The
development of resistance to drugs poses one of the greatest threats to
malaria control and has been linked to recent increases in malaria morbidity
and mortality. Drug resistance has been confirmed in only 2 of the 4 human
malaria parasite species, Plasmodium falciparum and P. vivax.
Drug-resistant
P. falciparum
Chloroquine
resistant P. falciparum (CRPF) first developed independently in
3 to 4 foci in Southeast Asia, Oceania , and South America in the late
1950's and early 1960's. Since then, chloroquine resistance has spread
to nearly all areas of the world where falciparum malaria is transmitted.
P.
falciparum has also developed resistance to nearly all of the other
currently available antimalarial drugs, such as sulfadoxine/ pyrimethamine,
mefloquine, halofantrine, and quinine. Although resistance to these drugs
tends to be much less widespread geographically, in some areas of the
world, the impact of multi-drug resistant malaria can be extensive.
Drug-resistant
P. vivax
Chloroquine
resistant P. vivax (CRPV) malaria was first identified in 1989
among Australians living in or traveling to Papua New Guinea. CRPV has
also now been identified in Southeast Asia, on the Indian subcontinent,
and in South America. Vivax malaria, particularly from Oceania, also exhibits
decreased susceptibility to primaquine.
Tests
for Drug Resistance
There
are 4 basic methods for testing malaria for drug resistance: in vivo tests,
in vitro tests, molecular characterization, and animal models. Of these,
only the first 3 are routinely done.
In
vivo tests: In these tests, patients with clinical malaria are given
a treatment dose of an antimalarial drug under observation and are monitored
over time for either failure to clear parasites or for reappearance of
parasites.
In
vitro tests: In these tests, blood samples from malaria patients are
obtained and the malaria parasites are exposed to different concentrations
of antimalarial drugs in the laboratory. Some methods call for adaptation
of parasites to culture first, while others put blood directly from patients
into the test system.
Molecular
characterization: For some drugs (chloroquine, SP and similar drugs,
atovaquone), molecular markers have been identified that confer resistance.
Molecular techniques, such as polymerase chain reaction (PCR) or gene
sequencing can identify these markers in blood taken from malaria-infected
patients.
For
a general overview of drug resistance and methods for testing for drug
resistance in malaria:
Drug
Resistance In Malaria (WHO, 2001)
For
a detailed description of the in vivo methods:
Assessment
And Monitoring of Antimalarial Drug Efficacy for The Treatment of Uncomplicated
Falciparum Malaria (WHO, 2003) (471
KB/68 pages)
Drug
Resistance: Malaria (WHO webpage)
Page last modified : April 23, 2004
Content source: Division of Parasitic Diseases
National Center for Zoonotic, Vector-Borne, and Enteric Diseases (ZVED)
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