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Introduction Obesity accounts for a substantial and growing burden of disease globally. Body adiposity is highly heritable, and human genetic studies can lead to biological and therapeutic insights. Rationale Whole-exome sequencing of hundreds of thousands of individuals is complementary to approaches used to date in obesity genetics and has the potential to identify rare protein-coding variants with large phenotypic impact. We sequenced the exomes of 645,626 individuals from the UK, the US, and Mexico and estimated associations of rare coding variants with body mass index (BMI), a measure of overall adiposity used to define obesity in clinical practice. We complemented exome sequencing with fine-mapping of common alleles, polygenic score analysis, and in vitro and in vivo modeling work. Results We identified 16 genes for which the burden of rare nonsynonymous variants was associated with BMI at exome-wide statistical significance (inverse-variance weighted meta-analysis P < 3.6 × 10−7), including associations at five brain-expressed G protein–coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). We observed an overrepresentation of genes highly expressed in the hypothalamus, a key center for the neuroendocrine regulation of energy balance. Protein-truncating variants in GPR75 were found in ~4/10,000 sequenced people and were associated with 1.8 kg/m2 lower BMI, 5.3 kg lower bodyweight, and 54% lower odds of obesity in heterozygous carriers. Knock out of Gpr75 in mice resulted in resistance to weight gain in a high-fat diet model, which was allele-dose dependent (25% and 44% lower weight gain, respectively, for heterozygous Gpr75−/+ mice and knockout Gpr75−/− mice compared with wild type) and accompanied by improved glycemic control and insulin sensitivity. Protein-truncating variants in CALCR were associated with higher BMI and obesity risk, whereas protein-truncating variants in GIPR and two missense alleles [Arg190→Gln (Arg190Gln), Glu288Gly], which we show result in loss of function in vitro, were associated with lower adiposity. Among monogenic obesity genes in the leptin-melanocortin pathway, heterozygous predicted loss-of-function variants in LEP, POMC, PCSK1, and MC4R (but not LEPR) were associated with higher BMI. Rare protein-truncating variants in UBR2, ANO4, and PCSK1 were associated with more than twofold higher odds of obesity in heterozygous carriers, similar to predicted-deleterious nonsynonymous variants in MC4R, which are considered the most common cause of monogenic obesity. Polygenic predisposition due to >2 million common genetic variants influenced the penetrance of obesity in rare variant carriers in an additive fashion. Conclusion These results suggest that inhibition of GPR75 may be a therapeutic strategy for obesity and illustrate the power of massive-scale exome sequencing for the identification of large-effect coding variant associations and drug targets for complex traits.

Context Chronic kidney disease (CKD) and diabetes are associated with dyslipidemia, metabolic abnormalities, and atherosclerotic risk. Nuclear magnetic resonance (NMR) spectroscopy provides much more detail on lipoproteins than traditional assays. Methods In about 38 000 participants from the Mexico City Prospective Study, aged 35 to 84 years and not using lipid-lowering medication, NMR spectroscopy quantified plasma concentrations of lipoprotein particles, their lipidic compositions, and other metabolic measures. Linear regression related low estimated glomerular filtration rate (eGFR; Results Among the 38 081 participants (mean age 52 years, 64% women), low eGFR was present for 4.8% (306/6403) of those with diabetes and 1.2% (365/31 678) of those without diabetes. Among both those with and without diabetes, low eGFR was significantly associated with higher levels of 58 NMR measures, including apolipoprotein B (Apo-B), the particle numbers of most Apo-B containing lipoproteins, the cholesterol and triglycerides carried in these lipoproteins, several fatty acids, total cholines and phosphatidylcholine, citrate, glutamine, phenylalanine, β-OH-butyrate, and the inflammatory measure glycoprotein-A, and significantly lower levels of 13 NMR measures, including medium and small high-density lipoprotein particle measures, very low-density lipoprotein particle size, the ratio of saturated:total fatty acids, valine, tyrosine, and aceto-acetate. Conclusions In this Mexican population with high levels of adiposity and diabetes, low kidney function was associated with widespread alterations in lipidic and metabolic profiles, both in those with and without diabetes. These alterations may help explain the higher atherosclerotic risk experienced by people with CKD.

Aims Results of previous studies of abdominal adiposity and risk of vascular-metabolic mortality in Hispanic populations have been conflicting. We report results from a large prospective study of Mexican adults with high levels of abdominal adiposity. Methods and results A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist–hip ratio, and waist–height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35–74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40–74 years were 2.32 [95% confidence interval (CI) 1.84–2.94] for waist circumference, 2.22 (1.71–2.88) for the waist–hip ratio, 2.63 (2.06–3.36) for the waist–height ratio, and 1.58 (1.29–1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27–1.41), 1.31 (1.23–1.39), 1.38 (1.31–1.45), and 1.18 (1.13–1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75–0.86). Conclusions In this study of Mexican adults, abdominal adiposity (and in particular the waist–height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.

OBJECTIVE To investigate the trends in diabetes prevalence, diagnosis, and management among Mexican adults who were participants in a long-term prospective study. RESEARCH DESIGN AND METHODS From 1998 to 2004, 159,755 adults from Mexico City were recruited to a prospective study, and from 2015 to 2019, 10,144 survivors were resurveyed. Diabetes was defined as self-reported diagnosis, glucose-lowering medication use, or HbA1c ≥6.5%. Controlled diabetes was defined as HbA1c RESULTS During 1998–2004 and 2015–2019, 99,623 and 8,986 participants were aged 45–84 years. Diabetes prevalence had increased from 26% in 1998–2004 to 35% by 2015–2019. Of those with diabetes, the proportion previously diagnosed had increased from 76% to 89%, and glucose-lowering medication use among them had increased from 80% to 94%. Median HbA1c among those with diabetes had decreased from 8.2% to 7.3%, and the proportion of participants with controlled diabetes had increased from 16% to 37%. Use of blood pressure–lowering medication among those with previously diagnosed diabetes had increased from 35% to 51%, and their use of lipid-lowering therapy had increased from 1% to 14%. The excess mortality risk associated with diabetes accounted for 34% of deaths at ages 35–74 years, of which 5% were attributable to controlled and 29% to inadequately controlled diabetes. CONCLUSIONS Inadequately controlled diabetes is a leading cause of premature adult death in Mexico. Improvements in diabetes management have increased diagnosis and control, but substantial opportunities remain to improve treatment, particularly with lipid-lowering therapy.

Summary Background Diabetes is a cause of at least a third of all deaths in Mexican adults aged 35–74 years, with the excess mortality due mainly to vascular disease, renal disease, infection, and acute diabetic crises. We aimed to analyse the effect of diabetes duration and glycaemic control on death rate ratios (RRs) for these causes and to assess the relevance to cause-specific mortality of undiagnosed diabetes. Methods About 100 000 women and 50 000 men aged 35 years or older from Mexico City were recruited into a blood-based prospective study between April 14, 1998, and Sept 28, 2004, and followed up until Jan 1, 2016, for cause-specific mortality. Participants who, at recruitment, reported any chronic disease other than diabetes and those who had missing data for HbA 1c or diabetes duration were excluded. We used Cox models to estimate the associations of undiagnosed or previously diagnosed diabetes (almost all type 2) with risk of mortality from vascular disease, renal disease, and infection, exploring among those with previously diagnosed diabetes the independent relevance of diabetes duration ( 1c ( 1c with mortality in participants without diabetes at recruitment. Findings 133 662 participants were aged 35–74 years and had complete data and no other chronic disease. 16 940 (13%) had previously diagnosed diabetes, 6541 (5%) had undiagnosed diabetes, and 110 181 (82%) had no diabetes. Among participants with previously diagnosed diabetes, glycaemic control was poor (median HbA 1c 8·9% [IQR 7·0–10·9]), and was worse in those with longer duration of disease at recruitment. Compared with participants without diabetes, the death RRs at ages 35–74 years for the combination of vascular, renal, or infectious causes were 3·0 (95% CI 2·7–3·4) in those with undiagnosed diabetes, 4·5 (4·0–5·0) for the 5042 participants with a diabetes duration of less than 5 years, 6·6 (6·1–7·1) for the 7713 participants with a duration of 5 years to less than 10 years, and 11·7 (10·7–12·7) for the 4185 participants with a duration of at least 10 years. Similarly, the death RRs were 5·2 (4·8–5·7) for those with HbA 1c less than 9%, 6·8 (6·2–7·4) for those with HbA 1c of 9% to less than 11%, and 10·5 (9·7–11·5) for those with HbA 1c of at least 11%. Diabetes was not strongly associated with the combination of deaths from other causes apart from acute glycaemic crises. Among participants without diabetes, higher HbA 1c was not positively related to mortality. Interpretation In Mexico, the rates of death from causes strongly associated with diabetes increased steeply with duration of diabetes and were higher still among people with poor glycaemic control. Delaying the onset of type 2 diabetes, as well as improving its treatment, is essential to reduce premature adult mortality in Mexico. Funding Wellcome Trust, the Mexican Health Ministry, the Mexican National Council of Science and Technology, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.

In Mexico, mosquito vector-borne diseases are of public health concern as a result of their impact on human morbidity and mortality. The use of insecticides against adult mosquitoes is one of the most common ways of controlling mosquito population densities. However, the use of these compounds has resulted in the development of insecticide resistance. The aim of this study was to estimate susceptibility to six pyrethroids, two carbamates and two organophosphates in Mexican populations of Stegomyia aegypti (Linnaeus, 1762) (= Aedes aegypti) (Diptera: Culicidae) mosquitoes. Bottle insecticide susceptibility tests, with 1 h exposure, were performed on adult mosquitoes from 75 localities across 28 states. At 30 min of exposure, the proportion of fallen mosquitoes was recorded. After 60 min of exposure, mosquitoes were recovered in non-treated containers and mortality was determined at 24 h after the set-up of the experiment. In general, the carbamate insecticides represented the most effective group in terms of the proportion of mosquitoes fallen at 30 min (72-100%) and 24-h mortality (97-100%). High and widespread resistance to pyrethroids Types I and II and, to a lesser extent, to organophosphates was observed. Insecticide susceptibility among and within states was highly variable.

Héctor Gallardo-Rincón,1 Rodrigo Saucedo-Martínez,1 Ricardo Mujica-Rosales,1 Evan M Lee,2 Amy Israel,2 Braulio Torres-Beltran,3 Úrsula Quijano-González,3 Elena Rose Atkinson,3 Pablo Kuri-Morales,4 Roberto Tapia-Conyer1 1Fundación Carlos Slim, Mexico City, Mexico; 2Lilly Global Health, Eli Lilly and Company, Vernier, Switzerland; 3C230 Consultores, Mexico City, Mexico; 4Mexican Ministry of Health, Mexico City, Mexico Purpose: The purpose of this study is to evaluate how the benefits of online continuing medical education (CME) provided to health care professionals traveled along a patient “educational chain”. In this study, the educational chain begins with the influence that CME can have on the quality of health care, with subsequent influence on patient knowledge, disease self-management, and disease biomarkers. Methods: A total of 422 patients with at least one noncommunicable disease (NCD) treated in eight different Mexican public health clinics were followed over 3years. All clinics were participants in the CASALUD Model, an NCD care model for primary care, where all clinic staff were offered CME. Data were collected through a questionnaire on health care, patient disease knowledge, and self-management behaviors; blood samples and anthropometric measurements were collected to measure patient disease biomarkers. Results: Between 2013 and 2015, the indexes measuring quality of health care, patient health knowledge, and diabetes self-management activities rose moderately but significantly (from 0.54 to 0.64, 0.80 to 0.84, and 0.62 to 0.67, respectively). Performing self-care activities – including owning and using a glucometer and belonging to a disease support group– saw the highest increase (from 0.65 to 0.75). A1C levels increased between 2013 and 2015 from 7.95 to 8.41% (63–68mmol/mol) (P

In Mexico, the use of repellents to prevent insects from landing and biting is a common practice. However, variation in the efficiency of natural and synthetic repellents has been observed. In this study, we evaluated the repellency and protection time of 16 synthetic and 13 natural-based commercial products against Aedes aegypti (L.) from an endemic dengue area (Jojutla, Morelos) in Central Mexico. The "arm exposure" cage test was used to assess the efficacy of the repellents. Tests were conducted by three adult volunteers. Results showed that DEET (N, N-Diethyl-3-methylbenzamide) repellents provided the highest protection and duration times against Ae. aegypti. However, low repellency and short-time protection was observed (when compared with the manufacturers' protection times). Natural-based products did not repel (either landing or biting) mosquitoes for >30 min. These results show that most of the repellent products did not provide satisfactory levels of personal protection against mosquito bites. Frequent reapplication of repellents (synthetic and natural-based) may compensate for their short duration of action. Repellent efficacy data must be integrated into the decision-making process for an optimal response to the local (or specific region) situation.

espanolIntroduccion: Las epidemias de influenza son de mayor riesgo en los extremos de la vida y en personas con comorbilidades. La vacunacion efectiva previene la aparicion de casos graves y disminuye la mortalidad. Objetivo: Describir las defunciones por influenza en Mexico con antecedente de vacunacion oportuna, de 2010 a 2018. Metodo: Estudio transversal descriptivo en el que se utilizo la base de datos del Sistema de Vigilancia Epidemiologica de Influenza. Resultados: De 2010 a 2018 fallecieron por influenza 65 personas con vacunacion, 55 % (n = 36) de las cuales por tipo A (H1N1), 51 % (n = 33) del sexo femenino, la mediana de edad fue de 57 anos, 21 % (n = 14) no cumplia la definicion operacional de enfermedad tipo influenza o infeccion respiratoria aguda grave, 83 % (n = 54) tenia al menos una comorbilidad; las comorbilidades mas frecuentes fueron diabetes mellitus e hipertension arterial (32 % cada una); 55 % (n = 36) recibio tratamiento antiviral y solo 8 % (n = 5) no presentaba comorbilidades y tenia tratamiento con oseltamivir. Conclusiones: Las defunciones por influenza con vacunacion oportuna representan un porcentaje muy bajo del total. La vacunacion contra influenza ha sido una estrategia de prevencion especifica que disminuye la carga de la enfermedad. EnglishIntroduction: Influenza epidemics are of higher risk at the extremes of life and in people with comorbidities. Effective vaccination prevents the occurrence of serious cases and decreases mortality. Objective: To describe deaths from influenza with a history of timely vaccination, from the 2010 to the 2018 season in Mexico. Method: Cross-sectional, descriptive study where the Influenza Epidemiological Surveillance System database was used. Results: From 2010 to 2018, 65 vaccinated individuals died from influenza, from which 55% of cases (n = 36) were due to type A (H1N1), 51% (n = 33) were females, median age was 57 years, 21 % (n = 14) did not meet the operational definition of influenza-like illness or severe acute respiratory infection, 83% (n = 54) had at least one comorbidity, with the most common being diabetes mellitus and hypertension (32% each); 55% (n = 36) of deaths received antiviral treatment and only 8% (n = 5) had no comorbidities and received treatment with oseltamivir. Conclusions: Deaths from influenza with timely vaccination represent a very low percentage of the totality. Vaccination against influenza has been a specific prevention strategy that decreases disease burden.

BACKGROUND: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. OBJECTIVE: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. DESIGN: Prospective study. SETTING: 2 Mexico City districts. PARTICIPANTS: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A(1c) level of 7% or greater, diabetes, or other chronic diseases were excluded. MEASUREMENTS: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. RESULTS: Among 115 400 participants aged 35 to

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.

The first week of September 2013, the National Epidemiological Surveillance System identified two cases of cholera in Mexico City. The cultures of both samples were confirmed as Vibrio cholerae serogroup O1, serotype Ogawa, biotype El Tor. Initial analyses by PFGE and by PCR-amplification of the virulence genes, suggested that both strains were similar, but different from those previously reported in Mexico. The following week, four more cases were identified in a community in the state of Hidalgo, located 121 km northeast of Mexico City. Thereafter a cholera outbreak started in the region of La Huasteca. Genomic analyses of the four strains obtained in this study confirmed the presence of Pathogenicity Islands VPI-1 and -2, VSP-1 and -2, and of the integrative element SXT. The genomic structure of the 4 isolates was similar to that of V. cholerae strain 2010 EL-1786, identified during the epidemic in Haiti in 2010.

Chronic noncommunicable diseases (NCDs), including can- cer, have become the leading cause of human morbidity and mortality. In Mexico, cancer is the third leading cause of death, with a high incidence among the economically active popula- tion, a high proportion of advanced stages at diagnosis and limited care coverage for patients. However, no public policy aimed at managing this important public health problem has been developed and implemented to date. This manuscript describes the first interinstitutional proposal of a National Program for Cancer Control, considering the known risk factors, early detection, treatment, palliative care and patient rehabilitation. This manuscript also outlines a series of thoughts on the difficulties and needs that the Mexican health system faces in achieving the main objectives of the program: to decrease the incidence of cancer, to increase survival and to improve the quality of life for this group of patients. DOI: http://dx.doi.org/10.21149/spm.v58i2.7804

Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is a species of mosquito that is currently widespread in Mexico. Historically, the mosquito has been distributed across most tropical and subtropical areas lower than 1700 m a.s.l. Currently, populations that are found at higher altitudes in regions with cold and dry climates suggest that these conditions do not limit the colonization and population growth of S. aegypti. During a survey of mosquitoes in September 2015, larvae of S. aegypti mosquitoes were found in two different localities in Mexico City, which is located at about 2250 m a.s.l. Mexico City is the most populous city in Mexico and has inefficient drainage and water supply systems. These factors may result in the provision of numerous larval breeding sites. Mosquito monitoring and surveillance are now priorities for the city.

Despite vaccination programs, influenza still represents a significant disease burden in Mexico. We conducted an observational, retrospective analysis to better understand the epidemiological situation of the influenza virus in Mexico. Analysis of the seasonal patterns of influenza A and B were based on the Directorate General of Epidemiology dataset of influenza-like illness(ILI), and severe acute respiratory infection(SARI) that were recorded between January 2010 and December 2013. Our objectives were 1) to describe influenza A and B activity, by age group, and subtype and, 2) to analyze the number of laboratory-confirmed cases presenting with ILI by influenza type, the regional distribution of influenza, and its clinical features. Three periods of influenza activity were captured: August 2010-January 2011, December 2011-March 2012, and October 2012-March 2013. Cases were reported throughout Mexico, with 50.3% (n = 10,320) of cases found in 18-49 year olds. Over the entire capture period, a total of 76,085 ILI/SARI episodes had swab samples analyzed for influenza, 27% were positive. During the same period, influenza A cases were higher in the 18-49 years old, and influenza B cases in both 5-17 and 18-49 age groups. Peak activity occurred in January 2012 (n = 4,159) and December 2012 (n = 348) for influenza A and B respectively. This analysis confirms that influenza is an important respiratory pathogen for children and adults in Mexico despite vaccination recommendations. School-age children and adolescents were more prone to influenza B infection; while younger adults were susceptible to both influenza A and B viruses. Over the seasons, influenza A and B co-circulated.

In Mexico, Aedes aegypti (L.) (Diptera: Culicidae) is the primary vector of Dengue, Zika, and Chikungunya viruses. Control programs include community participation using personal protection such as household aerosol insecticides. In both, urban or rural areas, the use of aerosol insecticides is a common practice to avoiding mosquito biting. Thus, information on the efficacy of commercial products must be available. This study reports the efficacy of 13 household aerosol insecticides against Ae. aegypti from an endemic dengue area in Mexico. To test each insecticide, six netting cages, containing 10 non-blood fed female mosquitoes each one, were placed in different locations inside a bedroom. Readings at 30 min and 24 h after exposure were recorded. No products showed 100% mortality after 30 min of exposure. Only three products killed the 100% of the individuals 24 h after exposure. Results showed a high mortality variance among insecticides. Location in the room also impacts the insecticide efficacy. Mosquitoes located inside cabinets or with behind an obstacle (preventing an accurate insecticide exposure) showed lower mortalities. Products and spraying methods could and should be improved.

To assess the possible circulation of Zika virus (ZIKV) prior to the first documented case in Mexico, we reanalyzed the stored samples from the states of Veracruz and Yucatan, which were originally collected to test for dengue (DENV) and chikungunya (CHIKV) but were negative for these viruses despite the symptomatology. The samples were originally collected between the 30 and 46 epidemiological weeks (EW) when the ZIKV was not yet declared as a Public Health Emergency of International Concern (PHEIC). From the total 4016 negative samples, a total of one hundred samples, 50 from Veracruz (CHIK− DENV−) and 50 from Yucatan (4 CHIK− DENV− and 46 CHIK− or DENV−), were tested for Zika virus by using RT-PCR. Results showed that in Veracruz and Yucatan, 20 % (10/50) and 70 % (35/50) were, respectively, ZIKV positive, indicating unequivocally the presence of ZIKV at least since July 2015. We also tested non-confirmed suspect measles cases from early 2015 for ZIKV by RT-PCR. Remarkably in 11 Mexican states, 86 % (18/21) were positive with the earlier symptoms onset as early as May 2015. Finally, RT-PCR analyses on RNA extracted from Aedes aegypti mosquitoes captured from January to March 2015 showed the presence of ZIKV, strongly suggesting that the vector was already carrying the virus at the start of 2015.

Background We report on the results of an entomovirological surveillance system of Aedes populations performed by the Ministry of Health of the central state of San Luis Potosi, Mexico. Methods Indoor adult Aedes aegypti and Aedes albopictus pools collected at San Martin, Tamazunchale, Ciudad Valles, Metlapa, Ebano, Tamuin and Axtla during the dry season of 2016 were examined for the presence of dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses using real-time PCR. Results Both Ae. aegypti and Ae. albopictus were found to be infected with ZIKV in the absence of confirmed symptomatic human cases. Conclusions The entomovirological surveillance system analysed here identified both Ae. aegypti and Ae. albopictus infected with ZIKV which triggered an immediate aggressive vector control campaign.

19 p., Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. Materials and methods We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. Results Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. Conclusions Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.

Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor.From 1998 through 2004, we recruited approximately 50,000 men and 100,000 women 35 years of age or older into a prospective study in Mexico City, Mexico. We recorded the presence or absence of previously diagnosed diabetes, obtained and stored blood samples, and tracked 12-year disease-specific deaths through January 1, 2014. We accepted diabetes as the underlying cause of death only for deaths that were due to acute diabetic crises. We estimated rate ratios for death among participants who had diabetes at recruitment versus those who did not have diabetes at recruitment; data from participants who had chronic diseases other than diabetes were excluded from the main analysis.At the time of recruitment, obesity was common and the prevalence of diabetes rose steeply with age (3% at 35 to 39 years of age and20% by 60 years of age). Participants who had diabetes had poor glycemic control (mean [±SD] glycated hemoglobin level, 9.0±2.4%), and the rates of use of other vasoprotective medications were low (e.g., 30% of participants with diabetes were receiving antihypertensive medication at recruitment and 1% were receiving lipid-lowering medication). Previously diagnosed diabetes was associated with rate ratios for death from any cause of 5.4 (95% confidence interval [CI], 5.0 to 6.0) at 35 to 59 years of age, 3.1 (95% CI, 2.9 to 3.3) at 60 to 74 years of age, and 1.9 (95% CI, 1.8 to 2.1) at 75 to 84 years of age. Between 35 and 74 years of age, the excess mortality associated with previously diagnosed diabetes accounted for one third of all deaths; the largest absolute excess risks of death were from renal disease (rate ratio, 20.1; 95% CI, 17.2 to 23.4), cardiac disease (rate ratio, 3.7; 95% CI, 3.2 to 4.2), infection (rate ratio, 4.7; 95% CI, 4.0 to 5.5), acute diabetic crises (8% of all deaths among participants who had previously diagnosed diabetes), and other vascular disease (mainly stroke). Little association was observed between diabetes and mortality from cirrhosis, cancer, or chronic obstructive pulmonary disease.In this study in Mexico, a middle-income country with high levels of obesity, diabetes was common, glycemic control was poor, and diabetes was associated with a far worse prognosis than that seen in high-income countries; it accounted for at least one third of all deaths between 35 and 74 years of age. (Funded by the Wellcome Trust and others.).

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.

Supplemental Digital Content is available in the text., Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111 911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35 to 89 years, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic and diastolic blood pressure of 2 markers of general adiposity (body mass index and height-adjusted weight) and 4 markers of central adiposity (waist circumference, hip circumference, waist:hip ratio, and waist:height ratio), adjusted for relevant confounders. Mean (SD) adiposity levels were: body mass index (28.7±4.5 kg/m2), height-adjusted weight (70.2±11.2 kg), waist circumference (93.3±10.6 cm), hip circumference (104.0±9.0 cm), waist:hip ratio (0.90±0.06), and waist:height ratio (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 SD higher measured adiposity marker was associated with a 3 mm Hg higher systolic blood pressure and 2 mm Hg higher diastolic blood pressure (SEs

To the Editor: Zika virus is an emerging arbovirus spread by Aedes aegypti mosquitoes and belongs to the genus Flavivirus of the Spondweni serocomplex (1,2). Most often, signs and symptoms of infection are maculopapular rash, fever, arthralgia, myalgia, headache, and conjunctivitis; edema, sore throat, cough, and vomiting occur less frequently. Zika virus is an RNA virus containing 10,794 nt, and diagnostic tests include PCRs on acute-phase serum samples to detect viral RNA (1). The genome contains 5′ and 3′ untranslated regions flanking a single open reading frame (ORF) that encodes a polyprotein that is cleaved into the structural proteins capsid (C), premembrane/membrane (prM), and envelope (E), and 8 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B, and NS5) (3). Genetic studies in which nucleotide sequences derived from the NS5 gene were used indicated 3 Zika virus lineages: East African, West African, and Asian (4,5). In Brazil, the first identified cases of dengue-like syndrome with subsequent Zika virus confirmation were documented in the early months of 2015 in the state of Rio Grande do Norte (6). Later that year, autochthonous transmission was reported in Colombia and Suriname during October–November (5) and Puerto Rico in December (6,7). During the same period, imported cases in the United States and Mexico were reported (6). By December 2015, we had already identified at least 15 autochthonous and 1 imported Zika cases in Mexico, initially detected by real-time reverse transcription PCR (RT-PCR). Here, we report on the documentation of a case of Zika virus infection in a male traveler returning to Mexico from Colombia in October 2015. On October 21, 2015, we identified an imported case of Zika virus infection in the central state of Queretaro, Mexico. The patient, a 26-year-old man, had visited Santa Martha, Colombia, during the previous 12 days. Symptoms including fever, muscle pain, mild to moderate arthralgia, arthritis, back pain, chills, and conjunctivitis began on October 19, two days after his return to Mexico. A sample was collected at a primary healthcare clinic. Initial molecular testing for dengue virus at the Queretaro Public Health Laboratory was negative; to test for Zika virus, the sample was sent to the National Reference Laboratory (InDRE), where viral RNA was extracted from it by using the QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany). We used real-time RT-PCR for diagnosis, using the Superscript III system (Invitrogen, Carlsbad, CA, USA) and primers and probes previously reported (8). Using Zika virus nucleotide sequence data in the Primer3Plus web interface (8), we amplified a 760-bp fragment with the following primers for partial characterization of viral NS5 coding gene: ZikV9113Fwd TTYGAAGCCCTTGGATTCTT and ZikV9872Rev CYCGGCCAATCAGTTCATC. We used the QIAGEN One-Step RT-PCR Kit as follows: reverse transcription at 50°C for 30 min, followed by an activation step at 95°C for 15 min and 35 cycles of 94°C for 30 sec, 55°C for 30 sec, and 72°C for 1 min, and a final extension step at 72°C for 10 min. We sequenced amplicons in the ABI PRISM 3130xl Genetic Analyzer instrument using the BigDye Terminator v3.1 Cycle Sequencing kit (Applied Biosystems, Foster City, CA). The partial sequence of the identified strain ((MEX/InDRE/14/2015) was deposited in GenBank under accession no. {"type":"entrez-nucleotide","attrs":{"text":"KU556802","term_id":"984943318","term_text":"KU556802"}}KU556802. We performed phylogenetic analysis to compare the extracted sequences with a database of 39 available nucleotide sequences from GenBank (Figure). Sequences from NS5 data were aligned, the dataset was adjusted to a common size of 531 pb, and a phylogenetic tree was constructed in MEGA6 (http://www.megasoftware.net) from aligned nucleotide sequences. The maximum-likelihood statistical algorithm and the Tamura-Nei substitution model with 1,000 replicates for bootstrap were used. Phylogenetic analyses showed that the partially sequenced strain MEX/InDRE/14/2015 belongs to the Zika virus Asian lineage and is closely related to those reported from Brazil and Suriname in 2015 (Figure). The phylogeny does show some genetic distance with respect to strains causing outbreaks in 2014 in the Americas, suggesting acquired genetic changes probably caused by adaptations during the spread of the virus, similar to those observed for chikungunya virus (9). Figure Phylogenetic analysis of nonsegmented protein 5 partial sequences of Zika virus isolated from a traveler returning from Colombia to Mexico (MEX/InDRE/14/2015; black dot), October 2015, showing close relationship Zika virus strains reported from Brazil ... We conducted a nonsynonymous mutation analysis using the NS5 protein from the Zika virus isolated in French Polynesia in 2013 (903 aa; GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"KJ776791.1","term_id":"631250742","term_text":"KJ776791.1"}}KJ776791.1) as a reference. The strain MEX/InDRE/14/2015bears the mutation markers K546R, K642R, and E561K, which cause the differentiation of the Asian lineage from the clades representing the African lineage (Figure). In addition, we observed that markers A527I, G588K, K531R, R648N, and S704D were acquired during the virus dispersion from Southeast Asia to the Pacific region and the Americas. In summary, we identified Zika virus in a traveler who returned from Colombia to Mexico in October 2015. A partial sequence of the NS5 gene showed that the isolate from this patient was closely related to those described elsewhere in the Western Hemisphere belonging to the Asian lineage, particularly to 2 strains identified in Brazil and Suriname during 2015.

We identified 25 autochthonous chikungunya virus cases in Mexico, initially detected by RT-PCR targeting the E1 gene and propagated in C6/36 Aedes albopictus cells, in 2014. To determine the type of virus found, in a previous report, the genomes of 2 CHIKV strains were fully sequenced. Genome sequence analysis revealed that these isolates from Mexico belonged to the Asian genotype, and a phylogenetic association with the circulating strain in the British Virgin Islands was also established in the same year. This was further supported by changes in specific amino acids, E2-V368A and 6K-L20M. For these reasons, it can be inferred that the route of virus entry to Mexico was held across the countries in the Caribbean and Central America. The presence of E1-A226V mutation associated with more efficient replication in the salivary gland of the A. albopictus mosquito was not observed. Interestingly, a newly acquired NSP4-S399C mutation was observed; however, the significance of changes in amino acid found in non-structural proteins in autochthonous strains remains to be elucidated.

Background This article analyses the epidemiological research developments in Latin America and the Caribbean (LAC). It integrates the series commissioned by the International Epidemiological Association to all WHO Regions to identify global opportunities to promote the development of epidemiology. Methods Health situations of the regions were analysed based on published data on selected mortality, morbidity and risk factors. Epidemiological publication output by country was estimated by Medline bibliometrics. Internet and literature searches and data provided by key informants were used to describe perspectives on epidemiological training, research and funding. Findings Despite important advances in recent decades, LAC remains the world's most unequal region. In 2010, 10% of the LAC's people still lived in conditions of multidimensional poverty, with huge variation among countries. The region has experienced fast and complex epidemiological changes in past decades, combining increasing rates of non-communicable diseases and injuries, and keeping uncontrolled many existing endemic and emerging diseases. Overall, epidemiological publications per year increased from 160 articles between 1961 and 1970 to 2492 between 2001 and 2010. The increase in papers per million inhabitants in the past three decades varied from 57% in Panama to 1339% in Paraguay. Universities are the main epidemiological training providers. There are at least 34 universities and other institutions in the region that offer postgraduate programmes at the master’s and doctoral levels in epidemiology or public health. Most LAC countries rely largely on external funding and donors to initiate and sustain long-term research efforts. Despite the limited resources, the critical mass of LAC researchers has produced significant scientific contributions. Future needs The health research panorama of the region shows enormous regional discrepancies, but great prospects. Improving research and human resources capacity in the region will require establishing research partnerships within and outside the region, between rich and poor countries, promoting collaborations between LAC research institutions and universities to boost postgraduate programmes and aligning research investments and outputs with the current burden of disease.

Background While most of the global burden from chronic diseases, and especially vascular diseases, is now borne by low and middle-income countries, few large-scale epidemiological studies of chronic diseases in such countries have been performed. Methods From 1998–2004, 52 584 men and 106 962 women aged ≥35 years were visited in their homes in Mexico City. Self reported diagnoses of chronic diseases and major disease risk factors were ascertained and physical measurements taken. Age- and sex-specific prevalences and means were analysed. Results After about age 50 years, diabetes was extremely common – for example, 23.8% of men and 26.9% of women aged 65–74 reported a diagnosis. By comparison, ischaemic heart disease was reported by 4.8% of men and 3.0% of women aged 65–74, a history of stroke by 2.8% and 2.3%, respectively, and a history of cancer by 1.3% and 2.1%. Cancer history was generally more common among women than men – the excess being largest in middle-age, due to breast and cervical cancer. At older ages, the gap narrowed because of an increasing prevalence of prostate cancer. 51% of men and 25% of women aged 35–54 smoked cigarettes, while 29% of men and 41% of women aged 35–54 were obese (i.e. BMI ≥30 kg/m2). The prevalence of treated hypertension or measured blood pressure ≥140/90 mmHg increased about 50% more steeply with age among women than men, to 66% of women and 58% of men aged 65–74. Physical inactivity was highly prevalent but daily alcohol drinking was relatively uncommon. Conclusion Diabetes, obesity and tobacco smoking are highly prevalent among adults living in Mexico City. Long-term follow-up of this and other cohorts will establish the relevance of such factors to the major causes of death and disability in Mexico.

Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns. Electronic supplementary material The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.