Maria Cristina dos Santos

FY polymorphisms and vivax malaria in inhabitants of Amazonas State, Brazil

Although the importance of glycoprotein Duffy in the human red cells invasion process by Plasmodium vivax merozoites has been demonstrated, little is known about the associations of FY polymorphisms with malaria vivax parasitic density. In this study, we investigated the associations of the SNPs 125 G>A, 265 C>T, and 298 G>A on FY gene and the SNP –33T>C on GATA box with the vivax malaria parasitic density in inhabitants of Amazon State, Brazil. Verifications of P. vivax, as well as the definition of parasitism, were determined by standard screening tests in 497 patients. FY phenotyping was performed in all samples by hemagglutination using gel cards. Molecular analysis for FY/GATA polymorphisms were performed by polymerase chain reaction–restriction fragment length polymorphism. Our data showed that in this population, FY*A/FY*B-33 and FY*B/FY*B-33 genotypes may be a selective advantage, reducing the frequency of P. vivax infection in the studied area. FY*A/FY*B and FY*A/FY*A genotypes showed to be associated with the rise of the frequency of P. vivax infection, and FY*B/FY*X and FY*A/FY*X showed to be associated with the low levels of parasitism. These results suggest that natural adaptations, in malaria-endemic regions, could be leading to the arising of partial defense mechanisms against P. vivax, which is different from the previously described in African descents, as well as adaptations that could be increasing the susceptibility of human to this kind of malaria.

Snakebites and Scorpion Stings in the Brazilian Amazon: Identifying Research Priorities for a Largely Neglected Problem

Envenomings by snakebites and scorpion stings impose a high burden worldwide and result in considerable social and economic impact [1]. It is estimated that snakebite rates are as high as over 1.8 million cases per year, with associated deaths reaching more than 90,000 cases annually [2]. However, snakebites are a neglected condition with no associated WHO programmes for control and prevention. The countries most affected by snakebites are located in the intertropical zone in areas with high rates of field use for agriculture where the main affected populations are adult men working in agricultural activities [1]. Approximately two billion people are living in areas at risk for scorpion stings, with over one million accidents occurring annually worldwide [3]. However, the true burden of snakebites and scorpion stings is probably higher and difficult to estimate since only a few countries have a reliable system for epidemiological surveillance of these events. In Brazil, the Ministry of Health implemented the National Program for Snakebites Control in 1986, extended to other poisonous animals in 1988. Since then, antivenom (AV) production has been standardized and all the AV production from the three national laboratories (Instituto Butantan, Fundacao Ezequiel Dias, and Instituto Vital Brazil) was acquired by the Ministry of Health for distribution free of charge to patients. Five types of snake AVs are currently available: Bothrops AV (main one), Crotalus AV, Bothrops-Crotalus AV, Bothrops-Lachesis AV, and Micrurus AV. For scorpion stings, there are two types of AVs available in Brazil: Tityus scorpion AV and a polyvalent AV against Loxosceles and Phoneutria spiders and the Tityus scorpion. Table 1 summarizes information on snake and scorpion AVs produced in Brazil. Table 1 Venom pools used for snake and scorpion AVs production in Brazil. In 2013, 27,181 and 78,091 cases of snakebites and scorpion stings were reported by the Brazilian Ministry of Health, respectively [4]. The highest incidence was in the North region (52.6 cases/100,000 inhabitants) followed by the Midwest (16.4/100,000). These values, expected to be higher in remote areas of the Brazilian Amazon [5], may be underestimated due to considerable underreporting. Fig 1 presents the spatial distribution of snakebites and scorpion stings in the Brazilian Amazon. Fig 1 Spatial distribution of snakebites and scorpion stings in the Brazilian Amazon in 2013.

Older Age and Time to Medical Assistance Are Associated with Severity and Mortality of Snakebites in the Brazilian Amazon: A Case-Control Study

The Amazon region reports the highest incidence of snakebite envenomings in Brazil. We aimed to describe the epidemiology of snakebites in the state of Amazonas and to investigate factors associated with disease severity and lethality. We used a nested case-control study, in order to identify factors associated with snakebite severity and mortality using official Brazilian reporting systems, from 2007 to 2012. Patients evolving to severity or death were considered cases and those with non-severe bites were included in the control group. During the study period, 9,191 snakebites were recorded, resulting in an incidence rate of 52.8 cases per 100,000 person/years. Snakebites mostly occurred in males (79.0%) and in rural areas (70.2%). The most affected age group was between 16 and 45 years old (54.6%). Fifty five percent of the snakebites were related to work activities. Age ≤15 years [OR=1.26 (95% CI=1.03-1.52); (p=0.018)], age ≥65 years [OR=1.53 (95% CI=1.09-2.13); (p=0.012)], work related bites [OR=1.39 (95% CI=1.17-1.63); (p<0.001)] and time to medical assistance >6 hours [OR=1.73 (95% CI=1.45-2.07); (p<0.001)] were independently associated with the risk of severity. Age ≥65 years [OR=3.19 (95% CI=1.40-7.25); (p=0.006)] and time to medical assistance >6 hours [OR=2.01 (95% CI=1.15-3.50); (p=0.013)] were independently associated with the risk of death. Snakebites represent an occupational health problem for rural populations in the Brazilian Amazon with a wide distribution. These results highlight the need for public health strategies aiming to reduce occupational injuries. Most cases of severe disease occurred in the extremes of age, in those with delays in medical attention and those caused by Micrurus bites. These features of victims of snakebite demand adequate management according to well-defined protocols, including prompt referral to tertiary centres when necessary, as well as an effective response from surveillance systems and policy makers for these vulnerable groups.

Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance

Previous studies identified the functional polymorphism 1858C/T in the gene PTPN22 in association with several autoimmune diseases and with resistance to tuberculosis (TB). This study is the first to investigate the association between pulmonary TB and the PTPN22 1858C/T polymorphism in the Brazilian Amazon. We conducted a case-control study involving a group of 413 individuals, comprised of 208TB carriers and 205 controls. No significant association between the PTPN22 1858T allele frequency in controls (2.4%) and TB carriers (2.7%, p=0.982, odds ratio (OR)=0.89, 95% confidence interval=0.37-2.13) was identified in the Brazilian Amazon population. An additional evaluation by meta-analysis, however, suggested a protective role of the T allele in relation to TB (pooled OR=0.44, p=0.011). These results suggest that the PTPN22 1858T allele serves as a protective genetic factor for TB in those individuals who carry this minor allele.

CONSTITUINTES QUÍMICOS E ATIVIDADE ANTIEDEMATOGÊNICA DE Peltodon radicans (LAMIACEAE)

Most of the snakebite incidents in the Amazon region involve Bothrops atrox, whose venom presents the most potent edematogenic and necrotic activities in the genus. This work describes the studies of isolation of the chemical constituents and antiedematogenic activity of the species Peltodon radicans (Lamiaceae), which is used in the treatment of snakebites and scorpion stings in the region. The extracts presented aliphatic hydrocarbons, 3b-OH,b-amirin (1), 3b-OH,a-amirin (2), b-sitosterol (3), stigmasterol (4), ursolic acid (5), 2a,3b,19a-trihydroxy-urs-12-en-28-oic acid (tormentic acid, 6), methyl 3b-hydroxy,28-methyl-ursolate (7), sitosterol-3-O-b-D-glucopyranoside (8), and stigmasterol-3-O-b-D-glucopyranoside (9). The flower extracts presented the higher antiedematogenic activity. This is the first report on the study of the flowers, stem, and roots of this plant.