Comparative activities of chloroquine mefloquine and sulphadoxine-pyrimethamine on in vivo and ex vivo male reproductive functions in mammalian models

Comparative reproductive activities of chloroquine, mefloquine and sulphadoxine-pyrimethamine were explored in albino Wistar rats and semen from West African Dwarf Buck [WADB] with a view to elucidating the mechanism of action of these drugs on malereproduction. Five adult male rats were administered 0.5 mL distilled water and served as the control. Five rats each were administered orally chloroquine [10 mg kg -1 b.w.], mefloquine [10 mg kg -1 b.w.] and sulphadoxine-pyrimethamine [5 mg kg -1 b.w.] orally, for four weeks. Each group had it's own recovery group. Sperm counts, motility and morphology were reduced in rats treated with these drugs in the order mefloquine [p<0.05]> chloroquine > sulphadoxine-pyrimethamine. There was an appreciable recovery in the motility of sperms in all recovery groups. Semen samples from WADB were extended separately with chloroquine, mefloquine and sulphadoxine-pyrimethamine. Extender 1 [first control] had no PENSTRIP [Penicillin and Streptomycin combination] while extender 2 [standard extender; second control] had PENSTRIP. Semen in extenders 3, 4 and 5 were treated with chloroquine, mefloquine and sulphadoxine-pyrimethamine, respectively. Spermatozoa progressive motility in these extenders examined under the microscope at 24 h for 5 days significantly reduced in mefloquine [p<0.01], slightly with chloroquine and unchanged with sulphadoxine-pyrimethamine. The pH of the extenders was significantly reduced in duration dependent manner in mefloquine while it remained unchanged with chloroquine and sulphadoxine-pyrimethamine. The results suggest the safety of sulphadoxine-pyrimethamine and chloroquine in preservation of semen ex vivo while the negative impact of mefloquine could reside within the testis or epididymis

Toxoplasmosis-dermatomiositis: una asociación fortuita? / Toxoplasmosis-polymiositis-dermatomyositis: a fortuitous association?

Se describe el caso de una paciente de veinte años de edad con dermatopolimiositis (DM/PM) y toxoplasmosis (Tx). El tratamiento para Tx instituido precozmente mejoró la respuesta de la enferma. Los pacientes con DM/PM deberían ser estudiados para Tx a través de la detección de IgG, IgM y también IgA específica

Insuficiência renal aguda por sulfadiazina: relato de caso / Acute renal failutre due to sulfadiazine: a case review

Sulfadiazina e pirimetamina são drogas importantes para o tratamento da toxoplasmose cerebral. Estamos descrevendo o caso de um paciente que desenvolveu insuficiência renal aguda por precipitação de cristais de sulfadiazina e formação de cálculos renais. O diagnóstico do quadro de insuficiência renal aguda foi clínico e laboratorial, sendo importante a presença de inúmeros cristais de sulfadiazina no exame comum de urina e de cálculos renais observados na ecografia abdominal...

Neurotoxoplasmose em pacientes com síndrome de imunodeficiência adquirida: estudo de 33 casos / Central nervous system toxoplasmosis in patients with the acquirred immunodeficiency syndrome: study od 30 cases

Os autores estudaram, retrospectivamente, as manifestações clínicas de 33 pacientes adultos com o diagnóstico de Síndrome de Imunodeficiência Adquirida (SIDA) e neurotoxoplasmose, internados no Serviço de Doenças Infecciosas e Parasitárias do Hospital Universitário Antônio Pedro no período de abril de 1986 a dezembro de 1994, realizando uma correlação com os achados neurorradiológicos e os achados neuropatológicos de 10 pacientes. Dos 33 pacientes estudados, 27 (81,8 por cento) eram do sexo masculino, com predomínio do grupo etário compreendido entre 20 e 40 anos (72,6 por cento). Quanto ao comportamento de risco, observou-se um predomínio da transmissão por via sexual. As manifestações neurológicas mais freqüentes foram: sinais de localização (26 casos - 78,7 por cento); alterações do estado mental (24 casos - 72,7 por cento); cefaléia (20 casos - 60,6 por cento) e crise convulsiva generalizada (18 casos - 54,5 por cento). Quanto aos achados neurorradiológicos, verificou-se que a grande maioria dos pacientes apresentava lesões múltiplas (19 casos - 57,5 por cento) localizadas em hemisférios cerebrais (24 casos - 72,7 por cento) e núcleo da base (16 casos - 48,4 por cento) com captação nodular do contraste (16 casos - 48,4 por cento). Verificou-se ainda que o edema perilesional estava presente em 28 (84,8 por cento) casos e produziu efeito de massa em 16 (48,4 por cento). A instituição do tratamento para neurotoxoplasmose foi acompanhada de resposta parcial em 27 (82,0 por cento) pacientes, resposta completa em dois (6,0 por cento) e ausência de resposta em quatro (12,0 por cento). Na maioria dos casos (20 pacientes - 83,2 por cento), o tempo de sobrevida após o início da terapêutica foi inferior a 12 meses, sendo que em 15 (62,4 por cento) deles foi inferior a seis meses. O estudo histopatológico do Sistema Nervoso Central (SNC) foi realizado em 10 (41,6 por cento) dos 24 pacientes que evoluíram para o óbito. Em todos os casos observou-se alterações morfológicas do SNC. A neurotoxoplasmose ativa foi diagnosticada em cinco (50 por cento) casos, em todos havendo concordância entre o diagnóstico clínico, neurorradiológico e os achados neuropatológicos. Em quatro casos, a neurotoxoplasmose foi considerada a causa primária de morte. Nos cinco pacientes restantes foi constatada a presença de lesões cicatriciais, algumas de aspecto cístico, localizadas em hemisférios cerebrais, núcleos da base e tronco cerebral

Hiperpigmentación cutáneo-mucosa en pacientes HIV positivos / Muco-cutaneous hyperpigmentation in HIV patients

Las alteraciones en la pigmentación cutáneo-mucosa en los pacientes infectados por el virus HIV pueden ser frecuentes, pero su etiología está aún en discusión. Se analizó el seguimiento dermatológico desde 1988 hasta 1995 de 320 casos infectados por el virus del HIV, donde 61 eran mujeres y 259 varones, cuyas edades promedio fueron de 26,6 años en los primeros y 22,2 en los segundos. Del total de casos (320), se observó hiperpigmentación cutáneo-mucosa difusa en el 16,32 por ciento de los casos e hiperpigmentación de mucosa y semimucosa oral exclusivamente en 2 mujeres (0,77 por ciento) y 12 varones (4,18 por ciento). En nuestra experiencia, la hiperpigmentación se comportó como un marcador de mal pronóstico, dado que en menos de 6 meses de su aparición, los pacientes presentaron complicaciones más severas que los llevaron a la muerte

Artemether-pyrimethamine in the treatment of pyrimethamine-resistant falciparum malaria.

In vitro susceptibility and clinical response of multidrug resistant Plasmodium falciparum to the combination artemether-pyrimethamine were evaluated in patients with acute uncomplicated falciparum malaria. Sixty patients were randomized to receive 3 oral regimens of the combination artemether-pyrimethamine as follows: Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen-III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All patients had a rapid initial response to treatments with 95% of parasitemia being cleared within the first 24 hours. PCT24hours and PCT48hours were similar among the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2-day, and 3-day combination regimen, respectively). Fever was cleared within 48 hours in all patients in either group. Transient mild nausea, vomiting and loss of appetite were found in a few patients during the first 2 days of treatment. Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs 2-day regimen), the reason for withdrawal was not associated with drug-related adverse effects. Only 53 patients were therefore qualified for the efficacy assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day combination regimens, respectively, who had reappearance of the parasitemia between days 11 and 21. The cure rates of the 3 treatment groups were statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3-day combination regimen, respectively). Two patients developed P. vivax malaria on days 20 and 24. All of the isolates were highly resistant to pyrimethamine, with MIC of 10(-5) M. There is potential advantage of this combination therapy in reducing the dosage and treatment period of artemisinin derivative, which is therefore likely to improve complaince in clinical practice. The use of a 3-day combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in areas where P. falciparum is sensitive to pyrimethamine eg in Africa.

Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial.

At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half-strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical trials of mefloquine with tetracycline.

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.

Proguanil/sulfamethoxazole malaria chemoprophy-laxis on the Thai-Cambodian border.

383 Thai soldiers on the Thai-Cambodian border were entered into a randomized malaria chemoprophylactic trial. Proguanil (200 mg/day) combined with sulfamethoxazole (1000 or 1500 mg/day) were compared to a standard combination of weekly pyrimethamine/dapsone (Maloprim). Men receiving proguanil/sulfamethoxazole had a significantly lower malaria attack rate than those taking pyrimethamine/dapsone. This was true of both the first five-week phase in which 1000 mg of sulfamethoxazole was used (0.11 vs 0.26; p less than 0.001) and in the second ten weeks in which 1500 mg of sulfamethoxazole was used (0.13 vs 0.30; p less than 0.001). Combined relative efficacy indicated that proguanil/sulfamethoxazole was better than pyrimethamine/dapsone by 64% for Plasmodium vivax and by 38% for P. falciparum. Unenforced compliance as measured by returned pills was greater than 86% in both groups. No serious drug side-effects were observed. Proguanil/sulfamethoxazole may represent a useful chemoprophylactic option in areas of multiple drug-resistant malaria.

Oral lichenoid reactions during antimalarial prophylaxis with sulphadoxine-pyrimethamine combination.

The prevalence of clinically observed oral lichenoid reaction in 186 Malay army personnel using Fansidar for 9 weeks was found to be 4.8%. The prevalence was found to be 0.5% in 186 army personnel who had stopped using Fansidar for 2 months and 0% in 143 army personnel (control group) who had not used Fansidar for at least 4 months. The lesion showed a higher prevalence for the gingiva. There was no correlation between cigarette smoking and the occurrence of these lesions in each group.

Toxicidad hematológica por pirimetamina / Hematologic toxicity by Pirimetamine

Caso presentado en el Hospital Central de Sanidad de las Fuerzas Policiales, de una paciente de 33 años, gestante de 22 semanas y diagnosticada de toxoplasmosis. Recibió como tratamiento pirimetamina (2, 4 diamino 5-P- clorofenil-etil-pirimidina). Luego de una semana de terminado el tratamiento: presentó malestar general, náuseas, vómitos, epixtasis y rash cutáneo eritematoso. Al ingresar a este nosocomio por emergencia, los exámenes de laboratorio revelaron: plaquetas menos de 10,000 x mm3, leucocitos 600 x mm3, Hb 9.10 gr/100 ml. El efecto antifólico de la pirimetamina, aunado a la gestación en donde el consumo de ácido fólico está incrementado, puede llevar a ésta a una severa insuficiencia medular