Screening of inmates transferred to Spain reveals a Peruvian prison as a reservoir of persistent Mycobacterium tuberculosis MDR strains and mixed infections.

It is relevant to evaluate MDR-tuberculosis in prisons and its impact on the global epidemiology of this disease. However, systematic molecular epidemiology programs in prisons are lacking. A health-screening program performed on arrival for inmates transferred from Peruvian prisons to Spain led to the diagnosis of five MDR-TB cases from one of the biggest prisons in Latin America. They grouped into two MIRU-VNTR-clusters (Callao-1 and Callao-2), suggesting a reservoir of two prevalent MDR strains. A high-rate of overexposure was deduced because one of the five cases was coinfected by a pansusceptible strain. Callao-1 strain was also identified in 2018 in a community case in Spain who had been in the same Peruvian prison in 2002-5. A strain-specific-PCR tailored from WGS data was implemented in Peru, allowing the confirmation that these strains were currently responsible for the majority of the MDR cases in that prison, including a new mixed infection.

[Mycobacterium avium lung infection in HIV/AIDS patient: first report in Peru]. / Infección pulmonar por Mycobacterium avium en paciente VIH/SIDA: primer reporte en Perú

The Mycobacterium avium complex (MAC) is a pathogen found in the environment which causes infections in immunocompetent and immunocompromised patients. One case is presented: an HIV positive, 38 year old male patient, infected with P. jirovecii and apparently infected with Mycobacterium tuberculosis since 2009. He was treated with antibiotic therapy for pneumocystosis and antituberculosis (TB) therapy, which achieved a partial improvement. In 2012, the patient underwent a culture test and new anti TB treatment. Upon suspicion of a drug resistant TB strain, it was recommended to perform the mycobacterial identification. The culture test was positive and the genotypic result was positive for MAC. The first case of an HIV/AIDS patient with MAC lung infection in Peru is reported, as well as a brief review of the epidemiological, clinical and treatment aspects to the case.

[Molecular test Genotype® MTBDRplus, an alternative to rapid detection of multidrug resistance tuberculosis]. / Prueba molecular Genotype® MTBDRplus, una alternativa para la detección rápida de tuberculosis multidrogorresistente.

The Genotype®MTBDRplus molecular test is a method that allows identification of the most frequent mutations associated with resistance to major first-line antituberculosis drugs, Isoniazid (INH) and Rifampicin (RFP). The aim of this study was to evaluate the performance of the molecular test with culture and smear- positive sputum samples. We evaluated 95 cultures and 100 sputum samples with resistance profiles previously determined by the reference method "Agar Plate Proportions" (APP). The molecular test from cultures showed a sensitivity of 100 %, 97,5 % and 96,97 % for RIF, INH and MDR respectively while from sputums the sensitivity was 95,65 %, 96,77 % and 95,24 % for RIF, INH and MDR respectively. We conclude that the molecular test Genotype®MTBDRplus is a very useful tool to detect resistance to isoniazid and rifampicin simultaneously (MDR-TB) in up to 72 hours from sputum samples or cultures.

[Cost analysis of rapid methods for diagnosis of multidrug resistant tuberculosis in different epidemiologic groups in Perú]. / Análisis de costos de los métodos rápidos para diagnóstico de tuberculosis multidrogorresistente en diferentes grupos epidemiológicos del Perú.

OBJECTIVES: To evaluate the costs of three methods for the diagnosis of drug susceptibility in tuberculosis, and to compare the cost per case of Multidrug-resistant tuberculosis (MDR TB) diagnosed with these (MODS, GRIESS and Genotype MTBDR plus®) in 4 epidemiologic groups in Peru. MATERIALS AND METHODS: In the basis of programmatic figures, we divided the population in 4 groups: new cases from Lima/Callao, new cases from other provinces, previously treated patients from Lima/Callao and previously treated from other provinces. We calculated the costs of each test with the standard methodology of the Ministry of Health, from the perspective of the health system. Finally, we calculated the cost per patient diagnosed with MDR TB for each epidemiologic group. RESULTS: The estimated costs per test for MODS, GRIESS, and Genotype MTBDR plus® were 14.83. 15.51 and 176.41 nuevos soles respectively (the local currency, 1 nuevos sol=0.36 US dollars for August, 2011). The cost per patient diagnosed with GRIESS and MODS was lower than 200 nuevos soles in 3 out of the 4 groups. The costs per diagnosed MDR TB were higher than 2,000 nuevos soles with Genotype MTBDR plus® in the two groups of new patients, and lower than 1,000 nuevos soles in the group of previously treated patients. CONCLUSIONS: In high-prevalence groups, like the previously treated patients, the costs per diagnosis of MDR TB with the 3 evaluated tests were low, nevertheless, the costs with the molecular test in the low- prevalence groups were high. The use of the molecular tests must be optimized in high prevalence areas.

Effect of pyrazinamidase activity on pyrazinamide resistance in Mycobacterium tuberculosis.

Resistance of Mycobacterium tuberculosis to pyrazinamide is associated with mutations in the pncA gene, which codes for pyrazinamidase. The association between the enzymatic activity of mutated pyrazinamidases and the level of pyrazinamide resistance remains poorly understood. Twelve M. tuberculosis clinical isolates resistant to pyrazinamide were selected based on Wayne activity and localization of pyrazinamidase mutation. Recombinant pyrazinamidases were expressed and tested for their kinetic parameters (activity, k(cat), K(m), and efficiency). Pyrazinamide resistance level was measured by Bactec-460TB and 7H9 culture. The linear correlation between the resistance level and the kinetic parameters of the corresponding mutated pyrazinamidase was calculated. The enzymatic activity and efficiency of the mutated pyrazinamidases varied with the site of mutation and ranged widely from low to high levels close to the corresponding of the wild type enzyme. The level of resistance was significantly associated with pyrazinamidase activity and efficiency, but only 27.3% of its statistical variability was explained. Although pyrazinamidase mutations are indeed associated with resistance, the loss of pyrazinamidase activity and efficiency as assessed in the recombinant mutated enzymes is not sufficient to explain a high variability of the level of pyrazinamide resistance, suggesting that complementary mechanisms for pyrazinamide resistance in M. tuberculosis with mutations in pncA are more important than currently thought.