A question raised by NJWhite remains open. If the hypothesis can be extended beyond the study area then, “the epidemiological pattern of fluoroquinolone resistance in enteric bacteria (before the introduction of inexpensive fluoroquinolones) should have mirrored that of chloroquine use, with high levels in parts of Africa and Asia.” Available data are few but suggest that they do not. We screened for nalidixic acid resistance in fecal Escherichia coli isolates in south west Nigeria between 1986 and 1998 (Okeke, IN, Fayinka, ST and Lamikanra, A (2000) Antibiotic resistance trends in Escherichia coli from apparently healthy Nigerian students (1986-1998). Emerging Infectious Diseases. 6, 393-396). This is a part of the world where chloroquine was used intensively at that time and continues to exert heavy selection pressure. Our unpublished data reveal that in the formal health system, 97% of febrile patients received chloroquine in the 1980s. Moreover, chloroquine was used intensively in the 60s and 70s as part of, and following the first malaria eradication initiative. The authors are right in presupposing that very few investigators screened for quinolone resistance, however we needed to do so because we used nalidixic acid-resistant recipients in conjugation experiments. We found that nalidixic acid resistance was low/absent during between 1986 and 1998. Other studies involving fecal isolates recovered before 2000, performed by us and other workers, make similar findings (for example Okeke, et al. Journal of Infectious Diseases, 181, 252-260) More recently, we screened samples from the same location isolated in 2005 and find that resistance to nalidixic acid approaches 20% and ciprofloxacin resistance has emerged. Coincident with this emergence is the introduction and now widespread use of ciprofloxacin and perfloxacin. (Before 2000, quinolone antimicrobials were available but too expensive to be accessed by most of the population. They were rarely used outside secondary and tertiary care institutions, and even there only as second-line therapies).

Overall, these data do not support a role for chloroquine selection in the emergence of quinolone resistance in that region. Instead, they suggest that the recent introduction and indiscriminate of quinolone antibacterials as the primary source of selective pressure. We are currently studying the mechanisms of resistance in recent isolates from Nigeria and Ghana and will report our findings when these studies are completed. We however think the study was rigorously performed and find the data intriguing, raising important questions that should be addressed before the likely ‘bringing back’ of chloroquine as a front-runner antimalarial. Are there other factors that combine with chloroquine use to select for QREC in South America that were absent from West Africa in the 1980s? If so, what are they and what is the prognosis for selective pressure in other parts of the world? Is there a metabolite at play, that present in one population and not in the other?