Evolution of the E2 region of hepatitis C virus in an infant infected by mother-to-infant transmission.

To demonstrate vertical transmission of hepatitis C virus from an HCV infected woman and to assess the evolution of HCV quasispecies in the infant, the variable E2 region was analyzed in one mother-infant pair at birth and in serial samples from the infected baby. Sequence analysis of the E2 region obtained by means of direct sequencing of PCR products of mother-infant pair at birth, showed that the sequence of the dominant strain in the infant was related closely but not identical to that of her mother. The HCV population in mother-infant pair at birth and in serial samples of the infant was analyzed by polymerase-chain reaction-mediated Single Strand Conformational Polymorphism analysis (SSCP), which can distinguish DNA fragments of the same size as different electrophoretic migration of single stranded DNA. Single Strand Polymorphism analysis revealed that the infant was infected with two mutant genomes whereas the mother had a unique variant. The prevalent strain detected in the baby was not dominant in the mother at delivery and the pattern of quasispecies in the infant at birth was not the same as her mother, suggesting that the infant acquired the infection in utero. Changes in the dominant strain and evolution of the pattern of quasispecies in the infant from the 10th month of age were possibly due to the immune selection of escape mutants.

Cerebrospinal fluid beta 2-microglobulin in AIDS related central nervous system involvement.

We measured cerebrospinal fluid (CSF) and serum beta 2-microglobulin (beta 2-M) in Acquired Immunodeficiency Syndrome (AIDS) patients with or without clinical evidence of central nervous system (CNS) involvement. The CSF beta 2-M level was significantly higher than the serum level in AIDS patients with neurological symptoms, but not in AIDS without neurological symptoms, suggesting an increased shedding of this protein in CSF, as a result of rapid cellular turnover within CNS. CSF beta 2-M level increases both in Human Immunodeficiency Virus type 1 (HIV-1) related and in opportunistic CNS syndromes, confirming that beta 2-M is a non specific marker of CNS involvement in AIDS. Nevertheless, the highest CSF beta 2-M values were observed in patients with severe dementia and autoptic diagnosis of multifocal giant cells encephalitis (MGCE) without other opportunistic diseases. This observation could have important implications for monitoring AIDS dementia complex in AIDS patients. Finally, 5 out of 7 (71%) AIDS patients with cryptococcal meningitis showed a decline in CSF beta 2-M level well related to the decrease of cryptococcal antigen (Crypto-Ag) titres and the clinical remission. This data suggests that CSF beta 2-M determination could be used as a useful test in monitoring efficacy of therapy of CNS pathologies in AIDS patients.

A retrospective study of primary and maintenance therapy of toxoplasmic encephalitis with oral clindamycin and pyrimethamine.

Fourteen patients with AIDS and toxoplasmic encephalitis, who could not be treated with the standard regimen of pyrimethamine and a sulfonamide due to a previous history of bone marrow suppression and severe allergic reactions to sulfonamides, were treated with oral clindamycin and pyrimethamine. All 14 patients received a 100 mg loading dose of pyrimethamine orally followed by 50 mg/day plus clindamycin orally (600-900 mg q8h). The duration of primary treatment ranged from 6 to 8 weeks. All patients also received folinic acid (15 mg/day orally). Maintenance therapy consisted of 25 mg/day of pyrimethamine and clindamycin (300 mg q6h or 450 mg q8h). A complete or partial clinical or neuroradiological response was observed in all patients at the end of two months of primary therapy. Ten of 14 patients showed complete resolution of clinical signs, and 8 of 14 patients showed complete resolution of neuroradiologic signs. All 14 patients continued the maintenance regimen, and although there were no relapses, symptoms that had not resolved by the end of the second month of acute therapy tended to remain unchanged.

Raised serum beta 2 microglobulin levels in different stages of human immunodeficiency virus infection.

Serum beta 2 microglobulin (beta 2-M) levels were determined in patients with Acquired Immunodeficiency Syndrome (AIDS), AIDS Related Complex (ARC), Persistent Generalized Lymphadenopathy (PGL), healthy intravenous drug addicts (IVDA) and heterosexual controls. Seventy-eight out of 79 AIDS patients (98.7%) exhibited elevated beta 2-M levels. High levels of beta 2-M were also found in 83 of 100 (83%) of PGL/ARC patients and in 24 of 56 (42.8%) healthy IVDA. Patients with AIDS had significantly higher mean beta 2-M levels when compared with all other groups. The mean levels of PGL/ARC patients were significantly higher than those of healthy IVDA and the mean levels for healthy IVDA significantly differ from those of the heterosexual controls. After 2-24 months of follow up three out of four PGL/ARC patients whose serum beta 2-M was greater than 8.0 mg/l developed AIDS.

Impairment of in vitro natural antibacterial activity in HIV-infected patients.

Circulating PBMC of healthy subjects possess an in vitro natural antibacterial (NA) against enteropathogenic bacteria, including Salmonella species. The effector cell of NA activity is a CD: 4+, 8-, Leu-8/TQ-1+ T lymphocyte acting against bacteria via cytophylic IgA in a mechanism similar to antibody-dependent cellular activity. Because AIDS is a profound immunodeficiency caused by HIV involving primarily CD4 lymphocytes and in particular the Leu-8/TQ-1 subset, it was of interest to assess NA activity of HIV+ subjects at various stages of the disease. Results indicate that NA activity against Salmonella typhi and Salmonella paratyphi C is significantly decreased in AIDS as well as in lymphadenopathy syndrome patients. Furthermore, sera containing IgA against salmonellae were not able to arm PBMC from HIV+ patients. The humoral response against S. typhi-LPS was also greatly decreased after HIV infection, in contrast to the known hypergammaglobulinemia seen in these subjects. Defective NA activity might contribute to the increased incidence of salmonellosis observed in AIDS.

IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells.