Transfusion-associated AIDS: serologic evidence of human T-cell leukemia virus infection of donors.

An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.

Antibodies to human T-cell leukemia virus membrane antigens (HTLV-MA) in hemophiliacs.

Along with homosexual men, Haitians, and intravenous drug abusers, hemophiliacs are at high risk of contracting acquired immunodeficiency syndrome (AIDS). An earlier study revealed that 36 percent of a group of the AIDS patients had antibodies to cell membrane antigens associated with the human T-cell leukemia virus (HTLV-MA), whereas only 1.2 percent of matched asymptomatic homosexual controls had these antibodies. In the present experiments, serum samples from 172 asymptomatic hemophiliacs were examined for the presence of antibodies to HTLV-MA. Such antibodies were detected in 5 to 19 percent of the hemophiliacs examined from four geographical locations, but in only 1 percent or less of laboratory workers, normal blood donors, donors on hemodialysis, or donors with chronic active hepatitis.

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

HIV and hemophilic children's growth.

The acquired immune deficiency syndrome (AIDS) often has profound effects on growth; however, the effects of human immunodeficiency virus (HIV) on asymptomatic children's growth are unknown. Before heat inactivation/HIV donor screening of factor concentrates, many hemophilic children became infected with HIV. We evaluated four hemophilic groups without AIDS, using age-standardized growth parameters: group 1, 41 HIV-seropositive children (median age of 13 years); group 2, 11 HIV-seronegative children (median age of 4 years); group 3, 20 children frequently receiving concentrates, evaluated before 1979 (median age of 9 years); and group 4, 11 children rarely receiving concentrates, evaluated before 1979 (median age of 6 years). Median height for age (HA), weight for age (WA), and weight for height (WH) of groups 1 and 2 exceeded the 50th percentile of referent norms. HA, WA, WH, and weight/height did not vary significantly by group, nor did these decline over periods of 11 to 70 months. However, for those less than 11 years of age in group 1, HA declined by 25 percentile points over at least a 3 year period. Also, group 1's T helper-to-suppressor cell ratios at 12 +/- 3 months following the latest growth evaluation were positively associated with both HA and WA at the last evaluation. Eight children were evaluated before 1979 and again after they seroconverted to HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.

HTLV-I antibody status in hemophilia patients treated with factor concentrates prepared from U.S. plasma sources and in hemophilia patients with AIDS.

Serum samples from 85 Austrian hemophilia patients treated with lyophilized factor concentrates prepared from U.S. plasma sources, 24 hemophilia patients from Georgia on a home therapy program with factor concentrates, and 10 U.S. hemophilia patients with acquired immunodeficiency syndrome (AIDS) were analyzed by two different methods for the presence of antibodies to the major internal antigen of human T-cell leukemia virus I (HTLV-I) p24. All but one, a Georgia sample, were negative. The absence of antibody to HTLV-I p24 in the serum of European hemophilia patients, of U.S. hemophilia patients with no symptoms of AIDS, and of U.S. hemophilia patients with AIDS is interpreted as an indication of the lack of ready transmissibility of HTLV-I in lyophilized factor concentrates.

Extended cryopreservation of Mansonella ozzardi microfilariae concentrated from human peripheral blood.

Microfilariae of Mansonella ozzardi, concentrated from human blood, frozen with a cryoprotectant chemical, and stored at liquid or vapor-phase liquid nitrogen temperatures were motile when thawed after 2.5 years of preservation.

Lobomycosis in western Brazil: report of a clinical trial with ketoconazole.

We report a case of chronic lobomycosis, contracted by a rural resident of the westernmost Brazilian state, Acre, and substantiate that western Amazonia is now an endemic area for Loboa loboi. No changes in lesion morphology resulted from a prolonged course of oral therapy with ketoconazole administered in an attempt to prevent the progressive and destructive extension of the disease.

Epidemiologic studies among Amerindian populations of Amazonia. III. Intestinal parasitoses in newly contacted and acculturating villages.

The prevalences of intestinal parasites among the residents of three South American Indian villages in the process of acculturation were compared with those found in earlier unpublished surveys in two newly contracted village.s Although one individual in an acculturating village harbored 11 different intestinal parasites, in general the average number of different parasitic species carried per person was somewhat higher in the newly contacted villages. Helminth egg counts, performed on direct smears of each specimen from one newly contacted village, were low. There were no sex-associated differences in prevalences. The overall prevalences, unadjusted for age, were among the highest recorded for Amerindians. No Taenia species were present. Balantidium coli was present in two acculturating villages, concomitant with the beginning of agricultural practices which include raising swine. No cases of moderate or severe protein-calorie malnutrition was observed in any of the villages during the surveys. These limited data provide a baseline for future comparisons and, perhaps, a glimpse into the past.

Epidemiologic studies among Amerindian populations of Amazônia. I. Pyoderma: prevalence and associated pathogens.

Pyoderma was studied among a representative sample of the residents of four remote Amerindian villages, Amazonas State, Brazil, during July-August 1976. The overall prevalence among the 775 inhabitants examined was 11%, with little intervillage variation. When the attack rates for the entire sample population were calculated by 5-year age intervals, the 0- to 4-year-olds had the highest rate, 31%. The highest prevalence, 38%, was found among 3-year-olds. Attack rates were not apparently related to sex. Cultures which were taken from representative pyoderma lesions from people in the four survey villages and from three additional villages were studied by a modified delayed culture technique for recovery of gram-positive pathogens from silica-gel desiccated swabs. Group A and group G B-hemolytic streptococci, coagulase positive Staphylococcus aureus, and Corynebacterium diphtheriae were isolated. Group A S. pyogenes was most commonly found, occasionally as the sole pathogenic species. No nephritogenic M-types were found, although most isolates were not M-typable. The T-types found corresponded to those previously reported as being pyoderma-associated. Most pyoderma-associated C. diphtheriae isolates were non-toxigenic. Biotypes gravis and mitis were equally represented.

Epidemiologic studies among Amerindian populations of Amazonia. II. Prepvalence of Mansonella ozzardi.

The prevalence of microfilaremia among Indians in 13 Amazon Indian villages was determined by examining Giemsa-stained peripheral blood smears and preparations from peripheral blood lymphocyte cultures. Mansonella ozzardi was the only species found in the 601 persons tested. Prevalence was highly village-specific, ranging from 0% in four villages to as high as 93% among persons aged 10 years and older in others. Comparisons of the two methods showed that the concentration effect of the peripheral blood lymphocyte culture preparations allowed the detection of a greater number of microfilaria-positive persons, especially women and children with lower levels of parasitemia.

Acquired immune deficiency syndrome associated with hemophilia in the United States.

Persons with hemophilia and other coagulation disorders were at risk for infection with HIV as a result of receiving blood products, particularly concentrated clotting factors. Because these products are now donor-screened and heat-treated to inactivate HIV, the risk of further infection in this population has been minimized. However, before the introduction of these interventions, many persons with hemophilia had been infected. As of Jan 4, 1988, 463 cases of hemophilia-associated AIDS had been reported to the Centers for Disease Control. Most patients had severe hemophilia and received commercially produced concentrated clotting factors. These patients may constitute as many as 25% of those hemophilic men known to be infected with HIV. Through heterosexual and perinatal transmission, the partners and offspring of persons with hemophilia can become infected with HIV. The seroprevalence rate for female sex partners of men with hemophilia may be as high as 21%, and 16 AIDS cases have already been reported. Counseling and public health interventions are needed to prevent the further spread of HIV infection in sex partners and offspring of these patients and to prevent the associated morbidity and fatalities. Because HIV infection can be transmitted by exposure to infected blood or blood components, health-care workers whose activities involve contact with infected blood or body fluids are also at risk for HIV infection. Prospective studies suggest this risk is very low; nevertheless, health-care workers need to adhere rigorously to infection-control precautions to minimize the risk of exposure to blood and body fluids. These precautions include wearing gloves, masks, protective eyewear, and gowns depending on the type of exposure anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of clinical studies evaluating the efficacy of HIV inactivation methods.

Seroconversion surveillance is informative and must be continued. The level of safety is now so high that individual candidate cases of seroconversion need exquisite investigation to exclude the possibility of another source of the HIV infection. Consequently, we must be mindful that the inappropriate assignment of an HIV seroconversion incident to a blood product not only misrepresents the risk associated with currently available blood products, but may unfairly and devastatingly damage the reputation of a necessary and precious biological product. Inappropriate anxiety about a product, with resultant abandonment of its therapeutic benefit, may drastically reduce available factor concentrates, encourage price escalations associated with shortages, and lead unsettled patients to reduce their levels of prescribed therapy--with life threatening consequences. By monitoring the HIV-antibody testing records for all collection sites of a company's source plasma procurement network, the number and percent of donors found to be confirmably HIB-antibody positive might provide a clue to possible changes in the level of the undetected virus burden introduced into the source plasma supply. However, the combined efforts to develop higher purity products, combined with stringent inactivation methods has resulted in a product mix in use in the U.S. and elsewhere that seems to carry a risk of HIV seroconversion of less than 1 per 1000 patient-years of therapy.

Some statistical issues in HIV vaccine trials.

Efficacy trials of prophylactic HIV vaccines will be among the most difficult clinical trials ever attempted. Not only will there be challenges with the recruitment and retention of high-risk uninfected individuals, there will be many statistical challenges to the design, conduct, analysis, and interpretation of these trials. General features of an efficacy trial are described, including choice for the primary endpoint and testing for and estimating vaccine efficacy. Secondary objectives of trials are also discussed. These include determining the correlates of protective immunity, assessing the impact of HIV genetic variation on vaccine efficacy, and using biological markers such as viral load and CD4+ lymphocyte cell count to gain insight on a vaccine's ability to prevent or delay disease. The use of biological markers as surrogates for disease outcome is discussed. Last, trial designs for studying several candidate vaccines or other HIV prevention strategies in a single trial are examined.

Modified culture technique for Corynebacterium diphtheriae isolation from desiccated swabs.

Corynebacterium diphtheriae was isolated from pyoderma and ulcerative skin lesions with a modified delayed culture procedure as late as 9 weeks after field collection of silica gel-desiccated swabs. Biotypes gravis and mitis were identified. Most isolates were nontoxigenic. Todd-Hewitt broth enrichment enhanced recovery of C. diphtheriae by 70%.

Distribution of HLA antigens in Ticuna Indians of Brazil: results of typing a leprosy-affected family.

HLA typing was performed in 1978, using antisera recognizing specificities defined by the Seventh Workshop, on lymphocytes separated and frozen in the field during a 1976 expedition among Amazonian Ticuna Indians. Family segregation of HLA antigens was used to ascertain haplotypes of a sample of essentially unrelated reproductive-age adults. "Expaternal" haplotypes were also included in the total of 81 haplotypes used for calculating the A and B locus gene frequencies. Common A and B locus antigens among the Ticuna were Aw24, Aw31, A2, Bw39, B40, Bw35, and B15.1. Bw53 were also present. No A or B locus "blanks" were found. A slight degree of European admixture was apparent. Bw16-reactive cells from certain persons consistently failed to react with Oxford antisera capable of recognizing the Bw38 or Bw39 subspecificities. Cw1 and Cw3 were found in association with typical South American Indian haplotypes. The results of HLA typing of a large extended family with multiple cases of leprosy are depicted and compared to recently reported family studied of leprosy.

An immune response profile model for immunogenicity quantitation.

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.