Kobsiri Chalermrut

Chloroquine sensitivity of Plasmodium vivax in Thailand.

Chloroquine has been the standard treatment for Plasmodium vivax malaria for more than 40 years in most regions of the world. Recently, however, chloroquine-resistant P. vivax has been reported from Oceania, several parts of Asia, and South America. In order to assess the situation in Thailand, 886 patients with vivax malaria who were admitted to the Bangkok Hospital for Tropical Diseases from 1992 to 1997 were followed prospectively. Most of the patients had been infected on the western border of Thailand and were experiencing their first malarial infection when admitted. All received oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) and then were randomized to receive primaquine (15 mg daily for 14 days) or no further treatment. All the patients were initially responsive to chloroquine, clearing their parasitaemias within 7 days, and there were no significant differences in the clinical or parasitological responses between those treated with primaquine and those given no further treatment. Plasmodium vivax parasitaemias re-appeared within 28 days of chloroquine treatment in just four patients. In each of these four cases, re-treatment with the same regimen of chloroquine resulted in eradication of the parasitaemia, with no further appearance of parasitaemia during the next, 28-day, follow-up period. These data indicate that virtually all acute (i.e. blood-stage) P. vivax infections acquired in Thailand can still be successfully treated with chloroquine.

Efficacy of DB289 in Thai Patients with Plasmodium vivax or Acute, Uncomplicated Plasmodium falciparum Infections

BACKGROUND DB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis. METHODS We tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23. RESULTS All patients cleared parasites by day 7, with a mean+/-SD clearance time of 43+/-41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate. CONCLUSIONS DB289 is a promising new antimalarial compound that could become an important component of new antimalarial combinations.

The Future Outlook of Antimalarial Drugs and Recent Work on the Treatment of Malaria

With the emergence of multidrug-resistant falciparum malaria, new drugs and drugs in combination are urgently needed. New antimalarial drugs investigated at the Hospital for Tropical Diseases of the Faculty of Tropical Medicine at Mahidol University in Bangkok, Thailand in recent years for treatment of uncomplicated and severe falciparum malaria are as follows: atovaquone, and artemisinin derivatives (artesunate, artemether, arteether, and dihydroartemisinin) combined with other antimalarials.Malarone, artemisinin derivatives combined with lumefantrine or doxycycline, and mefloquine combined with tetracycline or doxycycline have been evaluated with improvement of the cure rate in uncomplicated malaria. Artemisinin derivatives intravenously or intrarectally combined with mefloquine may be alternatives to intravenous quinine for treatment of severe malaria. In Thailand, drug treatment for uncomplicated malaria consists of the combinations or artesunate plus mefloquine or artemether plus lumefantrine or quinine plus tetracycline. In treatment of severe malaria, antimalarial drugs of choice are intravenous quinine or artemisinin derivatives.

Opisthorchis viverrini infection in Thailand: symptoms and signs of infection—a population-based study

A population-based study of the clinical, laboratory and ultrasonographic findings in patients suffering from mild or moderate opisthorchiasis in Prachinburi province, Thailand was conducted in 1990-1992. The effectiveness of treatment with praziquantel at 40 mg/kg body weight was evaluated. After treatment, a long-lasting, marked improvement in the well-being of the study group was observed. Symptoms common in opisthorchiasis infection decreased in intensity and the clinical response showed total or partial remission in 98% of all cases studied. Total and direct bilirubin concentrations decreased significantly and remained low up to the end of the follow-up period of 2 years, indicating a reduction in cholestasis. Also, white blood cell counts decreased initially, which can be interpreted as a reduction in inflammation intensity. No relationship was found between intensity of infection and age or clinical findings. Population-based treatment of opisthorchiasis appears to have had a significant impact on public health in north-east Thailand. However, it is also evident that drug therapy alone will not solve the opisthorchiasis problem, as indicated by the reinfection rate of almost 10% at the end of the study.

A comparison of three different dihydroartemisinin formulations for the treatment of acute uncomplicated falciparum malaria in Thailand.

We compared the safety and efficacy of three formulations of dihydroartemisinin for the treatment of acute uncomplicated falciparum malaria in patients who received a total dose of 600 mg dihydroartemisinin over 5 days. The first group was treated by dihydroartemisinin produced and formulated in the Peoples Republic of China, the second group was treated by dihydroartemisinin produced in Vietnam but formulated by the Government Pharmaceutical Organization of Thailand and the third group was treated by dihydroartemisinin produced and formulated by the Government Pharmaceutical Organization of Thailand. All patients were admitted to hospital to evaluate safety and efficacy for a total of 28 days. By the third day of treatment, most patients were blood-smear negative for parasites and none had serious adverse effects. Minor symptoms such as nausea, dizziness and headache were similar in the three groups and disappeared after 3 days of treatment. One-hundred and thirty-three patients completed the 28-day follow-up period. The cure rates of groups I, II and III were 80%, 85% and 92%, respectively (P > 0.02). There were no significant differences in fever clearance or parasite clearance among the three groups. We conclude that the three formulations of dihydroartemisinin produced and formulated in different countries were safe and effective in treating uncomplicated falciparum malaria acquired in Thailand.

New Fixed-Dose Artesunate-Mefloquine Formulation against Multidrug-Resistant Plasmodium falciparum in Adults: a Comparative Phase IIb Safety and Pharmacokinetic Study with Standard-Dose Nonfixed Artesunate plus Mefloquine

ABSTRACT A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs of malaria-induced hypotension occurring in the AS-MQ arm necessitated rescue treatment. There were no significant changes in hematology, biochemistry, or PR and QRS intervals. For all patients, mean Fridericia-corrected QT intervals were significantly (P ≤ 0.0027) prolonged on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with significant (P ≤ 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly similar to those of nonfixed AS plus MQ, and is a suitable replacement.

Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand

Objective  To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia.