Whole Genome Sequencing of Mycobacterium tuberculosis under routine conditions in a high-burden area of multidrug-resistant tuberculosis in Peru.

Whole Genome Sequencing (WGS) is a promising tool in the global fight against tuberculosis (TB). The aim of this study was to evaluate the use of WGS in routine conditions for detection of drug resistance markers and transmission clusters in a multidrug-resistant TB hot-spot area in Peru. For this, 140 drug-resistant Mycobacterium tuberculosis strains from Lima and Callao were prospectively selected and processed through routine (GenoType MTBDRsl and BACTEC MGIT) and WGS workflows, simultaneously. Resistance was determined in accordance with the World Health Organization mutation catalogue. Agreements between WGS and BACTEC results were calculated for rifampicin, isoniazid, pyrazinamide, moxifloxacin, levofloxacin, amikacin and capreomycin. Transmission clusters were determined using different cut-off values of Single Nucleotide Polymorphism differences. 100% (140/140) of strains had valid WGS results for 13 anti-TB drugs. However, the availability of final, definitive phenotypic BACTEC MGIT results varied by drug with 10-17% of invalid results for the seven compared drugs. The median time to obtain results of WGS for the complete set of drugs was 11.5 days, compared to 28.6-52.6 days for the routine workflow. Overall categorical agreement by WGS and BACTEC MGIT for the compared drugs was 96.5%. Kappa index was good (0.65≤k≤1.00), except for moxifloxacin, but the sensitivity and specificity values were high for all cases. 97.9% (137/140) of strains were characterized with only one sublineage (134 belonging to "lineage 4" and 3 to "lineage 2"), and 2.1% (3/140) were mixed strains presenting two different sublineages. Clustering rates of 3.6% (5/140), 17.9% (25/140) and 22.1% (31/140) were obtained for 5, 10 and 12 SNP cut-off values, respectively. In conclusion, routine WGS has a high diagnostic accuracy to detect resistance against key current anti-TB drugs, allowing results to be obtained through a single analysis and helping to cut quickly the chain of transmission of drug-resistant TB in Peru.

Factibilidad de una aplicación móvil para el monitoreo de contactos de tuberculosis multidrogorresistente en Perú

El presente estudio tuvo como objetivo realizar una validación de un aplicativo móvil Open Data Kit (AM-ODK) en contactos expuestos a tuberculosis multidrogorresistente (TB-MDR) en Lima. Utilizando un cuestionario en una aplicación en un dispositivo móvil Android, se registraron 129 contactos intradomiciliarios de 29 casos índice de TB-MDR en tratamiento, en diez establecimientos de salud de Lima Sur en agosto de 2018. Se encontró un tiempo medio de registro por contacto de cuatro minutos. La frecuencia de síntomas de TB activa entre los contactos de TB-MDR fue 3,1%. Treinta y un encuestados completaron un cuestionario de aceptabilidad; todos manifestaron sentirse cómodos o muy cómodos con el registro de sus datos en AM-ODK, aunque 10% expresó inquietudes sobre la confidencialidad. Se concluye que el AM-ODK fue una herramienta viable y aceptable para registrar contactos intradomiciliarios expuestos a casos con TB-MDR. Estudios futuros deberían considerar el uso de plataformas móviles para el monitoreo de contactos de TB-MDR.

This study aimed to validate an ODK digital mobile application (ODK-DMA) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru. Using a questionnaire in an application on a mobile device, we registered 129 household contacts of 29 index cases of MDR-TB under treatment in 10 health facilities in South Lima in August 2018. The mean time of registration per contact was found to be 4 minutes. The prevalence of active TB symptoms among MDR-TB contacts was 3.1%. An acceptability questionnaire was completed by 31 respondents; all reported feeling comfortable or very comfortable with recording their data in the ODK-DMA, although 10% expressed concerns about confidentiality. We concluded that the ODK-DMA was a feasible and acceptable tool for registering household contacts exposed to cases with MDR-TB. Future studies should consider the use of mobile platforms for the monitoring of MDR-TB contacts.

Pruebas de sensibilidad para Mycobacterium tuberculosis / Drug susceptibility tests for Mycobacterium tuberculosis

Los regímenes de tratamiento no adecuado y los problemas de adherencia del paciente han ocasionado que las tasas de resistencia de Mycobacterium tuberculosis hayan aumentado en el mundo, originando así la aparición de las cepas multidrogo resistentes (MDR) y con resistencia extensa a drogas (XDR). El Perú presenta altas tasas de TB-MDR, y ya se han reportado casos de TB-XDR. Las pruebas de sensibilidad buscan detectar los casos con cepas resistentes, permitiendo otorgar el mejor tratamiento al paciente y evitando la propagación de la enfermedad a otras personas. Esta revisión de pruebas de sensibilidad dirigida al médico noespecialista, se ha enfocado en las pruebas de sensibilidad disponibles según la Norma Técnica para el control de la Tuberculosis y otras que se encuentran en investigación.

Inadequate treatment regimens and poor compliance have led to increased rates of drug resistance in Mycobacterium tuberculosis around the world, leading to the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains. In Peru MDR-TB rates are amongst the highest in the world and XDR-TB cases have been reported for almost a decade. Drug susceptibility tests detect cases with resistant strains, providing the best treatment option to the patient and diminishing the spread of the disease. This review is directed at the non-specialist physician, focusing upon the drug susceptibility testsapproved by the National TB Program of Peru and others currently still under research.

Resultados postmórtem e infecciones oportunistas en pacientes VIH positivos de un hospitalpúblico del Perú / Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

Existen pocos estudios que reporten datos acerca de autopsias de pacientes con VIH en Sudamérica y ninguno que documente los resultados post mórtem en los pacientes con VIH/SIDA en el Perú. Objetivos: Determinar el espectro de las infecciones oportunistas y las causas de mortalidad en pacientes VIH-positivos en un hospital público en Lima. Asimismo, se revisa la información clínico-epidemiológica con respecto a la infección con VIH en el Perú. Materiales y métodos: Se incluyeron en este análisis retrospectivo, 16 autopsias relacionadas con VIH del Hospital Dos de Mayo, realizadas entre 1999-2004. Resultados: La causa primaria de la muerte fue establecida en 12 pacientes: uno murió de neoplasia y 11 de enfermedades infecciosas, incluyendo tres con infección pulmonar, siete con infección diseminada, y dos con infección del sistema nervioso central (un caso presentó patología dual). Las infecciones oportunistas fueron identificadas en 14 casos, incluyendo citomegalovirus, histoplasmosis, criptococcosis, toxoplasmosis, neumonía por Pneumocistis, aspergilosis, tuberculosis, virus de la varicela-zoster y criptosporidiosis. Catorce pacientes tenían por lo menos una enfermedad relacionada con el SIDA que no había sido sospechada clínicamente ni diagnosticada antes de la muerte. Por otra parte, 82% de los diagnósticos considerados de significancia clínica importante, no habían sido sospechados antes de la muerte. Conclusiones: El espectro y la frecuencia de ciertas infecciones oportunistas reportadas en el presente estudio lo diferencia de otros estudios de autopsias realizados en Sudamérica; destacando la importancia de realizar necropsias en VIH/SIDA en países de recursos limitados, con el fin de observar los patrones locales específicos de la enfermedad.

There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. Objectives: The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Material and methods: Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999-2004, were included in this retrospective analysis. Results: The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses deemed of important clinical significance, had not been suspected antemortem. Conclusions: The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locallyspecific disease patterns may be observed.