Real-time PCR for Francisella tularensis Types A and B

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 11, November 2006 1799 6.4 nmol/L and that showed an H243Y mutant type codon. The role of such a polymorphism appears unclear. We found no association between the 3-bp indel in G7 and in vitro dhART susceptibility because mutants were regularly distributed in highly susceptible isolates and in isolates having a diminished susceptibility. For our samples obtained during 2004–2006, the geometric mean IC50 value for dhART was very close to values found in Cameroon during 1997–1998 (mean dhART IC50 = 1.11 nmol/L) (9), in Senegal in 2001 (mean artemether IC50 = 1.3 nmol/L) (5), and in Republic of Congo during 2005–2006 (mean dhART IC50 = 1.02 nmol/L) (10). Ringwald et al. observed a narrower range of IC50s, but their series included only 65 samples (9). Previous comparisons between ACs suggested that dhART is 1.7 times more potent than artemether against P. falciparum (9). Thus, the highest IC50 value for artemether observed by Jambou et al. in Senegal (44.7 nmol/L) (5) is comparable to the highest IC50 value for dhART in our series (31.8 nmol/L). The resistance levels of ACs are still undefined. For artemether, Jambou et al. used a threshold of 30 nmol/L to evaluate the association between the S769N mutation and in vitro susceptibility. The presence of ATPase6 S769N was not associated with diminished in vitro susceptibility in our series. Conversely, the only S769N mutant that we observed was found in a fully susceptible isolate. Thus, we confirmed that polymorphism exists in this gene in positions 769 and 243, but we did not prove an association between these point mutations and resistance to ACs. Similarly, our results did not support the hypothesis of an association between the 3-bp indel in G7 and resistance to ACs. ACs, considered the most important class of antimalarial drugs, merit close surveillance for susceptibility. Continued monitoring of the efficacy of their associated partner drugs also appears to be essential.