Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1 percent) of the patients were cured and 44 (37.9 percent) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92 percent while those of CH+CQ was 85 percent. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38 percent treatment failure for CQ reported in this study is higher than the 10 percent recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per æl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR.

A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.

Malaria: tratamiento y quimioprofilaxis / Malaria: treatment and prophylaxis

Malaria es una patología reemergente en el mundo y en América en particular; se revisan aspectos epidemiológicos de la enfermedad en Perú. Las nuevas medidas de control propuestas por la OMS para reducir la mortalidad por malaria y su impacto socio-económico son: diagnóstico y tratamiento precoz de los pacientes; control del vector; detección y contención de epidemias; investigación local básica y aplicada que permita evaluar periódicamente la situación de malaria. Se describen los fármacos y esquemas terapéuticos y profilácticos recomendados para el manejo de la malaria

Avaliaçäo da eficácia da azitromicina e da pirimetamina, usadas isolada ou associadamente, no tratamento de infecçäo experimental de camundongos pelo Toxoplasma gondii / Evaluation of the efficacy of azithromycin and pyrimethamine, alone or in combination, for the treatment of experimental infection of mice with Toxoplasma gondii

Foi comprovada a eficácia da azitromicina e da pirimetamina no tratamento da infecçäo experimental de camundongos pelo Toxoplasma gondii. Houve administraçäo cotidiana, pela via oral de 200mg/kg e 12,5mg/kg, respectivamente durante dez dias. O uso dos medicamentos ocorreu mediante associaçäo ou näo e o emprego concomitante proporcionou o melhor resultado e convirá efetuar investigaçäo semelhante com cepa cistogênica do parasita

Investigations of incidence of pretreatment, drug sensitivity in vitro, and plasma levels of pyrimethamine in patients with multidrug resistant falciparum malaria following the three combination regimens of artemether/pyrimethamine.

The study was carried out to investigate the status of in vitro susceptibility of Plasmodium falciparum to pyrimethamine (PYR) in multidrug resistant area of the Thai-Myanmar border, the incidence of unregulated use of the combination of PYR with sulfadoxine (Fansidar) in this area and the relevance of pharmacodynamic and pharmacokinetic factors in determining the treatment outcome from the three combination regimens of ART/PYR (1-, 2- and 3-day regimens), in patients with acute uncomplicated falciparum malaria. The majority of patients had baseline PYR concentrations in the range of 1-100 (50.6%) or 100-500 (34.8%) ng/ml, while concentrations of more than 500 ng/ml were found in only 1.1%. All of the isolates exhibited high grade resistance to PYR with the minimum inhibition concentration (MIC) of as high as 10(-5) M. No association was observed between treatment outcome and the presence of baseline plasma PYR concentrations. In addition, lack of association between plasma concentrations during the acute phase (day-1 and -2) and treatment outcome was found.

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

Monitoring efficacy of commonly used antimalarials by a 14-day in-vivo test in a new settler's camp in endemic zone at Cox's Bazar.

The study was done in a new settler's camp "Barachara" under Sadar thana of Cox's Bazar district. It has a total population of 784 of all age groups, registered in the middle of the study period. A prospective evaluation of all cases of fever were done over 12 months, to see the pattern of febrile illness among the population and to compare the therapeutic efficacy of two alternative drug regimens for uncomplicated falciparum malaria (UM). Blood for malarial parasite (MP) was done in all cases of fever and was treated in line with the new clinical case definitions and treatment guidelines for malaria in Bangladesh. Slide positive UM cases were subjected to a "14-day in-vivo test" for therapeutic efficacy testing of antimalarial agents. The two drug regimens were randomised by lottery--a) 3 days oral chloroquine plus single dose sulphadoxin/pyrimethamine (CQ + SP) and, b) 3 days oral quinine plus single dose sulphadoxin/pyrimethamine (Q3 + SP). Drug administration was supervised by the field assistant and was followed up on days 3, 7 and 14 for blood slide examinations and clinical assessment. Sensitive response was observed in 79% of the cases in the CQ + SP group and 84% in the Q3 + SP group. Early treatment failure (persistently febrile and parasitaemic on days 3 or 7) was observed in 16% in the CQ + SP group and 9% in the Q3 + SP group. Both the evaluated drug regimens had less than 20% failures and can be used as alternative first line agents and Q3 + SP regimens can also be used as the second line agents for treatment failure (to chloroquine and/or SP) UM cases in the study area.

Avaliação clínica do quinino para o tratamento de malária por Plasmodium falciparum / The clinical evaluation of quinine for the treatment of Plasmodium falciparum malaria

O quinino foi o primeiro medicamento correntemente usado para tratar malária, tendo sido abandonado seu emprego principalmente após o início do emprego da cloroquina. A partir da década de 60 com o surgimento de resistência do P. falciparum à cloroquina voltou-se a utilizar o quinino isolado ou em associação para tratar tal infecção. Com o objetivo de avaliar clinicamente a resposta ao quinino de pacientes com malária por P. falciparum, analisamos os prontuários de 484 pacientes atendidos no Laboratório de Malária da SUCEN e acompanhados por pelo menos 28 dias, e que haviam recebido diferentes esquemas terapêuticos com quinino isolado ou em associação. Do total, 81,0% dos pacientes foram curados pelos esquemas empregados, sendo que dos restantes apenas 0,6% foram R2 e nenhum R3. Tais resultados mostram ainda que esquemas contendo quinino podem ser adequados para tratar malária por P. falciparum.

Quinine was the first antimalarial drug to be employed and also the first resistance was noticed to. After 1960 quinine urged to be reintroduced in routine therapy alone or in combination. Aiming at evaluating the effectiveness of different schedules we studied 484 patients seen at the Malaria Laboratory. We used quinine alone in 126 patients, quinine plus sulfadoxine and pyrimethamine in 119 patients and quinine plus tetracycline in 239 patients. The results shown that 81% of all patients were treated with success and only 0.6% were R2. and there is no R3. We emphasize a high resistance rate to quinine either alone (23.1%) or associated to sulfadoxine and pyrimethamine (37.8%). A higher resistance rate seen with the combination might be linked to the smaller dose of quinine used in that instance. It is worth noting the high cure rate with the quinine-tetracycline association.

Claritomicina associada com pirimetamina na toxoplasmose cerebral: relato de dois casos / Clarithromicyn associated with pyrimethamine in cerebral toxoplasmosis

The authors report the use and the outcome of claritromycin associated with pyrimethamine in the treatment of toxoplasma encephalites in two patients with AIDS. Both patients had the diagnosis stablished on clinical grounds, positive sorology (IgG) for toxoplasmosis and computed-tomographic (CT) scan of the brain showing lesions consistent with T. gondii encephalitis. The two patients were initially treated with pyrimethamine and sulfadiazine, which was changed to clindamycin due to allergic reactions. These reactions (skin rash) occurred with clindamycin as well and the patients were treated with claritromycin and pyrimethamine. The scheduled regimens were 1.5 to 2 g of clarithromycin plus 25 mg of pyrimethamine. The clinical response was very good in both cases with regression of neurologic signs and encephalitic abnormalities observed on CT scan. The authors suggest that clarithromycin associated with pyrimethamine may be an alternative treatment for toxoplasmosis in AIDS patients, who cannot receive or tolerate sulfa treatment.

Toxoplasmose e gravidez / Toxoplasmosis and preganncy

O presente trabalho tem como objetivo uma revisåo sumária sobre toxoplasmose e gravidez, abordando os principais aspectos da doença: transmissåo, formas clínicas, diagnóstico clínico e sorológico, recursos e esquemas terapêuticos

Tratamento de toxoplasmose cerebral / Treatment of cerebral toxoplasmosis

Foi revista a literatura sobre a terapêutica da toxoplasmose cerebral. Abordou-se a terapêutica do paciente imunocompetente que adquiriu a infecçäo; do paciente imunodeficiente e, especificamente, daquele portador da síndrome da imunodeficiência adquirida que tem como uma da doenças oportunísticas mais freqüentes a toxoplasmose cerebral; e da gestante e do feto que tenham adquirido a infecçäo aguda. A literatura indica como terapia de primeira escolha o emprego da combinaçäo da pirimetamina com a sulfadiazina. Novos medicamentos, ainda em experimentaçäo, e esquemas alternativos também säo discutidos

Phase III double-blind comparative study of Fansimef and Lariam for the curative treatment of Plasmodium falciparum infections in Thailand.

A double-blind comparative study of Fanismef-mefloquine/sulfadoxine/pyrimethamine (MSP) and Lariam-mefloquine (MEF) for the treatment of falciparum malaria, was carried out at malaria clinics in Kanchanaburi, in western Thailand, in the years 1987 and 1988. The cure rates obtained were 96% for the MSP group and 93% for the MEF and there was no significant difference. Vomiting and diarrhea were common side effects in both the MSP and MEF groups. Less common side effects were epigastric pain, minor skin rashes and dizziness. Significant differences in vomiting and epigastric pain only occurred in the patients who did not have these symptoms before treatment: vomiting MSP 23%, MEF 8%, epigastric pain MSP 22% and MEF 11%.

Efficacy of sulfalene and pyrimethamine combination drugs alone and with quinine in treatment of P. falciparum cases in chloroquine resistant areas of north east India.

Studies were carried out in some areas of Assam, Nagaland, West Bengal and Mizoram where chloroquine resistant strains of Plasmodium falciparum were present during 1983 and 1984, to see the efficacy of treatment of P. falciparum cases with SLP alone or with quinine sulphate. The findings have indicated that SLP in the dosage of sulfalene (1000 mg) + Pyrimethamine (50 mg) is suitable for treatment of P. falciparum cases not responding to chloroquine therapy in N.E. India. Treatment with sulfalene (1500 mg) + Pyrimethamine (75 mg) has no advantage over the SLP (1000 + 50) mg. Combination of quinine (1000 mg x 3 days) + SLP (1000 + 50) mg is better with 100 per cent cure rate. In Karhi Anglong district (Manja PHC) of Assam response to these drug combination is however less.

Gametocytocidal effect of primaquine in a chemotherapeutic malaria control trial in North Sumatra, Indonesia.

The effect of primaquine as a gametocytocidal drug was investigated in 218 P. falciparum (Pf) malaria cases detected during passive case detection (PCD) from August to December 1985 in two coastal villages of North Sumatra, where chloroquine-resistant and Fansidar-sensitive Pf was prevalent. Sulfonamide + pyrimethamine (SP) in combination with primaquine (Pr) was administered in Kuala Tanjung village and SP alone in Nana Siam village. Parasitologically confirmed Pf cases were followed up to observe the fluctuation of gametocytemia after the treatment. In 87 cases treated with SP alone, no significant change was observed in gametocyte positivity rate (GPR) and density on day 2 and day 7. In 131 cases treated with SP and Pr, no significant change was found on day 2 but significant reduction was observed in GPR and density on day 7. The gametocyte positive cases on day 7 were followed up weekly until gametocytes disappeared. SP alone did not reduce GPR from day 0 to week 2, then afterward GPR began to decline but was still 11.5% at week 5. On the other hand, SP with Pr reduced GPR from 77% on day 0 to 30% on day 7, after which GPR declined further to 7% at week 3. Reduction of parasite rate was observed in Kuala Tanjung after the PCD activities, reflecting a reduction in Pf prevalence rate from 18.6% in August 1985 to 2.9% in January 1986. These data indicate that a single dose of Pr 45 mg with SP was partially effective in reducing gametocytes and reducing malaria prevalence rate when administered through PCD activities.

Antimalarial and toxic effect of triple combination of pyronaridine, sulfadoxine and pyrimethamine.

The triple combination of pyronaridine, sulfadoxine and pyrimethamine which has been proven to be efficient in delaying emergence of drug resistance of rodent malarial parasites was further studied for potential application to malaria control. The antimalarial effect of the triple combination on Plasmodium berghei ANKA-infected mice and the toxic effects in mice and rats were additive. A single dose of pyronaridine 500 mg in combination with sulfadoxine, 1000 or 1500 mg, and pyrimethamine, 50 or 75 mg, given to 72 acute falciparum malaria patients resulted in a 100% cure rate with nil or mild side effects, and no recrudescence of asexual parasite over 4-week follow-up. Preliminary experiments on the drug effect on sporogony showed that the drug combination at the dose used could not completely interrupt the sporozoite formation although many retarded oocysts were found.