Monitoring Plasmodium falciparum chloroquine resistance in Yunnan Province, China, 1981-2006.

The emergence and spread of drug resistant malaria parasites are an important factor contributing to the global resurgence of malaria, demonstrating the essence of drug resistance surveillance in endemic areas. In the malarious border regions of Yunnan Province, China, we have selected three study sites to monitor in vitro and in vivo resistance of Plasmodium falciparum parasites to chloroquine (CQ) from 1981 to 2006. In vitro studies using the microtest clearly showed high degree of CQ resistance in the early 1980s, when CQ was replaced by artemether monotherapy for falciparum malaria. In subsequent in vitro surveys performed in the early 1990s and 2003-2004, we found reductions in both the concentrations inhibiting 50% parasite growth (IC(50)s) and the percentage of resistant parasites at all study sites, although the degrees of the reduction varied among sites. Even though amodiaquine has never been used in this area, there were consistently high levels of resistance to this drug, confirming crossresistance between CQ and amodiaquine. In vivo clinical studies were consistent with the results of the in vitro assays. The overall rate of resistant clinical cases decreased from 97% in 1981-1983 to 40% in 2005-2006. Collectively, whereas a general trend of reduction in CQ resistance was observed in Yunnan, variations among sites existed in this relatively small area, probably as the result of both geographical heterogeneity of malaria epidemiology in Yunnan and different levels of CQ resistance in neighboring countries.