Vivax malaria resistant to treatment and

prophylaxis with chloroquine

G.S. Murphy, MD, a, H. Basri, MD, Purnomo, MSa, E.M. Andersen, PhDa, M.J. Bangs, MSa, J. Gorden,
ABa, K. Sorensen, MDa, D.L. Mount, MSb, A.A. Lal, PhDb, A.R. Purwokusumo, MDc, S. Harjosuwarno, S.L.
Hoffman, MDd

a US Naval Medical Research Unit No 2, Jakarta, Indonesia

b Malaria Branch, Centers for Disease Control, Atlanta, Georgia, U.S.A.

c Ministry of Health, Republic of Indonesia, Jakarta, Indonesia

d Naval Medical Research Institute, Bethesda, Maryland, U.S.A.

Abstract

Chloroquine has been the treatment of choice for vivax malaria for more than 40 years. Lately, several
case-reports have suggested the emergence of resistance to chloroquine in Plasmodiumvivax in Papua
New Guinea and Indonesia. We undertook prospective treatment and prophylaxis trials of chloroquine
in children and adults with vivax malaria living in Irian Jaya (Indonesian New Guinea). 46 villagers with P
vivax parasitaemia were treated with chloroquine by mouth (25 mg base/kg body weight divided over 3
days) and followed up for 14 days. Parasitaemia cleared initially but recurred within 14 days in 10 (22%)
subjects. All recurrences were in children younger than 11 years, 7 of whom were younger than 4 years;
the failure rate among children under 4 was 70%. 7 of the patients with recurrences were given a second
course of chloroquine. In all, the infections initially cleared but recurrent parasitaemia developed in 5
(71%) within 14 days. Whole-blood chloroquine concentrations were consistently above those
previously shown to cure P vivax blood infections (90 μg/L whole blood). Subjects whose initial
infections cleared and who had no parasitaemia on day 14 received weekly prophylaxis with
chloroquine. Despite the presence of expected blood chloroquine concentrations, P vivax parasitaemia
developed in 9 of 17 subjects receiving prophylaxis during 8 weeks of follow-up (median time to
parasitaemia 5·3 weeks). Chloroquine can no longer be relied upon for effective treatment or
chemoprophylaxis of P vivaxblood infections acquired in this part of New Guinea. Lancet 1993; 341: 96-
100.
Primaquine Therapy for Malaria
J. Kevin Baird and Stephen L. Hoffman

Author Affiliations

US Naval Medical Research Center Detachment, Lima, Peru

Sanaria, Rockville, Maryland

Reprints or correspondence: Capt. J. Kevin Baird, US Naval Medical Research Center

Detachment, American Embassy Lima, APO AA 34031, USA (bairdk@nmrc.navy.mil).

Abstract

Primaquine is the only available drug for preventing relapse of malaria, and confusion
surrounds its use. This review examines the wide range of clinical applications of primaquine
described in the medical literature between 1946 and 2004. The risk of relapse of Plasmodium
vivax malaria without primaquine therapy ranged from 5% to 80% or more, depending largely
upon geographic location. Supervision of therapy profoundly impacts the risk of relapse, and
almost all reports of malaria resistant to primaquine are associated with lack of such
supervision. We nonetheless suspect that there is widespread resistance to the standard course
of primaquine therapy, which is 15 mg primaquine base daily for 14 days. Clinical evidence
confirms that a course of 15 mg daily for just 5 days, a regimen widely used in areas where
malaria is endemic, has no discernible efficacy. This review supports a recommendation for a
regimen of 0.5 mg/kg primaquine daily for 14 days, on the basis of superior efficacy and good
tolerability and safety in nonpregnant persons without glucose-6-phosphate dehydrogenase
deficiency.

Footnotes

Financial support. This work was supported in part by the US Department of Defense Global
Emerging Infections Surveillance Program.

Potential conflict of interest. J.K.B. and S.L.H.: No conflict.

The views and opinions expressed herein are those of the authors and do not purport to reflect
those of the US Navy, the US Department of Defense, or Sanaria, Inc.