Schistosoma egg-induced liver pathology resolution by Sm-p80-based schistosomiasis vaccine in baboons.

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway.

Role of antibody dependent cell mediated cytotoxicity (ADCC) in Sm-p80-mediated protection against Schistosoma mansoni.

Schistosomiasis is a major health problem in the developing world and for international travelers to the endemic countries. Existing strategies to control schistosomiasis have had limited successes so far. The addition of an effective vaccine in existing control measures would be greatly beneficial in reducing the impact of the disease. In this regard, Sm-p80 mediated protection against intestinal schistosomiasis caused by Schistosoma mansoni has been observed to be promising in two animal models of infection and disease. In this study, the role of antibody dependent cell mediated cytotoxicity (ADCC) was deciphered in Sm-p80-mediated protection especially in the elimination of lung stage schistosomula. This was achieved using lung lavage cells and lung cells that were isolated from mice immunized with and without Sm-p80 formulated in a recombinant vaccine formulation. Significant differences were observed in cytotoxicity assays using immune sera with the lung lavage cells which showed 51% more killing of schistosomula and elevated levels of nitric oxide in the supernatants were detected compared to controls.

Generalized lymphadenopathy secondary to an invasive fungal infection in an apparently healthy patient.

A 47-year-old woman with a history of anemia and deep vein thrombosis presented to the hospital with worsening leg edema despite treatment with warfarin. Initial laboratory results revealed leukopenia, anemia and abnormal liver enzymes. Computed tomography and positron emission tomography scans showed generalized lymphadenopathy. Cultures were negative, and lymph node and bone marrow biopsies were inconclusive. Because her clinical presentation suggested malignancy, 2 distinct regimens of empiric chemotherapy were given. She was also treated with antibiotics and antifungal drugs. After 1 month of hospitalization, the patient died. Her autopsy revealed an invasive fungal infection consistent with aspergillosis but no malignancy. Histologic studies of the lymph nodes revealed reactive inflammation without fungi. Generalized lymphadenopathy is an unusual presentation of aspergillosis, and only a few cases have been reported in patients without predisposing risk factors. These cases had granulomatous inflammation. This case demonstrates that invasive aspergillosis should be considered in patients with diffuse lymphadenopathy.