In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

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The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.

A B S T R A C T Human as well as murine granulocytes have been shown to kill the larval stages of helminth parasites; the mechanism of this cell-mediated cytotoxicity is, however, poorly understood. The present study was designed to assess the role of peroxidative processes in killing of schistosomula of Schistosoma mansoni by human granulocytes in vitro. The rate of H202 production by human neutrophils, eosinophils, and basophils was measured upon incubation with schistosomula alone or in the presence of specific antibody or complement. Opsonized parasites (antibody and/or complement) increased the rate of H202 production by neutrophils, eosinophils, and basophils by respective percentages of 500, 500, and 371. The rate of H202 release was directly related to the number of granulocytes and to the proportion of cells attached to the surface of the schistosomula. Increased hydrogen peroxide release occurred by 10 min of incubation and was demonstrable up to 16 h after addition of leukocytes to schistosomula. The primary source of this oxygen product was found to be the granulocytes adherent to the schistosomula and not those that remained unattached. Hydrogen peroxide production by neutrophils and eosinophils was quantitatively similar (schistosomula coated with antibody plus complement stimulated 5 x 106 neutrophils and eosinophils to release H202 at respective rates of 0.35 and 0.40 nmol/min). Granulocyte-mediated parasite killing correlated with rate of H202 generation; both processes were inhibited by catalase. To define further the role of oxidative metabolites, neutrophils and eosinophils of two subjects with chronic granThis work was presented, in part, at the national meeting of the Association of American Physicians, Washington, D. C. 1980.Receivedfor publication 24 April 1980 and in revisedform 12 September 1980. ulomatous disease were used; marked reduction of granulocyte-mediated parasite mortality was observed.Peroxidase was required for H202-mediated killing. Addition of the peroxidase inhibitors azide (1 mM), cyanide (1 mM), or aminotriazole (1 cM) to neutrophilschistosomula mixtures significantly reduced parasite cytotoxicity (P < 0.01); similar reduction was observed when eosinophils were used (P <0.01). Fixation of halide (iodide) to trichloroacetic acid-precipitable protein (2.4-6.0 nmol/h per 107 neutrophils) was demonstrated in the presence of granulocytes, opsonins, and parasites; this process was completely inhibited by 1 mM azide.These data indicate that contact between the surfaces of human granulocytes and schistosomula results in release of cellular hydrogen peroxide and iodination. The generation of H202 and its interaction with peroxidase appear to be crucial in effecting in vitro granulocyte-mediated parasite cytotoxicity.

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Testing saliva for the detection of human immunodeficiency virus (HIV) antibodies has many potential advantages for epidemiologic surveillance. A commercial ELISA kit and a standardized in-house immunoblot (IB) system were slightly modified to enhance antibody detection in saliva. Frozen saliva specimens from Toronto Sexual Contact Study participants (including sequential saliva specimens collected during seroconversion) were tested as were fresh saliva samples collected from a population of street-based intravenous drug users (IVDUs). HIV antibody results on saliva were compared with HIV serostatus determined by ELISA and IB on serum or dried blood spots. The overall sensitivity was 98.3% (117/119) for the kit and 99.2% (118/119) for IB; the specificity was 100% (429/429). In the IVDU population, compliance in the voluntary submission of specimens increased from 69% agreeing to provide blood samples to 89% agreeing to provide blood, saliva, or both. Saliva specimens can be easily collected under difficult field conditions with minimal training and provide a valuable alternative to testing blood for HIV-seroprevalence studies.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

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