More Primaquine Resistance in Plasmodium vivax
Abstract & Commentary
Synopsis: Primaquine frequently failed to prevent relapses of Plasmodium vivax malaria that had been acquired in Somalia.
Source: Smoak BL, et al. Plasmodium vivax infections in U.S. Army troops: Failure of primaquine to prevent relapse in studies from Somalia. Am J Trop Med Hyg 1997;56:231-234.
Smoak and colleagues report their experience with soldiers in whom Plasmodium vivax malaria, acquired in Somalia, developed or relapsed despite terminal prophylaxis or treatment with primaquine.
A total of 75 male soldiers were studied who developed malaria due to P. vivax after return from deployment in Somalia. The median time of deployment for the cases had been 73 days (range, 31-153 days). All had received directly observed mefloquine prophylaxis while in Somalia, but only 63% reported taking all four doses after leaving that country. Forty-five of the 75 also received terminal prophylaxis with primaquine. Based on calculations for one unit, the failure rate for primaquine prophylaxis was estimated to be 16%.
The median time from the last dose of mefloquine to the onset of symptoms of malaria was 69 days (range, 11-242 days) and was not dissimilar in those who also received primaquine. After treatment with standard courses of chloroquine or quinine plus doxycycline, 60 of the 75 patients with malaria received a standard radical curative course of primaquine (15 mg of base daily for 14 days). Of the 60 patients, 26 (43%) nonetheless relapsed after a median of 75 days (range, 22-193 days). This was not dissimilar from the relapse rate in those who did not receive primaquine, which was 47% (7 of 15). An additional seven patients relapsed, but it was not possible to determine if they had or had not received primaquine.
Despite all patients having received terminal therapy with primaquine after their first relapse, eight had a second relapse at a median interval of 107 days (range, 31-127 days). Eighteen patients had been given primaquine in a higher than usual dose of 30 mg base daily for 14 days; three (17%) of these patients relapsed.
COMMENT BY STAN DERESINSKI, MD, FACP
In 1993, I commented on a report in the Morbidity & Mortality Weekly Report concerning the occurrence of P. vivax malaria in military personnel returning from Somalia (Infect Dis Alert 1993;12:190-191; MMWR Morb Mortal Wkly Rep 1993;42:524-526). Those affected had taken mefloquine or doxycycline prophylaxis, but had not been offered terminal prophylaxis with primaquine because P. vivax infection had been thought to be rare in Somalia, with most cases of malaria acquired in that country due to P. falciparum.
This proved not to be the case. Smoak et al speculate upon the possible reasons for this misapprehension. They suggest that extrapolating from diagnosed cases in a semi-immune population may grossly underestimate the incidence of P. vivax malaria because of the relatively mild disease produced and the likelihood of self-treatment with readily available chloroquine. Furthermore, P. vivax requires the presence of Duffy blood group antigens in order to enter erythrocytes. These antigens are absent in most black Africans, a fact consistent with the finding that, in the study reviewed here, the P. vivax attack rate among black soldiers was less than one-fourth that of white soldiers. Approximately one-third of Somalis, however, do express one of the Duffy antigens, thus allowing for a reservoir of persisting P. vivax infection.
Primaquine resistance in P. vivax was originally reported from Papua New Guinea and later from Southeast Asia and Central and South America. I ended my 1993 comment by saying, "To my knowledge, primaquine resistance has not been reported from Africa." However, in 1995, primaquine resistance in Kenya, Sudan, and Ethiopia was reported (Jelinek T, et al. Am J Trop Med Hyg 1995;52:322-324). Thus, it is not surprising that primaquine resistant P. vivax is also present in Somalia, which borders on two of those countries. It is likely that primaquine resistance will become a common problem in the relatively near future.
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