Effects of sulfamethoxazole on murine ocular toxoplasmosis in interferon-gamma knockout mice.
OBJECTIVE
To evaluate the effects of sulfamethoxazole (SMX) on experimental ocular toxoplasmosis by quantitative competitive polymerase chain reaction (QC-PCR) assay.


METHODS
Wild-type (WT) C57BL/6 and WT BALB/c mice and interferon-gamma knockout (GKO) mice were infected orally with Toxoplasma gondii of the Fukaya strain. Mice were classified into groups. The first group (G1) remained untreated, the second group (G2) had a short SMX treatment period, and the third group (G3) received treatment continuously. WT and GKO mice were divided into G1 and G3, and G1, G2, and G3, respectively. T. gondii burdens were evaluated by QC-PCR assay. The effect on stage distribution was analyzed by reverse transcription-PCR.


RESULTS
SMX significantly decreased mortality among the infected WT C57BL/6 and GKO mice. In WT G1 mice, T. gondii DNA was detected in all organs and tissues, although in G3 mice it was detected only in the brain. In GKO C57BL/6 G1 mice, the protozoan proliferated much more actively than in the WT mice. In the GKO C57BL/6 G2 mice, the number of T. gondii was less than in G1 during the treatment, although the protozoan reappeared after cessation of treatment. In GKO C57BL/6 G3 mice, T. gondii DNA was detected in the brain, optic nerve, and retina, but not in the iris, choroid, sclera, and blood. In GKO BALB/c mice, the patterns of the kinetics of protozoan abundance in various organs were similar or were milder than those in GKO C57BL/6 mice. In SMX-treated GKO mice, the percentage of bradyzoites increased and that of tachyzoites decreased in the organs and tissues.


CONCLUSIONS
SMX decreased the parasitic load in both WT and GKO mice. SMX decreased the tachyzoite load but did not completely eliminate bradyzoites in GKO mice. The present mouse model was used successfully to assess treatment effects in a quantitative fashion.
Norose
Kazumi
K
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba, Japan. norose@faculty.chiba-u.jp
Aosai
Fumie
F
Mun
Hye-Seong
HS
Yano
Akihiko
A
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002825:Chorioretinitis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000469:parasitology; D016054:DNA, Protozoan / Q000032:analysis; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013420:Sulfamethoxazole / Q000627:therapeutic use*; D015996:Survival Rate; D014122:Toxoplasma / Q000187:drug effects / Q000235:genetics; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000469:parasitology; D014126:Toxoplasmosis, Ocular / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000469:parasitology
D000890:Anti-Infective Agents; D016054:DNA, Protozoan; D007371:Interferon-gamma; D013420:Sulfamethoxazole