Oxytocin, a main breastfeeding hormone, prevents hypertension acquired in utero: A therapeutics preview.

Hypertension is a major risk factor for ischemic heart disease and stroke, leading causes of morbidity and death worldwide. Intrauterine growth restriction (IUGR), caused by an excess of glucocorticoid exposure to the fetus, produces an imbalance in oxidative stress altering many biochemical and epigenetic gene transcription processes exposing the fetus and neonate to the 'thrifty' phenotype and pervasive polymorphisms appearance damaging health, cognitive, and behavioral processes in later life. OT is a major regulator of oxidative stress radicals that plays a major role in neonatal maturation of the central nervous system and many peripheral tissues expressing oxytocin/oxytocin-receptor (OT/OTR) system in the early postnatal period. OT and OTR are damaged by IUGR and early stress. This review highlights the fact that hypertension is likely to be a legacy of preterm birth due to IUGR and failure to meet nutritional needs in early infancy when fed formula instead of breastfeeding or human milk.

Genotypic testing for HIV-1 drug resistance using dried blood samples.

In third-world countries, dried blood samples (DBS) are a convenient alternative to plasma for monitoring viral load during HIV-1 therapy. In this study, we evaluated the feasibility of using DBS to perform HIV-1 drug resistance genotyping in a ViroSeq assay in which the protease and reverse transcriptase regions of the pol gene are analyzed. Fifty-seven antiretroviral genotypes from plasma samples were tested, and drug resistance genotypes were determined. Only 38.6% paired DBS samples were sequenced. Failure to amplify DNA from DBS samples generally correlated with plasma viral loads below log(10) 5.1. The majority of the mutations identified in plasma pol sequences were also found in their DBS counterpart, with a concordance in genotype interpretation of 96.4%. Several factors were identified that could potentially improve both the sensitivity and the quality of genotype data, such as sample storage conditions and sequence analysis. Therefore, DBS sampling is useful to determine viral load and drug resistance genotypes in HIV patients.

Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México.

BACKGROUND: In 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems. METHODS: From 2003 to 2006, four nation-wide cross-sectional probabilistic population based surveys were conducted using a four stage sampling design. Thirty thousand households were visited in each survey. The number of IMSS members interviewed ranged from 79,797 respondents in 2003 to 117,036 respondents in 2006. RESULTS: The four surveys showed a substantial increase in coverage indicators for each age group: children, completed schemes of vaccination (> 90%), iron supplementation (17.8% to 65.5%), newborn screening for metabolic disorders (60.3% to 81.6%). Adolescents, measles - rubella vaccine (52.4% to 71.4%), hepatitis vaccine (9.3% to 46.2%), use of condoms (17.9% to 59.9%). Women, measles-rubella vaccine (28.5% to 59-2%), cervical cancer screening (66.7% to 75%), breast cancer screening (> 2.1%). Men, type 2 diabetes screening (38.6% to 57.8%) hypertension screening (48-4% to 64.0%). Older adults, pneumococcal vaccine (13.2% to 24.9%), influenza vaccine (12.6% to 52.9) Regarding the unmet needs, the prevalence of anemia in children was 30% and a growing prevalence of overweight and obesity, type 2 diabetes, and hypertension was found in men, women and older adults. CONCLUSION: PREVENIMSS showed an important increase in the coverage of preventive services and stressed the magnitude of the old and new challenges that this healthcare system faces. The unsolved problems such as anemia, and the emerging ones such as overweight, obesity, among others, point out the need to strength preventive care through designing and implementing innovative programs aimed to attain effective coverage for those conditions in which prevention obtains substandard results.

Use of dried blood samples for monitoring hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) infection is a problem in several regions of the world with limited resources. Blood samples dried on filter paper (DBS) have been successfully used to diagnose and monitor several infectious diseases. In Mexico there is an urgent need for an affordable and easy sampling method for viral load (VL) testing and monitoring of chronic HBV infection. The purpose of this work was to validate the utility of DBS samples for monitoring HBV infection in patients from Mexico City. METHODS: Matched samples of plasma and DBS on filter paper from 47 HBV infected patients from the Instituto Mexicano del Seguro Social (IMSS), were included. To evaluate the DNA stability and purity from DBS stored at different temperature conditions, samples from ten patients were stored at 4 degree, 25 degree, and 37 degree C for 7 days. After DBS elution and DNA extraction, the purity of these samples was determined measuring the O.D. rate 260/280. The DBS utility for molecular studies was assessed with PCR assays to amplify a 322 bp fragment from the "a" determinant region of the HBV "S" gene. The VL from all samples was determined to evaluate the correlation between plasma and DBS matched samples. RESULTS: The quality of the DNA from DBS specimen is not adversely affected by storage at 4 degree, 25 degree and 37 degree C for up 7 days. Statistical ANOVA analyses did not show any significant difference. The same amplification efficiency was observed between DNA templates from samples stored at different temperatures. The Pearson correlation between the VL from DBS and plasma matched samples was 0.93 (p = 0.01). The SD was 1.48 for DBS vs.1.32 for Plasma, and an average of log10 copies/mL of 5.32 vs. 5.53. ANOVA analysis did not show any statistically significant difference between the analyzed groups (p = 0.92). CONCLUSION: The results provide strong evidence that the isolation and quantification of DNA-HBV from DBS is a viable alternative for patient monitoring, and molecular characterization of the virus variants circulating in Mexico.

Lewis antigen expression by Helicobacter pylori strains colonizing different regions of the stomach of individual patients.

The diversity in the expression of Lewis antigens (Le) of 226 single colonies of Helicobacter pylori isolated from four regions of the stomach of eight adults is shown. Le(y) was expressed more in strains colonizing antrum than in strains colonizing fundus, whereas Le(x) was more common in fundus strains. cagA(+) strains were more associated with Le-negative strains.

A primary Helicobacter pylori infection does not protect against reinfection in children after eradication therapy.

BACKGROUND: Helicobacter pylori infection is one of the most common chronic infections in the world, and is acquired mainly during childhood. It is not clear to which extent a primary infection protects the child from reinfection. Our aim was to determine the possible protection conferred by a primary infection against H. pylori reinfection in children. METHODS: A follow-up study with 120 children distributed in two cohorts; the first included 80 children without previous H. pylori infection (primo-infection cohort); the second included 40 infected children successfully eradicated (reinfection cohort). Cohorts were monitored during 2 years with urea-breath-test (UBT) at 3, 6, 9, 12, 18 and 24 months for the acquisition of H. pylori infection. We compared the rate of reinfection in eradicated children with the rate of infection in children without previous infection. H. pylori infection during the follow-up was analyzed and compared between cohorts using chi2 and survival curves. A questionnaire was performed for the evaluation of possible risk factors for infection in both cohorts. RESULTS: No significant differences in rates of primo-infection or reinfection were found; 17 (21.2%) primo-infections and 10 (25%) reinfections were documented. Most of the primo-infections (14/17) occurred in the first year of follow-up. In contrast, reinfection episodes occurred more frequently during the second year (6/10). In both cohorts, most infections were transient. Risk factors were similar for both, primo and reinfection cohorts. CONCLUSION: A primary infection does not protect from reinfection in the population of children studied.

Lyme Neuroborreliosis is a Severe and Frequent Neurological Disease in Mexico.

OBJECTIVE: To describe clinical cases with neurological manifestations associated with Borrelia burgdorferi infection in a large cohort of children and adults from Mexico. MATERIAL AND METHODS: Patients with neurological manifestation (cranial neuritis, radiculoneuritis, meningitis and encephalomyelitis) were recruited in one pediatric and two general hospitals, during January 2006-December 2015. Blood and cerebrospinal fluid (CSF) samples were drawn from each patient at inclusion. IgM and IgG antibodies against B. burgdorferi were detected using a commercial ELISA test, and confirmed by Western-Blot test (WB) using three different antigens from Borrelia burgdorferi complex. Following CDC criteria were considered true cases with both positive tests. RESULTS: Of 606 patients recruited, 403 (66.5%) were adults and 203 (33.4%) children, 50.5% were male. B. burgdorferi infection was diagnosed in 168 patients (27.7%), 97 adults, mean age 42 ± 14.7 years and 71 children, mean age 9.6 ± 5 years; early disseminated disease occurred in 130 cases (77.4 %) and chronic stage in 38 (22.6 %). A previous tick bite was reported by 21% cases, and 5% recalled an erythema migrans lesion. Polyradiculoneuropathy and encephalomyelitis were the most common manifestations, whereas 14.8% presented an initial Guillain-Barré Syndrome. B. burgdorferi sensu stricto was identified in 142 (84%) cases, B. garinii in 14 (8%), B. afzelii in three, and nine cases presented coinfection with two species. CONCLUSION: Lyme neuroborreliosis is a frequent condition in patients with neurological diseases in Mexico.

High correlation of human immunodeficiency virus type-1 viral load measured in dried-blood spot samples and in plasma under different storage conditions.

BACKGROUND: To measure HIV-1 RNA concentration requires venous extraction of blood, use of RNAase-free materials, and transport in a cold chain, which makes difficult the management of samples in developing countries. We evaluated the utility of the determination of HIV-1 RNA concentration in blood samples dried on filter paper (DBS) and subjected to different conditions, as contrasted with determination in plasma. METHODS: HIV-1 RNA concentration was determined in HIV-infected patients in DBS and in plasma samples. Samples were subjected to the following: DBS were stored at 4, 22, and 37 degrees C for 1, 3, and 7 days; samples from patients from four regions of Mexico were mailed to a reference laboratory; DBS were sent under environmental conditions; and plasma samples were sent frozen. HIV-1 RNA concentrations were determined by NucliSens in DBS and by Amplicor test in plasma. RESULTS: HIV-1 RNA concentration determined in DBS subjected to different temperatures and times had a significant correlation (r=0.99) with those obtained in plasma. When compared with values in plasma, Kappa agreement coefficients of values in DBS stored for 7 days at 4, 22, and 37 degrees C were 0.98, 0.83, and 0.94, respectively. Quantification of HIV-1 RNA in 108 DBS mailed from remote areas with different climates demonstrated significant correlation with those obtained in plasma (r=0.95; p <0.001). CONCLUSIONS: DBS is a simple and reliable method to measure HIV-1 RNA concentration, especially when samples are mailed from remote areas to a reference center. This collection method is an economic and suitable alternative for use in developing countries.

Active life expectancy of older people in Mexico.

BACKGROUND: Social and economic development together with demographic changes and health interventions have resulted in an increase in life expectancy and a rapidly ageing population in Mexico. Whether people will live longer active and independent lives is still, however, unknown. We will address this question, providing the first estimates of active life expectancy by age, sex and local regional area in Mexico. METHODS: Active life expectancy was calculated using the Sullivan method with abridged life tables. Information on the older Mexican population covered by the Mexican Institute of Social Security (IMSS) and the number of deaths for the same group in the year 2000 was obtained from the Office for Health Statistics and Information at IMSS in Mexico. Information on ability to perform basic activities of daily living was obtained from the National Survey on Ageing carried out in IMSS during 1998-99. RESULTS: For males and females combined, active life expectancy decreased from 26.9 years at 60 years to 5.7 years at 85 years. Women's life expectancy exceeded that of men but women lived more years dependent. Similarly, older people in geographical areas with longer life expectancy spent a lower proportion of remaining life active. CONCLUSION: The success in increasing life expectancy above average in some groups of older people covered by IMSS has been accompanied by increments in the proportion of remaining years dependent upon others for help in basic self-care activities.

Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients.

Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

Natural rotavirus infection is not associated to intussusception in Mexican children.

AIMS: To determine whether natural rotavirus infection or infection by another enteropathogen is associated to intussusception (IS); and to describe the seasonality of IS compared with severe diarrhea (SD) and rotavirus SD in Mexican children. METHODS: A prospective, observational, multicenter and case-control study was conducted in Mexico City from December 1999 to February 2001. Cases were children younger than 1 year old hospitalized for IS; diagnosis was made by clinical features, radiologic and/or surgery findings. Controls were children younger than 1 year old hospitalized for another disease than a gastrointestinal illness (NGI). Cases and controls were paired by age and date of admission (+/-3 months; for both), in a 1:2 ratio. A surveillance of IS cases, SD and rotavirus SD episodes was conducted during the study period. Stool samples collected soon after IS resolution or at admission were tested for rotavirus, adenovirus, astrovirus, bacteria and parasites. RESULTS: Thirty cases of IS and 60 controls with NGI were studied. Rotavirus was not detected in any case of IS. Adenovirus (17%) was the only enteropathogen detected in IS. Rotavirus (8%), adenovirus (2%), astrovirus (2%) and bacteria (2%) were detected in NGI. Rotavirus infection was not associated with IS (odds ratio, 0; 95% confidence interval, 0-2.9), whereas adenovirus infection was strongly associated as risk factor for IS (odds ratio undefined; P = 0.003), compared with NGI. Seasonal variation in admissions for IS was small, whereas admissions for SD and rotavirus SD showed a marked seasonal increase during fall-winter. CONCLUSIONS: In Mexican children, rotavirus infection was not associated to IS; whereas a significant association was observed between adenovirus and IS. Also there was no increase in IS cases during the sharply defined fall-winter rotavirus outbreak. Observations from this controlled study suggest that natural rotavirus infection is not a risk factor for IS. This information may have implications for development of a safer and effective rotavirus vaccine.

Diarrhea morbidity and mortality in Mexican children: impact of rotavirus disease.

AIM: To analyze changes in prevalence and seasonality of diarrhea morbidity and mortality and to evaluate the impact of rotavirus disease among Mexican children younger than 5 years old. METHODS: Diarrhea surveillance was performed from 1990 to 2002. Rotavirus testing was performed on stool specimens from 1996 to 2002. Data were obtained from different surveillance systems considering a nationwide representation in Mexico. Diarrhea morbidity and mortality rates were analyzed against time to determine trends or seasonal patterns. RESULTS: Improvement of surveillance for all diarrhea episodes denoted an initial morbidity increase from 1995 to 1999, followed by a decrease by 2002, without any seasonal pattern. However, from 1990 to 1995, morbidity for severe diarrhea decreased 63%. From 1996 to 2002, 62-68% of severe diarrhea episodes occurring during the fall-winter season (FWS) were rotavirus-positive compared with 6-12% in the spring-summer season (SSS). From 1990 to 2002, diarrhea mortality decreased 84%. Higher mortality rates for children younger than 1 year old coincided precisely during the FWS, annually. Both severe diarrhea episodes and diarrhea deaths denoted a changing seasonal pattern. In 1990-1991, 2 waves of increased diarrhea activity occurred. The increase in SSS was much more pronounced than that in FWS. From 1992 to 1995 for severe diarrhea and from 1993 to 2002 for diarrhea deaths, the SSS frequencies subsequently reduced, whereas the FWS peaks remained annually. CONCLUSIONS: A significant reduction in morbidity and mortality of severe diarrhea has occurred from 1990 and 2002 in Mexican children younger than 5 years old. This is a consequence of preventive programs initiated for cholera control since 1991, which had greater impact on SSS diarrhea and limited response for FWS diarrhea, when rotavirus is mainly present. Currently rotavirus diarrhea requires new prevention strategies and specific control measures, such as a specific national vaccine program.

Evaluation of the enzyme-linked immunoelectrotransfer blot assay for diagnosis of neurocysticercosis in children.

Neurocysticercosis is a common problem in developing countries, and it causes neurologic disorders in children. Immunodiagnosis with Taenia solium glycoproteins as an antigen has been validated in adults but not in children. The aim of this work was to evaluate a Taenia solium glycoproteins-based enzyme-linked immunoelectrotransfer blot assay in children with neurocysticercosis. Twenty-five confirmed cases of neurocysticercosis and 50 healthy children from the same community were included. The test had a sensitivity of 72% and a specificity of 96%. Sensitivity was higher (100%) in cases with multiple cysts and in multiple sites. Sensitivity was higher when cysts were in parenchyma (86%) than when they were in the subarachnoid space. The most frequently recognized proteins were 24, 39 to 42, and 50 kDa. Diagnosis was more efficient in serum than in cerebrospinal fluid. Western blot is a reliable method for serologic diagnosis of neurocysticercosis in children. Multiple cysts and infections in multiple sites elicited a stronger immune response.

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients.

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson's χ(2) and/or Fisher's exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.

Seroepidemiology of giardiasis in Mexico.

Prevalence of antibodies against Giardia duodenalis was determined by enzyme-linked immunosorbent assay in serum samples from a national serologic survey of Mexico that included all geographic areas and socioeconomic and demographic data for each person sampled. The country was divided into four regions on the basis of development (high, medium high, medium low, and low). Of 3,461 serum samples tested, 1,914 (55.3%) were positive for IgG antibodies against Giardia duodenalis. Seropositivity was age-specific; the probability of seropositivity increased 4.9-fold (95% confidence interval [CI] = 3.16-7.64) in adolescents 10-19 years of age, 8.0-fold (95% CI = 5.19-12.53) in young adults 20-39 years of age, and 12.6-fold (95% CI = 7.93-20.28) in adults more than 40 years of age. Giardia duodenalis seropositivity was associated with male sex (odds ratio = 1.40, 95% CI = 1.22-1.61). No association was found between seropositivity and socioeconomic variables or regional development status.

Giardia duodenalis: analysis of secreted proteases upon trophozoite-epithelial cell interaction in vitro.

Protease secretion by Giardia duodenalis trophozoites upon interaction with epithelial cells and its association with the parasite adhesion was studied in co-cultures of parasites with IEC6 epithelial cell monolayers in the presence or absence of protease inhibitors. Proteolytic activity in supernatants from trophozoites was enhanced when they were co-cultured with IEC6 cells. This activity was strongly inhibited by pre-incubation of live trophozoites with E-64 and TPCK and a concomitant inhibition of parasite adhesion to IEC6 cells was observed. These data suggest that trophozoites secrete cysteine-type proteases that play a role in the adhesion of G. duodenalis to epithelial cells.

Age-specific immune response to HspA in Helicobacter pylori-positive persons in Mexico.

The immune response to heat shock protein A (HspA) in Helicobacter pylori-positive adults increases with age in developed countries. This response has not been studied with children or in developing countries (G. I. Pérez-Pérez, J. M. Thiberge, A. Labigne, and M. J. Blaser, J. Infect. Dis. 174:1046-1050, 1996). As determined by using a specific enzyme-linked immunosorbent assay, HspA seropositivity among 592 individuals in Mexico was <10% in children and increased to >40% in adults.

Specific serum immunoglobulin G response to urease and CagA antigens of Helicobacter pylori in infected children and adults in a country with high prevalence of infection.

Few studies have analyzed the immune response to Helicobacter pylori CagA and urease antigens across age groups in the same population. The aim of this study was to analyze the serologic immunoglobulin G (IgG) response to CagA and urease proteins in children and adults with gastrointestinal symptoms and belonging to the same population and similar socioeconomic levels. The serologic response was studied in 352 children and 293 adults with gastrointestinal symptoms. IgG antibodies against CagA and urease were tested by enzyme-linked immunosorbent assay methods using highly purified recombinant antigens. H. pylori infection was defined as a positive result in a serologic assay using whole-cell H. pylori extracts as the antigen. We found, in H. pylori-positive children, a seroprevalence of 46.9% to CagA and 16.2% to urease, whereas in H. pylori-positive adults, a seroprevalence of 78.9% to CagA and 59% to urease was found. In children, the magnitude of the response to CagA was significantly higher and the response to urease was significantly lower than those in adults. The kinetics of serologic response to CagA and to urease across age groups was contrastably different. Whereas CagA is a strong immunogen, urease is a poor immunogen during natural infection. These differences in the humoral response may be important for the short-term or long-term outcome of the infection. These results add to our knowledge of the epidemiology of H. pylori infection.