Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. .

Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the Brazilian Amazon Basin: to treat or not to treat?

In this study, we determined whether the treatment of asymptomatic parasites carriers (APCs), which are frequently found in the riverside localities of the Brazilian Amazon that are highly endemic for malaria, would decrease the local malaria incidence by decreasing the overall pool of parasites available to infect mosquitoes. In one village, the treatment of the 19 Plasmodium falciparum-infected APCs identified among the 270 residents led to a clear reduction (Z = -2.39, p = 0.017) in the incidence of clinical cases, suggesting that treatment of APCs is useful for controlling falciparum malaria. For vivax malaria, 120 APCs were identified among the 716 residents living in five villages. Comparing the monthly incidence of vivax malaria in two villages where the APCs were treated with the incidence in two villages where APCs were not treated yielded contradictory results and no clear differences in the incidence were observed (Z = -0.09, p = 0.933). Interestingly, a follow-up study showed that the frequency of clinical relapse in both the treated and untreated APCs was similar to the frequency seen in patients treated for primary clinical infections, thus indicating that vivax clinical immunity in the population is not species specific but only strain specific.

Species structure of sand fly (Diptera: Psychodidae) fauna in the Brazilian western Amazon

We surveyed areas of the state of Rondônia in western Amazon for phlebotomine, which are potential vectors of leishmaniasis. A total of 5,998 specimens were captured, resulting in the identification of 48 species within the Lutzomyia (99.98 percent) and Brumptomyia (0.02 percent) genera. The predominant species was Lutzomyia davisi, followed by Lutzomyia umbratilis, Lutzomyia llanosmartinsi, Lutzomyia c. carrerai, Lutzomyia dendrophyla, Lutzomyia nevesi and Lutzomyia whitmani. All sand flies identified as vectors for cutaneous leishmaniasis in Brazil, i.e., Lu. davisi, Lu. umbratilis, Lu. c. carrerai and Lu. whitmani, were found in the surveyed areas.

Malária e aspectos hematológicos em moradores da área de influência dos futuros reservatórios das hidrelétricas de Santo Antônio e Jirau, Rondônia, Brasil / Malaria and hematological aspects among residents to be impacted by reservoirs for the Santo Antônio and Jirau Hydroelectric Power Stations, Rondônia State, Brazil

Em Rondônia, prevê-se a construção de mais duas usinas hidrelétricas (UHE) no rio Madeira, a montante da cidade de Porto Velho, Rondônia, Brasil (de Santo Antônio e Jirau). O objetivo deste trabalho foi analisar a prevalência da malária antes do início da implantação das obras civis e fazer considerações sobre os impactos da doença com o ingresso de milhares de trabalhadores e agregados atraídos pelas oportunidades de emprego e comércio. Os resultados obtidos mostram que a malária se faz presente em toda região, em variados graus de prevalência. Além disso, a existência de potenciais portadores assintomáticos de malária entre a população nativa pode ter relevância epidemiológica e deve ser considerada nos programas de controle da malária, vinda tanto das autoridades públicas quanto das empresas responsáveis pela instalação das UHE, visando o diagnóstico e tratamento precoce, controle vetorial, abastecimento de água e aplicação de infra-estrutura nos centros urbanos.

In Rondônia State, Brazil, two new hydroelectric plants, Santo Antônio and Jirau, are scheduled for construction on the Madeira River, upriver from the State capital, Porto Velho. The current study analyzes malaria prevalence before the construction and provides information on the possible impacts of malaria burden related to the influx of thousands of persons attracted by direct and indirect employment opportunities. According to the findings, malaria is present throughout the region, with varying prevalence rates. The existence of potential asymptomatic malaria carriers among the local population may be epidemiologically relevant and should be considered in the malaria control programs organized by public authorities and companies responsible for building the power plants, aimed at early diagnosis and treatment, vector control, water supply, and infrastructure in the urban areas.

Characterization of Shigella spp. by antimicrobial resistance and PCR detection of ipa genes in an infantile population from Porto Velho (Western Amazon region), Brazil

The incidence of Shigella spp. was assessed in 877 infants from the public hospital in Rondônia (Western Amazon region, Brazil) where Shigella represents the fourth cause of diarrhea. Twenty-five isolates were identified: 18 were Shigella flexneri, three Shigella sonnei, three Shigella boydii and one Shigella dysenteriae. With the exception of S. dysenteriae, all Shigella spp. isolated from children with diarrhea acquired multiple antibiotic resistances. PCR detection of ipa virulence genes and invasion assays of bloody diarrhea and fever (colitis) were compared among 25 patients testing positive for Shigella. The ipaH and ipaBCD genes were detected in almost all isolates and, unsurprisingly, all Shigella isolates associated with colitis were able to invade HeLa cells. This work alerts for multiple antibiotic resistant Shigella in the region and characterizes presence of ipa virulence genes and invasion phenotypesin dysenteric shigellosis.

Endemias e epidemias na Amazônia: malária e doenças emergentes em áreas ribeirinhas do Rio Madeira: um caso de escola / Endemics and epidemics in the Amazon

Após fazer uma análise da evolução da malária na Amazônia brasileira, detalhando em particular a situação em Rondônia e no município de Porto Velho, onde ocorreram episódios dramáticos de epidemias de malária no passado, os autores apresentam o quadro atual da prevalência de malária nas áreas do Vale do Rio Madeira, que sofrerão impactos com a construção das hidrelétricas de Santo Antônio e Jirau, e alertam sobre a situação particular da malária em áreas ribeirinhas. Nessas áreas, observam-se alta incidência de malária vivax e falciparum, a presença de grande número de portadores assintomáticos de parasitas e altas densidades do vetor Anopheles darlingi o ano todo. Esses elementos, associados à provável chegada de migrantes oriundos de áreas não-endêmicas de Rondônia e de outros Estados do país, atraídos pela possibilidade de trabalho nessas hidrelétricas e oportunidades de comércio, lazer, educação e atividades domésticas, criam condições favoráveis à ocorrência de epidemias de malária e de outras doenças tropicais se não forem realizadas intervenções adequadas de controle, em particular no domínio do saneamento.

Rotavirus and adenovirus in Rondônia

Acute gastroenteritis is one of the most common diseases in humans worldwide. Viral gastroenteritis is a global problem in infants and young children. In this study the incidence of diarrhea was assessed in 877 hospitalized children under five years old, over a period of 24 months and distributed in 470 cases of diarrhea and 407 age-matched group with other pathologies, as control group. Two antigen detection techniques based on enzyme immunoassay (EIA) and latex particles were used for detection of rotavirus and adenovirus. Rotavirus A was a major cause of gastroenteritis with 23.6 percent of cases, being 90 percent of these cases in young children. Adenovirus infections was detected by EIA with frequency of 6.4 percent. Rotavirus and adenovirus were detected in 10.1 and 1.7 percent of stools from control group, respectively. Interestingly, the frequency of the youngest children in the control group excreting Rotavirus A was comparable to that detected in stools from diarrheic children. We cannot rule out the existence of other enteric viruses because the etiology of 171 cases of diarrhea was not determined and active search for astrovirus and calicivirus was not done. This is the first study that shows the presence of enteric viruses in the infantile population from Western Brazilian Amazonia and it was important to help physicians in the treatment of viral gastroenteritis.

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.

Microsatellite characterization of Plasmodium falciparum from symptomatic and non-symptomatic infections from the Western Amazon reveals the existence of non-symptomatic infection-associated genotypes

In Western Amazon areas with perennial malaria transmission, long term residents frequently develop partial immunity to malarial infection caused either by Plasmodium falciparum or P. vivax, resulting in a considerable number of non-symptomatically infected individuals. For yet unknown reasons, these individuals sporadically develop symptomatic malaria. In order to identify if determined parasite genotypes, defined by a combination of eleven microsatellite markers, were associated to different outcomes - symptomatic or asymptomatic malaria - we analyzed infecting P. falciparum parasites in a suburban riverine population. Despite of detecting a high degree of diversity in the analyzed samples, several microsatellite marker alleles appeared accumulated in parasites from non-symptomatic infections. This result may be interpreted that a number of microsatellites, which are not directly related to antigenic features, could be associated to the outcome of malarial infection. The result may also point to a low frequency of recombinatorial events which otherwise would dissociate genes under strong immune pressure from the relatively neutral microsatellite loci.

The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions...

O desafio da malária: o caso brasileiro e o que se pode esperar dos progressos da era genômica / The malaria challenge: the Brazilian case and what can be expected from progress in genomics

A área endêmica de malária no Brasil se estende atualmente à totalidade da região amazônica, com cerca de 500 mil casos anuais, em geral com situações de baixa e média endemicidade mas ainda apresentando focos de alto risco. Fatores demográficos e socioeconômicos são dominantes nos desafios que enfrentam os Serviços de Saúde Pública no controle da malária. No presente artigo são discutidos fatores determinantes da instabilidade da situação endêmica bem como a necessidade de ações permanentes de vigilância e de intervenção dos Serviços de Saúde para que se evitem surtos epidêmicos e alastramento das áreas endêmicas. No artigo, em seguida, apresenta-se uma síntese de progressos recentes nos estudos da era genômica e pós-genômica sobre o parasita, o vetor e o hospedeiro humano que podem favorecer, no futuro, o desenvolvimento e a melhoria dos métodos de controle da malária.

Enteropathogens associated with diarrheal disease in infants of poor urban areas of Porto Velho, Rondônia: a preliminary study

One hundred and thirty cases of diarrhea and 43 age-matched controls, 0 to 5 years old, were studied in a pediatric outpatient unit from a poor peri urban area of Porto Velho, Rondônia. Eighty percent of diarrheal cases were observed in the groups under 2 years of age. Rotavirus (19.2 percent) was the most frequent enteropathogen associated with diarrhea, followed by Shigella flexneri (6.15 percent) and S. sonnei (1.5 percent) and Salmonella sp. (6.9 percent). Four cases of E. coli enterotoxigenic infections (3.1 percent), E. coli enteropathogenic (EPEC)(2.3 percent) one case of E. coli enteroinvasive infection (0.8 percent) and one case of Yersinia enterocolitica (0.8 percent) were also identified. Mixed infections were frequent, associating rotavirus, EPEC and Salmonella sp. with Entamoeba histolytica and Giardia lamblia

Ciências biológicas e biotecnologia: realidades e virtualidades

Os enormes progressos das ciências biológicas ocorridos nas últimas décadas abrem grandes perspectivas benéficas para o homem no terreno das aplicações, em particular no domínio da agronomia e da biomedicina. A sociedade brasileira deverá romper com essa situação, em que os progressos beneficiam apenas setores privilegiados, e promover a educação e divulgação científicas de qualidade a todos os níveis, concentrando sua aplicação em domínios essenciais para vencer atrasos e deformações da sociedade brasileira. Se a ciência e a tecnologia não tiverem relação direta com a realidade do dia-a-dia, traduzindo-se em melhoria da situação material e cultural do conjunto da sociedade, estarão se arriscando a evoluir para uma situação de atividade apenas virtual.