The fourth national anti-tuberculosis drug resistance survey in Peru.

BACKGROUND: Peru has one of the highest burdens of multidrug-resistant tuberculosis (MDR-TB), but universal drug susceptibility testing (DST) has not yet been achieved.OBJECTIVE: To estimate the proportion of drug resistance among smear-positive TB patients in Peru.DESIGN: From September 2014 to March 2015, we performed a national drug resistance survey of patients aged ≥15 years; TB was diagnosed based on sputum smear positivity. We performed DST at the National Reference Laboratory of the Peruvian National Institute of Health, Lima, Peru, using the proportion method in Middlebrook 7H10 agar for four first-line drugs and six second-line drugs, and the Wayne method for pyrazinamide.RESULTS: Of the 1908 new and 272 previously treated patients included in the analysis, 638 (29.3%) patients had resistance to at least one first-line drug. MDR-TB was diagnosed in 7.3% of new and 16.2% of previously treated patients (P < 0.001). There were five (0.2%) patients with extensively drug-resistant TB.CONCLUSION: MDR-TB has increased to 7.3% in new patients from 5.3% in the previous survey, indicating that resistance to anti-tuberculosis drugs is increasing in Peru. Ongoing community transmission of resistant strains highlights an urgent need for early diagnosis, optimised treatment and effective contact tracing of MDR-TB patients.

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.

Reliability of the MODS assay decentralisation process in three health regions in Peru.

OBJECTIVE: To deliver rapid isoniazid (INH) and rifampicin (RMP) drug susceptibility testing (DST) close to the patient, we designed a decentralisation process for the microscopic observation drug susceptibility (MODS) assay in Peru and evaluated its reliability. METHODS: After 2 weeks of training, laboratory staff processed ≥ 120 consecutive sputum samples each in three regional laboratories. Samples were processed in parallel with MODS testing at an expert laboratory. Blinded paired results were independently analysed by the Instituto Nacional de Salud (INS) according to pre-determined criteria: concordance for culture, DST against INH and RMP and diagnosis of multidrug-resistant tuberculosis (MDR-TB) ≥ 95%, McNemar's P > 0.05, kappa index (κ) ≥ 0.75 and contamination 1-4%. Sensitivity and specificity for MDR-TB were calculated. RESULTS: The accreditation process for Callao (126 samples, 79.4% smear-positive), Lima Sur (n = 130, 84%) and Arequipa (n = 126, 80%) took respectively 94, 97 and 173 days. Pre-determined criteria in all regional laboratories were above expected values. The sensitivity and specificity for detecting MDR-TB in regional laboratories were >95%, except for sensitivity in Lima Sur, which was 91.7%. Contamination was 1.0-2.3%. Mean delay to positive MODS results was 9.9-12.9 days. CONCLUSION: Technology transfer of MODS was reliable, effective and fast, enabling the INS to accredit regional laboratories swiftly.

Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting.

We examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005-2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11,711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.

Electronic laboratory system reduces errors in National Tuberculosis Program: a cluster randomized controlled trial.

OBJECTIVE: To evaluate the impact of the e-Chasqui laboratory information system in reducing reporting errors compared to the current paper system. DESIGN: Cluster randomized controlled trial in 76 health centers (HCs) between 2004 and 2008. METHODS: Baseline data were collected every 4 months for 12 months. HCs were then randomly assigned to intervention (e-Chasqui) or control (paper). Further data were collected for the same months the following year. Comparisons were made between intervention and control HCs, and before and after the intervention. RESULTS: Intervention HCs had respectively 82% and 87% fewer errors in reporting results for drug susceptibility tests (2.1% vs. 11.9%, P = 0.001, OR 0.17, 95%CI 0.09-0.31) and cultures (2.0% vs. 15.1%, P < 0.001, OR 0.13, 95%CI 0.07-0.24), than control HCs. Preventing missing results through online viewing accounted for at least 72% of all errors. e-Chasqui users sent on average three electronic error reports per week to the laboratories. CONCLUSIONS: e-Chasqui reduced the number of missing laboratory results at point-of-care health centers. Clinical users confirmed viewing electronic results not available on paper. Reporting errors to the laboratory using e-Chasqui promoted continuous quality improvement. The e-Chasqui laboratory information system is an important part of laboratory infrastructure improvements to support multidrug-resistant tuberculosis care in Peru.

Programmatic implementation of rapid DST for Mycobacterium tuberculosis in Peru.

BACKGROUND: Performance characteristics of novel rapid drug susceptibility tests (DST) for Mycobacterium tuberculosis may change when moving from research to implementation in actual public health practice. We describe the performance characteristics of a direct, rapid DST when implemented in Lima, Peru. METHODS: A district laboratory validated conventional proportions and nitrate reductase methods. We collected data on samples submitted for DST from January 2005 to June 2007 and calculated frequency of testing and results, and median time to test results. RESULTS: A total of 4102 DSTs were performed by conventional DST and 895 by nitrate reductase. Results were obtained from 72.8% of samples by conventional DST and from 70.2% of those processed by Griess; respectively 26.4% and 31.5% were multidrug-resistant tuberculosis. The median time from sample collection to test result was 31 days for Griess vs. 99 days for conventional DST. CONCLUSIONS: Preliminary experience with the Griess method demonstrates favorable performance under program conditions.

Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient?

Timely diagnosis and effective, safe treatment are essential to reduce transmission and improve outcomes for patients with tuberculosis. Aside from laboratory methods, many programmatic factors influence the overall turnaround time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured each step in the overall TAT required for MDR-TB in two of five health districts of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and appropriate treatment, was 5 months, almost twice as long as the bacteriological procedures per se. Expensive investments in laboratory technology may yield low returns unless the programmatic aspects of the diagnostic process are streamlined at the same time.

Frecuencia de microbacterias identificadas en el laboratorio de referencia de tuberculosis del Perú (1989 - 1990) / Frequency of mycobacteries identification in the laboratory of reference of tuberculosis at Peru (1989 - (1990)

Se estudiaron 954 cepas cuyo aislamiento primario se realizó de muestras clínicas provenientes de todas las regiones del país durante 1989-1990. El objetivo del estudio fue determinar la frecuencia de microbacterias tuberculosas y no tuberculosas en el Laboratorio Nacional de Referencia de Tuberculosis del Perú. Para el aislamiento se utilizó el medio de Lowenstein Jensen. El mayor número de muestras y sus cultivos correspondientes fueron de secreciones pulmonares (97 por ciento); hubo 3 micobacterias no tuberculosas de muestras de orina. La frecuencia de aislamientos de micobacterias tuberculosas en 1989 y 1990 fue de 100 por ciento y 99.3 por ciento respectivamente. Se encontró 4 micobacterias no tuberculosas que correspondieron a M. fortuitum. Los resultados permiten afirmar que M. tuberculosis sigue siendo la micobacteria aislada con mayor frecuencia en las muestras estudiadas.