Therefore the 1,270%rise in P. vivax and the 916% increase in total malaria cases during the epidemic period of late 2002, implies a dramatic increase in chloroquine use at that time. It is notable that this data consists of the reported incidence of smear positive and thus TREATEDcases, and therefore does reflect actual chloroquine use. Chloroquine levels were measured in the water in a nonepidemic year and thus may have been higher at other times. Although the levels we detected are unlikely to select for fluoroquinolone resistance, detection of chloroquine in the river, likely as a result of human waste, may be an indirect measure of the high volume of chloroquine use in the region. As traditional dosing for P. vivax used by the medics includes chloroquine 1 g PO then 500 mg PO 6 hours later, and then 500 mg PO daily62 more days, very high concentrations are achieved in the upper gut, and these concentrations would exceed those which were used in vitro to generate resistance. A gradient of concentrations would likely be generated throughout the intestines and this may facilitate the emergence of resistance. A recent report demonstrated that fluoroquinolone resistance may result in an increase inmortality from E. coli infections due to the increased likelihood of inadequate empirical antimicrobial therapy. A similar phenomenon likely also occurs in other organisms treated empirically with quinolones. Indeed persons in these very U0126 MEK inhibitor remote AmerindianGuyanese communities were found to carry multiple other quinolone resistant gram negative organisms including Salmonella. Quinolone antibiotics have an important role in the PB 203580 supply therapy of many tropical infectious diseases such as typhoid fever, non-typhoidal Salmonella, Shigella and enterotoxigenic E. coli infections. They also are important in both the tropics and in temperate regions in the treatment of gonorrhoea, urinary tract infections, upper and lower respiratory tract infections, are becoming increasingly important in the therapy of tuberculosis, and have widespread use in hospitalized patients. These antibiotics have excellent oral bioavailability, and do not require refrigeration, making them a critical component of our antibacterial armamentarium in the tropics, and for these reasons the development of resistance to these agents has important consequences. As chloroquine use is widespread throughout the tropics our findings may represent an important public health problem. In fact, although P. falciparum chloroquine resistance is widespread, use of quinoline antimalarials will likely continue, and may increase, as they are used in artemisinin combination therapy.