Convergent trends and spatiotemporal patterns of Aedes-borne arboviruses in Mexico and Central America.

BACKGROUND: Aedes-borne arboviruses cause both seasonal epidemics and emerging outbreaks with a significant impact on global health. These viruses share mosquito vector species, often infecting the same host population within overlapping geographic regions. Thus, comparative analyses of the virus evolutionary and epidemiological dynamics across spatial and temporal scales could reveal convergent trends. METHODOLOGY/PRINCIPAL FINDINGS: Focusing on Mexico as a case study, we generated novel chikungunya and dengue (CHIKV, DENV-1 and DENV-2) virus genomes from an epidemiological surveillance-derived historical sample collection, and analysed them together with longitudinally-collected genome and epidemiological data from the Americas. Aedes-borne arboviruses endemically circulating within the country were found to be introduced multiple times from lineages predominantly sampled from the Caribbean and Central America. For CHIKV, at least thirteen introductions were inferred over a year, with six of these leading to persistent transmission chains. For both DENV-1 and DENV-2, at least seven introductions were inferred over a decade. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV, DENV-1 and DENV-2 in Mexico share evolutionary and epidemiological trajectories. The southwest region of the country was determined to be the most likely location for viral introductions from abroad, with a subsequent spread into the Pacific coast towards the north of Mexico. Virus diffusion patterns observed across the country are likely driven by multiple factors, including mobility linked to human migration from Central towards North America. Considering Mexico's geographic positioning displaying a high human mobility across borders, our results prompt the need to better understand the role of anthropogenic factors in the transmission dynamics of Aedes-borne arboviruses, particularly linked to land-based human migration.

Vibrio parahaemolyticus Is Associated with Diarrhea Cases in Mexico, with a Dominance of Pandemic O3:K6 Clones.

In the present study, we conducted surveillance of the V. parahaemolyticus strains present in clinical samples from six geographical regions of Mexico (22 states) from 2004 to 2011. The serotype dominance, virulence genes, presence of pandemic O3:K6 strains, and antibiotic resistance of the isolates were investigated. In total, 144 strains were isolated from the clinical samples. Seven different O serogroups and twenty-five serovars were identified. Most clinical isolates (66%, 95/144) belonged to the pandemic clone O3:K6 (tdh+, toxRS/new+ and/or orf8+) and were detected in 20 of the 22 states. Among the pandemic clones, approximately 17.8% (17/95) of the strains cross-reacted with the antisera for the K6 and K59 antigens (O3:K6, K59 serotype). Other pathogenic strains (tdh+ and/or trh+, toxRS/new-, orf8-) accounted for 26.3%, and the nonpathogenic strains (tdh- and/or trh-) accounted for 7.6%. Antimicrobial susceptibility testing showed that most of the strains were resistant to ampicillin (99.3%) but were sensitive to most tested antibiotics. The level of multidrug resistance was 1.3%. Our results indicate that pandemic O3:K6 is present in most Mexican states, thus, constant surveillance of V. parahaemolyticus strains in diarrhea patients is a public health priority and is useful for conducting risk assessments of foodborne illnesses to prevent V. parahaemolyticus outbreaks. Overall, our observations indicate that the pandemic O3:K6 clone of V. parahaemolyticus has become a relatively stable subpopulation and may be endemically established in Mexico; therefore, constant surveillance is needed to avoid new outbreaks of this pathogen.

Epidemiological surveillance of chikungunya fever in Mexico since its introduction in 2014-2016 and identification of circulating genotypes.

In 2014, the chikungunya virus (CHIKV) was detected for the first time in Mexico, the identified strain was the one corresponding to the Asian genotype which was phylogenetically grouped with the strains that circulated in the British Virgin Islands outbreak and was later classified with lineages of Caribbean strains. In three years, 13,569 cases of chikungunya were registered in Mexico. Although the transmission and spread of the virus are now considered a moderate risk, the danger that the virus reemerges is not ruled out due to the infestation of Aedes mosquitoes. In this study, we reviewed the chikungunya fever (CHIKF) cases reported between 2014 and 2016 to reanalyze the data. Seventeen cases were selected from different states where the circulation of the virus had been reported. Statistical data were analyzed and a retrospective analysis was carried out. Nucleic acid sequences were determined of these 17 samples. 2015 was the year with the highest number of cases (92.8%) and they were detected in 28 states of the country. There is a predominance of females, and the most affected age group was between 25 and 44 years. In 2016, CHIKV genotypes were not known, in this study the presence of the Asian genotype of Caribbean lineage was confirmed. The presence of the West African and ECSA genotypes was phylogenetically ruled out. The sequences obtained were deposited in GeneBank.

Complete genome sequence of a coxsackievirus type A24 variant causing an outbreak of acute haemorrhagic conjunctivitis in southeastern Mexico in 2017.

Cases of acute haemorrhagic conjunctivitis (AHC) caused by a coxsackie virus A24 variant (CV-A24v) in Mexico have been reported since 1987; however, no molecular data on the causative strains have been available. Here, we report the identification of the etiological agent responsible for the most recent AHC outbreak in southeastern Mexico (at the end of 2017) as well as the complete genome sequences of seven isolates, using next-generation sequencing (NGS). Phylogenomic analysis of the CV-A24v sequences reported here showed similarity to contemporary strains causing AHC outbreaks in French Guiana and Uganda, forming a novel clade related to genotype IV. Moreover, a specific mutational pattern in the non-structural proteins was identified in the 2017 isolates. This is the first report of genetic characterization of CV-A24v isolates obtained in Mexico.

Evaluation of serological diagnostic tests of human brucellosis for prevention and control in Mexico.

Brucellosis is a zoonosis mainly present in developing countries. The WHO reports 500,000 new cases every year. From 2012 to 2016, 13,677 cases were reported in Mexico, with 2.00 to 2.64 rate per 100,000 inhabitants. To analyze the diagnostic algorithm of brucellosis in Mexico, we compared the commercial laboratory tests ELISA, Brucellacapt®, and lateral flow test (LFT) in a study of 473 individuals from two endemic Mexican populations. All patients were treated in first-level medical units for presenting brucellosis compatible symptoms and without a history of the disease. Clinical-epidemiological information was gathered and initial serum samples were obtained to react with anti-Brucella antibodies; subsequent samples were collected at follow-up treatment visits. Using the Rose Bengal screening, we found 165 negative samples and 308 positive reactive samples, of which 222 cases were confirmed and 234 were positive on at least one marker (IgG or IgM) or LFT. When Brucellacapt® was used, similar results to those observed with the conventional algorithm were found as judged by the Cohen's kappa coefficient (κ) (0.813, 95% CI 0.7788-0.8472). Similar κ indices between conventional algorithm and ELISA pair were found, 0.7038 (95% CI 0.6555-0.7521), representing high similarity between both groups of diagnosis. We conclude that conventional serodiagnoses, Brucellacapt® and LFT, presented inconclusive results and poor correlation between them. By contrast, ELISA test pair (IgG + IgM) presented high correlation with the conventional algorithm and greater capacity for correct positive and negative classification.

Desde el ISET al InDRE. III. Instituto de Salubridad y Enfermedades Tropicales: crisis y renovación, 1965-1989.

This paper analyzes the situation and the changes made in the Institute of Sanitary and Tropical Diseases between 1965 and 1989 to become the National Institute of Epidemiological Diagnosis and Reference. Three major stages are identified during this period: crisis, transition and renewal. The factors that led to the crisis, the decisions made to overcome it and to harmonize the work of laboratories with epidemiological and public health criteria are discussed. The recognition obtained by researchers of the Institute despite the crisis is described, as well as the way the institution managed to continue with projects despite the changing global situation. The transition included the arrival of a new generation of professionals with modern computer-based and conceptual tools and the remarkably well met challenge of participating in national surveys with rigorous criteria. All this moved the institution to define its profile towards diagnosis and reference.

El artículo analiza la situación y los cambios efectuados en el Instituto de Salubridad y Enfermedades Tropicales entre 1965 y 1989 para transformarse en el Instituto Nacional de Diagnóstico y Referencia Epidemiológicos. Se identifican tres grandes etapas en el periodo: crisis, transición y renovación. Se señalan los elementos que llevaron a la crisis, las decisiones que se tomaron para salir de ella y armonizar el trabajo de los laboratorios con criterios epidemiológicos y de salud pública. Se citan las distinciones obtenidas por investigadores del Instituto a pesar de la crisis y se describe cómo la institución logró seguir con proyectos a pesar de la cambiante situación mundial. La transición incluyó la llegada de una nueva generación de profesionales con modernas herramientas informáticas y conceptuales y el desafío de participar en encuestas nacionales con criterios rigurosos. Todo ello movió a la institución a definir su perfil hacia el diagnóstico y la referencia.

Algoritmo diagnóstico para la confirmación de casos de sarampión y rubéola en México.

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.

Debido a la implementación exitosa de las estrategias de eliminación del sarampión y la rubéola, México enunció la interrupción de la transmisión endémica del sarampión en 1996 y de la rubéola en 2008. Después de un proceso de verificación, la región de las Américas fue declarada libre de rubéola y del síndrome de rubéola congénita en 2015 y del sarampión en 2016. Para mantener el estatus de eliminación en México es esencial continuar con la vigilancia por laboratorio en el marco de la Red Mundial de Laboratorios de Sarampión y Rubéola. El Instituto de Diagnóstico y Referencia Epidemiológicos, a través de la Red Nacional de Laboratorios de Salud Pública, garantiza resultados oportunos y confiables ante la posible reintroducción de estos y otros patógenos emergentes.

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.

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.

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.

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.

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.

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.

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.

Guillain-Barré Syndrome Associated With Zika Virus Infection: A Prospective Case Series From Mexico.

Background: On May 2016, anticipating the rainy season from June to October in Mexico, we expected an increase in cases of Zika virus (ZIKV) infections. With the goal of identifying cases of GBS associated with ZIKV infection, a prospective joint study was conducted by a reference center for neurological patients and the Secretary of Health in Mexico City from July 2016 to November 2016. Methods: Serum, cerebrospinal fluid, urine, and saliva were tested by RT-PCR for ZIKV, dengue virus, and chikungunya virus in patients referred from states with reported transmissions of ZIKV infection, and with clinical symptoms of GBS according to the Brighton Collaboration criteria. Clinical, electrophysiological, and long-term disability data were collected. Results: In the year 2016 twenty-eight patients with GBS were diagnosed at our institute. In five hospitalized patients with GBS, RT-PCR was positive to ZIKV in any collected specimen. Dengue and chikungunya RT-PCR results were negative. All five patients had areflexic flaccid weakness, and cranial nerves affected in three. Electrophysiological patterns were demyelinating in two patients and axonal in three. Three patients were discharged improved in 10 days or less, and two patients required intensive care unit admission, and completely recovered during follow-up. Conclusion: Our results are similar to those reported from the state of Veracruz, Mexico, in which out of 33 samples of urine of patients with GBS two had a positive RT-PCR for ZIKV. Simultaneous processing of serum, CSF, urine, and saliva by RT-PCR may increase the success of diagnosis of GBS associated to ZIKV.

Urban and semi-urban mosquitoes of Mexico City: A risk for endemic mosquito-borne disease transmission.

Since past century, vector-borne diseases have been a major public health concern in several states of Mexico. However, Mexico City continues to be free of endemic mosquito-borne viral diseases. The city is the most important politic and economic state of Mexico and one of the most important city of Latin America. Its subtropical highland climate and high elevation (2240 masl) had historically made the occurrence of Aedes species unlikely. However, the presence of other potential disease vectors (Culex spp, Culiseta spp), and the current intermittent introductions of Aedes aegypti, have revealed that control programs must adopt routine vector surveillance in the city. In this study, we provide an updated species list from a five-years of vector surveillance performed in Mexico City. A total of 18,553 mosquito larvae were collected. Twenty-two species from genus Culex, Aedes, Culiseta, Anopheles, Lutzia and Uranotaenia were observed. Nine new mosquito records for the city were found. Ae. albopictus was recorded for the first time in Mexico City. Interestingly, a new record, Ae. epactius was the most frequent species reported. Cx. pipiens quinquefasciatus exhibited the highest number of individuals collected. We detected six areas which harbor the highest mosquito species records in the city. Cemeteries included 68.9% of our collection sites. Temporarily ponds showed the highest species diversity. We detected an increasing presence of Ae. aegypti, which was detected for three consecutive years (2015-2017), predominantly in the warmer microclimates of the city. We found a possible correlation between increasing temperature and Ae. aegypti and Ae. albopictus expanding range. This study provides a starting point for developing strategies related to environmental management for mosquito control. The promotion of mosquito control practices through community participation, mass media and education programmes in schools should be introduced in the city.

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.