The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector.

Høgh, Birthe; Gamage-Mendis, Asoka C.; Butcher, G. A.; Thompson, Ricardo; Begtrup, Kamilla; Mendis, Chandana; Enosse, Sónia; Dgedge, Martinho; Barreto, Jorge; Eling, W.M.C.; Sinden, Robert E.

doi:10.4269/ajtmh.1998.58.176

Cited by 97 publications

(80 citation statements)

References 37 publications

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“…Hay estudios epidemiológicos que sugieren que la presión medicamentosa posterior al uso de antipalúdicos sin actividad gametocitocida inmediata también puede aumentar la producción de esas células sexuales y la transmisión de P. falciparum (56)(57)(58)(59), pero no es claro si la elevada prevalencia de gametocitos observada después del uso de antipalúdicos contra P. falciparum se debe a la inducción de la gametocitogénesis por el fármaco o si es consecuencia de la supervivencia y maduración posterior al tratamiento de la células ya existentes (60).…”

Section: Antipalúdicos Y Gametocitos De P Falciparumunclassified

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

Carmona‐Fonseca¹,

Arango²,

Blair³

2008

biomedica

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Introducción. Las relaciones de la gametocitemia de Plasmodium falciparum con el tratamiento antipalúdico han sido poco estudiadas en América. Objetivo. Describir relaciones de la gametocitemia falciparum con el tratamiento con amodiaquina-sulfadoxina-pirimetamina, artesunato-sulfadoxina-pirimetamina o amodiaquinaartesunato. Materiales y métodos. Se usó un diseño experimental, aleatorio, no balanceado, no ciego. El seguimiento fue de 21 a 28 días. La eficacia terapéutica se clasificó según el protocolo de la Organización Mundial de la Salud, 1998. Resultados. Se evaluaron 241 pacientes en Turbo, El Bagre y Zaragoza (Antioquia, Colombia). El esquema de amodiaquina-sulfadoxina-pirimetamina tuvo igual eficacia que el de artesunatosulfadoxina-pirimetamina y amodiaquina-artesunato para controlar las fallas terapéuticas el día 21. Hubo cuatro fallas (1,66%). El esquema de amodiaquina-sulfadoxina-pirimetamina fue menos eficaz que los tratamientos con artesunato para reducir la presencia de gametocitos. Al séptimo día, ninguno de los tres tratamientos había eliminado totalmente los gametocitos. La mayoría (56%) de nuestros pacientes no tenía gametocitos antes del tratamiento y nunca los desarrolló. El tiempo para eliminar los gametocitos que se tenían al iniciar el tratamiento no fue mayor cuando la gametocitemia inicial era mayor. Conclusión. Los tres tratamientos fueron iguales en cuanto a eficacia terapéutica e incapacidad de eliminar los gametocitos en siete días.Palabras clave: malaria/terapia, malaria falciparum, Plasmodium falciparum, antipalúdicos, amodiaquina, sulfadoxina, pirimetamina, Artemisia annua. Gametocytemia in falciparum malaria treated with amodiaquine or artesunateIntroduction. Antimalarial treatment effects on Plasmodium falciparum gametocytemia has been the focus of few studies in the Americas. Objective. Relationships are described that occur between falciparum gametocytemia and the treatment with amodiaquine-sulfadoxine-pyrimethamine, artesunate-sulfadoxinepyrimethamine or amodiaquine-artesunate. Materials and methods. The experimental design consisted of a randomized selection of patients not balanced or blinded. A total of 241 patients were evaluated, residents of Turbo, El Bagre and Zaragoza (Antioquia, Colombia).The follow up occurred 21-28 days after antimalarial treatment. The World Health Organization (1998) protocol was used. Results. The therapeutic efficacy of amodiaquine-sulfadoxine-pyrimethamine, artesunatesulfadoxine-pyrimethamine and amodiaquine-artesunate were equal at day 21 of the follow up. Four cases (1.7%) were therapeutic failures. Amodiaquine-sulfadoxine-pyrimethamine was less effective than the artesunate treatments in reducing the gametocyte load. On day 7, none of the three traetments had eliminated completely the gametocytes. Most patients (56.0%) were observed not to have circulating gametocytes pre-treatment and did not develop them later. Conclusion. The three treatment schemes were similar in their therapeutic efficacy and in their incapacity to eliminate gametocyte...

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Section: Antipalúdicos Y Gametocitos De P Falciparumunclassified

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

Carmona‐Fonseca¹,

Arango²,

Blair³

2008

biomedica

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“…If the parasite population is`stressed', as with the use of partially e¡ec-tive drugs, gametocytogenesis increases (Carter & Miller 1979) and gametocytaemia becomes more likely. Gametocytes formed following treatment of a resistant infection may have reduced transmission potential (Hogh et al 1998). Recrudescent infections have been present in the body for longer than primary infections, and the parasite population has been under`stress' from a partially e¡ective treatment.…”

Section: (M) Resistance and Transmission Potentialmentioning

confidence: 99%

Antimalarial drug resistance and combination chemotherapy

White

1999

Phil. Trans. R. Soc. Lond. B

506

467

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Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration^e¡ect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the chance of a resistant mutant surviving is the product of the per parasite mutation rates for the individual drugs, multiplied by the number of parasites in an infection that are exposed to the drugs. Artemisinin derivatives are particularly e¡ective combination partners because (i) they are very active antimalarials, producing up to 10 000-fold reductions in parasite biomass per asexual cycle; (ii) they reduce malaria transmissibility; and (iii) no resistance to these drugs has been reported yet. There are good arguments for no longer using antimalarial drugs alone in treatment, and instead always using a combination with artemisinin or one of its derivatives.

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“…However, gametocytes have been found to be resistant to many of the commonly used antimalarials, such as the 4-aminoquinolines; and sulfadoxinepyrimethamine has been reported to increase the production of gametocytes, which could enhance transmission (2,12,21,36). Consequently, even after successful treatment for clinical symptoms, an individual can still transmit the malaria parasite for at least a week.…”

mentioning

confidence: 99%

Inhibition of Plasmodium falciparum Oocyst Production by Membrane-Permeant Cysteine Protease Inhibitor E64d

Ekşi

Czesny

Gemert³

et al. 2007

Antimicrob Agents Chemother

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During asexual intraerythrocytic growth, Plasmodium falciparum utilizes hemoglobin obtained from the host red blood cell (RBC) as a nutrient source. Papain-like cysteine proteases, falcipains 2 and 3, have been reported to be involved in hemoglobin digestion and are targets of current antimalarial drug development efforts. However, their expression during gametocytogenesis, which is required for malaria parasite transmission, has not been studied. Many of the available antimalarials do not inhibit development of sexual stage parasites, and therefore, the persistence of gametocytes after drug treatment allows continued transmission of the disease. In the work reported here, incubation of stage V gametocytes with membrane-permeant cysteine protease inhibitor E64d significantly inhibited oocyst production (80 to 100%). The same conditions inhibited processing of gametocyte-surface antigen Pfs230 during gametogenesis but did not alter the morphology of the food vacuole in gametocytes, inhibit emergence, or block male exflagellation. E64d reduced the level of oocyst production more effectively than that reported previously for falcipain 1-knockout parasites, suggesting that falcipains 2 and 3 may also be involved in malaria parasite transmission. However, in this study only falcipain 3 and not falcipain 2 was found to be expressed in stage V gametocytes. Interestingly, during gametocytogenesis falcipain 3 was transported into the red blood cell and by stage V was localized in vesicles along the RBC surface, consistent with a role during gamete emergence. The ability of a membrane-permeant cysteine protease inhibitor to significantly reduce malaria parasite transmission suggests that future drug design should include evaluation of gametogenesis and sporogonic development.The clinical symptoms of malaria are caused by asexually replicating parasites, but malaria parasite transmission requires that a subpopulation of parasites undergo sexual differentiation. In the species of parasite responsible for the most virulent form of malaria, Plasmodium falciparum, complete maturation into mature stage V gametocytes takes 10 to 12 days in the human host. Once stage V gametocytes are taken up by a mosquito, gametogenesis is stimulated and, after fertilization, the zygote differentiates into an ookinete. The ookinete then migrates to the basal surface of the midgut and forms an oocyst, where tens of thousands of infectious sporozoites are produced.Both asexual and sexual stage parasites are present concurrently in an infected individual and therefore would both be exposed to antimalarial drugs. However, gametocytes have been found to be resistant to many of the commonly used antimalarials, such as the 4-aminoquinolines; and sulfadoxinepyrimethamine has been reported to increase the production of gametocytes, which could enhance transmission (2, 12, 21, 36). Consequently, even after successful treatment for clinical symptoms, an individual can still transmit the malaria parasite for at least a week. Therefore, it is important to d...

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The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector.

Cited by 97 publications

References 37 publications

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

Antimalarial drug resistance and combination chemotherapy

Inhibition of Plasmodium falciparum Oocyst Production by Membrane-Permeant Cysteine Protease Inhibitor E64d

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