A carregar...
Publicação
Estudos epidemiológicos e resistência aos antimaláricos em Timor Leste
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 162.01 KB | Adobe PDF | |||
| 514.06 KB | Adobe PDF | |||
| 687.54 KB | Adobe PDF | |||
| 1.02 MB | Adobe PDF | |||
| 220.25 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
A malária constitui um grave problema de saúde pública na República Democrática de Timor Leste (RDTL), caracterizada por ser uma doença endémica em todos os distritos, com as mais elevadas taxas de mortalidade e morbilidade nas crianças e mulheres grávidas. Desde a independência em 2002, o número de casos da
malária tem vindo a aumentar e a inexistência de dados epidemiológicos e poucos estudos ligados à resistência aos antimaláricos alertaram para a necessidade de
actualizar o conhecimento da situação, com o objectivo de fomentar uma política de intervenção no domínio da vigilância e controlo da malária no país. Deste modo, este
trabalho teve como finalidade avaliar a frequência da malária em cada distrito estudado, identificar e caracterizar os factores causais da sua distribuição e os diversos factores socio-económicos envolvidos na transmissão e determinar a prevalência de mutações nos genes pfcrt, pfmdr1, pfdhfr, pfdhps em Plasmodium falciparum e pvdhfr e pfdhps em Plasmodium vivax, responsáveis pela resistência aos fármacos oficialmente em uso no país.
Neste contexto, foi efectuado um estudo epidemiológico onde foram colhidas amostras sanguíneas por Busca Passiva (BP) nos Hospitais/Clínicas e Busca Activa
(BA) em domicílios individuais, distribuídos por seis distritos da RDTL, nos quais se pesquisou posteriormente a presença dos parasitas P. falciparum e P. vivax,
recorrendo as duas técnicas laboratoriais distintas: microscopia óptica e Polymerase Chain Reaction (PCR).
Relativamente aos resultados obtidos no levantamento epidemiológico, a frequência e a distribuição da malária observada na população traduzem uma prevalência de 25,8% (112/434, na BP) e 5,1% (11/216, na BA), tendo-se observado maior prevalência nos grupos etários com menos de 14 anos de idade em relação aos indivíduos com idade superior ou igual aos 15 anos de idade. Verificou-se maior predomínio de infecção no sexo masculino relativamente ao sexo feminino.Adicionalmente, confirmou-se que várias características socio-económicas estão associadas à ocorrência de malária, tais como: tipo e condições precárias de habitação, criação de animais junto das habitações, trabalho/ocupação que expõe mais ao contacto com o mosquito vector. Por outro lado, os indivíduos que não utilizam redes mosquiteiras como protecção têm maior probabilidade de se encontrarem infectados. A proporção dos indivíduos com infecção da malária entre as zonas de residência foi analisada e comparada, não tendo sido demonstradas diferenças significativas, o que possibilitaria acções semelhantes a implementar para o controlo da malária no País.
No que respeita à pesquisa de mutações em genes de plasmódio previamente apontados como moduladores de fármaco-resistência, foram detectadas elevadas prevalências de alelos mutantes em ambas as espécies, P. falciparum e P. vivax, sugerindo que a resistência pode ser igualmente prevalente. Neste âmbito, realça-se a observação de que um grande número de amostras de P. falciparum (82,5%) era portador de 4 mutações distribuídas pelos genes dhfr e dhps, padrão este previamente
associado à falência terapêutica com sulfadoxina-pirimetamina (SP).
Adicionalmente, demonstrou-se a existência da mutação pfcrt K76T, associada à resistência à cloroquina, em todos os isolados analisados, demonstrando que a mesma atingiu a fixação. Relativamente às amostras de P. vivax, a prevalência dos alelos mutantes 58R e 117N no gene pvdhfr foi de 79% e 81,6%, respectivamente, enquanto que 73,7% dos parasitas continham ambas mutações em simultâneo (“duplos mutantes”). Colectivamente, conclui-se que utilização continuada dos fármacos cloroquina e SP poderá contribuir para o contínuo aumento de mutações
nos genes supracitados e consequente ineficácia clínica dos mesmos no tratamento do Plasmodium falciparum e Plamodium vivax.
Em conclusão, a detecção da prevalência dos polimorfismos genéticos de resistência constitui uma ferramenta acessória de fármaco vigilância e a identificação
de características sócio-economicos envolvidas na transmissão da malária permitirá a elaboração e implementação de campanhas melhoradas de prevenção e/ou controlo da malária na RDTL.
Malaria is one of the Democratic Republic of East Timor (DRET) major public health problems. This disease is endemic in all districts, with the highest morbidity and mortality rates reported in children and pregnant women. Since the country’s independence in 2002, the number of malaria cases has increased and the absence of epidemiological data and few studies linked to antimalarial resistance highlighted the need to update knowledge on the situation, with the objective of stimulating improved intervention policies, towards better drug surveillance and malaria control. Under this circumstances, the objectives of this study were to evaluate malaria frequency in each district studied, to identify and to characterize the casual factors of its distribution and the several socio-economics factors involved in its transmission and to determine the prevalence of mutations in the pfcrt, pfmdr1, pfdhfr, pfdhps genes of P. falciparum and the pvdhfr and pfdhps genes in P. vivax, previously involved in resistance to the drugs in official use in the country. In this context, blood sample collections were carried out by Passive Case Detection (PCD) in hospitals/clinics or Active Case Detection (ACD) in individual households, distributed among six districts of the RDTL. Each sample was inspected for presence of P. falciparum and P. vivax parasites through two different experimental approaches: optical microscopy and Polymerase Chain Reaction. The epidemiological survey for frequency and malaria distribution in the population demonstrated a prevalence of 25,8% (112/434) and 5,1% (11/216), using PCD and ACD, respectively. Higher malaria prevalence occurred in the age groups of less than 14 years of age in relation to individuals with age equal or above 15 years. Additionally, malarial infection was shown to be more predominant in males than in females. Several socio-economic parameters were associated to malaria occurrence, such as: type and precarious household conditions, animal keeping near households and type of work/occupation more prone to mosquito vector exposure. Also, individuals that didn't use protective bed-nets were shown to have a higher probability of being infected. The proportion of malaria-infected individuals among different geographical areas was analyzed and compared, but no significant differences were detected. This scenario should facilitate the implementation of a global malaria control in the Country based on similar measures for the different regions. Inspection of mutations in plasmodium genes previously proposed as drug response modulators, highlighted high prevalence of mutant alleles in both P. falciparum and P. vivax, suggesting that in vivo resistance may be equally prevalent. In this context, it is noted that a high percentage of P. falciparum isolates (82.5%) carried 4 mutations distributed among the dhfr and dhps genes, known to be directly related to sulphadoxine + pyrimethamine (SP) treatment failure. Additionally, it was demonstrated that the pfcrt K76T mutation, associated to chloroquine resistance, was present in all isolates analyzed, demonstrating that it has reached fixation. For P. vivax, the prevalence of mutations in the pvdhfr gene was of 79% and 81.6% for the for 58R, 117N alleles, respectively, whilst 73.7% of the samples harboured both mutation in simultaneous (“double mutants”) Collectively, it may be conjectured that that the constant use of SP and chloroquine will contribute to the continuous increase of mutations in the above-mentioned genes and consequent clinical inefficacy of these drugs in the treatment of P. falciparum and P. vivax. In conclusion, assessing the prevalence of genetic polymorphisms associated to drug resistance can be used as an accessory tool for drug surveillance, and the identification of socio-economic factors involved in malaria transmission will allow the elaboration and implementation of improved malaria control and/or prevention campaigns in the DRET.
Malaria is one of the Democratic Republic of East Timor (DRET) major public health problems. This disease is endemic in all districts, with the highest morbidity and mortality rates reported in children and pregnant women. Since the country’s independence in 2002, the number of malaria cases has increased and the absence of epidemiological data and few studies linked to antimalarial resistance highlighted the need to update knowledge on the situation, with the objective of stimulating improved intervention policies, towards better drug surveillance and malaria control. Under this circumstances, the objectives of this study were to evaluate malaria frequency in each district studied, to identify and to characterize the casual factors of its distribution and the several socio-economics factors involved in its transmission and to determine the prevalence of mutations in the pfcrt, pfmdr1, pfdhfr, pfdhps genes of P. falciparum and the pvdhfr and pfdhps genes in P. vivax, previously involved in resistance to the drugs in official use in the country. In this context, blood sample collections were carried out by Passive Case Detection (PCD) in hospitals/clinics or Active Case Detection (ACD) in individual households, distributed among six districts of the RDTL. Each sample was inspected for presence of P. falciparum and P. vivax parasites through two different experimental approaches: optical microscopy and Polymerase Chain Reaction. The epidemiological survey for frequency and malaria distribution in the population demonstrated a prevalence of 25,8% (112/434) and 5,1% (11/216), using PCD and ACD, respectively. Higher malaria prevalence occurred in the age groups of less than 14 years of age in relation to individuals with age equal or above 15 years. Additionally, malarial infection was shown to be more predominant in males than in females. Several socio-economic parameters were associated to malaria occurrence, such as: type and precarious household conditions, animal keeping near households and type of work/occupation more prone to mosquito vector exposure. Also, individuals that didn't use protective bed-nets were shown to have a higher probability of being infected. The proportion of malaria-infected individuals among different geographical areas was analyzed and compared, but no significant differences were detected. This scenario should facilitate the implementation of a global malaria control in the Country based on similar measures for the different regions. Inspection of mutations in plasmodium genes previously proposed as drug response modulators, highlighted high prevalence of mutant alleles in both P. falciparum and P. vivax, suggesting that in vivo resistance may be equally prevalent. In this context, it is noted that a high percentage of P. falciparum isolates (82.5%) carried 4 mutations distributed among the dhfr and dhps genes, known to be directly related to sulphadoxine + pyrimethamine (SP) treatment failure. Additionally, it was demonstrated that the pfcrt K76T mutation, associated to chloroquine resistance, was present in all isolates analyzed, demonstrating that it has reached fixation. For P. vivax, the prevalence of mutations in the pvdhfr gene was of 79% and 81.6% for the for 58R, 117N alleles, respectively, whilst 73.7% of the samples harboured both mutation in simultaneous (“double mutants”) Collectively, it may be conjectured that that the constant use of SP and chloroquine will contribute to the continuous increase of mutations in the above-mentioned genes and consequent clinical inefficacy of these drugs in the treatment of P. falciparum and P. vivax. In conclusion, assessing the prevalence of genetic polymorphisms associated to drug resistance can be used as an accessory tool for drug surveillance, and the identification of socio-economic factors involved in malaria transmission will allow the elaboration and implementation of improved malaria control and/or prevention campaigns in the DRET.
Descrição
Palavras-chave
Parasitologia médica Malária Epidemiologia Antimaláricos Resistência
Contexto Educativo
Citação
Editora
Instituto de Higiene e Medicina Tropical