Efficacy of primaquine in preventing short and long latency Plasmodium vivax relapses in Nepal.
Rijal KR., Adhikari B., Ghimire P., Banjara MR., Thakur GD., Hanboonkunupakarn B., Imwong M., Chotivanich K., Day NPJ., White NJ., Pukrittayakamee S.
BACKGROUND:Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously. METHODS:Patients with P. vivax malaria were randomized to receive chloroquine (CQ: 25 mg base/kg given over 3 days) alone or together with primaquine (CQ+PQ: 0.25 mg base/kg/day for 14 days) and followed intensively for one month, then at 1-2 month intervals for one year. Parasite isolates were genotyped. RESULTS:101 (49%) patients received CQ and 105 (51%) received CQ+PQ. In the CQ+PQ arm there were 3 (4.1%) recurrences in the 73 patients who completed one year follow-up compared with 22 (28.2%) of 78 in the CQ only arm; risk ratio (95% CI) 0.146 (0.046 to 0.467): p<0.0001. Microsatellite genotyping showed relatively high P. vivax genetic diversity; mean He 0.843 (He 0.570 to 0.989) with low multiplicity of infection (mean MOI: 1.05) reflecting a low transmission pre-elimination setting. Of the 12 genetically homologous relapses 5 (42%) occurred in a cluster after 9 months indicating long latency. CONCLUSION:Although there may be emerging chloroquine resistance, the combination of chloroquine and the standard dose 14 day primaquine is highly efficacious in providing radical cure of short and long latency P. vivax malaria in Nepal.