We describe a patient with human immunodeficiency virus type-1 (HIV) infection and alveolar echinococcosis (AE) with a focus on two messages. Despite being severely immunocompromised over years the patient exhibited a long-term asymptomatic course of AE. This is in clear contrast to reports describing accelerated courses of AE in immunocompromised patients. The patient had therapeutic mebendazole drug levels with only 1/10 of the normal drug dose. He was co-treated with protease inhibitors for his HIV infection. These drugs are known as strong inhibitors of cytochrome P450 3A4 (CYP3A4)-dependent metabolism. We speculate that benzimidazoles and protease inhibitors interfere at the CYP3A4-level. The first report of co-infection of HIV and accelerated AE was in a young girl with an extremely low CD4 cell count and an abrogated lymphoproliferative responsiveness to parasite antigen stimulation. Since the CD4 cell count in our patient remained in the range of 27-150 cells/microl, we speculate that there was a critical threshold of immunosupression for constraining AE. Initial treatment with albendazole for AE added to the current highly active antiretroviral treatment (HAART), and suppressive toxoplasmosis therapy became complicated by pancytopenia. After full recovery of the bone marrow, mebendazole was introduced with a new HAART and the previously prescribed toxoplasmosis maintenance therapy. Surprisingly, efficient mebendazole levels were achieved with an uncommonly low dose. These observations suggest that the benzimidazoles, albendazole and mebendazole, may interact with protease inhibitors, which are known for their strong inhibition of the CYP3A4.

Leflunomide's anti-HIV activity and clinical profile make it an attractive candidate for further study of its effects. Since HIV RNA levels are an effective predictor of AIDS-free survival, leflunomide's partial suppression of HIV RNA may be valuable in certain patients.

Tonsils seem to be the ideal source for lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.

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