Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni.
BACKGROUND
The near exclusive use of praziquantel (PZQ) for treatment of human schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes.


RESULTS
We measured susceptibility to PZQ of isolates of Schistosoma mansoni obtained from patients from Kisumu, Kenya continuously exposed to infection as a consequence of their occupations as car washers or sand harvesters. We used a) an in vitro assay with miracidia, b) an in vivo assay targeting adult worms in mice and c) an in vitro assay targeting adult schistosomes perfused from mice. In the miracidia assay, in which miracidia from human patients were exposed to PZQ in vitro, reduced susceptibility was associated with previous treatment of the patient with PZQ. One isolate ("KCW") that was less susceptible to PZQ and had been derived from a patient who had never fully cured despite multiple treatments was studied further. In an in vivo assay of adult worms, the KCW isolate was significantly less susceptible to PZQ than two other isolates from natural infections in Kenya and two lab-reared strains of S. mansoni. The in vitro adult assay, based on measuring length changes of adults following exposure to and recovery from PZQ, confirmed that the KCW isolate was less susceptible to PZQ than the other isolates tested. A sub-isolate of KCW maintained separately and tested after three years was susceptible to PZQ, indicative that the trait of reduced sensitivity could be lost if selection was not maintained.


CONCLUSIONS
Isolates of S. mansoni from some patients in Kisumu have lower susceptibility to PZQ, including one from a patient who was never fully cured after repeated rounds of treatment administered over several years. As use of PZQ continues, continued selection for worms with diminished susceptibility is possible, and the probability of emergence of resistance will increase as large reservoirs of untreated worms diminish. The potential for rapid emergence of resistance should be an important consideration of treatment programs.
Melman
Sandra D
SD
Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America.
Steinauer
Michelle L
ML
Cunningham
Charles
C
Kubatko
Laura S
LS
Mwangi
Ibrahim N
IN
Wynn
Nirvana Barker
NB
Mutuku
Martin W
MW
Karanja
Diana M S
DM
Colley
Daniel G
DG
Black
Carla L
CL
Secor
William Evan
WE
Mkoji
Gerald M
GM
Loker
Eric S
ES
Am J Trop Med Hyg. 1995 Jul;53(1):61-2
7625534
J Infect Dis. 1997 Jul;176(1):304-7
9207389
Parasitol Res. 2003 Jun;90 Supp 1:S3-9
12811543
Am J Trop Med Hyg. 2006 Jul;75(1):83-92
16837713
J Parasitol. 1999 Jun;85(3):397-403
10386428
Int J Parasitol. 2001 Sep;31(11):1227-35
11513892
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7754-8
1679236
Exp Parasitol. 1971 Aug;30(1):1-10
5157124
Lancet Infect Dis. 2006 Jul;6(7):411-25
16790382
Am J Trop Med Hyg. 1999 Jun;60(6):932-5
10403323
Clin Microbiol Infect. 2008 Apr;14 Suppl 3:22-31
18318876
Trop Med Int Health. 2009 Apr;14(4):450-7
19222824
J Parasitol. 2008 Apr;94(2):537-41
18564758
Trop Med Int Health. 2001 Nov;6(11):864-73
11703840
Am J Trop Med Hyg. 1994 Jul;51(1):83-8
8059919
Am J Trop Med Hyg. 1998 Aug;59(2):307-11
9715952
Trends Parasitol. 2002 Mar;18(3):125-9
11854090
Curr Opin Infect Dis. 2006 Dec;19(6):577-82
17075334
Lancet. 2002 Aug 24;360(9333):592-6
12241930
Trop Geogr Med. 1994;46(4 Spec No):209-19
7825223
Clin Microbiol Rev. 2007 Jan;20(1):79-114
17223624
Int J Parasitol. 2004 Mar 29;34(4):527-33
15013742
Acta Trop. 2003 May;86(2-3):243-54
12745141
Naunyn Schmiedebergs Arch Pharmacol. 1978 Oct;304(3):309-15
714190
Trans R Soc Trop Med Hyg. 1987;81(4):641-4
3127965
Am J Trop Med Hyg. 1992 Jun;46(6):737-44
1621899
Mol Ecol. 2005 Oct;14(12):3889-902
16202103
Int J Parasitol. 2004 Jul;34(8):971-7
15217736
Z Parasitenkd. 1977 Jul 21;52(2):129-50
410178
Onderstepoort J Vet Res. 2001 Mar;68(1):55-67
11403431
Expert Opin Drug Discov. 2008 Feb;3(2):173-86
23480221
Int J Parasitol. 2004 Jul;34(8):979-87
15217737
Am J Trop Med Hyg. 2006 Feb;74(2):342-4
16474094
Int J Parasitol. 2005 Jun;35(7):787-91
15925597
PLoS Negl Trop Dis. 2008 Apr 16;2(4):e222
18414646
Parasitol Today. 1998 Oct;14(10):434-5
17040836
Trends Parasitol. 2004 Feb;20(2):92-7
14747023
Mol Biochem Parasitol. 2009 Mar;164(1):57-65
19100294
Emerg Infect Dis. 2000 Nov-Dec;6(6):585-94
11076716
Trends Parasitol. 2003 Nov;19(11):509-15
14580962
Int J Parasitol. 2009 Oct;39(12):1353-62
19464296
Am J Trop Med Hyg. 1996 Aug;55(2):214-8
8780463
J Infect Dis. 2001 Aug 15;184(4):488-96
11471107