Hemoglobin and HFE gene polymorphisms in Brazilian populations in regions endemic for malaria

Our objective was to determine how the distribution of red blood cell diseases is related to malaria occurrence in north Brazil, a region endemic for malaria. We evaluated the incidence of two mutations in the HFE gene, H63D and C282Y, in two study groups: a control blood donor group, with no indication of malaria infection, and a group constituted of malaria patients of four states of the Amazonian region. The hemoglobin polymorphisms were obtained by HPLC and classical laboratory methodologies, and the two mutations in the HFE gene were assayed by PCR-RFLP. We found a high frequency of alpha thalassemia, but there were no significant differences between blood donors and malaria patients. There were also no significant differences in the frequencies of HbA(2); however, the frequency of HbF was significantly different in individuals with malaria from Para and Rondonia. The mean number of reticulocytes was significantly reduced in the blood donors from the northern region, suggesting an adaptive strategy of these populations to parasitic attack by Plasmodium. Most individuals were heterozygous for the H63D allele of the HFE gene in both study groups. In the blood donors group, the greatest frequency of the H63D allele was found in Caucasians of all the states. In the malaria patients group in Rondonia, there was a high frequency of the H63D allele among the non-Caucasians. In the other states, and in the malaria patients group, the H63D allele was the most frequent among the Caucasians. Based on our results, we suggest that the maintenance of polymorphism of the mutations in the gene HFE can be explained by selective factors other than malaria, or it is due to simple allelic oscillation and by the constant gene flow among the populations in Brazil.

Purine nucleoside phosphorylase: A potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.

On the study of the dynamical aspects of parasitemia in the blood cycle of malaria

Malaria is an important cause of morbidity and mortality worldwide. One striking aspect regarding malaria is the fact that individuals living in endemic areas do not develop immunity against the parasite, falling ill whenever they are exposed tothe parasite. The understanding of why immunity is not developed in the usual way against Plasmodium is crucial to the improvement of treatment and prevention. In this work, we study some aspects of the dynamics of the blood cycle of malaria using both modelling and data analysis of observed case-histories described by parasitemia time series. By comparing our simulations with experimental results we have shown that the different behaviour observed among patients may be associated to differences in the efficiency of the immune system to control the infection. © EDP Sciences/Societa Italiana di Fisica/Springer-Verlag 2007.

Urban and suburban malaria in Rondônia (Brazilian Western Amazon) II. Perennial transmissions with high anopheline densities are associated with human environmental changes

Longitudinal entomological surveys were performed in Vila Candelária and adjacent rural locality of Bate Estaca concomitantly with a clinical epidemiologic malaria survey. Vila Candelária is a riverside periurban neighborhood of Porto Velho, capital of the state of Rondônia in the Brazilian Amazon. High anopheline densities were found accompanying the peak of rainfall, as reported in rural areas of the region. Moreover, several minor peaks of anophelines were recorded between the end of the dry season and the beginning of the next rainy season. These secondary peaks were related to permanent anopheline breeding sites resulting from human activities. Malaria transmission is, therefore, observed all over the year. In Vila Candelária, the risk of malaria infection both indoors and outdoors was calculated as being 2 and 10/infecting bites per year per inhabitant respectively. Urban malaria in riverside areas was associated with two factors: (1) high prevalence of asymptomatic carriers in a stable human population and (2) high anopheline densities related to human environmental changes. This association is probably found in other Amazonian urban and suburban communities. The implementation of control measures should include environmental sanitation and better characterization of the role of asymptomatic carriers in malaria transmission.

Biodiversity Can Help Prevent Malaria Outbreaks in Tropical Forests

Background: Plasmodium vivax is a widely distributed, neglected parasite that can cause malaria and death in tropical areas. It is associated with an estimated 80-300 million cases of malaria worldwide. Brazilian tropical rain forests encompass host- and vector-rich communities, in which two hypothetical mechanisms could play a role in the dynamics of malaria transmission. The first mechanism is the dilution effect caused by presence of wild warm-blooded animals, which can act as dead-end hosts to Plasmodium parasites. The second is diffuse mosquito vector competition, in which vector and non-vector mosquito species compete for blood feeding upon a defensive host. Considering that the World Health Organization Malaria Eradication Research Agenda calls for novel strategies to eliminate malaria transmission locally, we used mathematical modeling to assess those two mechanisms in a pristine tropical rain forest, where the primary vector is present but malaria is absent. Methodology/Principal Findings: The Ross-Macdonald model and a biodiversity-oriented model were parameterized using newly collected data and data from the literature. The basic reproduction number (R0) estimated employing Ross-Macdonald model indicated that malaria cases occur in the study location. However, no malaria cases have been reported since 1980. In contrast, the biodiversity-oriented model corroborated the absence of malaria transmission. In addition, the diffuse competition mechanism was negatively correlated with the risk of malaria transmission, which suggests a protective effect provided by the forest ecosystem. There is a non-linear, unimodal correlation between the mechanism of dead-end transmission of parasites and the risk of malaria transmission, suggesting a protective effect only under certain circumstances (e.g., a high abundance of wild warm-blooded animals). Conclusions/Significance: To achieve biological conservation and to eliminate Plasmodium parasites in human populations, the World Health Organization Malaria Eradication Research Agenda should take biodiversity issues into consideration. © 2013 Laporta et al.

Estrutura eletrônica de materiais orgânicos: moléculas antimalariais de sulfonamidas e anilinoquinolinas

Pós-graduação em Ciência e Tecnologia de Materiais - FC

Análise da expressão e silenciamento de genes do trato digestivo de Anopheles aquasalis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aspectos filogenéticos e sorológicos envolvidos na caracterização das variantes da proteína circunsporozoítica de Palsmodium vivax

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização do mecanismo fotossintético e aspectos relacionados à floração de Artemisia annua L

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of Antimalarial Activity and Toxicity of a New Primaquine Prodrug

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modelo discreto para o ciclo eritrocitário da Malária

In this work, some aspects of the erythrocyte cycle of the malaria parasite was incorporated into a cellular automata model to simulated the major factors leading to disruption of the erythrocyte cycle and consequent appearance of gametocytes, which infected the mosquitoes. Furthermore, the time seies of parasitaemia of infected patients was analyzed and compared to simulated data. The results suggested that differences in the temporal patterns of the asexual parasitaemia are associated with different effectiveness of the immune system in controlling the infection

Plantas utilizadas no tratamento de malária e males associados por comunidades tradicionais de Xapuri, AC e Pauini, AM

Pós-graduação em Agronomia (Horticultura) - FCA

Diagnóstico sorológico e molecular de agentes transmitidos por artrópodes em aves carnívoras

Pós-graduação em Medicina Veterinária - FCAV

Evidence for temporal population replacement and the signature of ecological adaptation in a major Neotropical malaria vector in Amazonian Peru

The major Neotropical malaria vector, Anopheles darlingi, was reintroduced into the Iquitos, Loreto, Peru area during the early 1990s, where it displaced other anophelines and caused a major malaria epidemic. Since then, case numbers in Loreto have fluctuated, but annual increases have been reported since 2012. The population genetic structure of An. darlingi sampled before and after the introduction of long-lasting insecticidal nets (LLINs) was investigated to test the hypothesis of temporal population change (2006 vs. 2012). Current samples of An. darlingi were used to test the hypothesis of ecological adaptation to human modified (highway) compared with wild (riverine) habitat, linked to forest cover. In total, 693 An. darlingi from nine localities in Loreto, Peru area were genotyped using 13 microsatellite loci. To test the hypothesis of habitat differentiation in An. darlingi biting time patterns, HBR and EIR, four collections of An. darlingi from five localities (two riverine and three highway) were analysed. Analyses of microsatellite loci from seven (2006) and nine settlements (2012-2014) in the Iquitos area detected two distinctive populations with little overlap, although it is unclear whether this population replacement event is associated with LLIN distribution or climate. Within the 2012-2014 population two admixed subpopulations, A and B, were differentiated by habitat, with B significantly overrepresented in highway, and both in near-equal proportions in riverine. Both subpopulations had a signature of expansion and there was moderate genetic differentiation between them. Habitat and forest cover level had significant effects on HBR, such that Plasmodium transmission risk, as measured by EIR, in peridomestic riverine settlements was threefold higher than in peridomestic highway settlements. HBR was directly associated with available host biomass rather than forest cover. A population replacement event occurred between 2006 and 2012-2014, concurrently with LLIN distribution and a moderate El Niño event, and prior to an increase in malaria incidence. The likely drivers of this replacement cannot be determined with current data. The present-day An. darlingi population is composed of two highly admixed subpopulations, which appear to be in an early stage of differentiation, triggered by anthropogenic alterations to local habitat.

Malaria and Vascular Endothelium

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)