Charoenlarp P

Randomised trial of mefloquine-tetracycline and quinine-tetracycline for acute uncomplicated falciparum malaria

The combination of mefloquine plus tetracycline was compared with quinine plus tetracycline in a randomised therapeutic trial in 102 patients with acute uncomplicated falciparum malaria in Thailand. Quinine plus tetracycline is considered the standard treatment for the highly drug-resistant strains of P. falciparum found in this area. Fifty patients received mefloquine (750 mg given immediately, followed by 500 mg 6 h later) with tetracycline and 52 patients received quinine (600 mg every 8 h for seven days) with tetracycline. Tetracycline was administered to both groups in doses of 250 mg four times daily. All patients were admitted to the hospital for 28 days to exclude re-infection. Ninety-three patients completed the study; nine patients left prior to completion of follow-up for reasons unrelated to their treatment. Cure rates for the two groups were 94% (44/47) for mefloquine plus tetracycline and 98% (45/46) for quinine plus tetracycline. Parasite and fever clearance times were shorter for the group treated with mefloquine but the differences were not statistically significant. Nearly all patients (94%) treated with quinine developed cinchonism compared with only 12% treated with mefloquine; all other symptoms following treatment were similar. Thirteen patients (26%) treated with quinine also developed delayed primary attacks of P. vivax during the follow-up period; none developed in the patients treated with mefloquine. These results support the contention that the combination of mefloquine plus tetracycline is equally effective and less toxic than quinine plus tetracycline for treatment of acute uncomplicated falciparum malaria in areas requiring combination therapy for drug resistance.

Randomized trial of mefloquine alone and artesunate followed by mefloquine for the treatment of acute uncomplicated falciparum malaria

Mefloquine is the main antimalarial used for treatment of falciparum malaria patients at the malaria clinics in Thailand. However, the cure rate with mefloquine alone has declined seriously in recent years. The efficacy and tolerability of a sequential treatment of artesunate followed by mefloquine was therefore compared with those of mefloquine alone, in a randomized therapeutic trial involving 125 patients with acute uncomplicated falciparum malaria. Sixty-three patients received mefloquine alone (750 mg given immediately, followed by 500 mg 6 h later) and 62 each received 800 mg artesunate over 2 days (200 mg every 12 h) followed 6 h later by a single, 750-mg dose of mefloquine. All patients were admitted to the hospital in Bangkok for 28 days to exclude re-infection. Most patients (107) completed the study; 18 left the hospital prior to completion of follow-up for reasons unrelated to their treatment. Cure rates for the two groups were 74% (42/57) for mefloquine alone and 92% (46/50) for artesunate followed by mefloquine. The mean parasite clearance time was significantly shorter (P < 0.001) in the group treated with the sequential combination than in the group treated with mefloquine alone, but the mean fever clearance times were not significantly different (P = 0.26). Most patients responded well to the treatment regimens and none suffered from serious toxic adverse reactions. Only four patients who were treated with mefloquine alone had parasitaemia persisting to day 7 (RII), thus requiring alternative follow-up treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic metabolism in severe falciparum malaria: caffeine clearance study.

Falciparum malaria is known to cause abnormalities in the liver. Hepatic metabolism in patients with falciparum was studied by caffeine clearance and the results were related to the severity of the disease. Caffeine (3.5 mg/kg) was administered orally to patients with severe (N = 10) or uncomplicated (N = 9) falciparum malaria. The plasma clearances during illness averaged 0.67 +/- 0.27 ml/min kg for the severe cases and 0.98 +/- 0.36 ml/min kg for the uncomplicated cases (P < 0.05). In the severe patients, clearances during illness (0.67 +/- 0.27 ml/min kg) were less than those in convalescence (2.15 +/- 0.91 ml/min kg) (P < 0.0001). However, in the uncomplicated cases, the clearances during illness and in convalescence were similar (P > 0.05) and clearance rates in convalescence were similar for the severe and uncomplicated cases (P > 0.05). Hepatic microsomal metabolism is apparently slow in severe falciparum malaria but reverts to normal in convalescence. Liver metabolic function does not appear to be significantly affected in uncomplicated malaria.

Antithrombin III and antivenom reversal of coagulopathy in rats envenomated with Malayan pit viper venom

The therapeutic effects of antithrombin III (AT-III) and unrefined equine antivenom in the treatment of coagulopathy induced by Malayan pit viper (Calloselasma rhodostoma) venom were assessed in 42 adult Wistar rats. Following intramuscular venom injection (2 micrograms/g body weight), serial blood samples were taken from the femoral vein for measurement of whole blood clotting time and AT-III activity. There was progressive depletion of AT-III and blood ceased to clot a mean (S.E.) of 164 (8.3) min after venom injection. Coagulopathy was reversed by a high dose antivenom (10 micrograms/g) or a lower dose of antivenom (5 micrograms/g) in combination with AT-III (> or = 0.1 U/g; P < 0.01) but not 5 micrograms/g antivenom or AT-III alone. Following successful treatment, the mean plasma AT-III activity remained above 90%. In this animal model, systemic envenomation by the Malayan pit viper causes uncoagulable blood associated with AT-III consumption. The dose of antivenom required to reverse this coagulopathy can be reduced by half by the addition of AT-III sufficient to maintain blood concentrations within the normal range.