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Population diversity and transmission dynamics of Plasmodium sp.
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Apesar dos esforços desenvolvidos nas últimas décadas, a malária continua a ser um dos maiores problemas de saúde pública no mundo, sendo a principal causa de morbilidade e mortalidade principalmente na África Subsaariana.
Fazer uma análise global, que integre todos os intervenientes deste sistema complexo, que engloba três entidades biológicas, fatores socioeconómicos e ambientais, não é fácil, mas pensamos ser um ponto fulcral para um maior conhecimento sobre esta doença. Neste estudo, utilizando um conjunto completo de amostras – sangue periférico e mosquitos – pretendeu-se analisar este complexo sistema de forma abrangente.
Deste modo, este trabalho teve como principais objetivos: 1) Caraterizar as populações parasitárias circulantes nos dois hospedeiros – humano e mosquito vetor - através da identificação das espécies de Plasmodium presentes; marcadores moleculares
de diversidade (Pfmsp2) e marcadores moleculares associados a resistência a fármacos (mutações pontuais nos genes Pfdhps, Pfdhfr, Pfcrt e Pfmdr1); 2) Analisar as pressões seletivas atuantes sobre os genes associados a resistência a fármacos e 3) Analisar a diversidade de genes do mosquito vetor - AgTG1 e AgTG2 - tentando relacioná-los com a presença/ausência de infeção.
As amostras biológicas utilizadas para este trabalho foram recolhidas em três países diferentes: na Guiné Equatorial continental foram colhidas amostras de sangue e mosquitos adultos em duas localidades, Miyobo e Ngonamanga. Em Angola obtiveramse as amostras de sangue em quatro localidades diferentes (Gabela, Porto Amboim, Kissala – Sumbe e Praia – Sumbe) e foram ainda usados neste estudo mosquitos adultos provenientes de Antula, Guiné-Bissau.
Em relação ao primeiro e segundo objetivos deste trabalho, foi possível constatar a presença das quatro espécies de Plasmodium em ambos os hospedeiros, com prevalências superiores às reportadas oficialmente, incluindo P. vivax, espécie que ainda não tinha sido detetada na Guiné Equatorial continental. Detetou-se igualmente
indivíduos Duffy negativos infetados com duas estirpes diferentes de Plasmodium vivax (P. vivax clássico e o P. vivax VK247). Relativamente às mutações pontuais associadas à resistência aos antimaláricos, constatou-se que de um modo geral estas ocorriam em elevada prevalência. Verificou-se igualmente que a resistência à pirimetamina encontrase bem estabelecida neste país, enquanto a resistência à sulfadoxina terá tido uma introdução mais recente. Relativamente ao terceiro e último objetivo deste trabalho, constatou-se que os dois genes estudados - AgTG1 e AgTG2- apresentam fortes sinais de
seleção positiva, podendo estar envolvidos no reconhecimento de organismos patogénicos, e por conseguinte envolvidos numa resposta contra a infeção.
Por fim, este trabalho permitiu concluir que na Guiné Equatorial continental existem as quatro espécies de Plasmodium, incluindo a espécie P. vivax que até à data não estava descrita no país. Foi encontrada uma elevada prevalência de mutações associadas à resistência à sulfadoxina-pirimetamina, pelo que se recomenda uma
contínua monitorização destas mutações. Por fim constatou-se que os genes AgTG1 e AgTG2 apresentam fortes sinais de de seleção positiva, podendo estar envolvidos no reconhecimento de organismos patogénicos, e por conseguinte envolvidos numa resposta contra a infeção. Por fim, este trabalho permitiu concluir que na Guiné Equatorial continental existem as quatro espécies de Plasmodium, incluindo a espécie P.vivax que até à data não estava descrita no país. Foi encontrada uma elevada prevalência de mutações associadas à resistência à sulfadoxina-pirimetamina, pelo que se recomenda uma contínua monitorização destas mutações. Por fim constatou-se que os genes AgTG1 e AgTG2 apresentam fortes sinais de seleção positiva, podendo estar envolvidos na resposta à infeção por Plasmodium.
Despite all efforts made over the past decades, malaria remains a major public health problem in the world, affecting mainly the Sub-Saharan Africa. A comprehensive analysis that integrates all factors in this complex system, which consists of three biological entities, socio-economic and environmental factors, is not easy, but it is crucial for a better understanding of this disease. In this study, using a complete set of peripheral blood samples and mosquitoes, we intended to analyse this complex system. So, the main objectives of this study were to: 1) Characterise the circulating parasite populations in the two hosts – human and mosquito vector - through the identification of Plasmodium species; molecular marker diversity (Pfmsp2) and drug resistance-associated markers (mutations in the genes Pfdhps , Pfdhfr , Pfcrt and Pfmdr1; 2) analyse the selective pressures acting on genes associated with drug resistance and 3 ) analyse the diversity of genes in the mosquito vector - AgTG1 and AgTG2 - trying to relate them to the presence / absence of infection. The biological samples used in this study were collected in three different countries: blood samples were collected in mainland Equatorial Guinea (in two villages: Miyobo and Ngonamanga) and in Angola (in four different villages: Gabela, Porto Amboim, Kissala - Sumbe and Praia - Sumbe); mosquitoes were collected, also, in the two villages of Equatorial Guinea and in Antula, Guinea Bissau. Regarding the first and second objectives of this study, it was possible to detect the presence of the four Plasmodium species in both hosts, with prevalence higher than officially reported, including Plasmodium vivax, a species that had not been previously described in this country. Duffy negative individuals infected with two different strains of P. vivax (VK247 and classic strains) were also found. Concerning the molecular markers associated to drug resistance, high prevalence was found. Results also demonstrated that pyrimethamine resistance has been established for a while in mainland Equatorial Guinea as shown by several selection signatures in the parasite genome, while sulphadoxine had a more recent introduction in this country.Finally and regarding the third and final objective of this study, it was found that the both genes studied - AgTG1AgTG2 - showed strong signs of positive selection. This study revealed that the four Plasmodium species are present in mainland Equatorial Guinea, including P. vivax, specie that had not been described yet in this country. High prevalence of mutation in genes associated with resistance to the sulphadoxine-pyrimethamine combination were found, so it is recommended a close and continuous monitoring of these mutations frequency, since there is the danger of an eventual reduction in the efficacy of combined therapy. Finally it was found that the AgTG1 and AgTG2 genes show strong positive selection signals, which may be involved in recognition and immune response triggered by the mosquito against the invading pathogens, like Plasmodium.
Despite all efforts made over the past decades, malaria remains a major public health problem in the world, affecting mainly the Sub-Saharan Africa. A comprehensive analysis that integrates all factors in this complex system, which consists of three biological entities, socio-economic and environmental factors, is not easy, but it is crucial for a better understanding of this disease. In this study, using a complete set of peripheral blood samples and mosquitoes, we intended to analyse this complex system. So, the main objectives of this study were to: 1) Characterise the circulating parasite populations in the two hosts – human and mosquito vector - through the identification of Plasmodium species; molecular marker diversity (Pfmsp2) and drug resistance-associated markers (mutations in the genes Pfdhps , Pfdhfr , Pfcrt and Pfmdr1; 2) analyse the selective pressures acting on genes associated with drug resistance and 3 ) analyse the diversity of genes in the mosquito vector - AgTG1 and AgTG2 - trying to relate them to the presence / absence of infection. The biological samples used in this study were collected in three different countries: blood samples were collected in mainland Equatorial Guinea (in two villages: Miyobo and Ngonamanga) and in Angola (in four different villages: Gabela, Porto Amboim, Kissala - Sumbe and Praia - Sumbe); mosquitoes were collected, also, in the two villages of Equatorial Guinea and in Antula, Guinea Bissau. Regarding the first and second objectives of this study, it was possible to detect the presence of the four Plasmodium species in both hosts, with prevalence higher than officially reported, including Plasmodium vivax, a species that had not been previously described in this country. Duffy negative individuals infected with two different strains of P. vivax (VK247 and classic strains) were also found. Concerning the molecular markers associated to drug resistance, high prevalence was found. Results also demonstrated that pyrimethamine resistance has been established for a while in mainland Equatorial Guinea as shown by several selection signatures in the parasite genome, while sulphadoxine had a more recent introduction in this country.Finally and regarding the third and final objective of this study, it was found that the both genes studied - AgTG1AgTG2 - showed strong signs of positive selection. This study revealed that the four Plasmodium species are present in mainland Equatorial Guinea, including P. vivax, specie that had not been described yet in this country. High prevalence of mutation in genes associated with resistance to the sulphadoxine-pyrimethamine combination were found, so it is recommended a close and continuous monitoring of these mutations frequency, since there is the danger of an eventual reduction in the efficacy of combined therapy. Finally it was found that the AgTG1 and AgTG2 genes show strong positive selection signals, which may be involved in recognition and immune response triggered by the mosquito against the invading pathogens, like Plasmodium.
Descrição
Palavras-chave
Parasitologia médica Saúde pública Malária Plasmodium sp Plasmodium vivax Mosquito anopheles Taxa de morbilidade Taxa de mortalidade
Contexto Educativo
Citação
Editora
Instituto de Higiene e Medicina Tropical