Pertussis in Mexico from 2000 to 2019: A real-world study of incidence, vaccination coverage, and vaccine effectiveness.

BACKGROUND: The national immunization program in Mexico includes a 3-dose primary series of pertussis vaccine and a toddler booster dose. In Mexico, whole-cell pertussis vaccines (wP) were switched in 2007 to acellular pertussis vaccines (aP). METHODS: This retrospective study using Mexican National Databases of Health and population surveillance (2000-2019) assessed the incidence of pertussis, infant pertussis vaccination coverage, and vaccine effectiveness (VE) against clinically-diagnosed and/or laboratory-confirmed pertussis in children aged 6.5-18.5 or 24.5 months for the primary series, and children aged 18.5 or 24.5-48.5 months for the toddler booster. RESULTS: The incidence of pertussis sharply increased in 2012 and was highest in 2012, 2015, and 2016 (0.84-0.94/100,000 person-years). Coverage was highest for the first dose in the primary series, decreasing for each subsequent dose. The VE against notified pertussis was 96.4% (95% CI: 94.7, 97.6) for the first three doses of wP vaccine (2000-2007) and 95.7% (95% CI: 95.1, 96.2) for the first three doses of aP vaccine (2008-2019). CONCLUSIONS: Our findings suggested high levels of vaccine effectiveness overall were achieved for the aP and wP vaccines in Mexico between 2000 and 2019.

Mathematical modeling of Dengue virus serotypes propagation in Mexico.

The Dengue virus (DENV) constitutes a major vector borne virus disease worldwide. Prediction of the DENV spread dynamics, prevalence and infection rates are crucial elements to guide the public health services effort towards meaningful actions. The existence of four DENV serotypes further complicates the virus proliferation forecast. The different serotypes have varying clinical impacts, and the symptomatology of the infection is dependent on the infection history of the patient. Therefore, changes in the prevalent DENV serotype found in one location have a profound impact on the regional public health. The prediction of the spread and intensity of infection of the individual DENV serotypes in specific locations would allow the authorities to plan local pesticide spray to control the vector as well as the purchase of specific antibody therapy. Here we used a mathematical model to predict serotype-specific DENV prevalence and overall case burden in Mexico.

Exposición a radiación ionizante en médicos residentes de ortopedia en un hospital de referencia.

OBJECTIVE: To describe and analyze the exposure to ionizing radiation of orthopedic residents. METHOD: A prospective study was carried out to evaluate the degree of exposure to ionizing radiation with a bandage dosimeter placed under the lead apron for medical residents for 10 months. An online survey measured the degree of knowledge about radiation safety. RESULTS: 54 resident physicians participated. 55.6% report having knowledge of the existence of radiological protection equipment and 40.7% report that they had previous training in its use. 77.8% use the leaded apron and 31.5% use thyroid protection. 81.5% were positioned less than 1 meter from the source of the X-ray production of the arc in C. The total mean radiation exposure was 2.9 ± 2.17 mSv (95% confidence interval: 1.25-14.28; p = 0.424). CONCLUSIONS: Orthopedic residents present radiation doses below the International Commission on Radiological Protection recommended limit. However, there is a lack of knowledge of radiation protection and as well as a lack of interest and ignorance of the adverse effects of radiation.

OBJETIVO: Describir y analizar la exposición a radiación ionizante de los residentes de ortopedia. MÉTODO: Se realizó un estudio prospectivo para evaluar el grado de exposición a radiación ionizante con un dosímetro de placa colocado debajo del mandil plomado a médicos residentes, por 10 meses. Mediante una encuesta en línea se midió el grado de conocimientos sobre seguridad radiológica. RESULTADOS: Participaron 54 médicos residentes. El 55.6% refiere tener conocimiento de la existencia de equipo de protección radiológica y el 40.7% refiere que tuvo entrenamiento previo en su uso. El 77.8% utiliza el mandil plomado y el 31.5% la protección tiroidea. El 81.5% se posicionó a menos de 1 metro de la fuente de producción de rayos X del arco en C. La exposición a la radiación media total fue de 2.9 ± 2.17 mSv (intervalo de confianza del 95%: 1.25-14.28; p = 0.424). CONCLUSIONES: Los médicos residentes de ortopedia presentan dosis de radiación menores que el límite recomendado por la International Commission on Radiological Protection. Sin embargo, existe una falta de conocimientos sobre protección radiológica, así como falta de interés e ignorancia de los efectos adversos de la radiación.

Stochastic epidemiological model: Simulations of the SARS-CoV-2 spreading in Mexico.

In this paper we model the spreading of the SARS-CoV-2 in Mexico by introducing a new stochastic approximation constructed from first principles, where the number of new infected individuals caused by a single infectious individual per unit time (a day), is a random variable of a time-dependent Poisson distribution. The model, structured on the basis of a Latent-Infectious-(Recovered or Deceased) (LI(RD)) compartmental approximation together with a modulation of the mean number of new infections (the Poisson parameters), provides a good tool to study theoretical and real scenarios.

Burden of disease and associated complications of hepatitis a in children and adults in Mexico: A retrospective database study.

BACKGROUND: Hepatitis A virus (HAV) infection is a leading cause of viral hepatitis in children, yet the HAV vaccine is not included in the national immunization program (NIP) in Mexico. This study addresses an identified evidence gap of the burden of hepatitis A disease, complications, and associated costs in Mexico by analyzing surveillance and healthcare data. Data review included disease morbidity (incidence and hospitalization), mortality, and healthcare resource utilization costs. METHODS: In this observational, retrospective database study, we conducted a systematic screening, extraction, and analysis of outcome data from the national surveillance system in Mexico from January 2000 to December 2019. RESULTS: During the analysis period (2000-2019), the average incidence rate/year of HAV cases was 14.7 (5.4-21.5) per 100,000 inhabitants. Children 1-9 years of age (YoA) had the highest average incidence rate/year with 47.8 (14.7-74.5). The average hospitalization rate/year due to HAV infection was 5.8% (2.9-9.6%). Although the highest burden of HAV continued to be in children (1-9 YoA), an increase in incidence and hospitalizations (with complications) in older age groups (≥ 10-64 YoA) was observed. The annual average fatality rate was estimated to be 0.44% (0.26-0.83%) of which 28.8% of deaths were concentrated in adults ≥ 65 YoA. The total direct costs of medical attention due to HAV and related complications were estimated at $382 million Mexican pesos. CONCLUSION: The overall results suggest an uptrend in HAV infections in adolescents/adults compared to children in Mexico. Therefore, as the overall incidence risk of HAV infection decreases, the mean age of infection increases. This consequently increases the risk of severity and complications in older age groups, thus increasing the demand for healthcare resources. Our findings provide evidence for including the inactivated HAV vaccine in the Mexican NIP.

Probability of consolidation constrains novel serotype emergence in dengue fever virus.

Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this behavior is intriguing. Here, we explore the effect of various parameters on likelihood of new serotype emergence. In order to determine the time scales of such an event, we used a Timed Markov Transmission Model to explore the influences of sylvatic versus peri-urban transmission, viral mutation rate, and vertical transmission on the probabilities of novel serotype emergence. We found that around 1 000 years are required for a new serotype to emerge, consistent with phylogenetic analysis of extant dengue serotypes. Furthermore, we show that likelihood of establishing chains of mosquito-human-mosquito infection, known as consolidation, is the primary factor which constrains novel serotype emergence. Our work illustrates the restrictions on and provides a mechanistic explanation for the low probability of novel dengue virus serotype emergence and the low number of observed DENV serotypes.

Pertussis infant morbidity and mortality trends after universal maternal immunisation in Mexico: An ecological database study with time-series analysis.

INTRODUCTION: Pertussis is a highly contagious infectious disease caused by Bordetella pertussis and a leading cause of infant mortality in Mexico. The Tetanus-diphtheria-acellular pertussis (Tdap) vaccine was recommended in the Mexican Immunisation Programme for pregnant women in 2013. We describe pertussis morbidity and mortality trends in infants ≤2 and ≤12 months of age), before and after maternal Tdap immunisation implementation in Mexico. METHODS: An ecological retrospective database study was performed in the Mexican National and Workers Social Security Institutes (IMSS; ISSSTE). Data were collected on confirmed pertussis ambulatory cases, hospitalisations, and deaths, plus vaccination coverage (Tdap; Diphtheria-tetanus-acellular pertussis [DTPa]) and population estimates. Descriptive and regression time-trend analyses were performed for pertussis morbidity and mortality in infants between pre- (2010-2012) and post- (2014-2018) maternal Tdap immunisation periods. RESULTS: Around 1 million infants a year are covered in IMSS/ISSSTE databases. Average full primary infant DTPa vaccine coverage was 71.4%-72.7% nationally. Since 2013, annual maternal Tdap vaccine coverage ranged from 70%-93%. Between 2010-2018, 2,024 pertussis cases, 2,518 hospitalisations and 71 deaths were reported in infants. Among infants 0-2 months old (maternal immunisation target group), there was a significant decrease, post-maternal vaccination, in pertussis incidence (49.9%, p < 0.000), hospitalisation (70.0%, p < 0.000) and mortality (82.4%, p = 0.003). In infants 0-12 months old, pertussis hospitalisations (28.9%, p = 0.000) and mortality (36.2%, p = 0.059) decreased, but incidence increased (61.8%, p = 0.000). CONCLUSION: After maternal immunisation was implemented, there was a decreasing trend in incidence, hospitalisation and death due to pertussis in infants 0-2 months old. Increases in incidence reported in 0-12-month-olds are likely due to major changes in diagnosis and reporting introduced during the study period as well as limited vaccination and health coverage in some states. These findings confirm the important contribution of the Tdap maternal immunisation programme in reducing pertussis disease burden, particularly severe disease, among infants in Mexico.

Use of DNA sequencing for noncommunicable diseases in low-income and middle-income countries' primary care settings: A narrative synthesis.

OBJECTIVE: To present a systematic narrative review, informed by international experience, on the use of genomic analysis technologies in the primary care of noncommunicable chronic diseases (NCDs) during the last 20 years. METHODS: We used the methodology for conducting systematic reviews proposed by the Center for Coordination and Information on Evidence for Policies and Practices. The selected articles were organized by time, place, study design, and type of DNA sequencing. Finally, we analyzed the implications of our findings for health systems in middle-income and low-income countries focusing on a NCD high prevalence country such as México. RESULTS: Evidence concerning the use of DNA sequencing in primary care for NCDs was scarce and geographically concentrated in high-income countries. Use was limited by costs, insufficient knowledge among health care personnel, and a lack of confidence on the part of users. CONCLUSIONS: The use of DNA sequencing for primary care of NCDs is a challenge for low- and middle-income countries. More evidence is needed on cost effectiveness, public funding mechanisms, and the training of health care personnel for its implementation.

Vaccine coverage and compliance in Mexico with the two-dose and three-dose rotavirus vaccines.

Worldwide, rotavirus infection has been a leading cause of severe diarrhea morbidity and mortality. Two rotavirus vaccines have been used in the National Immunization Program (NIP) in Mexico; two-dose Rotarix from 2006 to 2011 and three-dose RotaTeq since 2011. This study assessed coverage (receiving at least one dose or full dose series) in eligible infants, compliance (% completing dose series and % completing series on schedule) in eligible infants vaccinated with Rotarix (2010) versus RotaTeq (2012), using Mexican Social Security Institute data nationwide and by regions. In 2010, 80.7% received at least one dose of Rotarix, 75.6% received both doses and 57.0% received both doses on schedule. In 2012, 85.7% received at least one dose of RotaTeq, 61.0% received all three doses and 43.2% received all three doses on schedule. More eligible infants received all doses with Rotarix versus RotaTeq (p < 0.001). Among infants vaccinated with Rotarix versus RotaTeq, 93.7% versus 71.1% completed full series (p < 0.001), and 75.5% versus 70.9% completed full series on schedule (p = 0.105), respectively. The full series coverage and compliance decreased in all regions with RotaTeq compared with Rotarix. In conclusion, rotavirus vaccination has successfully reduced morbidity and mortality in children under 5 years in Mexico. This study found significant differences in full series coverage and compliance among infants and a higher proportion of completed scheduled at an earlier age in Mexico when comparing a two-dose vaccine in 2010 with a three-dose vaccine in 2012. Such differences might need to be taken into consideration to maximize NIP benefits, including early protection of the rotavirus vaccination program.

Prediction of dengue outbreaks in Mexico based on entomological, meteorological and demographic data.

Dengue virus has shown a complex pattern of transmission across Latin America over the last two decades. In an attempt to explain the permanence of the disease in regions subjected to drought seasons lasting over six months, various hypotheses have been proposed. These include transovarial transmission, forest reservoirs and asymptomatic human virus carriers. Dengue virus is endemic in Mexico, a country in which half of the population is seropositive. Seropositivity is a risk factor for Dengue Hemorrhagic Fever upon a second encounter with the dengue virus. Since Dengue Hemorrhagic Fever can cause death, it is important to develop epidemiological mathematical tools that enable policy makers to predict regions potentially at risk for a dengue epidemic. We formulated a mathematical model of dengue transmission, considering both human behavior and environmental conditions pertinent to the transmission of the disease. When data on past human population density, temperature and rainfall were entered into this model, it provided an accurate picture of the actual spread of dengue over recent years in four states (representing two climactic conditions) in Mexico.

Cost-Effectiveness of Blood Donation Screening for Trypanosoma cruzi in Mexico.

An estimated 2 million inhabitants are infected with Chagas disease in Mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. After vector-borne transmission, Trypanosoma cruzi is principally transmitted to humans via blood transfusion. Despite initiation of serological screening of blood donations or donors for T. cruzi since 1990 in most Latin American countries, Mexico only finally included mandatory serological screening nationwide in official Norms in 2012. Most recent regulatory changes and segmented blood services in Mexico may affect compliance of mandatory screening guidelines. The objective of this study was to calculate the incremental cost-effectiveness ratio for total compliance of current guidelines from both Mexican primary healthcare and regular salaried worker health service institutions: the Secretary of Health and the Mexican Institute for Social Security. We developed a bi-modular model to analyze compliance using a decision tree for the most common screening algorithms for each health institution, and a Markov transition model for the natural history of illness and care. The incremental cost effectiveness ratio based on life-years gained is US$ 383 for the Secretary of Health, while the cost for an additional life-year gained is US$ 463 for the Social Security Institute. The results of the present study suggest that due to incomplete compliance of Mexico's national legislation during 2013 and 2014, the MoH has failed to confirm 15,162 T. cruzi infections, has not prevented 2,347 avoidable infections, and has lost 333,483 life-years. Although there is a vast difference in T. cruzi prevalence between Bolivia and Mexico, Bolivia established mandatory blood screening for T.cruzi in 1996 and until 2002 detected and discarded 11,489 T. cruzi -infected blood units and prevented 2,879 potential infections with their transfusion blood screening program. In the first two years of Mexico's mandated program, the two primary institutions failed to prevent due to incomplete compliance more potential infections than those gained from the first five years of Bolivia's program. Full regulatory compliance should be clearly understood as mandatory for the sake of blood security, and its monitoring and analysis in Mexico should be part of the health authority's responsibility.

Lower IgG somatic hypermutation rates during acute dengue virus infection is compatible with a germinal center-independent B cell response.

BACKGROUND: The study of human B cell response to dengue virus (DENV) infection is critical to understand serotype-specific protection and the cross-reactive sub-neutralizing response. Whereas the first is beneficial and thus represents the ultimate goal of vaccination, the latter has been implicated in the development of severe disease, which occurs in a small, albeit significant, fraction of secondary DENV infections. Both primary and secondary infections are associated with the production of poly-reactive and cross-reactive IgG antibodies. METHODS: To gain insight into the effect of DENV infection on the B cell repertoire, we used VH region high-throughput cDNA sequencing of the peripheral blood IgG B cell compartment of 19 individuals during the acute phase of infection. For 11 individuals, a second sample obtained 6 months later was analyzed for comparison. Probabilities of sequencing antibody secreting cells or memory B cells were estimated using second-order Monte Carlo simulation. RESULTS: We found that in acute disease there is an increase in IgG B cell diversity and changes in the relative use of segments IGHV1-2, IGHV1-18, and IGHV1-69. Somewhat unexpectedly, an overall low proportion of somatic hypermutated antibody genes was observed during the acute phase plasmablasts, particularly in secondary infections and those cases with more severe disease. CONCLUSIONS: Our data are consistent with an innate-like antiviral recognition system mediated by B cells using defined germ-line coded B cell receptors, which could provide a rapid germinal center-independent antibody response during the early phase of infection. A model describing concurrent T-dependent and T-independent B cell responses in the context of DENV infection is proposed, which incorporates the selection of B cells using hypomutated IGHV segments and their potential role in poly/cross-reactivity. Its formal demonstration could lead to a definition of its potential implication in antibody-dependent enhancement, and may contribute to rational vaccine development efforts.

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BACKGROUND: An alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries. METHODS: We evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed. RESULTS: Radiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms. CONCLUSIONS: Given the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography.

Opportunity cost for early treatment of Chagas disease in Mexico.

BACKGROUND: Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. METHODOLOGY/PRINCIPAL FINDINGS: A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. CONCLUSIONS/SIGNIFICANCE: In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

A beta-complex statistical four body contact potential combined with a hydrogen bond statistical potential recognizes the correct native structure from protein decoy sets.

We present a new four-body knowledge-based potential for recognizing the native state of proteins from their misfolded states. This potential was extracted from a large set of protein structures determined by X-ray crystallography using BetaMol, a software based on the recent theory of the beta-complex (ß-complex) and quasi-triangulation of the Voronoi diagram of spheres. This geometric construct reflects the size difference among atoms in their full Euclidean metric; property not accounted for in a typical 3D Delaunay triangulation. The ability of this potential to identify the native conformation over a large set of decoys was evaluated. Experiments show that this potential outperforms a potential constructed with a classical Delaunay triangulation in decoy discrimination tests. The addition of a statistical hydrogen bond potential to our four-body potential allows a significant improvement in the decoy discrimination, in such a way that we are able to predict successfully the native structure in 90% of cases.

A literature review of reporting standards of HIV progression models.

OBJECTIVE: We conducted a systematic review of HIV progression models to identify the mathematical structures used, the main research questions and key model aspects in terms of quality and robustness. METHODS: We searched for articles published before February 2009 that described models of HIV progression in humans. We included two strategies of search with and without MeSH terms. We classified the models by their mathematical structure and research question. We created a checklist of desirable features of the models, reviewed and classified the articles to inform our conclusions. RESULTS: Among 3491 articles found, 93 met the inclusion criteria. Among the selected articles, 60 used transition models, 25 applied differential equations, and eight had other structures. We did not find a relation between the type of question explored and the modeling method used. None of the studies complied with the complete set of items in the checklist, but 6.5% cover at least 90% of them. CONCLUSION: There is an enormous heterogeneity of HIV modeling exercises in terms of methods used and topics addressed, as well as in the presentation of key aspects of the articles in terms of quality and robustness.

[Cost-effectiveness of breast cancer screening policies in Mexico]. / Costo-efectividad de políticas para el tamizaje de cáncer de mama en México.

OBJECTIVE: Generate cost-effectiveness information to allow policy makers optimize breast cancer (BC) policy in Mexico. MATERIAL AND METHODS: We constructed a Markov model that incorporates four interrelated processes of the disease: the natural history; detection using mammography; treatment; and other competing-causes mortality, according to which 13 different strategies were modeled. RESULTS: Strategies (starting age, % of coverage, frequency in years)= (48, 25, 2), (40, 50, 2) and (40, 50, 1) constituted the optimal method for expanding the BC program, yielding 75.3, 116.4 and 171.1 thousand pesos per life-year saved, respectively. CONCLUSIONS: The strategies included in the optimal method for expanding the program produce a cost per life-year saved of less than two times the GNP per capita and hence are cost-effective according to WHO Commission on Macroeconomics and Health criteria.

Costo-efectividad de políticas para el tamizaje de cáncer de mama en México / Cost-effectiveness of breast cancer screening policies in Mexico

OBJETIVO: Generar información de costo-efectividad para optimizar las políticas para el cáncer de mama (CaMa) en México. MATERIAL Y MÉTODOS: Se construyó un modelo Markov que incorpora cuatro procesos interrelacionados del CaMa: la evolución natural, la detección con mamografía, el tratamiento y la dinámica de mortalidad por otras causas, a partir del cual se modelaron 13 estrategias. RESULTADOS: Las estrategias (edad de inicio, porcentaje de cobertura, periodicidad en años)= (48, 25, 2), (40, 50, 2) y (40, 50, 1) representan la ruta óptima de expansión del programa, con un costo por año de vida ganado de 75.3, 116.4 y 171.1 (miles de pesos), respectivamente. CONCLUSIONES: Las estrategias sobre la vía óptima de expansión del programa producen una razón de costo por año de vida ganado menor a dos veces el PIB per cápita, por lo que se encuentran dentro de lo que se considera una intervención costo-efectiva según los criterios de la OMS.

OBJECTIVE: Generate cost-effectiveness information to allow policy makers optimize breast cancer (BC) policy in Mexico. MATERIAL AND METHODS: We constructed a Markov model that incorporates four interrelated processes of the disease: the natural history; detection using mammography; treatment; and other competing-causes mortality, according to which 13 different strategies were modeled. RESULTS: Strategies (starting age, percent of coverage, frequency in years)= (48, 25, 2), (40, 50, 2) and (40, 50, 1) constituted the optimal method for expanding the BC program, yielding 75.3, 116.4 and 171.1 thousand pesos per life-year saved, respectively. CONCLUSIONS: The strategies included in the optimal method for expanding the program produce a cost per life-year saved of less than two times the GNP per capita and hence are cost-effective according to WHO Commission on Macroeconomics and Health criteria.