Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes’ midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies

Morbidity surveillance in the municipalities of the area of influence during the construction of the hydroelectric plant Porce II (EPM, Antioquia, Colombia, 1997-2000)

ABSTRACT: This study presents the behavior of the morbidity in the four municipalities in area of influence during the construction of the hydroelectric project Porce II, as a part of the social and environmental management developed by EPM (Medellín Public Services Company) through the system of epidemiological surveillance of Porce II. The morbidity profile denotes the presence of problems associated to deficient economic and social conditions like bacterial and parasitic diseases that affect the respiratory and digestive system and the skin. In addition, the pioneer experience of this system of epidemiological surveillance generated an important contribution in the design and realization of surveillances systems on public health that allow the diagnosis of high-priority problems in the health of the populations in the influence areas during the construction of hydroelectric macro projects.RESUMEN: Se presenta el comportamiento de la morbilidad en los cuatro municipios del área de influencia durante la construcción del proyecto hidroeléctrico Porce II, que se realizó como parte de la gestión social y ambiental desarrollada por Empresas Públicas de Medellín, ESP (Empresa de Servicios Públicos) a través del sistema de vigilancia epidemiológica Porce II. Las enfermedades transmisibles de notificación obligatoria y otros eventos de vigilancia epidemiológica fueron registradas durante cada periodo epidemiológico del año, según causa, género y edad a partir de diferentes fuentes de información. La morbilidad fue agrupada siguiendo la pauta de la Décima Clasificación Internacional de Enfermedades o CIE 10. El perfil de morbilidad observado en la región denota la presencia de problemas asociados a condiciones económicas y sociales deficientes, como son las enfermedades de origen bacteriano y parasitario que afectan las vías respiratorias, el sistema digestivo y la piel. La experiencia piloto de la implementación de este sistema de vigilancia epidemiológica generó un aporte importante para el país, en el diseño y ejecución de sistemas de vigilancia en salud pública durante la construcción de macroproyectos hidroeléctricos, que permite la identificación y análisis de los problemas prioritarios de salud de las poblaciones ubicadas en el área de influencia

Morphological aspects of immature stages of Migonemyia migonei (Diptera: Psychodidae, Phlebotominae), an important vector of Leishmaniosis in South America, described by scanning electron microscopy.

We describe the immature stages of Migonemyia migonei, which is the vector of Leishmania (Viannia) braziliensis, the etiological agent of cutaneous leishmaniasis in South America, and a putative vector of Leishmania infantum chagasi. Scanning Electron Microscopy (SEM) was used to refine the description of the structures of the egg, all instar larvae, and the pupa. The eggs have polygonal cells on the egg exochorion, and differences between larval and pupal chaetotaxy have been highlighted. Different sensillary subtypes-trichoidea, basiconica, coelonica and campanoformia-were observed in the larval stages. The results presented herein contribute to the taxonomy of Mg. migonei and may contribute to future studies on the phylogeny of this important vector species