, P < 0.001) were more likely to develop TB. CONCLUSION: The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.

Tratamiento de la fasciolasis hepática humana con triclabendazole / Treatment of human hepatic fasciolasis with triclabendazole

El presente estudio pretende valorar el efecto del triclabendazole sobre la distomatosis hepática en humanos, producida por la Fasciola hepática. Para ello se trató 70 pacientes con fasciolasis demostrada por exámenes seriados de heces, con triclabendazole a 12 mg/Kg. de peso diarios por dos días. El control parasitológico se realizó a los 15 y 45 días de administrado el tratamiento. Se encontró curación parasitológica en 83 por ciento de la población estudiada y tratada una sola vez, el 14 por ciento necesitó un segundo tratamiento y el 3 por ciento un tercero, y no se reportó efectos colaterales importantes atribuibles al tratamiento. Se concluye en consecuencia que el triclabendazole tiene una eficacia alta y buena tolerancia en el tratamiento de la fasciolasis hepática en humanos.

[TREATMENT OF HUMAN HEPATIC FASCIOLASIS WITH TRICLABENDAZOLE] / Tratamiento de la Fasciolasis Hepática Humanacon Triclabendazole.

This study has the purpose to evaluate the effect of triclabendazole over human fasciolasis produced by Fasciola hepatica. 70 patients with positive stools studies for fasciolasis were treated with 12 mg/kg/ day of triclabendazole for 2 days.The control stools tests were performed 15 and 45 days after the treatment was finished. Parasitologic negativitation of stools was found in 83% of those patients who recieved 1 cycle of treatment. 14% needed 2 cycles and 3% a third one.No important side effects were reported because of treatment. We conclude that triclabendazole is highly efficient and good against liver fasciolasis in humans.