The effect of lopinavir/ritonavir and lopinavir/ritonavir loaded PLGA nanoparticles on experimental toxoplasmosis.

A marked reduction has been achieved in the incidence and clinical course of toxoplasmic encephalitis after the introduction of protease inhibitors within the treatment regimen of HIV (HIV-PIs). This work was undertaken to study for the first time, the efficacy of HIV-PIs, lopinavir/ritonavir (L/R), as a therapeutic agent in acute experimental toxoplasmosis. Lopinavir/ritonavir (L/R) were used in the same ratio present in aluvia, a known HIV-PIs drug used in the developing countries in the treatment regimens of AID's patient. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as a delivery system to L/R therapy. L/R alone or after its encapsulation on PLGA were given to Swiss strain albino mice that were infected with RH virulent toxoplasma strain. Both forms caused parasitological improvement in both mortality rate and parasite count. The higher efficacy was achieved by using L/R PLGA together with minimizing the effective dose. There was significant reduction in the parasite count in the peritoneal fluid and the liver. Parasite viability and infectivity were also significantly reduced. The anti-toxoplasma effect of the drug was attributed to the morphological distortion of the tachyzoites as evident by the ultrastructure examination and suppressed the egress of tachyzoites. L/R also induced changes that suggest apoptosis and autophagy of tachyzoites. The parasitophorous vacuole membrane was disrupted and vesiculated. The nanotubular networks inside the parasitophorous vacuole were disrupted. Therefore, the present work opens a new possible way for the approved HIV-PIs as an alternative treatment against acute toxoplasmosis. Furthermore, it increases the list of the opportunistic parasites that can be treated by this drug. The successful in vivo effect of HIV-PIs against Toxoplasma gondii suggests that this parasite may be a target in HIV treated patients, thus decrease the possibility of toxoplasmic encephalitis development.

Encephalitozoon cuniculi infection among immunocompromised and immunocompetent humans in Egypt.

BACKGROUND: Encephalitozoon cuniculi infects a wide range of homoeothermic animals, including man. Complications due to this microsporidian have been reported only in immunocompromised patients. Reports on E. cuniculi in immunocompetent humans are lacking, most probably, because it is not linked to any clinical manifestations in such hosts. The present work was carried out with the aim of studying, for the first time in Egypt, the prevalence of E. cuniculi infection of urinary tract among non-HIV immunocompromised patients and immunocompetent individuals. It tested also the influence of some factors on the risk of infection. METHODS: Blood and urine samples were collected from 88 persons (44 non-HIV immunocompromised patients and 44 subjects as immunocompetent control group). IFAT serological assay and Weber's green modified trichrome stain (MTS) urine smears were carried out. Molecular study by PCR was also performed to detect DNA of E. cuniculi in urine samples. A full history sheet was fulfilled for each subject to test the suspected risk factors. RESULTS: The IFAT examination confirmed the presence of antibodies against E. cuniculi in 44.3% of the human subjects. The seroprevalence of E. cuniculi was significantly higher in the immunocompromised patients compared with the immunocompetent individuals (77.3% versus 11.4%). Compared with IFAT (the gold standard), the sensitivity and specificity of Weber's green MTS smears were 69.23% and 89.80%. By using PCR, no positive cases were detected among human subjects. CONCLUSION: A high prevalence of E. cuniculi infection in the studied individuals was noted. Although infection was found in some immunocompetent individuals, the immune status of the host remains the corner stone for occurrence of the infection.