Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

Ivermectin modulated cerebral γ-aminobutyric acid (GABA) and reduced the number of chronic Toxoplasma gondii cysts significantly in the brains of immunocompromised mice.

Disruption of GABAergic signaling could exaggerate the inflammatory reaction associated with Toxoplasma gondii infection, as well as produce neurophysiological consequences including seizures that occur within the brain tissues. The current study aimed to evaluate the efficacy of ivermectin (IVM) in treating latent cerebral toxoplasmosis and define its role in the neuromodulation of cerebral tissue GABA expression, conducted in an immunocompromised dexamethasone-treated mouse model infected with the ME49 Toxoplasma strain. The control (non-infected non-treated) group showed a mean of 22.1 ± 0.71 for local expression of GABA. Significantly lower expression (3.78 ± 1.38) was recorded in the infected non-treated group (p ≤ 0.05). On the contrary, a significantly higher expression was reported in the group infected and treated with IVM than in the infected non-treated group (19.8 ± 0.8). While the infected spiramycin (SP)-treated group reported a significantly lower level than the control. Non-infected groups that received only IVM or SP recorded 22.3 ± 0.45 and 22 ± 0.89 respectively with no significant difference. IVM is shown in this work, not only to reduce the size and the number of Toxoplasma cystic lesions within the brain significantly with a reduction rate of 68.85% but to also increase the level of GABA local expression significantly in addition to improving cerebral histopathology. Thus, IVM by its ability to modulate GABA expression may improve such clinical situations, if used as a treatment either exclusively or in combination with other medications.

Serodiagnosis of Toxocara antibodies among infants and pregnant women suspected of ocular or visceral toxocariasis using two types ELISA antigens.

BACKGROUND: The diagnosis of toxocariasis heavily depends on immunological tests because the number of parasites is usually few in infected tissues, unless they migrate into an organ such as eye. In general, patients with ocular toxocariasis have serum anti-T canis antibody titres that are significantly lower than those with visceral toxocariasis. OBJECTIVE: To diagnose the asymptomatic toxocariasis in infants before two years old and suspected pregnant women by an ELISA method utilizing two different antigens of TEE and capture TEX. METHODS: This work was carried out between 8/2005 and 4/2006. Specimens of serum collected from 79 infants (apparent healthy) aged between 4 weeks to 30 moths (51 females and 28 males) Also, 28 specimens of serum were collected from asymptomatic pregnant women aged between 18-32 years old and all their infants (17 females and 11 males that their ages were as mentioned above). Serodiagnosis by ELISA was done by using two antigens, Toxocara canis embryonated egg antigen (TEE) and Toxocara canis antigen capture ELISA. RESULTS: Toxocara antibodies were found in 7 and 12 pregnant women, when tested by TEE and capture TEX ELISA respectively. Three out of 28 and 7 out of 28 infant sera were positive for Toxocara antibodies when tested by TEE ELISA and capture TEX ELISA respectively. Active ocular toxocariasis was only diagnosed in the left eye of one mother. All inactive ocular toxocariasis were diagnosed by capture TEX ELISA, except one infant serum, which was diagnosed by TEE ELISA. CONCLUSION: The capture TEX ELISA was able to discriminate positive and negative toxocariasis samples better than TEE ELISA. In addition, sample analyses by both capture TEX ELISA and TEE ELISA is recommended in children and young adults, when toxocariasis is considered in the differential diagnosis of the ocular diseases.

Effect of interferon-alpha on experimental Schistosoma mansoni infection in mice.

To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 (group II), week 3 (group III), week 6 (group IV) and week 10 (group V) post-infection. TGF-beta1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine (liver/intestine ratio less than 1), with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I (p < 0.05). In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them (all parameters p < 0.05), especially in Gs IV & V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV & V. TGF-beta1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups.