Specific and Nonspecific Responses to Plasmodium falciparum Blood-Stage Parasites and Observations on the Gametocytemia in Schoolchildren Living in a Malaria-Endemic Area of Mozambique

Høgh, Birthe; Thompson, Ricardo; Hetzel, Charlotte; Fleck, S. L.; Kruse, Nicole; Jones, Ian W.; Dgedge, Martinho; Barreto, Jorge; Sinden, Robert E.

doi:10.4269/ajtmh.1995.52.50

Cited by 34 publications

(27 citation statements)

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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).…”

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“…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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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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“…Nevertheless, CQ and SP are active against young gametocytes before their appearance in the peripheral circulation. 17,18 The once-common view that gametocytogenesis induction is not observed after treatment with CQ or SP 19 has faded considerably following the demonstration that CQ increases the gametocytogenesis of P. chabaudi in vivo and P. falciparum in vitro. 20,21 Pyrimethamine is clearly sporontocidal; it inhibits dihydrofolate reductase in sensitive strains, damaging ookinetes and reducing oocyst numbers.…”

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Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine.

Robert¹,

Awono-Ambene²,

Hesran³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

105

102

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Abstract. Plasmodium falciparum gametocytemia and its related infectivity for mosquitoes was studied in 115 patients (median age ϭ 18 years, range ϭ 4-45) with simple malaria attacks who lived in the hypoendemic area of Dakar, Senegal. Patients were included in a 28-day in vivo sensitivity test after treatment with chloroquine (CQ, n ϭ 82) or sulfadoxine plus pyrimethamine (SP, n ϭ 33). The prevalence of resistant infections was 58.5% in those treated with CQ and 0% in those treated with SP. The gametocytemia peaked at day 7 after treatment. The maximal gametocyte prevalence was 38.2% in the CQ-sensitive infection group, 89.6% in the CQ-resistant group, and 97.0% in those treated with SP. The maximal geometric mean gametocytemia was 2.19/l in the CQ-sensitive infection group, 29.12/l in the CQ-resistant group and 85.55/l in those treated with SP. The period between appearance of the first clinical symptom and treatment was positively related to gametocyte prevalence at days 0 and 2. Experimental infection of wild Anopheles arabiensis using membrane feeders was performed at days 0 and 7, and mosquito infectivity was measured by oocyst detection on the midgut. At day 0, 14.1% of the patients had infected at least 1 mosquito, and at day 7, this value was 38.5%. The mean percentage of infected mosquitoes was 3.2% at day 0 and 12.6% at day 7. At day 7 after treatment with CQ, the relative risk for patients with resistant infections of infecting anophelines was 4.07 higher than in those with sensitive infections. No difference was observed in infectivity for mosquitoes between RI-type resistance and the RII ϩ RIII-type resistance. A sporonticidal effect of SP was observed at day 7 after treatment. These data show that P. falciparum gametocytes and their infectivity for mosquitoes were differentiated according to the drug used, its efficacy, and the duration of symptoms before treatment; they were not dependent on the density of asexual stages. Prompt treatment of malaria cases performed at the beginning of symptoms could limit the spread of resistant parasites.The factors that trigger and regulate the switch from asexual to sexual development of the malaria parasite remain largely mysterious, 1,2 but may involve both genetic mechanisms 3 and environmental mechanisms, 4 especially when conditions deteriorate. Completion of Plasmodium falciparum gametocytogenesis (from merozoite to morphologically mature gametocyte) takes 10-12 days in vivo, 5,6 an estimate that is consistent with the 10 days observed in vitro. 7 In the peripheral blood stream, the mature gametocyte has a halflife of 2.4 days and 1 gametocyte generation may persist for up to 3 weeks. 8 In continuous culture, the progeny of a single schizont is either only asexual parasites or only gametocytes, indicating a commitment to 1 or the other path of development prior to the merozoite stage. 9 The passage of the malaria parasite from humans to the mosquito vector is characterized by one word: variability. This intriguing phenomenon has been observed by many inv...

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“…The absence of post-treatment gametocytemia in the majority of chloroquine-treated patients is in agreement with the results of a previous study. 10 The underlying reason may be related to the activity of chloroquine against immature gametocytes, which are sequestered in deep organs during the maturation process. Subjects treated with pyronaridine were more likely to have post-treatment gametocytemia than subjects treated with chloroquine (relative risk ϭ 3.26, 95% confidence interval [CI] ϭ 2.16-4.91; P Ͻ 0.001), suggesting that pyronaridine has either no activity or less activity than chloroquine against immature gametocytes.…”

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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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Specific and Nonspecific Responses to Plasmodium falciparum Blood-Stage Parasites and Observations on the Gametocytemia in Schoolchildren Living in a Malaria-Endemic Area of Mozambique

Cited by 34 publications

References 0 publications

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

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

Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine.

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

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