Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine.

Protection against clinical disease and prevention of the renal carrier state remain the key objectives of vaccination against leptospirosis in the dog. In the present paper, groups of dogs were vaccinated twice with a commercial bacterin (EURICAN L) containing Leptospira interrogans serovars icterohaemorrhagiae and canicola and challenged with heterologous representatives of both serovars at 2 weeks (onset of immunity) or 14 months (duration of immunity) after the second vaccination. Control dogs were not vaccinated against leptospirosis and kept with the vaccinated dogs. The challenges, irrespective of the serovar, reliably produced clinical signs consistent with Leptospira infection in the control pups with up to 60% mortality. As expected clinical disease in the adult controls was less severe, but we were able to induce morbidity and mortality as well. Under these extreme challenge conditions, clinical signs in the vaccinated dogs were rare, and when observed, mild and transient in nature. Following experimental infection, 100% of the control pups and 83% of the adult controls became renal carriers. Despite the heavy challenges, none of the 18 vaccinated puppies (onset of immunity studies) and only 2 out of the 16 vaccinated adult dogs (duration of immunity studies) developed a renal carrier state. These results show that a primary course of two doses of EURICAN L provided quick onset and long-term protection against both clinical leptospirosis and the renal carrier stage. This vaccine should provide veterinarians with a powerful tool to prevent clinical disease in dogs and zoonotic transmission of leptospirosis to humans.

Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy.

Hepatitis C virus (HCV)-related liver fibrosis progression is accelerated in human immunodeficiency virus (HIV)-infected patients. The effect of protease inhibitor (PI) therapy on liver fibrosis is unknown. The aim of this work was to analyze the impact of PI therapy on HCV-related liver fibrosis in HIV/HCV coinfected patients. We evaluated in a long-term follow-up retrospective cohort study the influence of antiretroviral therapy containing PI on liver fibrosis in 182 consecutive HIV/HCV coinfected patients. At liver biopsy, 63 patients had received PI and 119 patients had never been treated with PI. Relationships between liver histologic features, age, alcohol consumption, CD4 cell count, HIV-RNA load, and antiretroviral regimens were analyzed. Liver fibrosis stage was lower in patients receiving PIs by comparison with patients who had never received PIs (P =.03). The 5-, 15-, and 25-year cirrhosis rates were 2% versus 5%, 5% versus 18%, and 9% versus 27%, respectively, in patients who had received PIs compared with PI-untreated patients (P =.0006). Multivariate analysis identified 4 independent predictors of progression to cirrhosis: absence of protease inhibitor therapy (relative risk [RR] = 4.74, 95% confidence interval [CI], 1.34-16.67), heavy alcohol consumption (> or = 50 g daily) (RR = 4.71, 95% CI, 1.92-11.57), low CD4 cell count (<200/microL) (RR = 2.74, 95% CI, 1.17-6.41), and age at HCV contamination (> or = 20 years) (RR = 2.37, 95% CI, 1.04-5.38). In conclusion, protease inhibitor therapy might not accelerate progression to HCV-related cirrhosis. Furthermore, chronic use of antiretroviral therapy containing PI together with reduction of alcohol consumption and maintenance of high CD4 count could have a beneficial impact on liver fibrosis progression in HIV/HCV coinfected patients.

Protein p126: a parasitophorous vacuole antigen associated with the release of Plasmodium falciparum merozoites.

The p126 protein is synthesized by P. falciparum between the 32nd and the 36th hour of the erythrocytic cycle, and is localized in the parasitophorous vacuole. It is processed when schizonts rupture and the major fragments (50, 47 and 18 kDa), which are released into culture supernatant, have been characterized using monoclonal antibodies. The 47 kDa fragment has been mapped at the N-terminus of the molecule. The portion of the protein p126 gene coding for this fragment contains 3 introns and is characterized by a sequence coding for 6 repeats of 8 aminoacids and by repeats of TCA/T-AGT coding for a polyserine sequence of 37 serines in a row for the FCR-3 strain. The 50 kDa fragment is also found in culture supernatant when merozoites are released from mature schizonts. The incubation of mature schizonts with leupeptin inhibits the release of merozoites and, in this case, a 56 kDa intermediate product is found. In those conditions, merozoites were observed free in the erythrocyte cytoplasm, the membrane of the parasitophorous vacuole being destroyed. The 50 kDa fragment can be obtained from the 56 kDa fragment by treatment with trypsin (a protease inhibited by leupeptin). Our results suggest that the processing of the 56 kDa fragment: 1) is protease-dependent, and could depend on a trypsin-like activity; 2) cannot occur after the release of merozoites because of the protease inhibitors contained in the serum; 3) does not occur before the release of merozoites, since no processed products of the protein p126 are observed in unruptured schizonts.(ABSTRACT TRUNCATED AT 250 WORDS)

C. parvum skin testing antigen: study on guinea pig model.

A skin-testing antigen produced from C. parvum has been developed for exploring cell-mediated immunity and specially C. parvum specific cell-mediated immunity by delayed cutaneous hypersensitivity (DCH) reaction. The DCH antigen and the techniques of intradermal injection and multiple puncture are described. DCH reactions are carried out in C. parvum specifically sensitized guinea pigs: sensitization procedure and adjuvant (IFA and CFA) effects are reported. Measures of DCH reactions for different antigen doses at various times (5-24-48 h) are reported; classical Mantoux and multiple puncture reactions are compared. The specificity of these DCH reactions are explored by comparing C. parvum antigen and tuberculin reactions in corynebacterium and mycobacterium sensitized guinea pigs.