SARS-CoV-2 infection fatality rate after the first epidemic wave in Mexico.

BACKGROUND: Estimates of SARS-CoV-2 infection fatality rates (IFRs) in developing countries remain poorly characterized. Mexico has one of the highest reported COVID-19 case-fatality rates worldwide, although available estimates do not consider serologic assessment of prior exposure nor all SARS-CoV-2-related deaths. We aimed to estimate sex- and age-specific IFRs for SARS-CoV-2 in Mexico. METHODS: The total number of people in Mexico with evidence of prior SARS-CoV-2 infection was derived from National Survey of Health and Nutrition-COVID-19 (ENSANUT 2020 Covid-19)-a nationally representative serosurvey conducted from August to November 2020. COVID-19 mortality data matched to ENSANUT's dates were retrieved from the death-certificate registry, which captures the majority of COVID-19 deaths in Mexico, and from the national surveillance system, which covers the subset of COVID-19 deaths that were identified by the health system and were confirmed through a positive polymerase chain reaction test. We analysed differences in IFRs by urbanization and region. RESULTS: The national SARS-CoV-2 IFR was 0.47% (95% CI 0.44, 0.50) using death certificates and 0.30% (95% CI 0.28, 0.33) using surveillance-based deaths. The IFR increased with age, being close to zero at age <30 years, but increasing to 1% at ages 50-59 years in men and 60-69 years in women, and being the highest at ≥80 years for men (5.88%) and women (6.23%). Across Mexico's nine regions, Mexico City (0.99%) had the highest and the Peninsula (0.26%) the lowest certificate-based IFRs. Metropolitan areas had higher certificate-based IFR (0.63%) than rural areas (0.17%). CONCLUSION: After the first wave of the COVID-19 pandemic, the overall IFR in Mexico was comparable with those of European countries. The IFR in Mexico increased with age and was higher in men than in women. The variations in IFRs across regions and places of residence within the country suggest that structural factors related to population characteristics, pandemic containment and healthcare capabilities could have influenced lethality at the local level.

Ookinete-Specific Genes and 18S SSU rRNA Evidenced in Plasmodium vivax Selection and Adaptation by Sympatric Vectors.

In the southern Pacific coast of Chiapas, Mexico (SM), the two most abundant vector species, Nyssorhynchus albimanus and Anopheles pseudopunctipennis, were susceptible to different Plasmodium vivax Pvs25/28 haplotypes. To broaden our understanding of the existing P. vivax in the area, genes encoding proteins relevant for ookinete development and the 18S rRNA were studied. P. vivax infectivity (percentage of infected mosquitoes and oocyst numbers) was evaluated by simultaneously feeding infected blood samples from patients to Ny. albimanus and An. pseudopunctipennis female mosquitoes. Three infectivity patterns were identified: one group of parasites were more infective to An. pseudopunctipennis than to Ny. albimanus, another group was more infective to Ny. albimanus, while a third group infected both vectors similarly. In 29 parasite isolates, the molecular variations of ookinete-specific genes and the 18S rRNA-type S were analyzed. Using concatenated sequences, phylogenetic trees, and Structure analysis, parasite clustering within SM isolates and between these and those from other geographical origins were investigated. A ML phylogenetic tree resolved two parasite lineages: PvSM-A and PvSM-B. They were associated to a different 18S rRNA variant. PvSM-A parasites had 18S rRNA variant rV2 and correspond to parasites causing high oocyst infection in Ny. albimanus. A new ML tree and Structure analysis, both comprising global sequences, showed PvSM-A clustered with Latin American parasites. Meanwhile, all isolates of PvSM-B had 18S rRNA variant rV1 and remained as unique genetic cluster comprising two subgroups: PvSM-Ba, producing high infection in An. pseudopunctipennis, and PvSM-Bb, causing similar oocyst infection in both vector species. PvSM-A parasites were genetically similar to parasites from South America. Meanwhile, PvSM-B were exclusive to southern Mexico and share ancestry with Asian parasites. The results suggest that these lineages evolved separately, likely by geographic and vector restriction.

Plasmodium vivax CSP-Pvs25 variants from southern Mexico produce distinct patterns of infectivity for Anopheles albimanus versus An. pseudopunctipennis, in each case independent of geographical origin.

BACKGROUND: The susceptibility of Anopheles albimanus and An. pseudopunctipennis to local Plasmodium vivax has been associated in southern Mexico with two ookinete surface proteins (Pvs25/28) polymorphism. Perhaps parasite population selection (i.e. adaptation to local vectors) contributes to this phenomenon. It is also possible that certain molecular interactions exist between P. vivax and each mosquito species independently of geographical origin. This study aimed to explore the susceptibility of An. albimanus and An. pseudopunctipennis (collected from different geographical sites) to P. vivax cspVk/Pvs25-130 haplotypes from southern Mexico. RESULTS: Of the 120 P. vivax-infected blood samples used to simultaneously feed An. albimanus and An. pseudopunctipennis mosquitoes originating from various geographical sites, 80 produced at least one infected mosquito species. Three parasite haplotypes were identified in infected blood: Vk210/Pvs25-A (12.5%), Vk210/Pvs25-B (20%) and Vk247/Pvs25-B (67.5%). Two parameters (the proportion of infected mosquitoes and number of oocysts/mosquito) showed a similar pattern for each mosquito species (independently of geographical origin). For An. albimanus mosquitoes (from the Pacific coast, Mexican gulf and Lacandon Forest lowlands), these two parameters were higher in specimens infected with P. vivax Vk210/Pvs25-A versus Vk210/Pvs25-B or Vk247/Pvs25-B (P < 0.001). For An. pseudopunctipennis mosquitoes (from the Pacific coast, northeast Mexico and east Guatemala foothills), the same two parameters were higher in specimens infected with Vk247/Pvs25-B or Vk210/Pvs25-B versus Vk210/Pvs25-A (P < 0.001). Higher infection rates were caused by Vk247/Pvs25-B than Vk210/Pvs25-B parasites in An. pseudopunctipennis (P = 0.011) and An. albimanus (P = 0.001). The greatest parasitaemia, gametocytaemia and microgamete formation was observed in Vk247/Pvs25-B infected blood, and each of these parameters correlated with each other and with the number of oocysts in An. pseudopunctipennis from the sympatric colony. CONCLUSIONS: Plasmodium vivax Vk247/Pvs25-B infections were the most prevalent, likely due to the higher parasitaemia produced in the susceptible vector (especially An. pseudopunctipennis). The analysis of mosquito-parasite interactions indicate that An. pseudopunctipennis and An. albimanus each have a unique pattern of transmitting genetic variants of P. vivax, and this is not dependent on geographical origin. The present findings highlight the importance of parasite genotyping to understand transmission dynamics and vectorial participation.

Implementation and Operational Research: Effect of Universal Access to Antiretroviral Therapy on HIV/AIDS Mortality in Mexico 1990-2011.

INTRODUCTION: Universal coverage of highly active antiretroviral therapy (HAART) for HIV/AIDS in Mexico was achieved in a staggered fashion. First, HAART was made available in 1997 for employees in the formal sector and subsequently, in 2003, for informal sector workers and the unemployed population. We evaluated the impact of this free universal HAART program on HIV/AIDS mortality in the Mexican population aged 15 years or older. METHODS: Time-series cross-sectional data analysis of standardized HIV/AIDS mortality rates (1990-2011) using marginal linear models with inflection points at 1994, 1997, and 2003. RESULTS: Men employed in the formal sector experienced the greatest effect of access to HAART, with a 32% reduction in mortality from 1997 to 2011 (P < 0.01). For men in this sector, mortality increased from 1990 to 2003, then stabilizing at 7 deaths per 100,000. For women in the informal sector, mortality increased from 1990 to 2011. We found large between-state variability: mortality decreased by 59% in Mexico City while it increased by 245% in Tabasco during the study period. Six of 32 states achieved statistically significant reductions in mortality while 5 states continued to experience increasing mortality rates despite universal HAART. CONCLUSIONS: Access to universal HAART has had relative success in Mexico. The heterogeneity of HIV/AIDS mortality by employment status, gender, and state of residence highlight urgent needs to improve health equity with pro-poor and gender-responsive programs and a call for country-specific operational research in HIV/AIDS prevention and treatment. Our results may apply to other countries seeking to implement universal access to antiretroviral therapy.

Bacteria in midguts of field-collected Anopheles albimanus block Plasmodium vivax sporogonic development.

Bacterial infections were investigated in midguts of insectary and field-collected Anopheles albimanus Weidemann from southern Mexico. Serratia marcescens, Enterobacter cloacae and Enterobacter amnigenus 2, Enterobacter sp., and Serratia sp. were isolated in field samples obtained in 1998, but only Enterobacter sp. was recovered in field samples of 1997 and no bacteria were isolated from insectary specimens. These bacteria were offered along with Plasmodium vivax infected blood to aseptic insectary An. albimanus, and the number of infected mosquitoes as well as the oocyst densities assessed after 7d. Plasmodium vivax infections in mosquitoes co-infected with En. amnigenus 2, En. cloacae, and S. marcensces were 53, 17, and 210 times, respectively, lower than in control mosquitoes, and the mean oocyst density in mosquitoes co-infected with En. cloacae was 2.5 times lower than in controls. Mortality was 13 times higher in S. marcensces-infected mosquitoes compared with controls. The overall midgut bacterial infection in mosquito field populations may influence P. vivax transmission, and could contribute to explain the annual variations in malaria incidence observed in the area.

[Geographical coverage of the Mexican Healthcare System and a spatial analysis of utilization of its General Hospitals in 1998]. / Cobertura geográfica del sistema mexicano de salud y análisis espacial de la utilización de hospitales generales de la Secretaría de Salud en 1998.

OBJECTIVE: To describe the geographical coverage of the Mexican Healthcare System (MHS) services and to assess the utilization of its General Hospitals. MATERIAL AND METHODS: A Geographic Information System (GIS) was used to include sociodemographic data by locality, the geographical location of all MHS healthcare services, and data on hospital discharge records. A maximum likelihood estimation model was developed to assess the utilization levels of 217 MHS General Hospitals. The model included data on human resources, additional infrastructure, and the population within a 25 km radius. RESULTS: In 1998, 10,806 localities with 72 million inhabitants had at least one public healthcare unit, and 97.2% of the population lived within 50 km of a healthcare unit; however, over 18 million people lived in rural localities without a healthcare unit. The mean annual hospital occupation rate was 48.5 +/- 28.5 per 100 bed/years, with high variability within and between states. Hospital occupation was significantly associated with the number of physicians in the unit, and in the Mexican Institute of Social Security units utilization was associated with additional health infrastructure, and with the population's poverty index. CONCLUSIONS: GIS analysis allows improved estimation of the coverage and utilization of MHS hospitals.

Sequence variation of ookinete surface proteins Pvs25 and Pvs28 of Plasmodium vivax isolates from Southern Mexico and their association to local anophelines infectivity.

The polymorphism of Pvs25 and Pvs28 ookinete surface proteins, their association to circumsporozoite protein repeat (CSPr) genotypes (Vk210 and Vk247) and their infectivity to local Anopheles albimanus and Anopheles pseudopunctipennis were investigated in Plasmodium vivax-infected blood samples obtained from patients in Southern Mexico. The pvs25 and pvs28 complete genes were amplified, cloned and sequenced; and the CSPr genotype was determined by PCR amplification and hybridization. The amino acid Pvs25 and Pvs28 polymorphisms were mapped to their corresponding protein structure. Infected blood samples were simultaneously provided through artificial feeders to both mosquito species; the ratio of infected mosquitoes and oocyst numbers were recorded. The polymorphism of pvs25 and pvs28 was limited to few nucleotide positions, and produced three haplotypes: type A/A parasites presented Pvs25 and Pvs28 amino acid sequences identical to that of Sal I reference strain; parasites type B1 presented a mutation 130 Ile-->Thr in Pvs25, while type B2 presented 87 Gln-->Lys/130 Ile-->Thr in the same molecule. Both types B1 and B2 parasites presented changes in Pvs28 at 87 Asn-->Asp, 110 Tyr-->Asn and five GSGGE/D repeat sequences between the fourth EGF-like domain and the GPI. Most P. vivaxparasites from the coastal plains and the overlapping region were Pvs25/28 A/A, CSPrVk210 and were infective only to An. albimanus (p< or =0.0001). Parasites originating in foothills were Pvs25/28 type B1/B or B2/B and CSPrVk210 or Vk247, and were more infective to An. pseudopunctipennis than to An. albimanus (p< or =0.001). These results and the analysis of Pvs25/28 from other parts of the world indicated that non-synonymous variations in these proteins occur in amino acid residues exposed on the surface of the proteins, and are likely to interact with midgut mosquito ligands. We hypothesize that these molecules have been shaped by co-evolutionary adaptations of parasites to their susceptible vectors.

The participation of secondary clinical episodes in the epidemiology of vivax malaria during pre- and post-implementation of focal control in the state of Oaxaca, Mexico.

The participation of vivax malaria secondary clinical was researched in a retrospective cohort of 33,414 confirmed cases occurring between 1994 and 2005 in the state of Oaxaca, Mexico. Secondary episodes occurred in 23.4% of all primary cases. An increase in secondary episodes was associated with primary cases occurring during the dry seasons (risk ratio [RR] = 1.68, 95% CI: 1.45-1.96). The incidence of secondary episodes peaked at an older age, occurred similarly in men and women mostly during low mosquito abundance, and had a uniform distribution among localities. A reduction in secondary episodes was associated with the administration of an increased dose and early administration of primaquine (RR = 0.32, 95% CI: 0.26-0.38). However, limitations to distinguish relapses from re-infections impede assessment of the new treatment effect on relapses and its contribution to malaria control in the area. These findings highlight the need for new therapeutic schemes to radical cure of P. vivax infections and operational research aimed at parasite pool elimination.

Plasmodium vivax: impaired escape of Vk210 phenotype ookinetes from the midgut blood bolus of Anopheles pseudopunctipennis.

The site in the midguts of Anopheles pseudopunctipennis where the development of Plasmodium vivax circumsporozoite protein Vk210 phenotype is blocked was investigated, and compared to its development in An. albimanus. Ookinete development was similar in time and numbers within the blood meal bolus of both mosquito species. But, compared to An. pseudopunctipennis, a higher proportion of An. albimanus were infected (P=0.0001) with higher ookinete (P=0.0001) and oocyst numbers (P=0.0001) on their internal and external midgut surfaces, respectively. Ookinetes were located in the peritrophic matrix (PM), but neither inside epithelial cells nor on the haemocoelic midgut surface by transmission electron microscopy in 24h p.i.-An. pseudopunctipennis mosquito samples. In contrast, no parasites were detected in the PM of An. albimanus at this time point. These results suggest that P. vivax Vk210 ookinetes cannot escape from and are destroyed within the midgut lumen of An. pseudopunctipennis.

Determinant factors for malaria transmission on the coast of Oaxaca State, the main residual transmission focus in Mexico.

OBJECTIVE: The purpose of this study was to investigate the influence of demographic, socioeconomic and ecological factors in malaria transmission in the most important residual transmission focus in Mexico, located in the state of Oaxaca. MATERIAL AND METHODS: The extension of the focus was determined by a spatial and time analysis of the distribution of malaria cases in the state between 1998 and 1999 using a Geographical Information System. A malaria transmission intensity index (MTII) was constructed based on the total number of cases during the study period and the duration and frequency of transmission outbreaks within the villages. The relationship between local determinants and malaria transmission intensity was investigated using multinomial and ordered logistic models. RESULTS: The distribution of villages according to their MTII was: 325 high, 341 medium, 142 low and 717 with no transmission. Localities of high MTII were associated with areas having a tropical climate with summer rains and low water evaporation. Most high MTII villages were located in elevations between 200 and 500 m above sea level, in the area around Pochutla City. The amount of temporary streams in the neighborhood of localities had a highly significant positive association with the MTII. Distance to roads was only significant in the high malaria MTII stratum. CONCLUSIONS: The main factors determining malaria transmission in the focus are related to good conditions for the breeding of mosquito vectors. The existence of short-range population movements around Pochutla, the main economically active city in the area, indicates the necessity to implement a system of epidemiological surveillance to halt the dispersion of new outbreaks.

Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial.

BACKGROUND: Pregnancy and breastfeeding mobilize lead stored in bone, which may be a hazard for the fetus and infant. We tested the hypothesis that in lactating women a dietary calcium supplement will lower blood lead levels. METHODS: Between 1994 and 1995 we conducted a randomized trial among women in Mexico City. Lactating women (N = 617; mean age = 24 years; mean blood lead level = 8.5 ug/dL) were randomly assigned to receive either calcium carbonate (1200 mg of elemental calcium daily) or placebo in a double-blind trial. Blood samples were obtained at baseline, and 3 and 6 months after the trial began. Blood lead was determined by graphite furnace atomic absorption spectroscopy. Bone lead was measured at baseline with a 109cd K x-ray fluorescence instrument. The primary endpoint was change in maternal blood lead level, which was analyzed in relation to supplement use and other covariates by multivariate generalized linear models for longitudinal observations. RESULTS: An intention-to-treat analysis showed that women randomized to the calcium supplements experienced a small decline in blood lead levels (overall reduction of 0.29 ug/dL; 95% confidence interval = -0.85 to 0.26). The effect was more apparent among women who were compliant with supplement use and had high bone lead levels (patella bone lead > or =5 microg/gm bone). Among this subgroup, supplement use was associated with an estimated reduction in mean blood lead of 1.16 ug/dL (95% confidence interval = -2.08 to -0.23), an overall reduction of 16.4%. CONCLUSIONS: Among lactating women with relatively high lead burden, calcium supplementation was associated with a modest reduction in blood lead levels.

Determinant factors for malaria transmission on the coast of Oaxaca State, the main residual transmission focus in Mexico / Factores determinantes de la transmisión de paludismo en la costa del estado de Oaxaca, el principal foco residual de transmisión en México

OBJECTIVE: The purpose of this study was to investigate the influence of demographic, socioeconomic and ecological factors in malaria transmission in the most important residual transmission focus in Mexico, located in the state of Oaxaca. MATERIAL AND METHODS: The extension of the focus was determined by a spatial and time analysis of the distribution of malaria cases in the state between 1998 and 1999 using a Geographical Information System. A malaria transmission intensity index (MTII) was constructed based on the total number of cases during the study period and the duration and frequency of transmission outbreaks within the villages. The relationship between local determinants and malaria transmission intensity was investigated using multinomial and ordered logistic models. RESULTS: The distribution of villages according to their MTII was: 325 high, 341 medium, 142 low and 717 with no transmission. Localities of high MTII were associated with areas having a tropical climate with summer rains and low water evaporation. Most high MTII villages were located in elevations between 200 and 500 m above sea level, in the area around Pochutla City. The amount of temporary streams in the neighborhood of localities had a highly significant positive association with the MTII. Distance to roads was only significant in the high malaria MTII stratum. CONCLUSIONS: The main factors determining malaria transmission in the focus are related to good conditions for the breeding of mosquito vectors. The existence of short-range population movements around Pochutla, the main economically active city in the area, indicates the necessity to implement a system of epidemiological surveillance to halt the dispersion of new outbreaks.

OBJETIVO: Investigar la participación de factores demográficos, socio-económicos y ecológicos en la transmisión de la malaria en el foco de transmisión residual más importante en México, localizado en el estado de Oaxaca. MATERIAL Y MÉTODOS: La extensión del foco se determinó por medio de un análisis espacio-temporal de la distribución de casos de malaria en el estado entre 1998 y 1999, usando un Sistema de Información Geográfico. Un índice de intensidad de transmisión de malaria (MTII, por sus siglas en inglés) se construyó basado en el número total de casos durante el periodo del estudio y la duración y frecuencia de brotes de transmisión dentro de las localidades. La relación de determinantes locales con el MTII se investigó por medio de modelos multinomiales logísticos. RESULTADOS: La distribución de localidades según su MTII fue de 325 alto, 341 medio, 142 bajo y 717 sin transmisión. Localidades con MTII alto estuvieron asociadas a las áreas de clima tropical con lluvias en verano y evaporación baja. La mayoría de las localidades con MTII alto se localizaron a elevaciones entre 200 y 500 msnm, en el área alrededor de la ciudad de Pochutla. La cantidad de arroyos temporales en la vecindad de localidades tuvo una asociación positiva significativa con el MTII. La cercanía a carreteras de localidades con MTII alto fue significativa. CONCLUSIONES: Los factores principales que determinan la transmisión de la malaria en el foco están relacionados con las condiciones favorables para la cría de mosquitos vectores. La participación de movimientos de población de rango cortos alrededor de Pochutla, la principal ciudad económicamente activa en el área, indica la necesidad de implementar un sistema de vigilancia epidemiológica para detener la dispersión de nuevos brotes.

Cobertura geográfica del sistema mexicano de salud y análisis espacial de la utilización de hospitales generales de la Secretaría de Salud en 1998 / Geographical coverage of the Mexican Healthcare System and a spatial analysis of utilization of its General Hospitals in 1998

Objetivo. Determinar la cobertura geográfica del Sistema Mexicano de Salud y analizar la utilización en 1998 de los hospitales de la Secretaría de Salud (SSA). Material y métodos. Se desarrolló un Sistema de Información Geográfica (SIG) con información sociodemográfica por localidad y ubicación espacial de unidades de atención de todo el sector salud, así como el registro de egresos por hospital de la SSA. Se determinó la utilización en 217 hospitales generales de la SSA mediante un modelo de estimación de máxima verosimilitud, que incluyó información sobre los recursos humanos, la infraestructura adicional y la población 25 km a la redonda. Resultados. En 1998, 10 806 localidades con 72 millones de habitantes contaban con al menos una unidad de atención de salud del sector público y 97.2 por ciento de la población se encontraba a menos de 50 km de una, pero más de 18 millones de personas vivían en localidades rurales sin unidades de atención. El promedio de ocupación fue de 48.5±28.5 por cada 100 camas/año, con gran variabilidad intra e interestatal. La utilización se asoció significativamente con el número de los médicos en la unidad, y en unidades del Instituto Mexicano del Seguro Social con la infraestructura adicional e índice de marginación. Conclusiones. La utilización del SIG eleva la capacidad analítica y proporciona estimadores más realistas de la cobertura y utilización de hospitales del sector