Evaluation of Efficacy of Chloroquine for Plasmodium Vivax Infection Using Parasite Clearance Times: A 10-Year Study and Systematic Review

<p><b>INTRODUCTION</b>Chloroquine, in combination with primaquine, is used as the firstline treatment for uncomplicated P. vivax malaria in Thailand. In view of the declining efficacy of chloroquine in many P. vivax endemic areas, the possibility of emergence of chloroquine- resistant P. vivax in Thailand is a concern. The aim of this study was to assess the trends in therapeutic efficacy of chloroquine and primaquine for the treatment of uncomplicated P. vivax malaria and to assess the utility of parasite clearance times as a measure of efficacy.</p><p><b>MATERIALS AND METHODS</b>This study consisted of: 1) review of medical records of patients who were hospitalised for a period during their treatment for uncomplicated P. vivax malaria at the Hospital for Tropical Diseases, Bangkok, Thailand between 2004 and 2013. Treatment consisted of chloroquine (1500 mg base administered over 3 days) or chloroquine (as before) plus primaquine (15 to 30 mg base/daily for 14 days from day 2); and 2) systematic review of the literature in English to assess current standards in the reporting of parasite clearance times.</p><p><b>RESULTS</b>The 28-day cure rate was 99.1%. The range of median parasite clearance time over the 10-year period was 46 to 59 hours, and there was statistical evidence for an increasing trend in parasite clearance times between 2009 and 2013. Heterogeneity was noted among previous chloroquine efficacy studies in the measurement and reporting of parasite clearance.</p><p><b>CONCLUSION</b>The treatment of P. vivax infection with a combination of chloroquine and primaquine has remained efficacious in Thailand. Increasing rates of parasite clearance in a population over time may be a useful early warning mechanism for the emergence of chloroquine resistance. The utility of monitoring time-trends in parasite clearance to detect resistance may be enhanced if parasite clearance measurements are standardised.</p>

Clinical efficacy of chloroquine versus artemether-lumefantrine for Plasmodium vivax treatment in Thailand

Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.

Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of Plasmidium vivax malaria in Thailand

We conducted a study to compare the safety and tolerability of anti-relapse drugs elubaquine and primaquine against Plasmodium vivax malaria. After standard therapy with chloroquine, 30 mg/kg given over 3 days, 141 patients with P. vivax infection were randomized to receive primaquine or elubaquine. The 2 treatment regimens were primaquine 30 mg once daily for 7 days (group A, n = 71), and elubaquine 25 mg once daily for 7 days (group B, n = 70). All patients cleared parasitemia within 7 days after chloroquine treatment. Among patients treated with primaquine, one patient relapsed on day 26; no relapse occurred with elubaquine treatement. Both drugs were well tolerated. Adverse effects occurred only in patients with G6PD deficiency who were treated with primaquine (group A, n = 4), whose mean hematocrit fell significantly on days 7, 8 and 9 (P = 0.015, 0.027, and 0.048, respectively). No significant change in hematocrit was observed in patients with G6PD deficiency who were treated with elubaquine (group B, n = 3) or in patients with normal G6PD. In conclusion, elubaquine, as anti-relapse therapy for P. vivax malaria, was as safe and well tolerated as primaquine and did not cause clinically significant hemolysis.