Effects of Chloroquine, Amodiaquine and Pyrimethamine-Sulfadoxine on Plasmodium Falciparum Gametocytemia

Strickland, G. Thomas; Fox, Emile; Sarwar, Mohammad; Khaliq, Amir A.; MacDonald, Michael R.

doi:10.4269/ajtmh.1986.35.259

Cited by 19 publications

(15 citation statements)

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“…Our data on the absence of gametocytocidal effect of chloroquine on mature P. falciparum gametocytes are in agreement with those of previous studies. 2,9 However, our observation that chloroquine-treated patients infected with chloroquine-sensitive parasites had lower gametocytemia, compared with the patient with chloroquine-resistant parasites, is consistent with the fact that chloroquine exerts an inhibitory action against immature gametocytes. 2 Forty-seven (64%) of 73 patients in the pyronaridine group and 16 (21%) of 77 patients in the chloroquine group without detectable gametocytes on day 0 subsequently developed gametocytemia.…”

supporting

confidence: 68%

Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria.

Ringwald¹,

Meche²,

Basco³

1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The effects of pyronaridine and chloroquine on mature Plasmodium falciparum gametocytes were compared in 161 patients treated with chloroquine or pyronaridine. Neither pyronaridine nor chloroquine showed gametocytocidal activity. The relative risks of post-treatment gametocytemia after pyronaridine and chloroquine treatment in the presence of chloroquine-resistant isolates were 1.25 and 11.5, respectively, suggesting that the use of chloroquine was associated with a high risk of favoring post-therapeutic gametocytemia in chloroquine-resistant infections.The intense and continuous transmission of Plasmodium falciparum is one of the important factors that maintain the high prevalence of malaria in most of tropical Africa. The available measures to reduce malaria transmission include vector control and the use of gametocytocidal drugs. Vector control in Africa has not had much impact on malaria control, except in pilot programs. 1 The currently available firstor second-line (chloroquine, amodiaquine, sulfadoxine-pyrimethamine) and third-line (quinine) drugs in Africa do not exhibit any direct gametocytocidal action on P. falciparum. 2 Pyronaridine is a new synthetic drug that is undergoing preclinical and clinical evaluation and may replace chloroquine in Africa. 3,4 We studied and compared the effects of pyronaridine and chloroquine on gametocytes in patients with acute uncomplicated falciparum malaria.The study was part of the clinical trials involving 184 symptomatic, malaria-infected African patients (96 adults and 88 children between 5 and 15 years of age) in Yaoundé, Cameroon.4,5 Patients were treated with either 25 mg/kg of chloroquine phosphate (n ϭ 93; 10 mg/kg on days 0 and 1 and 5 mg/kg on day 2) or 32 mg/kg of pyronaridine tetraphosphate (n ϭ 91; 16 mg/kg on day 0 in two divided doses and 8 mg/kg on days 1 and 2) after informed consent was obtained from the patients or their guardians. The study was approved by the Cameroonian National Ethics Committee. Giemsa-stained thick blood smear was examined for the detection and quantification of gametocytes. The clinical conditions and asexual parasitemia were monitored on days 0, 1, 2, 3, 4, 7, and 14 on an out-patient basis. Because of the slower developmental rate of gametocytes (8-10 days), compared with the 48-hr cycle of P. falciparum asexual erythrocytic forms, 6 gametocyte count was monitored on days 0, 3, 7, and 14. Gametocytes were counted against 3,000 white blood cells, and gametocyte density was determined from the white blood cell count and expressed as the number of gametocytes/l of blood.Thick blood smears were considered negative if no gametocyte was seen after counting 3,000 white blood cells. The patients were assigned to one of the following groups for the analysis of parasitologic responses of gametocytes: 1) absence of gametocytes during the 14-day follow-up period, including day 0, 2) pretreatment presence of gametocytes (which allows the evaluation of a possible gametocytocidal effect of antimalarial drugs), and 3) post-treatme...

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confidence: 68%

Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria.

Ringwald¹,

Meche²,

Basco³

1999

The American Journal of Tropical Medicine and Hygiene

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“…El efecto de la CQ y la SP sobre la gametocitemia no está bien establecido. Los estudios realizados al respecto muestran resultados diferentes y, por tanto, cualquier conclusión debe hacerse con cautela (7,(13)(14)(15)(16)(17)19,20). En nuestro estudio encontramos que los pacientes que fueron tratados con SP presentaron gametocitemia durante todo el seguimiento (en especial entre los días 3 y 14) más altas que los pacientes tratados con SP+CQ, pero las diferencias no fueron estadísticamente significativas; esto concuerda con lo encontrado en algunos estudios (15,17).…”

Section: Discussionunclassified

“…Diversos estudios han informado que el número de gametocitos circulantes en P. falciparum está influenciado tanto por aspectos del hospedero (la respuesta inmune), del parásito (la cantidad de parásitos asexuales y su capacidad para diferenciarse a gametocitos), como por aspectos externos (el tipo de medicamento suministrado en el control de los estadios asexuales) (1,3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Además, algunos estudios muestran que los pacientes con falla al tratamiento antimalárico o aquéllos que requieren más tiempo para eliminar los parásitos asexuales, presentan mayor número de gametocitos circulantes que los pacientes que responden adecuadamente al tratamiento o cuya parasitemia asexual desaparece más rápidamente con el tratamiento suministrado (11,17,18).…”

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“…Además, algunos estudios muestran que los pacientes con falla al tratamiento antimalárico o aquéllos que requieren más tiempo para eliminar los parásitos asexuales, presentan mayor número de gametocitos circulantes que los pacientes que responden adecuadamente al tratamiento o cuya parasitemia asexual desaparece más rápidamente con el tratamiento suministrado (11,17,18). Sin embargo, hay datos contradictorios acerca de la influencia que tienen los esquizonticidas sanguíneos sobre la gametocitemia de pacientes con malaria por P. falciparum (7,(12)(13)(14)(15)17,19).…”

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Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia.

Arango¹,

Álvarez²,

Carmona³

et al. 2004

biomedica

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Se ha informado que el número de gametocitos circulantes de Plasmodium falciparum está influenciado por aspectos como el nivel de endemicidad de la zona, la clase de esquizonticidas sanguíneos usados y la respuesta terapéutica a ellos. En Colombia son muy pocos los trabajos que han evaluado estas relaciones. Mediante un diseño experimental, se evaluó la gametocitemia (variable efecto) en función del nivel endémico de dos municipios de Antioquia, del tratamiento (sulfadoxina-pirimetamina y sulfadoxina-pirimetamina más cloroquina) y de la respuesta terapéutica (adecuada y fallida). Se estudiaron 148 pacientes con malaria por P. falciparum no complicada. La gametocitemia varía en función del tiempo de padecimiento de la malaria actual (mayor en Turbo que en Zaragoza) y esta variable debe controlarse para eliminar la aparente diferencia en las gametocitemias por municipio. No se hallaron diferencias estadísticamente significativas en la gametocitemia (porcentaje de pacientes con gametocitos circulantes y cantidad de ellos por microlitro) según el tratamiento y la respuesta terapéutica, aunque los niveles de gametocitos son mayores en los pacientes tratados sólo con sulfadoxinapirimetamina, respecto a quienes recibieron sulfadoxina-pirimetamina más cloroquina. Tampoco hubo diferencias en la gametocitemia según el sexo ni la edad de los pacientes, ni se halló correlación de ella con la parasitemia asexual. La diferencia en el nivel de gametocitemia encontrada entre los municiios de Turbo y Zaragoza parece estar influida por el tiempo transcurrido entre el inicio de los síntomas y la instauración del tratamiento.Palabras clave: gametocitemia, Plasmodium falciparum, Turbo, Zaragoza, cloroquina, sulfadoxina-pirimetamina, respuesta terapéutica. Gametocyte levels in response to differing malaria treatments in two municipalities of ColombiaPlasmodium falciparum gametocyte levels are influenced by level of regional endemicity, the antimalarial treatment, and the therapeutic response of patients. Few previous studies have related these factors in Colombia. Here, gametocytaemia was evaluated with respect to two treatment schemes (sulfadoxine/pyrimethamine and sulfadoxine/pyrimethamine plus chloroquine), the patient response (adequate or failure), and the locality (two areas of varying case frequency). One hundred forty-eight residents of Turbo and Zaragoza (Antioquia), all with uncomplicated malaria, were evaluated. The gametocytaemia and the rates of clinical malaria at the beginning of treatment were greater in Turbo than in Zaragoza. No statiscally significant differences in the gametocytaemia by treatment schemes or therapeutic responses were noted, although the patients who received SP had more gametocytes than those treated with SP+CQ. Gametocytaemia was not correlated with asexual parasitemia or sex and age of patient. The difference in the level of gametocytaemia between Turbo and Zaragoza appears to be influenced by the time elapsed between the appearance of symptoms and the beginning of treatment.

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“…Since this was not the case, it is reasonable to conclude that induction of the gametocytes seen in the majority of our patients had occurred before they had presented at the dispensary. Factors that modulate gametocytogenesis in vivo are poorly understood, 1,24 though conditions adverse to the survival of the asexual parasite such as chemotherapy, 7,25,26 clinical manifestations of malaria 27 and hematological disruptions 28 are thought to influence the production of gametocytes. Such symptom-related stress conditions detailed above may have been the reason for the observed increase in gametocyte rates.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania.

Akim

Drakeley²,

Kingo³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. We investigated the dynamics of Plasmodium falciparum gametocytemia in symptomatic patients attending a local dispensary in the Kilombero district, Tanzania. Consenting individuals aged one and above, with varying asexual and sexual parasitemias were treated appropriately and asked to return weekly for 28 days. Gametocyte prevalence was highest on Day 7 of follow-up in all age groups (overall 30.5%). Multifactorial analysis showed that young age ( 2 ϭ 18.4; P ϭ 0.004), high asexual parasitemia on presentation ( 2 ϭ 19.4; P ϭ 0.0007) and gametocyte positivity on presentation ( 2 ϭ 29.4; P ϭ 0.001) were all significantly associated with the presence of gametocytes on Days 7 and 14 of follow-up. High presentation of asexual parasitemia alone was positively correlated with higher gametocyte densities on both days of follow-up (F 4, 297 ϭ 2.0; P ϭ 0.049). Gametocyte incidence rates decreased significantly with age ( 2 ϭ 7.6, P Ͻ 0.005). In summary, in this group of chloroquine-treated individuals, gametocyte prevalence and incidence rates decreased with age, while densities remained relatively constant.

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Effects of Chloroquine, Amodiaquine and Pyrimethamine-Sulfadoxine on Plasmodium Falciparum Gametocytemia

Cited by 19 publications

References 0 publications

Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria.

Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria.

Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia.

Dynamics of P. falciparum gametocytemia in symptomatic patients in an area of intense perennial transmission in Tanzania.

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