Genetic Control of Mosquitoes: population suppression strategies

Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

Optimal Cut-Off Value for Homeostasis Model Assessment (HOMA) Index of Insulin-Resistance in a Population of Patients Admitted Electively in a Portuguese Cardiology Ward

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

Decreasing Incidence and Changes in Serotype Distribution of Invasive Pneumococcal Disease in Persons Aged Under 18 Years Since Introduction of 10-Valent and 13-Valent Conjugate Vaccines in Portugal, July 2008 to June 2012

The 10-valent pneumococcal conjugate vaccine (PCV10) became available in Portugal in mid-2009 and the 13-valent vaccine (PCV13) in early 2010. The incidence of invasive pneumococcal disease (IPD) in patients aged under 18 years decreased from 8.19 cases per 100,000 in 2008–09 to 4.52/100,000 in 2011–12. However, IPD incidence due to the serotypes included in the 7-valent conjugate vaccine (PCV7) in children aged under two years remained constant. This fall resulted from significant decreases in the number of cases due to: (i) the additional serotypes included in PCV10 and PCV13 (1, 5, 7F; from 37.6% to 20.6%), particularly serotype 1 in older children; and (ii) the additional serotypes included in PCV13 (3, 6A, 19A; from 31.6% to 16.2%), particularly serotype 19A in younger children. The decrease in serotype 19A before vaccination indicates that it was not triggered by PCV13 administration. The decrease of serotype 1 in all groups, concomitant with the introduction of PCV10, is also unlikely to have been triggered by vaccination, although PCVs may have intensified and supported these trends. PCV13 serotypes remain major causes of IPD, accounting for 63.2% of isolates recovered in Portugal in 2011–12, highlighting the potential role of enhanced vaccination in reducing paediatric IPD in Portugal.

Clinical and epidemiological findings during a measles outbreak occurring in a population with high vaccination coverage

From March 1991 to April 1992, 250 measles suspected cases were studied in the Municipality of Niterói, State of Rio de Janeiro. The median age found was 11 years and 76.0% of the cases were in school age children. Exposure histories were present in 149 patients and schools were the most frequent sites of transmission (45.0%). Vaccination status was known for 127 studied cases and 76.4% of them had received measles vaccine before their first birthday. One or more complications were reported for 68 cases aitd in 8.9% of the studied cases hospitalization was required. Frequency of complications varied according to each age group studied and were more commonly encountered among children < 1 year of age (55.6%). The history of previous vaccination did not diminish the number of complications of the cases studied. The results of this work show changes in age distribution of measles leading to sizeable outbreaks among teenagers and young adults.

Distribution of hepatitis C virus genotypes among different exposure categories in the State of Pará, Brazilian Amazon

INTRODUCTION: Epidemiological studies concerning HCV genotypic distribution in the Brazilian Amazon are scarce. Thus, this study determined the patterns of distribution of HCV genotypes among different exposure categories in the State of Pará, Brazilian Amazon. METHODS: A cross-sectional study was conducted on 312 HCV-infected individuals belonging to different categories of exposure, who were attended at the HEMOPA, CENPREN and a private hemodialysis clinic in Belém. They were tested for HCV antibodies using an immunoenzymatic test, RNA-HCV, using real-time PCR and HCV genotyping through phylogenetic analysis of the 5' UTR. The population groups were epidemiologically characterized according to data collected in a brief interview or medical consultation. RESULTS: Genotype 1 predominated in all the different categories of HCV exposure. HCV genotypic distribution among blood donors comprised genotypes 1 (94%) and 3 (6%). All patients with chronic hematologic diseases had HCV genotype 1. The genotypic distribution in illicit-drug users comprised genotypes 1 (59.6%) and 3 (40.4%). In patients under hemodialysis, genotypes 1 (90.1%), 2 (3.3%), and 3 (6.6%) were detected. Finally, the frequency of genotypes 1 and 3 was significantly different between the groups: BD and DU, PUH and DU, PUH and PCHD and PCHD and DU. CONCLUSIONS: The genotypic frequency and distribution of HCV in different categories of exposure in the State of Pará showed a predominance of genotype 1, regardless of the possible risk of infection.

Spatial distribution of schistosomiasis and geohelminthiasis cases in the rural areas of Pernambuco, Brazil

INTRODUCTION: The prevalence and intensity of geohelminth infections and schistosomiasis remain high in the rural areas of Zona da Mata, Pernambuco (ZMP), Brazil, where these parasites still represent a significant public health problem. The present study aimed to spatially assess the occurrences of schistosomiasis and geohelminthiasis in the ZMP. METHODS: The ZMP has a population of 1,132,544 inhabitants, formed by 43 municipalities. An ecological study was conducted, using secondary data relating to positive human cases and parasite loads of schistosomiasis and positive human cases of geohelminthiasis that were worked up in Excel 2007. We used the coordinates of the municipal headquarters to represent the cities which served as the unit of analysis of this study. The Kernel estimator was used to spatially analyze the data and identify distribution patterns and case densities, with analysis done in ArcGIS software. RESULTS: Spatial analysis from the Kernel intensity estimator made it possible to construct density maps showing that the northern ZMP was the region with the greatest number of children infected with parasites and the populations most intensely infected by Schistosoma mansoni. In relation to geohelminths, there was higher spatial distribution of cases of Ascaris lumbricoides and Trichuris trichiura in the southern ZMP, and greater occurrence of hookworms in the northern/central ZMP. CONCLUSIONS: Despite several surveys and studies showing occurrences of schistosomiasis and geohelminthiasis in the ZMP, no preventive measures that are known to have been effective in decreasing these health hazards have yet been implemented in the endemic area.

Spatial distribution and esterase activity in populations of Aedes (Stegomyia) aegypti (Linnaeus) (Diptera: Culicidae) resistant to temephos

INTRODUCTION:The need for studies that describe the resistance patterns in populations of Aedes aegypti (Linnaeus) in function of their region of origin justified this research, which aimed to characterize the resistance to temephos and to obtain information on esterase activity in populations of Aedes aegypticollected in municipalities of the State of Paraíba.METHODS:Resistance to temephos was evaluated and characterized from the diagnostic dose of 0.352mg i.a./L and multiple concentrations that caused mortalities between 5% and 99%. Electrophoresis of isoenzymes was used to verify the patterns of esterase activity among populations of the vector.RESULTS:All populations of Aedes aegypti were resistant to temephos, presenting a resistance rate (RR) greater than 20. The greatest lethal dose 50% of the sample (CL50) was found for the municipality of Lagoa Seca, approximately forty-one times the value of CL50 for the Rockefeller population. The populations characterized as resistant showed two to six regions of α and β-esterase, called EST-1 to EST-6, while the susceptible population was only seen in one region of activity.CONCLUSIONS:Aedes aegyptiis widely distributed and shows a high degree of resistance to temephos in all municipalities studied. In all cases, esterases are involved in the metabolism and, consequently, in the resistance to temephos.

Prevalence of neurocognitive disorders and depression in a Brazilian HIV population

AbstractINTRODUCTION:Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.METHODS:One hundred fourteen patients were evaluated in a cross-sectional study conducted in a public outpatient clinic for infectious diseases in Marília City, State of São Paulo, Brazil. Data were collected following consultation. Statistical analysis was performed in accordance with the nature and distribution of the data and hypotheses.RESULTS:According to the IHDS, 53.2% of the sampled patients were neuropsychologically impaired. According to the HAM-D17, 26.3% had depressive disorders. There were significant associations between the IHDS and the TGT and DS. Multiple regression analysis indicated that female gender, educational level, and cluster of differentiation 4 (CD4) levels were significantly and independently associated with neurocognitive impairment.CONCLUSIONS:The prevalence of neurocognitive impairment according to the IHDS is high and associated with female gender, education level, and low CD4 levels.

Cryptococcosis in Atlántico, Colombia: an approximation of the prevalence of this mycosis and the distribution of the etiological agent in the environment

ABSTRACTINTRODUCTION:Cryptococcosis is an invasive disease acquired by inhalation of infectious propagules from the environment. Currently, compulsory notification of the spread of this disease is not required in Colombia. However, reporting of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome cases to the National Surveillance System has suggested that there is a growing population at risk of contracting cryptococcosis. Few studies have described the occurrence of cryptococcosis in Colombia. Therefore, in this study, we examined the pathology of this disease in Atlántico, Colombia and determined the distributions of Cryptococcus neoformans and Cryptococcus gattii in the environment.METHODS:Clinical samples/isolates were gathered from cases of cryptococcosis previously diagnosed at health institutions in Atlántico, and surveys were completed by clinicians. The environmental study considered 32 sampling points and three tree species, i.e., Quickstick ( Gliricidia sepium ), Almond ( Terminalia catappa ), and Pink trumpet ( Tabebuia rosea ). Environmental and clinical samples/isolates were analyzed for phenotypic and genotypic confirmation.RESULTS:From 1997-2014, 41 cases of cryptococcosis were reported. The mean patient age was 40.5 years (range: 18-63 years); 76% were men, and 78% were HIV positive. Isolation was possible in 38 cases ( C. neoformans , molecular type VNI in 37 cases and C. gattii , molecular type VGI in one case). In 2012-2014, 2,068 environmental samples were analyzed with a positivity of 0.4% ( C. neoformans , molecular type VNI) in Almond and Pink trumpet trees.CONCLUSIONS:Cryptococcus neoformans , molecular type VNI had a higher prevalence than C. gattii and was associated with human exposure and the pathogenesis of cryptococcosis in this geographical region.

Distribution of hepatitis B infection in Brazil: the epidemiological situation at the beginning of the 21 st century

Abstract Brazil was formerly considered a country with intermediate hepatitis B endemicity, with large heterogeneity between Brazilian regions and areas of high prevalence, especially in the Amazon basin. Systematic vaccination of children was initiated in 1998. Between 2004 and 2009, a large population-based study reported decreased prevalence in all regions of Brazil. This review analyzed the current hepatitis B epidemiological situation in Brazil through a systematic search of the scientific literature in MEDLINE, LILACS, and CAPES thesis database, as well as disease notifications to the Information System for Notifiable Diseases. The search strategy identified 87 articles and 13 theses, resulting in 100 total publications. The most recent results indicate reduced hepatitis B prevalence nationwide, classifying Brazil as having low endemicity. Most studies showed HBV carrier prevalence less than 1%. However, there are still isolated regions with increased prevalence, particularly the Amazon, as well as specific groups, such as homeless people in large cities and isolated Afro-descendant communities in the center of the country. This review alsao detected successful vaccination coverage reported in a few studies around the country. The prevalence of anti-HBs alone ranged from 50% to 90%. However, isolated and distant localities still have low coverage rates. This review reinforces the downward trend of hepatitis B prevalence in Brazil and the need to intensify vaccination strategies for young people and adults in specific regions with persisting higher HBV infection prevalence.

Structure of Anopheles (Diptera: Culicidae) population in areas with different degrees of human settlement: Cantá - Roraima - Brazil

Malaria has still been one of the most important endemic diseases in the Amazonian region. This study presents the impact of human settlements on the structure of Anopheles population. Diversity, abundance, richness and distribution of the genus Anopheles were observed in two areas with different levels of human settlement in the Cantá city, Roraima State, Northern Brazil. The influence of the dry and rainy seasons on mosquito populations was also observed. Mosquito captures were performed between 6:00 and 10:00 pm during the dry (February and November) and rainy (May and August) seasons at four different sites of each area. Among the 11 species of Anopheles identified through the adults' characteristics, An. albitarsis s.l. (45.5%) and An. darlingi (19.2%) were the most abundant in the more intensively anthropized area while An. triannulatus (19.2%) was more common in the less modified area. Other species found were An. nuneztovari (10.9%), An. oswaldoi (2.0%), An. evansae (1.7%), An. brasiliensis (0.6%), An. intermedius (0.3%), An. mediopunctatus (0.5%), An. periassui (0.08%) and An. argyritarsis (0.04%). The highest mosquitoes' population density was observed in May and the lowest one was observed in February and November. These results demonstrate the existence of a high diversity of anophelines in the study areas, showing that anthropic changes in the environment and climate variability affect both the population density and relative abundance of these vectors.

Racial inequalities in the socioeconomic, demographic and health conditions of elderly from Maranhão State, Legal Amazon, Brazil: a population-based study

Aging with quality of life does not occur equally among the racial groups of Brazilian elderly, and few studies have analyzed this issue in the states of the Brazilian Legal Amazon. The objective of this study was to investigate racial inequalities in the socioeconomic, demographic and health conditions of elderly residents of Maranhão state, Brazil. The present work is a cross-sectional study of 450 elders aged 60 years or older included in the 2008 National Household Sample Survey. The prevalence of socioeconomic, demographic, health and habit indicators and of risk factors were estimated in white, brown and black racial categories that were self-reported by the survey participants. The chi-square test was used for comparisons (a=5%). The majority of the elderly respondents identified themselves as brown (66.4%) or white (23.3%). There were significant socioeconomic, demographic, habit and lifestyle differences among the racial groups. Most of the black and brown elderly lived alone, reported lower educational levels and were in the lowest quintile for income. These respondents were also highly dependent on the Unified Health System (Sistema Único de Saúde - SUS), exhibited low rates of screening mammograms and lower physical activity levels and had a greater proportion of smokers. However, there was no difference in the prevalence of health indicators or in the proportion of elderly by gender, age, social role in the family or the urban-rural location of the household. These results indicate the presence of racial inequalities in the socioeconomic and demographic status and in the practice of healthy habits and lifestyles among elderly from Maranhão, but suggest equity in health status. The results also suggest the complexity and challenges of interlinking race with socioeconomic aspects, and the findings reinforce the need for the implementation of public policies for these population groups.

Study to determine the cardiovascular risk ofthe population of Guimarães/Vizela, includingthe prevalence of arterial stiffness and early vascular aging syndrome

Tese de Doutoramento em Medicina.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging

BACKGROUND: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. METHOD: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. RESULTS: Mean PWV value for the entire population was 8.4?m/s (men: 8.6?m/s; women: 8.2?m/s; P?population exhibited PWV values above 10?m/s, with male predominance (17.2% of men aged 40-49 years had PWV?>?10?m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10?m/s 10 years later than men. CONCLUSION: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.

Normal values of echocardiographic measurements. A population-based study

OBJECTIVE: To describe echocardiographic measurements and left ventricular mass in a population sample of healthy adults inhabitants of the urban region of Porto Alegre. METHODS: An analytical, observational, population-based, cross-sectional study was done. Through a multi-stage probability sample, 114 individuals were selected to be submitted to a M-mode and two-dimensional echocardiogram with color Doppler. The analyses were restricted to healthy participants. Echocardiographic measurements were described by mean, standard deviation, 95 percentile and 95% confidence limits. RESULTS: A total of 100 healthy participants, with several characteristics similar to those from the original population, had a complete and reliable echocardiographic examination. The measurements of aorta, left atrium, interventricular septum, left ventricle in systole and diastole, left posterior wall and left ventricular mass, adjusted or not for body surface area or height, were significantly higher in males. The right ventricle size was similar among the genders. Several echocardiographic measurements were within standard normal limits. Interventricular septum, left posterior wall and left ventricular mass, adjusted or not for anthropometric measurements, and aortic dimensions had lower mean and range than the reference limits. CONCLUSION: The means and estimates of distribution for the measurements of interventricular septum, left posterior wall and left ventricular mass found in this survey were lower than those indicated by the international literature and accepted as normal limits.