Consensus recommendation on the treatment of malaria in Southeast Asia.
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Antimalarials↗
Biomedical subjects
E B Doberstyn
Publications and source records attributed to E B Doberstyn.
A phase II/III double-blind, dose-finding clinical trial of a combination of mefloquine, sulfadoxine, and pyrimethamine (Fansimef) in falciparum malaria.
Fansimef is a combination of 250 mg mefloquine (base), 500 mg sulfadoxine, and 25 mg pyrimethamine per tablet. One hundred and fifty adult male Brazilian patients at Belém (Pará), who had peripheral blood smears positive for Plasmodium falciparum, with or without clinical symptoms of falciparum malaria, were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. Of those receiving one tablet (48 patients), 81% were cured and 19% exhibited RI recrudescences. All the patients receiving two or three tablets of Fansimef (49 patients in each group) were cured. The rates of initial clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects included nausea, vomiting, dizziness, diarrhoea and abdominal pain, but these were mild and transient and required no specific treatment. The incidence of vomiting and nausea was highest in patients given the three-tablet dose. The results of various haematological, biochemical and urine analyses were not adversely altered by the administration of Fansimef.
Administration, Oral↗
Treatment of falciparum malaria with quinne and tetracycline or combined mefloquine/sulfadoxine/pyrimethamine on the Thai-Kampuchean border.
Three different regimens were compared for treatment of falciparum malaria in displaced Kampucheans living in encampments on the Thai-Kampuchean border in 1983: single dose 750 mg mefloquine, 1.5 g sulfadoxine, 75 mg pyrimethamine (MSP); 600 mg quinine 8-hourly for 3 days and 500 mg tetracycline 8-hourly for 7 days (Q3T7); or 600 mg quinine 8-hourly for 7 days and 500 mg tetracycline 8-hourly for 7 days (Q7T7). Radical cure rates were 98% (40/41) for MSP, 76% (32/42) for Q3T7 and 92% (33/36) for Q7T7. The criterion for treatment failure was reappearance of parasites by 35 days after commencement of treatment or no parasite clearance. Treatment failures comprised one case of reduction but no clearance of parasites (RII resistance) for MSP, 10 recrudescences (RI) for Q3T7 and 3 recrudescences (RI) for Q7T7. The radical cure rate for Q3T7 was significantly lower than that for MSP (P less than 0.01), whilst Q7T7 significantly from the other groups. Parasite clearance time was shorter (2.4 days) with MSP than with Q3T7 (3.5 days) and Q7T7 (3.3 days). There was little difference in side effects between the regimens, and tolerance was good. The MSP and Q7T7 regimens are both effective for treatment, but the single dose of MSP is much easier to manage than 7 days of quinine and tetracycline.
Cambodia↗
In vitro susceptibility of Plasmodium falciparum collected from pyrimethamine-sulfadoxine sensitive and resistant areas in Thailand.
Seventy Plasmodium falciparum isolates, collected from two geographically separate areas of Thailand, were tested for their in vitro responses to pyrimethamine, sulfadoxine, and a combination of these two drugs. The effects of pyrimethamine and pyrimethamine-sulfadoxine combinations against P. falciparum isolates were found to be significantly greater in a northern area where the combined drug was an effective therapeutic agent than in a south-eastern area, near the Thai-Kampuchean border, where the combined drug was no longer effective. However, the actions of sulfadoxine against parasites obtained from the two areas were not significantly different. There was no significant difference between the mean values of plasma 4-aminobenzoic acid (PABA) in falciparum malaria patients and in healthy controls. The test for PABA determinations used in this study gave positive readings with both PABA and sulfadoxine.
4-Aminobenzoic Acid↗
Resistance of Plasmodium falciparum.
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Africa↗
An epidemiological early warning system for malaria control in northern Thailand.
Parasitological data for the years 1973-81 were examined to determine the years of "acceptable" or "normal" transmission of malaria, for every district of northern Thailand. The monthly mean number of cases and the mean plus 2 standard deviations (SD) were calculated for the selected years and plotted on log-linear graph paper. The resulting graphs were distributed to the Malaria Sector Offices. Sector Chiefs were then responsible for plotting the monthly observed number of cases of malaria as the data became available; if the observed incidence was more than 2 SD greater than the "normal" mean for that month, the Zone and Regional Malaria Offices were informed. Retrospective analysis of data from districts where malaria outbreaks had occurred indicated that the method provides an effective warning of impending epidemics. It is expected that the resulting earlier implementation of appropriate remedial control measures will lead to a reduction in malaria incidence in the region.
Disease Outbreaks↗
Evaluation of the antimalarial activity of the phenanthrenemethanol halofantrine (WR 171,669).
Halofantrine (WR 171,669) was administered to 27 nonimmune subjects infected with the multi-drug resistant Vietnam Smith strain of Plasmodium falciparum. It was also administered to three other subjects, one infected with the Cambodian Buchanan strain of P. falciparum, and two with blood-induced infection with the Chesson strain of P. vivax. It cured infections with all three parasites. Against the highly chloroquine-resistant Smith strain, it was curative in single day treatment regimens. The drug was well tolerated and produced rapid clearance of parasitemia in every case.
Animals↗
An evaluation of five regimens for the outpatient therapy of falciparum malaria in Thailand 1980-81.
Five regimens for the radical treatment of falciparum malaria were compared in five geographically separate areas of Thailand. The cure rate for sulfadoxine-pyrimethamine was found to be low in the area of the Kampuchean border and in the northeastern and western parts of the country. This distribution may be related to the spread of resistant parasites through the migration of labourers. A 7-day course of quinine was found to be uniformly effective, with an overall cure rate of 90% in these primary infections with comparatively low parasitaemia.
Adolescent↗
Recent advances in malaria with special reference to Southeast Asia.
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Adult↗
Drug therapy for Plasmodium falciparum malaria resistant to pyrimethamine-sulfadoxine (Fansidar). A study of alternate regimens in Eastern Thailand, 1980.
A trial of drug regimens for treating Plasmodium falciparum malaria was conducted in a refugee camp in eastern Thailand where extensive 'Fansidar' (pyrimethamine-sulfadoxine) resistance had been demonstrated. The efficacy of quinine alone was compared to that of quinine combined with either fansidar or tetracycline. Quinine alone cleared the parasitaemia in 57 of 59 patients but failed to cure approximately one-third of these patients after 7 or 10 days of therapy. The addition of fansidar to quinine therapy did not significantly improve the overall cure rate. Tetracycline given for 10 days in combination with quinine cured all patients, suggesting that tetracycline should be considered in treating patients with falciparum malaria contracted in the area of the Thai-Kampuchean border.
Child↗
Current epidemiology of malaria in Southeast Asia.
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Asia, Southeastern↗
Chemosuppressive field trials in Thailand. IV. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by mefloquine (WR 142,490, A 4-quinolinemethanol).
The effect of various dosages of mefloquine hydrochloride (WR 142,490) and sulfadoxine-pyrimethamine in the suppression of malaria infections was studied in an area of northeastern Thailand highly endemic for both chloroquine-resistant Plasmodium falciparum and for P. vivax. Both preparations, in all regimens studied, were effective in greatly reducing the incidence of falciparum infections. Mefloquine was more active in preventing vivax parasitemia than sulfadoxine-pyrimethamine; however, this combination remains the commercially available regimen of choice where both parasites occur and P. falciparum is resistant to chloroquine.
Adolescent↗
Treatment of vivax malaria with sulfadoxine-pyrimethamine and with pyrimethamine alone.
The effect of pyrimethamine and the combination of pyrimethamine-sulfadoxine (Fansidar) upon the termination of the acute attack of vivax malaria was studied in Thailand. Pyrimethamine was found to be ineffective, providing clearance of parasitaemia in only two of six patients by the end of seven days following treatment. The combination, administered in a two-tablet single dose (sulfadoxine 1 gm, pyrimethamine 50 mg) eliminated parasitaemia in only six of ten patients within seven days. Three tablets (sulfadoxine 1 . 5 gm, pyrimethamine 75 mg) given to 11 patients, provided clearance of parasitaemia in all within seven days; however, mean parasite and fever clearance times in this group were prolonged at 90 and 50 hours respectively. Chloroquine remains the drug of choice for the termination of the acute attack of vivax malaria. Subsequent primaquine is necessary for the prevention of relapse.
Acute Disease↗
Single-dose therapy of falciparum malaria with mefloquine or pyrimethamine-sulfadoxine.
A single oral dose (1.5 g) of mefloquine hydrochloride cured all of 37 patients with falciparum malaria, and a single dose of pyrimethamine (75 mg) plus sulfadoxine (1.5 g) cured 34 of 38 patients. The rates at which parasitaemia and fever abated were similar for the two regimens but mefloquine was associated with a higher incidence of gastrointestinal side effects.
Clinical Trials as Topic↗
Sequential treatment with quinine and mefloquine or quinine and pyrimethamine-sulfadoxine for falciparum malaria.
Patients with falciparum malaria were studied in Thailand, an area of known chloroquine resistance. The patients were unselected and some had severe malaria, and they were randomly assigned to one of two sequential regimes. A short course of quinine (average 4 doses, equivalent to 2 g base) followed by a single dose of pyrimethamine-sulfadoxine (Fansidar) cured 92% of patients (36 out of 39), while a short course of quinine followed by a single 1-5-dose of mefloquine cured all of the 35 patients who could be followed up. Gastrointestinal side effects were minimal if at least 12 hours elapsed between the last dose of quinine and the mefloquine. Sequential quinine and mefloquine is the most effective treatment for patients with chloroquine-resistant falciparum malaria, including those with severe or complicated disease. Mefloquine, however, is not commercially available, and the similar regimen using Fansidar is almost as effective.
Adolescent↗
Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study.
A variety of leukocyte enzyme activities were studied in an 11-year-old female with chronic granulomatous disease (CGD) and several members of her family. Leukocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity was 17 nmol/min/mg protein in the patient; two brothers with symptoms of recurrent bacterial infections have G-6-PD activities of 58 and 37 nmol/min/mg protein; the activites of this enzyme in both parents, maternal grandmother, and one additional brother were within normal limits. Storage at 4 degrees or heating at 37 degrees over a 120-min period revealed a marked lability of G-6-PD activity in the patient's cells which could not be stabilized by the addition of NADP and 2-mercaptoethanol; this lability was not seen in other family members tested. Activities of leukocyte glutathione reductase were reduced in both parents and the two affected male siblings with values of 18, 23, 23, and 24 nmol/min/mg protein, respectively. Activities of leukocyte glutathione peroxidase were reduced in all of the immediate family members tested, with values ranging from 11.2 to 43 nmol/min/mg protein; the activity of this enzyme in the patient was 38.5. Leukocyte NADP content in the patient, father, and two affected male siblings were 16.5, 23.4, 22.2, and 28.2 nmol/15 min/10(7) leukocytes, respectively.
Adolescent↗
Single-dose therapy of Falciparum malaria using pyrimethamine in combination with diformyldapsone or sulfadoxine.
Patients with naturally acquired chloroquine-resistant falciparum malaria were studied in Thailand. The fixed combination of pyrimethamine 75 mg and sulfadoxine 1,500 mg (adult dose) cured 85% of patients with an average pretreatment parasite count of 60,000 per mm(3). The fixed combination of pyrimethamine 50 mg and 800 mg diformyldapsone (DFD) cured 43% of patients with an average pretreatment parasite count of only 17,000 per mm(3). The difference in cure rates was statistically significant (p less than 0.01). Pyrimethamine alone was ineffective. Pyrimethamine-DFD, in the dose tested, was not sufficiently active for the treatment of established infections. Pyrimethamine-sulfadoxine did produce an acceptable cure rate but clinical improvement was often slow. We do not recommend that pyrimethamine-sulfadoxine be administered alone. Optimal results are obtained when a short course of quinine (2 to 6 days) is given until parasitemia has been eliminated, then a dose of pyrimethamine-sulfadoxine to assist in the radical cure of the falciparum infection. A modification to the W.H.O. classification is suggested. An RIII response (early treatment failure) is diagnosed if the patient's clinical condition and/or parsite density worsens within a few hours after administration of the test regimen; distinct improvement occurring within a few hours of the subsequent initiation of an intravenous infusion of quinine confirms the diagnosis of an RIII response. The RII response has been defined as marked reduction, but not clearance of asexual parasitemia. It is suggested that an RII response may be diagnosed before 7 days have elapsed.
Adolescent↗