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Epidemiologic Notes and Reports Chloroquine-Resistant Plasmodium
falciparum Malaria in West Africa
On May 27, 1986, a 50-year-old American helicopter mechanic
traveled to Enugu, a city in the eastern state of Anambra, Nigeria.
While in Nigeria, he took chloroquine 300 mg base weekly for
malaria
chemoprophylaxis and continued this regimen after returning to the
United States via Lagos on December 6. He traveled only in eastern
Nigeria and did not travel to other malarious countries. On
December
9, he developed fever, chills, and headache, and was hospitalized
in
California on December 18.
On December 20, a peripheral blood smear revealed that 0.5% of
red
blood cells were infected with asexual Plasmodium falciparum
parasites, and treatment with chloroquine 1500 mg base was
administered over a 3-day period. He became afebrile on December
22,
and a peripheral blood smear on December 23 showed rare
trophozoites.
On December 27, he again became febrile, and a blood smear on
December
31 revealed a parasitemia of 1.0%. A whole-blood specimen
collected
on December 31 was analyzed by high performance liquid
chromatography
(1) and contained 151 ng of chloroquine/ml, indicating that the
treatment dosage of chloroquine had been adequately absorbed.
A parasite isolate collected on December 31 was assayed by the
48-hour in vitro test of Nguyen-Dinh and Trager (2) and found to be
resistant to chloroquine: parasite multiplication was inhibited
only
at 0.3 umol of chloroquine liter of medium, a concentration higher
than the accepted limit of in vitro chloroquine resistance (0.06
umol/L). The patient responded promptly to treatment with quinine
(650 mg three times daily for 3 days) and tetracycline (250 mg four
times daily for 7 days) and has remained well.
Reported by DV Jackson, MD, P Marcarelli, MD, G Segal, MD, Dept of
Infectious Diseases, Long Beach Veterans Administration/University
of
California, Irvine, SW Waterman, MD, County of Los Angeles Dept of
Health Svcs, RR Roberto, MD, California Dept of Health Svcs;
Control
Technology Br, Malaria Br, Div of Parasitic Diseases, Center for
Infectious Diseases, CDC. Editorial Note
Editorial Note: Chloroquine-resistant P. falciparum was first
confirmed in Africa in 1979 when a P. falciparum infection in a
traveler returning from Tanzania was not cured by a standard
treatment
regimen of chloroquine, and the infecting parasite was found to be
resistant to chloroquine in vitro (3). Subsequently,
chloroquine-resistant P. falciparum has spread throughout East and
Central Africa and, in 1985, was reported from as far west as
Cameroon
(4). A recent report from Benin (5) and the case from Nigeria
presented here indicate that chloroquine-resistant P. falciparum is
now present in West Africa as well.
These reports of chloroquine-resistant P. falciparum malaria
have
serious public health implications since malaria transmission in
much
of West Africa is intense and perennial. In Nigeria, the most
populous nation on the African continent, a change in the efficacy
of
chloroquine, the most widely used anti-malarial drug, could affect
many of the country's estimated 80-100 million residents. Since
chloroquine-resistance can extend rapidly after it is first
observed
in a geographic region, the efficacy of chloroquine will need to be
systematically monitored by health care personnel throughout West
Africa.
In accordance with Centers for Disease Control (CDC)
recommendations for short-term travelers to chloroquine-resistant
areas, travelers to Nigeria and Benin should take weekly
chloroquine
prophylaxis and should also carry pyrimethamine sulfadoxine
(FansidarR) to be taken in the event of a fever or flu-like illness
when medical attention is not readily available (6). Additionally,
since P. falciparum infections that are chloroquine prophylaxis
failures may respond poorly to full treatment dosages of
chloroquine
(7), they should be treated with anti-malarial medications that are
effective against chloroquine-resistant infections.
The Malaria Branch CDC is currently assisting in the
investigation
of additional cases of possible chloroquine-resistant P. falciparum
malaria acquired elsewhere in West Africa. CDC will update malaria
prophylaxis recommendations as further information regarding the
geographic extent of chloroquine-resistant P. falciparum becomes
available. Physicians treating patients with P. falciparum
infections
that were acquired in West Africa and that may represent
chloroquine
prophylaxis or treatment failures are encouraged to report these
cases
promptly to their local or state health departments and to the
Malaria
Branch CDC (telephone: weekdays (404)452-4046, nights and weekends
(404)329-2888).
References
Patchen LC, Mount DL, Schwartz IK, Churchill FC. Analysis of
filter-paper-absorbed, finger-stick blood samples for
chloroquine
and its major metabolite using high-performance liquid
chromatography with fluorescence detection. J Chromatography
1983;278:81-9.
Nguyen-Dinh P, Trager W. Plasmodium falciparum in vitro:
determination of chloroquine sensitivity of three new strains
by a
modified 48-hour test. Am J Trop Med Hyg 1980;29:339-42.
Campbell CC, Chin W, Collins WE, Teutsch SM, Moss DM.
Chloroquine-resistant Plasmodium falciparum from East Africa:
cultivation and drug sensitivity of the Tanzanian I/CDC strain
from an American tourist. Lancet 1979;ii:1151-4.
Sansonetti PJ, Lebras C, Verdier F, Charmot G, Dupont B,
Lapresle
C. Chloroquine-resistant Plasmodium falciparum in Cameroon
(Letter). Lancet 1985;i:1154-5.
Le Bras J, Hatin I, Bouree P, et al. Chloroquine-resistant
falciparum malaria in Benin. Lancet 1986;ii:1043-4.
CDC. Health information for international travel, 1986.
Atlanta,
Georgia: Public Health Service, 1986. DHHS publication no.
(CDC)
86-8280.
Weniger BG, Blumberg RS, Campbell CC, Jones TC, Mount DL,
Friedman
SM. High-level chloroquine resistance of Plasmodium falciparum
malaria acquired in Kenya. New Engl J Med 1982;307:1560-2.
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