Clinical studies to determine the optimal treatment for drug resistant malaria in Timika, Indonesia
Creators: name: Siswantoro, Hadjar
Publisher: name: Charles Darwin University
Year: 2006

description: Multidrug resistant strains of Plasmodium falciparum and P. vivax pose a significant challenge to Indonesian communities. In southern Papua, Indonesia we conducted a series of studies to determine the efficacy of the existing antimalarial regimens and to compare the safety and efficacy of two fixed dosed artemisinin combination therapies (artemether-lumefantrine/AL and dihydroartemisinin-piperaquine/DP). In the first study, consecutive patients with malaria due to P. falciparum, P. vivax, P. ovale or P. malariae presenting to a rural clinic were enrolled and treated with supervised CQ+SP (P. falciparum) or CQ (non-P. falciparum) and followed for 28- 42 days. In the second study, patients with symptomatic infections with P. falciparum and or P. vivax were randomized to receive either coartemether (AL) or artekin (DP). Patients with vivax recurrence within 42 days were retreated with amodiaquine monotherapy. The first study was completed in August 2005 and enrolled 207 patients (88 P. falciparum, 40 P. vivax, 15 mixed infections, 50 P. malariae and 14 P. ovale). Early treatment failures occurred in 4 of 86 (5%) patients with falciparum malaria, 6 of 37 (16%) patients with vivax malaria and none of those with P. ovale or P. malariae infections. The failure rate by day 28 for P. vivax was 73% (22/30). After correcting for reinfections the day 42 recrudescence rate for falciparum malaria was 52% [95%CI: 39-64] and in 29% (63/103) of cases this was in the presence of chloroquine levels above 30ng/ml. Retreatment with unsupervised quinine ± doxycycline resulted in further recurrence of malaria, however by day 28 57% [95%CI: 33-79] had had a further recurrence of P. falciparum infections. None of the patients with P. ovale or P. malariae had treatment failures within 28 days. In the second study, a total of 774 patients (474 P. falciparum, 176 P. vivax, 112 mixed infections, 12 P. malariae and P. ovale) were enrolled. The overall day 42 failure rates were 41.6% (122/293) for AL and 16.1% (44/273) for DP (RR=2.58 [95%CI 1.91-3.50]) p&lt;0.001. After correcting for reinfections, the day 42 recrudescence rate for P. falciparum was 1.4% [95%CI 0-5] after AL and 1.1% [95%CI 0-4] after DP with no difference between regimens. However recurrence of vivax occurred in 57% [95%CI 47-65] of patients treated with AL compared to 10% [95%CI 6-17] treated with DP, p&lt;0.001. Patients receiving DP were 2.1 fold [95%CI 1.2-3.8] less likely to be anaemic at the end of the study and 6.6 fold [95%CI 2.8-16] less likely to carry vivax gametocytes. We conclude that there is a high prevalence of antimalarial drug resistance of P. falciparum and P. vivax to the existing antimalarial drugs in this region and that chloroquine and SP therapy can no longer be advocated. DP and AL are safe and highly effective for the treatment of multidrug resistant uncomplicated malaria. However DP’s prolonged therapeutic activity reduces significantly the rates of falciparum reinfection and vivax relapse, and decreases the risk of anaemia and P. vivax gametocyte carriage. In this area DP has become the preferred treatment option for uncomplicated malaria.