Genotypesof Pneumocystis jiroveci Isolates Obtained in Harare,Zimbabwe, and London, UnitedKingdom

Abstract

Isolates of Pneumocystis jiroveci from sulfa-exposed and nonexposed patients from London, United Kingdom, and Harare, Zimbabwe, were genotyped. At the dihydropteroate synthase (DHPS) locus, there was evidence of selection pressure from sulfa drug exposure, and reversal of DHPS genotype ratios occurred when selection pressure was absent or was removed.

Epidemiology and clinical relevanceofPneumocystis jiroveciiFrenkel, 1976 dihydropteroate synthase gene mutations

“…There was reversal of the mutant-towild type genotype ratios when selection pressure was removed, as in 2000-2001. Based on this data the authors deduced that human Pneumocystis infection arises by recent transmission, because if reactivation of latent infection was the explanation, then no differences in DHPS genotypes would be observed over time or by geographical location, irrespective of patients' receipt of sulpha drugs (Miller et al, 2003). In a study conducted in France, involving patients' pulmonary specimens obtained between 1993 and 1998, the authors found a statistically significant association (P < 0.01) between DHPS gene mutations and prophylaxis with TMP-SMZ or dapsone (Santos et al, 1999).…”

“…In a study conducted in the UK, a decline in the proportion of P. jirovecii DHPS mutations was observed for the two time periods 1992-1993 (36 %) and 2000-2001 (17 %) of the study. The explanation for this decline was attributed to the decreased use of TMP-SMZ in the general population, since July 1995 in this country (Miller et al, 2003). In Italy, HIV-infected patients with PcP from two cities Rome and Milan, presented rates of DHPS mutations of 35 % in Rome and 8.4 to 40 %, Mise au point Parasite, 2010, 17, 219-232 in three studies involving patients followed in two different hospitals in Milan, between 1992 and 2004.…”

“…In total, these studies span a period between 1976 and 2007, involving patients and respective clinical data from United States of America (USA) and several countries in Europe. Eleven of those studies have demonstrated a significant association between the use of sulpha or sulphone agents for PcP prophylaxis in HIV-infected patients and the presence of DHPS mutations (Kazanjian et al, 1998;Ma et al, 1999;Helweg-Larsen et al, 1999;Santos et al, 1999;Kazanjian et al, 2000;Huang et al, 2000;Visconti et al, 2001;Ma et al, 2002;Miller et al, 2003;Nahimana et al, 2003;Zingale et al, 2003) (Table II). However, these studies used different PcP prophylaxis and exposure to sulpha drugs definitions, which limits the possibility of comparing results and detailing the analysis.…”

“…European specimens showed a higher prevalence of the wild-type sequence and a lower frequency of mutations than in the USA. These data suggest that there could be geographical variation in the prevalence of P. jirovecii DHPS gene mutations, possibly caused by intrinsic epidemiological factors that influence the circulation and transmission of different genotypes, or perhaps because of differing use of sulpha or sulphone drugs for PcP prophylaxis (Kazanjian et al, 1998;Armstrong et al, 2000;Beard et al, 2000;Miller et al, 2003;Costa et al, 2003;Esteves et al, 2008). Also in European countries a decline in the DHPS gene mutation frequency has already been described in the UK, France and Portugal in two different time periods (Miller et al, 2003;Latouche et al, 2003;Costa et al, 2003;Esteves et al, 2008), which may be reflecting the decreased use of prophylaxis with sulpha or sulphone drugs, following the introduction and widespread use of HAART in these countries (Morris et al, 2004).…”

“…In the African continent, three studies have been developed with the purpose to determine the P. jirovecii DHPS mutations rates in patients with PcP. One study conducted in Zimbabwe, for one year (1992)(1993), described a prevalence of 7.1 % of DHPS mutations in HIV-infected patients with PcP (Miller et al, 2003). In South Africa two studies ran in similar periods, 2000-2002 and 2000-2003, enrolling different populations (HIV-infected children and adults with PcP), in different regions of the country, with the purpose to determine the prevalence of P. jirovecii DHPS mutations.…”