Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City.

OBJECTIVE: To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). METHODS: Participants aged 12-17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. RESULTS: 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). CONCLUSION: TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Corrigendum: Coronavirus Disease-2019 Survival in Mexico: A Cohort Study on the Interaction of the Associated Factors.

[This corrects the article DOI: 10.3389/fpubh.2021.660114.].

Aleatory Trypanosoma cruzi Vertical Transmission in Chiapas, Mexico: A Case Report.

Congenital Chagas disease is considered a form of dispersion of Trypanosoma cruzi related to human migration from endemic, often rural to previously non-endemic urban areas. This fact increases the Chagas disease establishment risk inside of family members by vertical transmission pathway. Congenital Chagas disease cases in newborns could not identified by the health professional even in endemic regions. Here we present the first family cluster of Chagas disease cases from Chiapas: one of the most important endemic areas in South of Mexico, where vertical T. cruzi transmission incidence rate is ranged between 2% to 22% revealing an important public health problem. Two cases inside a family from Chiapas, México with positive antibodies against T. cruzi detected by ELISA are presented; one of them got the infection through vertical pathway. We think that congenital Chagas disease should not be ignored in a newborn born from an asymptomatic Chagas disease mother, who may transmit the parasite infection randomly.

Coronavirus Disease-2019 Survival in Mexico: A Cohort Study on the Interaction of the Associated Factors.

The pandemic caused by the new coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries. The most lethal clinical presentation is respiratory insufficiency, requiring attention in intensive care units (ICU). The most susceptible people are over 60 years old with comorbidities. The health systems organization may represent a transcendental role in survival. Objective: To analyze the correlation of sociodemographic factors, comorbidities and health system organization variables with survival in cases infected by SARS-CoV-2 during the first 7 months of the pandemic in Mexico. Methods: The cohort study was performed in a health system public basis from March 1st to September 30th, 2020. The included subjects were positive for the SARS-CoV-2 test, and the target variable was mortality in 60 days. The risk variables studied were: age, sex, geographic distribution, comorbidities, health system, hospitalization, and access to ICU. Bivariate statistics (X2-test), calculation of fatality rates, survival analyses and adjustment of confusing variables with Cox proportional-hazards were performed. Results: A total of 753,090 subjects were analyzed, of which the 52% were men. There were 78,492 deaths (10.3% of general fatality and 43% inpatient). The variables associated with a higher risk of hospital mortality were age (from 60 years onwards), care in public sectors, geographic areas with higher numbers of infection and endotracheal intubation without management in the ICU. Conclusions: The variables associated with a lower survival in cases affected by SARS-CoV-2 were age, comorbidities, and respiratory insufficiency (with endotracheal intubation without care in the ICU). Additionally, an interaction was observed between the geographic location and health sector where they were treated.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates.

Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.

Development of an alternative saliva test for diagnosis of SARS-CoV-2 using TRIzol: Adapting to countries with lower incomes looking for a large-scale detection program.

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 µL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.

COVID-19 pandemic: challenges ahead.

Since December 2019, health systems worldwide have faced the pandemic caused by the new severe acute respiratory syndrome coronavirus 2. The pandemic began in China and has spread throughout the world. This new coronavirus has a high transmission capacity and elevated lethality in people over 60 years old and in those with risk factors (obesity, diabetes, and systemic arterial hypertension); those characteristics have a different proportion in each country. At present, there is no specific, effective, and safe treatment to treat this virus. In this review, an analysis is made on the differences in epidemiological aspects of the disease and its presentation in pediatric patients; the poorly-based recommendation for using an empirical combination of antimalarials plus antimicrobials as antiviral treatment; the indication of intravenous steroids; and the possible influence of antihypertensive drugs on the course of the disease.

A partir de diciembre de 2019, los sistemas de salud de todos los países se han enfrentado a la pandemia causada por un nuevo coronavirus (SARS-CoV-2), el cual fue notificado por primera vez en China y se ha esparcido por todo el mundo. Este nuevo coronavirus posee una alta capacidad para transmitirse. A escala mundial la letalidad ha sido más alta en la población mayor de 60 años y en aquellos que tienen factores de riesgo (obesidad, diabetes e hipertensión arterial sistémica). Sin embargo, estas características varían en proporción en cada país. Hasta el momento no hay un tratamiento específico, eficaz y seguro para combatir este virus. En este artículo se realiza un análisis sobre las diferencias globales en los aspectos ­epidemiológicos y con relación a su presentación en pacientes pediátricos, así como de la recomendación, con pobre fundamento, del uso de la combinación de antimaláricos y antimicrobianos empíricos como antivirales. También se analizan la indicación de esteroides intravenosos y la posible influencia de los fármacos antihipertensivos en el curso de la enfermedad.

Co-infection of Dengue, Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez, Chiapas: Preliminary data. 2019.

INTRODUCTION: Dengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas. PRINCIPAL FINDINGS: The presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses. CONCLUSIONS: From 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.

Entomological and virological surveillance for dengue virus in churches in Merida, Mexico.

This study was designed to assess whether churches in endemic dengue districts in Merida, Mexico provide suitable breeding habitats for mosquitoes and are potential sites for dengue virus (DENV) transmission. Churches were inspected for immature and adult mosquitoes once every week from November 2015 to October 2016. A total of 10,997 immatures of five species were collected. The most abundant species were Aedes aegypti (6,051) and Culex quinquefasciatus (3,018). The most common source of immature Ae. aegypti were buckets followed by disposable containers. Adult collections yielded 21,226 mosquitoes of nine species. The most common species were Cx. quinquefasciatus (15,215) and Ae. aegypti (3,902). Aedes aegypti were found all year long. Female Ae. aegypti (1,380) were sorted into pools (166) and assayed for flavivirus RNA by RT-PCR and Sanger sequencing. Two pools were positive for DENV (DENV-1 and 2). In conclusion, we demonstrated that some churches in Merida are infested with mosquitoes all year long and they potentially serve as sites for DENV transmission and should therefore be considered for inclusion in mosquito and arboviruses control and surveillance efforts.

Evidence for suppression of Onchocerca volvulus transmission in the Oaxaca focus in Mexico.

Entomologic and serologic surveys were performed in four sentinel communities in the Oaxaca focus in southern Mexico to assess the level of transmission and exposure incidence to Onchocerca volvulus. All communities have been receiving ivermectin mass treatment twice per year since 1997. In one community, parasite DNA was detected by polymerase chain reaction-enzyme-linked immunosorbent assay in 2004 in one pool of 50 vector heads of 170 such pools (8,500 flies) examined, which indicated an estimated transmission potential of 6.7 third-stage larvae/person/year. No evidence for transmission was found in the three other communities in 13,650 flies examined. All persons in a cohort consisting of 117 children in the four communities remained serologically negative for antibodies recognizing a cocktail of recombinant antigens over a four-year period from 2001 to 2004, which indicated an exposure incidence of 0%. Taken together, these data suggest that transmission has been suppressed in the four communities.

Comparative analysis of two alternative models for epidemiological surveillance in the Mexican Malaria Control Program.

The current surveillance model used by the Malaria Control Program in a Mexican state was analyzed using a systematic evaluation of the model ("PAATI" programs, actions, activities, tasks and inputs) through a diagrammatic evaluation of all the components in the process. The actions, activities tasks and inputs of this surveillance model (based on active and passive malaria case detection using tick blood smears examination), as well as those of an innovative alternative model (based on passive malaria case detection using immunodiagnostic strips, with an overall sensitivity of 93.3% and specificity of 99.5%) were identified and evaluated. It was documented that although the same actions are carried out in both models, many more activities are necessary with more tasks and inputs (traditional: 19 activities and 55 tasks, alternative: 13 activities and 32 tasks) in the current one. Adjusting to a population of 10,000 inhabitants, 1000 prospective cases and 2 years of surveillance, the cost of diagnosing and treating one malaria case was of 8.97 US dollars in this model and of 6.34 US dollars in the alternative one.

Feasibility Study of an Optical Caustic Plasmonic Light Scattering Sensor for Human Serum Anti-Dengue Protein E Antibody Detection.

Antibody detection and accurate diagnosis of tropical diseases is essential to help prevent the spread of disease. However, most detection methods lack cost-effectiveness and field portability, which are essential features for achieving diagnosis in a timely manner. To address this, 3D-printed oblate spheroid sample chambers were fabricated to measure green light scattering of gold nanoparticles using an optical caustic focus to detect antibodies. Scattering signals of 20-200 nm gold nanoparticles using a green laser were compared to green light emitting diode (LED) light source signals and to Mie theory. The change in signal from 60 to 120 nm decreased in the order of Mie Theory > optical caustic scattering > 90° scattering. These results suggested that conjugating 60 nm gold nanoparticles and using an optical caustic system to detect plasmonic light scattering, would result in a sensitive test for detecting human antibodies in serum. Therefore, we studied the light scattering response of conjugated gold nanoparticles exposed to different concentrations of anti-protein E antibody, and a feasibility study of 10 human serum samples using dot blot and a handheld optical caustic-based sensor device. The overall agreement between detection methods suggests that the new sensor concept shows promise to detect gold nanoparticle aggregation in a homogeneous assay. Further testing and protocol optimization is needed to draw conclusions on the positive and negative predictive values for this new testing system.

Molecular studies of Onchocerca volvulus isolates from Mexico.

DNA from Onchocerca volvulus from Oaxaca and Chiapas, Mexico were used as templates to amplify members of the O-150 Onchocerca specific repeat sequence family. The resulting PCR amplicons all hybridized with OVS2, an oligonucleotide that has been previously shown to recognize amplicons derived from O. volvulus with 100% sensitivity. However, when PCR products amplified from the O. volvulus specific plasmid pOVS134 were used as a probe, most samples did not hybridize. Similarly, when PCR products amplified from DNA isolated from adult O. volvulus from Oaxaca were used as a probe, amplicons from adult worms from both Oaxaca and Chiapas were recognized, but PCR products from infected black flies from Chiapas were not recognized. Amplicons derived from an adult worm from Chiapas hybridized with PCR products produced from adult parasites from both Oaxaca and Chiapas and to PCR products derived from the DNA of infected black flies from Chiapas. These data, when taken together, suggest that differences exist among the repeat sequence populations of parasites from Oaxaca and Chiapas in Mexico, suggesting that the O-150 repeat sequence family may be a useful tool for biogeographic studies of O. volvulus in the Americas.

Antibodies to West Nile virus in asymptomatic mammals, birds, and reptiles in the Yucatan Peninsula of Mexico.

Surveillance for evidence of West Nile virus (WNV) infection in taxonomically diverse vertebrates was conducted in the Yucatan Peninsula of Mexico in 2003 and 2004. Sera from 144 horses on Cozumel Island, Quintana Roo State, 415 vertebrates (257 birds, 52 mammals, and 106 reptiles) belonging to 61 species from the Merida Zoo, Yucatan State, and 7 farmed crocodiles in Ciudad del Carmen, Campeche State were assayed for antibodies to flaviviruses. Ninety (62%) horses on Cozumel Island had epitope-blocking enzyme-linked immunosorbent assay (ELISA) antibodies to flaviviruses, of which 75 (52%) were seropositive for WNV by plaque reduction neutralization test (PRNT). Blocking ELISA antibodies to flaviviruses also were detected in 13 (3%) animals in the Merida Zoo, including 7 birds and 2 mammals (a jaguar and coyote) seropositive for WNV by PRNT. Six (86%) crocodiles in Campeche State had PRNT-confirmed WNV infections. All animals were healthy at the time of serum collections and none had a history of WNV-like illness.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates / Heterogeneidad internacional en las tasas de mortalidad pediátrica por COVID-19

Abstract Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Resumen Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

[ABSTRACT]. Objective. To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). Methods. Participants aged 12–17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. Results. 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). Conclusion. TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

[RESUMEN]. Objetivo. Describir la inmunogenicidad y la seguridad de una vacuna tetravalente contra el dengue (TAK-003) en adolescentes sanos residentes en Ciudad de México, considerada un área no endémica de dengue (NCT03341637). Métodos. Se asignó de manera aleatoria a un grupo de participantes de 12 a 17 años en una proporción 3:1 para que recibieran dos dosis (en el mes 0 y en el mes 3) de la vacuna TAK-003 o de un placebo. Se evaluó la inmunogenicidad mediante un análisis de microneutralización de anticuerpos neutralizantes del virus del dengue al inicio del estudio y en los meses 4 y 9. Se registraron los eventos adversos de notificación solicitada y los referidos por iniciativa propia después de cada vacunación. A lo largo del estudio se registraron los eventos adversos graves y los que requirieron atención médica. Resultados. Participaron 400 adolescentes y 391 (97,8%) finalizaron el estudio. 36 adolescentes (9%) fueron seropositivos a ≥1 serotipos (título recíproco ≥10) al inicio del estudio. La media geométrica de los títulos en las personas seronegativas vacunadas con TAK-003 al inicio del estudio fue de 328, 1743, 120 y 143 en el mes 4 y 135, 741, 46 y 38 en el mes 9 en relación con DENV-1, -2, -3 y -4, respectivamente. La media geométrica de los títulos de las personas que recibieron un placebo se mantuvo en <10. Las tasas de seropositividad tetravalente en los vacunados fueron 99,6% y 85,8% a los meses 4 y 9, respectivamente. Se consideró relacionado con el tratamiento un evento adverso con atención médica que tuvo lugar en cada grupo (TAK-003: eritema en el lugar de la inyección; placebo: faringitis). Conclusiones. TAK-003 fue inmunogénica ante los cuatro serotipos y bien tolerada en los adolescentes sin exposición previa al dengue que vivían en Ciudad de México.

[RESUMO]. Objetivo. Descrever a imunogenicidade e a segurança de uma vacina tetravalente contra dengue (TAK-003) em adolescentes saudáveis residentes da Cidade do México, área considerada não endêmica para dengue (ClinicalTrials.gov: NCT03341637). Métodos. Participantes com idade entre 12 e 17 anos foram randomizados a uma proporção de 3:1 para receber duas doses da vacina TAK-003 ou placebo (no mês 0 e no mês 3). A imunogenicidade foi avaliada pelos títulos de anticorpos neutralizantes contra dengue determinados em ensaio de microneutralização ao início do estudo, no mês 4 e no mês 9. A ocorrência de eventos adversos solicitados ou espontâneos foi registrada após cada rodada de vacinação. Eventos adversos graves e eventos adversos que exigiram atendimento médico foram monitorados ao longo de todo o estudo. Resultados. De 400 adolescentes incluídos na amostra estudada, 391 (97,8%) completaram o estudo. Trinta e seis (9%) apresentaram positividade basal a um ou mais sorotipos virais da dengue (título recíproco ≥10). A média geométrica dos títulos de anticorpos nos vacinados com TAK-003 que eram soronegativos ao início do estudo foi de 328, 1743, 120 e 143 no mês 4 e 135, 741, 46 e 38 no mês 9, contra os sorotipos virais DENV-1, DENV-2, DENV-3 e DENV-4, respectivamente. A média geométrica dos títulos de anticorpos no grupo placebo se manteve abaixo de 10. A taxa de soropositividade tetravalente nos vacinados foi de 99,6% no mês 4 e 85,8% no mês 9. Um único evento adverso que exigiu atendimento médico em cada grupo foi considerado relacionado ao tratamento (eritema no local de aplicação no grupo TAK-003 e faringite no grupo placebo). Conclusão. A vacina TAK-003 demonstrou ser imunogênica contra os quatro sorotipos virais da dengue e foi bem tolerada em adolescentes residentes da Cidade do México sem história pregressa de infecção pela dengue.

COVID-19 pandemic: challenges ahead / Pandemia de COVID-19: retos por enfrentar

Abstract Since December 2019, health systems worldwide have faced the pandemic caused by the new severe acute respiratory syndrome coronavirus 2. The pandemic began in China and has spread throughout the world. This new coronavirus has a high transmission capacity and elevated lethality in people over 60 years old and in those with risk factors (obesity, diabetes, and systemic arterial hypertension); those characteristics have a different proportion in each country. At present, there is no specific, effective, and safe treatment to treat this virus. In this review, an analysis is made on the differences in epidemiological aspects of the disease and its presentation in pediatric patients; the poorly-based recommendation for using an empirical combination of antimalarials plus antimicrobials as antiviral treatment; the indication of intravenous steroids; and the possible influence of antihypertensive drugs on the course of the disease.

Resumen A partir de diciembre de 2019, los sistemas de salud de todos los países se han enfrentado a la pandemia causada por un nuevo coronavirus (SARS-CoV-2), el cual fue notificado por primera vez en China y se ha esparcido por todo el mundo. Este nuevo coronavirus posee una alta capacidad para transmitirse. A escala mundial la letalidad ha sido más alta en la población mayor de 60 años y en aquellos que tienen factores de riesgo (obesidad, diabetes e hipertensión arterial sistémica). Sin embargo, estas características varían en proporción en cada país. Hasta el momento no hay un tratamiento específico, eficaz y seguro para combatir este virus. En este artículo se realiza un análisis sobre las diferencias globales en los aspectos epidemiológicos y con relación a su presentación en pacientes pediátricos, así como de la recomendación, con pobre fundamento, del uso de la combinación de antimaláricos y antimicrobianos empíricos como antivirales. También se analizan la indicación de esteroides intravenosos y la posible influencia de los fármacos antihipertensivos en el curso de la enfermedad.

Economic and disease burden of dengue in Mexico.

BACKGROUND: Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. METHODS AND FINDINGS: We estimated the annual economic and disease burden of dengue in Mexico for the years 2010-2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000-253,000) symptomatic and 119 (95%CL: 75-171) fatal dengue episodes annually on average (2010-2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151-292) million, or $1.56 (95%CL: 1.38-2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87-209) million or $0.80 per capita (95%CL: 0.62-1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36-99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. CONCLUSION: With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak, dengue burden may be significantly higher than that of the pre-vaccine level of rotavirus diarrhea. In sum, Mexico's potential economic benefits from dengue control would be substantial.