Diagnostic algorithm for the confirmation of cases of measles and rubella in Mexico

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples.

Human papillomavirus genotype 16 (HPV16) is the most frequent high-risk HPV (HR-HPV) identified in cervical precursor lesions and cervical cancer (CC) worldwide. The oncogenic potential of HPV16 is partly dependent on the lineage involved in the infection and the presence of clinically relevant mutations. In this report, we present the distribution of HR-HPV and the mutational profile and intra-host variability of HPV16 lineages, based on analysis of the long control region (LCR) and the E6 gene in samples with normal cytology (n = 39), squamous intraepithelial lesions (n = 25), and CC (n = 39). HR-HPV genotyping was performed using multiplex real-time PCR. HPV16 lineage assignments and mutation frequencies were determined by conventional PCR and Sanger DNA sequencing, and intra-patient viral populations were analyzed using next-generation sequencing (NGS). The most frequent HR-HPV type was HPV16, followed by HPV31 and HPV18. The frequency of HPV16 sublineages was A1/A2 > D2 > D3 and B1. Moreover, the most frequent mutations, both in samples from this study and in the available sequences from Mexican isolates in the GenBank database were LCR-G7518A, which is involved in carcinogenesis, and E6-T350G (producing L83V), associated with persistence of infection. Otherwise, deep sequencing revealed high conservation of viral lineages and mutations, independently of the stages studied. In conclusion, the high frequency and stability of these molecular markers, as well as the circulating viral lineages, could be related to the incidence of CC associated with HPV16. Hence, they deserve a broader analysis to determine the risk of specific populations for progression of the disease.

Desde el ISET al InDRE. II. Instituto de Salubridad y Enfermedades Tropicales: madurez y consolidación, 1940-1964 / From ISET to InDRE. II. Institute of Public Health and Tropical Diseases: maturity and consolidation, 1940-1964

Resumen El periodo que comienza en 1940 es crucial para la creación del moderno sistema de salud de México. El Instituto de Salubridad y Enfermedades Tropicales es la institución pionera en investigación en salud y en sus primeras dos décadas logra madurez y consolida líneas de investigación expresadas en casi 1700 publicaciones. También obtiene notoria visibilidad internacional y fue seleccionado como referencia regional para la vigilancia epidemiológica de influenza, estreptococo y salmonela. Su evolución se produjo con ritmo de innovación que iría disminuyendo para el final de ese periodo. Enfrentó limitaciones para renovar líneas de trabajo, investigadores y equipo de laboratorio, sin embargo, su papel en las decisiones de la salud pública del país siguió siendo central.

Abstract The period that starts in 1940 is crucial for the creation of Mexico’s modern health system. The Institute of Sanitary and Tropical Diseases is the pioneer institution in health research and on its first two decades it achieved maturity and consolidated lines of research expressed in almost 1700 publications. It also obtained notorious international visibility and was selected as a regional reference for epidemiological surveillance of influenza, streptococcus and salmonella. Its evolution took place with an innovation rhythm that would be decreasing by the end of this period. It faced limitations to renew lines of research, researchers and laboratory equipment. However, its role in public health decisions of the country remained central.

Desde el ISET al InDRE. I. Instituto de Salubridad y Enfermedades Tropicales: génesis y primeros años, 1934-1940 / From ISET to InDRE. I. Institute of Public Health and Tropical Diseases: genesis and early years, 1934-1940

Resumen La visión del gobierno cardenista y el proceso para crear el Instituto de Salubridad y Enfermedades Tropicales, considerado estratégico para la salud pública, fueron congruentes con las acciones llevadas a cabo: el Departamento de Salubridad Pública encargó al científico más relevante de la época, Eliseo Ramírez, el diseño y seguimiento del Instituto, que una comisión del Consejo Nacional de Educación Superior y la Investigación Científica revisó, aprobó y desde su inicio le confirió el carácter de investigación con vocación social y humanística. El Instituto de Salubridad y Enfermedades Tropicales se convirtió en el primer organismo posrevolucionario que nació con plazas bien remuneradas para realizar investigación de tiempo completo en México, ofreciendo servicio clínico y enseñanza y apoyando las campañas sanitarias en la prevención y control de las enfermedades. Sin duda fue un parteaguas en la salud pública mexicana y cristalizó las expectativas de varias generaciones de médicos e investigadores en salud para tener una institución de alto nivel. Es la más significativa institución de salud pública del país, con una nueva etapa como Instituto de Diagnóstico y Referencia Epidemiológicos; sin ella no se entiende la moderna salud pública de México.

Abstract Lázaro Cárdenas government vision, and the process to create the Sanitary and Tropical Diseases Institute, which is considered strategic for public health, were consistent with the actions that were carried out: the Department of Public Sanitary asked the most relevant scientist of those days, Eliseo Ramírez, to design and follow-up the Institute's project. A commission of the Higher Education and Scientific Research Council reviewed and approved the project and conferred this institution its nature of research center with social and humanistic vocation since its foundation. Sanitary and Tropical Diseases Institute became the first post-revolutionary health institution that was born with well-remunerated job positions to conduct full-time research in Mexico, offering clinical services, teaching and supporting disease prevention and control campaigns. It was with no doubt a milestone in Mexican public health and crystalized the expectations of several generations of physicians and health researchers about having a high-level institution. It is the most significant public health institution of the country, with a new phase as Institute of Epidemiological Diagnosis and Reference. Without it, Mexican modern public health cannot be understood.

Surveillance for the identification of cases of acute respiratory infection by enterovirus D68 in children in a tertiary level care hospital during 2014-2016. / Vigilancia epidemiológica para la identificación de casos de infección respiratoria aguda por enterovirus D68 en niños en un hospital de tercer nivel de atención durante 2014-2016

Background: The reemergence of enterovirus D68 (EV-D68) infections in the United States was reported from August-October 2014 (691 cases). In Mexico, an outbreak at the National Institute of Respiratory Diseases was reported (24 cases). The results of epidemiological surveillance of Enterovirus sp. (EV) and other respiratory viruses in a national pediatric tertiary care level hospital are presented. Methods: Following the alert issued by the reemergence of EV-D68 in 2014, epidemiological surveillance -which only detected respiratory viruses by PCR in patients with influenza-like illness using nasopharyngeal swabs- expanded to include children with asthma exacerbation or acute respiratory distress. Positive samples to EV were confirmed and typed by sequencing. Subsequent sequencing was used to obtain the complete viral genome. Results: Of 1705 samples, 13 were positive to EV. Patients with EV presented the following comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13 samples positive for EV, three were positive for EV-D68. These cases required invasive mechanical ventilation, presented no neurological involvement and survived. Conclusions: The impact of the population studied by EV-D68 was lower than that reported in Mexico during the same period. Cases of EV-D68 infection had multiple comorbidities, but few pulmonary comorbidities, which could explain the low attack rate. The epidemiological surveillance and infection prevention system may have contained the outbreak.

Introducción: La reemergencia de las infecciones por Enterovirus D68 (EV-D68) se reportó en los EE.UU. desde agosto-octubre de 2014 (691 casos). En México, un brote se reportó en el Instituto Nacional de Enfermedades Respiratorias (24 casos). Se presentan los resultados de la vigilancia epidemiológica en un hospital pediátrico nacional de tercer nivel para Enterovirus sp. (EV) y otros virus respiratorios. Método: Tras la alerta emitida por la reemergencia del EV-D68 en 2014, la vigilancia epidemiológica ­que solo detectaba virus respiratorios mediante PCR en pacientes con enfermedad tipo influenza mediante toma de hisopados nasofaríngeos­ se expandió para incluir niños con exacerbación de asma o dificultad respiratoria aguda. Las muestras positivas para EV fueron confirmadas y tipificadas por secuenciación. Posteriormente, se utilizó secuenciación de siguiente generación para obtener el genoma viral completo. Resultados: De 1705 muestras, 13 fueron positivas para EV. Los pacientes con EV presentaron la siguiente comorbilidad: enfermedad pulmonar crónica (7.7%), enfermedad neoplásica (15.4%), asma/rinitis alérgica (23%), neumonías de repetición (23%), y otras (23%). De las 13 muestras positivas para EV, tres resultaron positivas para EV-D68. Dichos casos requirieron ventilación mecánica invasiva, no tuvieron afectación neurológica y sobrevivieron. Conclusiones: La afectación por EV-D68 de la población estudiada fue menor que lo reportado en México durante el mismo periodo. Los casos de infección por EV-D68 presentan diversa comorbilidad, aunque escasas enfermedades pulmonares, lo cual pudiera explicar la baja tasa de ataque. La presencia del sistema de vigilancia epidemiológica establecido y la prevención de infecciones pudieron haber contenido el brote.

Vigilancia epidemiológica para la identificación de casos de infección respiratoria aguda por enterovirus D68 en niños en un hospital de tercer nivel de atención durante 2014-2016 / Surveillance for the identification of cases of acute respiratory infection by enterovirus D68 in children in a tertiary level care hospital during 2014-2016

Resumen Introducción: La reemergencia de las infecciones por Enterovirus D68 (EV-D68) se reportó en los EE.UU. desde agosto-octubre de 2014 (691 casos). En México, un brote se reportó en el Instituto Nacional de Enfermedades Respiratorias (24 casos). Se presentan los resultados de la vigilancia epidemiológica en un hospital pediátrico nacional de tercer nivel para Enterovirus sp. (EV) y otros virus respiratorios. Método: Tras la alerta emitida por la reemergencia del EV-D68 en 2014, la vigilancia epidemiológica -que solo detectaba virus respiratorios mediante PCR en pacientes con enfermedad tipo influenza mediante toma de hisopados nasofaríngeos- se expandió para incluir niños con exacerbación de asma o dificultad respiratoria aguda. Las muestras positivas para EV fueron confirmadas y tipificadas por secuenciación. Posteriormente, se utilizó secuenciación de siguiente generación para obtener el genoma viral completo. Resultados: De 1705 muestras, 13 fueron positivas para EV. Los pacientes con EV presentaron la siguiente comorbilidad: enfermedad pulmonar crónica (7.7%), enfermedad neoplásica (15.4%), asma/rinitis alérgica (23%), neumonías de repetición (23%), y otras (23%). De las 13 muestras positivas para EV, tres resultaron positivas para EV-D68. Dichos casos requirieron ventilación mecánica invasiva, no tuvieron afectación neurológica y sobrevivieron. Conclusiones: La afectación por EV-D68 de la población estudiada fue menor que lo reportado en México durante el mismo periodo. Los casos de infección por EV-D68 presentan diversa comorbilidad, aunque escasas enfermedades pulmonares, lo cual pudiera explicar la baja tasa de ataque. La presencia del sistema de vigilancia epidemiológica establecido y la prevención de infecciones pudieron haber contenido el brote.

Abstract Background: The reemergence of enterovirus D68 (EV-D68) infections in the United States was reported from August-October 2014 (691 cases). In Mexico, an outbreak at the National Institute of Respiratory Diseases was reported (24 cases). The results of epidemiological surveillance of Enterovirus sp. (EV) and other respiratory viruses in a national pediatric tertiary care level hospital are presented. Methods: Following the alert issued by the reemergence of EV-D68 in 2014, epidemiological surveillance -which only detected respiratory viruses by PCR in patients with influenza-like illness using nasopharyngeal swabs- expanded to include children with asthma exacerbation or acute respiratory distress. Positive samples to EV were confirmed and typed by sequencing. Subsequent sequencing was used to obtain the complete viral genome. Results: Of 1705 samples, 13 were positive to EV. Patients with EV presented the following comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13 samples positive for EV, three were positive for EV-D68. These cases required invasive mechanical ventilation, presented no neurological involvement and survived. Conclusions: The impact of the population studied by EV-D68 was lower than that reported in Mexico during the same period. Cases of EV-D68 infection had multiple comorbidities, but few pulmonary comorbidities, which could explain the low attack rate. The epidemiological surveillance and infection prevention system may have contained the outbreak.

Utility of high-throughput DNA sequencing in the study of the human papillomaviruses.

The Papillomaviridae family is probably the most diverse group of viruses that affect vertebrates. The study of the relationship between infection by certain types of human papillomavirus (HPV) and the development of neoplastic epithelial lesions is of particular interest because of the high prevalence of HPV-related carcinomas in populations of developing countries. To understand the mechanisms of infection and their association with different clinical manifestations, molecular tools play an important role in the description of new types of HPV, the characterization of effector properties of the viral factors, the specific diagnosis and monitoring of HPV types, and the alteration patterns at genetic level in the host. Technological advances in the field of DNA sequencing have led to the development of different next-generation sequencing systems, allowing obtaining a large amount of data and broadening the applications to study viral diseases. In this review, we summarize the main approaches and their perspectives where the use of massively parallel sequencing has been proved as a useful tool in the research of the HPV infection.

Caracterización clínica y epidemiológica de fiebre chikungunya en México / Clinical and epidemiological characterization of chikungunya fever in Mexico

RESUMEN El 6 de diciembre de 2013, la Organización Panamericana de la Salud (OPS) y la Organización Mundial de la Salud (OMS) notificaron la confirmación de los dos primeros casos de transmisión autóctona en la Región de las Américas de fiebre chikungunya (CHIK) en la isla de Saint Martin (Antillas Neerlandesas). Para el período 2013-2014, el total de casos confirmados fue de 25 627 distribuidos en 43 países, donde México reportó 155 casos en cinco estados. La información de los casos de CHIK en México se obtuvo de la base de datos de la Dirección General de Epidemiología, dependiente de la Secretaría de Salud de México. La distribución por sexo de los casos autóctonos confirmados de CHIK para el año 2015 indica 64% para el sexo femenino (5 583) y 36% para el sexo masculino (3 085). Los síntomas más frecuentes fueron: fiebre en 98% de los casos (8 564), seguido por cefalea con 91,6% (7 941), mialgias en 89,9% (7 792), artralgias leves en 73,5% (6 367), poliartralgias graves en 72,6% (6 295) y exantema en 58% (5 032). La presentación clínica de los casos autóctonos de CHIK en México ha mostrado algunas características clínicas diferentes de las que se han observado en los brotes de los países africanos, asiáticos y otras regiones de América, como por ejemplo un mayor porcentaje de casos con cefalea y mialgias y un menor porcentaje de casos con artralgias.(AU)

ABSTRACT On 6 December 2013, the Pan American Health Organization (PAHO) and the World Health Organization (WHO) reported confirmation of the first two cases of indigenous transmission of chikungunya fever (CHIK) in the Region of the Americas on the island of Sint Maarten (Netherlands Antilles). For the period 2013-2014, a total of 25 627 confirmed autochthonous cases were distributed in 43 countries, with Mexico reporting 155 cases in five states. Information on cases of CHIK in Mexico was obtained from the database of the General Directorate of Epidemiology (Ministry of Health of Mexico). The distribution of confirmed autochthonous cases of CHIK for 2015, by sex, was 64% female (5 583) and 36% male (3 085). The most frequent symptoms were fever in 98% of cases (8 564), followed by headache in 91.6% (7 941), myalgia in 89.9% (7 792), mild arthralgias in 73.5% (6 367), severe polyarthralgia in 72.6% (6 295), and exanthema in 58% (5 032). The clinical presentation of autochthonous cases of CHIK in Mexico has shown several clinical manifestations different from those seen in outbreaks in African and Asian countries and other regions in the Americas; for example, a greater percentage of cases with headache and myalgia and a smaller percentage of cases with arthralgia.(AU)