Recent advances in malaria with special reference to Southeast Asia.
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Biomedical subjects
Publications and source records attributed to T Harinasuta.
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Fourteen patients with falciparum malaria were successfully treated with oral quinidine. Twelve of these patients were followed for 35 days without recrudescence. In six patients the infection had already recrudesced after antimalarial treatment, which in two cases had included a full course of quinine. Quinidine caused no cardiotoxicity, although the electrocardiogram QTc interval was prolonged by more than 25% in four patients. In-vitro cultures from nine of these patients and a further seven patients with falciparum malaria showed that the minimum inhibitory concentration was consistently lower for quinidine than for quinine. Quinidine is an effective antimalarial drug for Plasmodium falciparum infections and may be more potent than quinine.
A sensitive and specific assay for primaquine in plasma and urine using gas chromatography/mass spectrometry has been developed and used to study the plasma kinetics of primaquine. Preliminary studies on the effects of single and multiple oral doses have been carried out. In both cases the drug was completely, or almost completely, removed from the plasma in 24 h. The concentration of primaquine in the plasma usually reached a peak 1-2 hours after oral administration. The plasma elimination half-life was about 4 h. Less than 1% of the dose was detected in the urine collected over a 24-h period following drug ingestion. When Caucasian volunteers were given primaquine and chloroquine concurrently, some of them developed significant methaemoglobinaemia. Primaquine was not detectable in the plasma of any of the volunteers, 24 h after each daily dose.
A clinical trial of Niclofolan on human opisthorchiasis was carried out in 60 patients admitted to the Hospital for Tropical Diseases. Two dosage regimen, 2 mg and 3 mg per kg body weight repeated after a 72 hour interval was administered to 31 and 4 patients respectively. Comparative evaluation with the placebo group of 25 patients was made by the Stoll count on day 20, 40 and 60 after treatment. On day 60 percentage egg reduction of the treated and the placebo groups were similar. Mild and transient side effects such as nausea, anorexia, myalgia and arthralgia were recorded in all 3 groups but more severe in the higher dosage group. In this study, Niclofolan failed in reducing the egg production of Opisthorchis viverrini.
Thirty-nine patients with tapeworm infection were treated with five grams of crude aqueous extract of Artocarpus lakoocha wood, "Puag-Haad". Seven of them vomited the drug immediately. Of the 32 patients, segments with scolices of Taenia saginata and of Taenia solium were recovered from 24 and 2 patients respectively. The side effects were vomiting and nausea.
A 40-year old Thai farmer with pulmonary paragonimiasis was treated with Praziquantel 25 mg/kg body weight, three times after meals for one day. On follow-up treatment during hospitalization he coughed up 7 adult lung flukes. The worms were identified as Paragonimus heterotremus. This is probably the first case report to demonstrate adult mature Paragonimus coughed up from man.
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A clinical trial of praziquantel was carried out in patients with opisthorchiasis using low dosages with 30 and 60 days follow-up. In group III, 30 patients treated with praziquantel 25 mg per kg body weight bid, for one day yielded a cure rate of 88%. In group IV, 12 patients received 25 mg per kg body weight in a single dose and gave a cure rate of 44 %. In group V, 55 patients received 40 mg per kg body weight in a single dose and yielded a cure rate of 91%. Mild and transient side effects were present in 54%, these included abdominal pain, lassitude, headache, dizziness, nausea, diarrhoea, myalgia and tachycardia. Clinical improvement was observed in most of the patients after one month and 33% of them were clinically cured in two months. The recommended dose of praziquantel for the treatment and control of opisthorchiasis in the endemic area is a single dose of 40 mg per kg body weight after meals.
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1 The kinetics of primaquine have been studied in twenty volunteers after single and multiple dose regimes. 2 The kinetic parameters were similar in glucose-6-phosphate dehydrogenase (G6PD) normal Thais, G6PD deficient Thais and in Caucasians. 3 The Caucasian subjects showed about 1% of the dose was excreted in the urine. 4 The kinetic parameters obtained from multiple dose studies in Thais were very similar to those obtained from single dose studies in Thais.
A single dose of 45 mg of primaquine base was effective in the elimination of gametocytes of the possibly chloroquine-resistant P. falciparum in Thailand. The gametocyte counts decreased markedly within 3.5 days showing significantly difference from the control in which mostly gametocytes still remain within 11.4 days. The development of the gametocytes in A. dirus was not observed after treatment. Primaquine can be used as gametocytocide and sporontocide for falciparum malaria in Thailand if the drug is administered when matured gametocytes appeared in the peripheral blood.
Praziquantel (Embay 8440) was found to be effective in eliminating egg of Opishtorchis viverrini. from the stools of 49 patients. Two regimens were used: Group I patients received 25 mg/kg body weight three times daily after meals for two consecutive days: and Group II patients received 25 mg/kg body weight three times daily after meals for one day. In both groups eggs were not detected in the faeces by day 60 and up to 4-8 months post treatment. Mild transient side effects were present in approximately 80% of patients of Group I, with milder side effects reported in Group II. Severe diarrhoea was present on day 0 in one patient from each group. Side reactions included headache, dizziness, myalgia and lassitude, however, no laboratory evidence of toxicity was detected.
Flubendazole, a parafluoro analoque of mebendazole, was given to 89 service men with hookworm, Trichuris trichiura and Ascaris lumbricoides infections. The drug was given either as two doses of 300 mg at 12 hour interval (regimen A) or as two doses of 300 mg at 24 hour interval (regimen B). At four weeks follow-up the mean percentage egg reduction for hookworm was 88% and 96% in regimen A and B respectively. There were too few cases of Trichuris and Ascaris infection to allow comparison of the two regimens, but flubendazole appeared to be as effective and the single day regimen more convenient than difetasone for trichuriasis and levamisole for ascariasis. Side effects were few, mild and transient.
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