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Transient rises in parasitaemia occur commonly during the treatment of falciparum malaria but their prognostic significance has not been well defined. Twelve-hourly parasite counts from 133 malaria patients who were ultimately cured were therefore compared with counts from 97 therapeutic failures to determine if increase in parasitaemia was a useful early indicator of poor treatment response. Parasitaemia in both groups frequently rose during the initial 12 h of therapy (41% of all patients), but rising counts thereafter were rarer in treatment successes (P < 0.01). The relative risk of treatment failure was 3.8 if the count was higher at 24 h than 12 h, rose to 7.8 for increases at 48-60 h, and was 13.7 and 19.4 for counts above admission levels at 48 h and 60 h. These data suggest a way to identify patients at high risk of treatment failure.

Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness.

Quinine was compared with a 9-phenanthrene methanol (WR33063) and a 4-quinoline methanol (WR30090) for the treatment of 207 patients with falciparum malaria in Southeast Thailand. Quinine eradicated parasitaemia (average 70 hours) more rapidly than either WR30090 (72 hours) or WR33063 (77 hours). But WR33063 had a higher cure rate (92%) than WR30090 (86%) or quinine (85%). The mean duration of fever and of parasitaemia were combined with the failure rate to form an arbitrary efficacy index. Using this concept WR33063 was the most effective drug. The recrudescence rate correlated with the degree and duration of parasitaemia and with the duration of fever. WR33063 was the least toxic drug. Side effects associated with WR30090 appeared to be headache, backache and urticaria. Quinine was the most toxic drug. All 3 drugs were inconvenient in having to be administered every 8 hours for 6 days. One patient did not respond to oral quinine but did respond to an intravenous quinine infusion (IVQ). A "Medication Ward Round" was perfected during the study and comprised sequential history, drug administration, physical examination, dose notation and patient observation. Falciparum nephrosis was diagnosed in one patient.

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.

Falciparum malaria in 104 Thai patients was treated with either Mefloquine or Fansidar and patients were examined for parasitaemia for the next 28 days. All but one of the 40 patients treated with Mefloquine were cured, but the cure rates for Fansidar were only 9 . 1% for the two-tablet regimen and 19 . 4% for the three-tablet regimen. Most failures were classified as RII. Serum sulpha levels indicated that the Fansidar was being absorbed. Immediate steps should be taken to eliminate this focus of resistance and to protect against further resistance to Fansidar by using it in combination with another effective anti-malarial and by vigorous vector control measures.

A clinical field trial was conducted to determine if mefloquine is effective in the treatment of malaria due to Plasmodium vivax. Forty patients with P. vivax malaria were treated with either mefloquine, chloroquine or chloroquine plus primaquine and followed for 28 days. All patients responded rapidly and were cured. There were no significant side effects.

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.

A battalion of Royal Thai Marine militia was assigned to take either 50 mg or 100 mg of doxycycline daily or pyrimethamine/dapsone weekly for malaria prophylaxis on the Thai-Kampuchean border for a 17 week period. Attack rates for the groups expressed as cases/100 men were 34 for 50 mg doxycycline, 18 for 100 mg doxycycline, and 52 for pyrimethamine/dapsone. The relative efficacy of the two doxycycline regimens compared to Maloprim were 1.6 and 1.4. Compliance with the daily drug nearly equalled that of the weekly regimen. This suggests that 100 mg of doxycycline daily can be effectively used for malaria prophylaxis by soldiers under operational conditions on the Thai-Kampuchean border.

Amodiaquine cured 38% (13/34) of patients with falciparum malaria in Southeast Thailand. Chloroquine cured 0% (0/13). The cure rates with amodiaquine were the same whether a 1.5 g or 2.0 g course was used. Most patients were resistant to amodiaquine at the RI level and to chloroquine at the RII level. In hospital, amodiaquine cleared parasitemia more frequently than did chloroquine. With the 2.0 g course of amodiaquine, the parasite clearance time was 77 hours; the fever clearance time of 36 hours was low and suggests that amodiaquine does not cause a drug fever. Because of resistance, chloroquine should not be used for falciparum malaria in Thailand. Routine use of amodiaquine is not indicated because more effective drugs are available.

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.