Background: The high current prevalence of P carinii dyhydropteroate synthase (DHPS) mutations in U.S. AIDS patients (pts) may be a result of widespread sulfa use. This study was performed to determine whether the prevalence of P carinii DHPS mutations in U.S. AIDS pts has increased over time, and to compare the current prevalence of these mutations in the U.S. with China, a country with a low background rate of sulfa use.

Methods: The P carinii DHPS gene from respiratory specimens from 145 AIDS pts with PCP between 1983–2000 from 5 U.S. medical centers and from 15 AIDS pts between 1999–2001 from 2 Chinese hospitals were PCR-amplified and sequenced. Results were analyzed according to year of PCP diagnosis and exposure to sulfa prophylaxis. Statistical comparisons were made by chi-square analysis.

Results: In the U.S., mutations were present in 58/145 (40%) during this time period.

 

Year	Sulfa Exposure # Mutation/total (%)	No Sulfa Exposure # Mutation/total (%)	Total # Mutation/total (%)
1983–1993	0/3 (0%)	0/23 (0%)	0/26 (0%)
1994–1995	6/13 (46%)	0/11 (0%)	6/24 (16%)
1996–1999	24/31 (77%)	14/44 (31%)	38/75 (50%)
2000	8/9 (88%)	6/11 (54%)	14/20 (70%)
Total	38/56 (68%)	20/89 (22%)	58/145 (40%)

 

Mutations were not present in any of the 26 pts with PCP prior to 1994. There was a significant increase in mutations in all AIDS pts from 16% in 1994 to 70% in 2000 (p < 0.01). Mutations were first observed in pts with prior sulfa prophylaxis exposure, and increased in percentage from 46% in 1994 to 88% in 2000. Later on, mutations then appeared in those without sulfa exposure, increasing from 31% in 1996 to 54% in 2000.

In China, mutations were present in 1 of the 15 pts (7%); none received sulfa prophylaxis.

Conclusions: In the U.S., mutant strains of P carinii have begun to appear recently and first appeared in pts exposed to sulfa prophylaxis. The prevalence of DHPS mutations in the U.S. has significantly increased over time, even in pts without prior sulfa exposure. These findings support the possibility that P carinii may be transmitted from person-person. In contrast, the current prevalence of DHPS mutations in China is markedly lower than that in the U.S., and is similar to the low prevalence of mutations found in the U.S. one decade ago.