Volume 69, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Clinical observations have shown that pyrimethamine resistance develops rapidly in endemic countries where antifolate drugs are used massively for the treatment of infections. To analyze this phenomenon, the response of clinical isolates to pyrimethamine and the dihydrofolate reductase () gene sequence were analyzed in 2000–2001 and compared with the results obtained since 1994 in Yaounde, Cameroon. Of 139 samples obtained in 2000–2001, 10 (7.2%) isolates were of the wild-type, 116 had pure mutant alleles (2 [1.4%] with a single mutation, 11 [7.9%] with double mutations, and 103 [74.1%] with triple mutations), and 13 (9.4%) had mixed alleles. With the exception of a single isolate with triple mutations (50% inhibitory concentration [IC] = 84.3 nM), all isolates with pure wild-type alleles (IC < 100 nM) and those with pure mutant alleles (between 1 and 3 point mutations; IC ≥ 100 nM) were clearly distinguished by drug sensitivity assays. The results of the two methods are highly correlated, and both methodologic approaches indicate an increasing proportion of pyrimethamine-resistant isolates in Yaounde over the past eight years (42–45% in 1994–1995, 63–67% in 1997–1998, and 88–92% in 2000–2001). At present, clinical isolates carrying triple mutations predominate in Yaounde. This situation calls for a regular surveillance of the efficacy of antifolate drugs by all available means, including clinical evaluation, drug sensitivity assays, molecular markers, and pharmacologic studies.


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  • Received : 07 Sep 2002
  • Accepted : 26 Apr 2003

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