Decreased Prevalence of the Plasmodium Falciparum Chloroquine Resistance Transporter 76t Marker Associated With Cessation of Chloroquine Use Against P. Falciparum Malaria in Hainan, People’s Republic of China

Abstract

The use of chloroquine treatment for Plasmodium falciparum malaria was abandoned in China in 1979 because of widespread drug resistance. Subsequent studies found decreases in the prevalence of chloroquine-resistant strains. To evaluate these decreases and assess the current status of chloroquine sensitivity in Hainan, China, we determined the prevalence of the P. falciparum chloroquine resistance transporter (PfCRT) 76T marker in the DNA of blood samples collected from 1978 to 2001. Results showed the presence of PfCRT 76T in 101 of 112 samples (90%) from 1978 to 1981, 30 of 43 samples (70%) from 1986, 22 of 34 samples (65%) from 1997 to 1998, and 37 of 68 samples (54%) from 2001. The prevalence of PfCRT 76T thus progressively decreased after chloroquine was discontinued as a treatment for P. falciparum malaria (chi(2) = 5.2, P < 0.022 [1978-1981 versus 1986]; chi(2) = 7.4, P < 0.006 [1978-1981 versus 1997-1998]; and chi(2) = 28.8, P < 0.0001 [1978-1981 versus 2001]). Reduced prevalence of the PfCRT 76T marker is consistent with greater rates of chloroquine sensitivity from in vitro drug assays of blood samples in 1997 and 2001. Monitoring for continued decreases will provide valuable information for future drug-use policies in China.

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

“…For example, a region of Malawi known for highly prevalent CQR was repopulated with drug-sensitive parasites within 10 years after CQ use was stopped (17). Similar recovery of CQ-sensitive P. falciparum populations was recently reported in Kenya and has also been observed in China (18,19). These changes in the absence of drug pressure have been explained by fitness costs that are carried by CQ-resistant mutants (20).…”

“…* Patterns of pfcrt and pfmdr1 haplotypes in malaria endemic regions also depend on the fitness costs of these haplotypes relative to the advantages they offer to parasite populations. In Malawi and Hainan Island, China, where CQ-resistant CVIET parasites (Dd2-or GB4-type pfcrt) from the large Southeast Asian-African sweep had once been selected almost completely, populations of wild-type CQ-sensitive parasites characterized by the haplotype CVMNK (HB3-type pfcrt) returned after withdrawal of CQ (17,18). These findings suggest that CVIET mutants are at a fitness disadvantage to wild-type forms in the *Consistent with the pfcrt-pfmdr1 interactions described in this study, pfmdr1 codon 1246Y with possible synergistic or compensatory influence of 86Y or 184Y has also been associated with treatment failures after AQ monotherapy or after AQ plus ACT in Tanzania (53).…”

The impact of malaria parasitism: from corpuscles to communities

“…Recent studies from Malawi showed that a policy that removed chloroquine as an available treatment in 1993 was followed by repopulation of the region with chloroquine-sensitive strains by 2001 (111). A similar but slower return of chloroquine-sensitive strains has also been observed in Hainan, People's Republic of China, where use of the drug against P. falciparum malaria was suspended in 1979 (112).…”

Distribution of Drug Resistance Genotypes in Plasmodium falciparum in an Area of Limited Parasite Diversity in Saudi Arabia

“…In addition, chloroquine, although not used for treatment of falciparum malaria, can be used for infections that are thought to be P. vivax but are actually unrecognized mixed infections or misdiagnosed P. falciparum infections. 46 A large number of expatriates from the Indian subcontinent may import P. vivax infection.…”