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Recombinant alpha-D-galactosidase (rGal) from soybean (Glycine max) hydrolyzed the immunodominant alpha-D-galactose residue from the B epitope of red blood cells. This converted type B erythrocytes to type O which are "universally" transfusable. Type B red blood cells were obtained from four different donors and enzymatically converted. Cell function parameters, including red cell indices, pH, methemoglobin, carboxyhemoglobin, osmotic fragility, hemolysis, 2,3-diphosphoglycerate, cholinesterase, ATP, and antigen typing of treated cells were compared to controls. These pilot studies indicate that rGal could have potential biotechnical application in the production of universally transfusable red blood cells.
We present a case of documented acute hepatitis C that occurred in a health care worker who sustained a needlestick injury while caring for an individual who was infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). According to the findings of third-generation serological assays performed during a follow-up of >1 year, the health care worker, who was treated with interferon-alpha (during weeks 2-6) and ribavirin (during weeks 5-9), did not develop antibodies against HCV, in spite of documentation of an HCV-specific T cell response.
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BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-uninfected Ethiopians have lower CD4 T cell counts than do other populations in Africa and industrialized countries. We studied whether this unique immunological profile results in shorter survival times in HIV-1-infected Ethiopians. METHODS: Data from an open cohort study of 149 HIV-1-infected factory workers in Ethiopia for 1997-2002 were used. To estimate survival times, a continuous-time Markov model was designed on the basis of CD4 T cell counts and World Health Organization clinical staging. By use of a random-effects model, decline in CD4 T cell counts was compared between HIV-1-infected Ethiopian and Dutch individuals. RESULTS: Median survival times were in the range of 9.1-13.7 years, depending on the approach used. This range is similar to that for populations in industrialized countries before the advent of antiretroviral therapy. Ethiopians had a lower annual decline in CD4 T cell counts than did Dutch individuals, which remained when groups with similar CD4 T cell count categories were compared. Moreover, the slower decline in CD4 T cell counts was not due merely to lower HIV-1 RNA loads or an absence of syncytium-inducing/X4 HIV-1 subtype C strains in Ethiopians. CONCLUSIONS: Low baseline CD4 T cell counts do not imply shorter survival times in Ethiopians than in other populations, presumably because of a slower decline in CD4 T cell counts.
The frequency of hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) I/II was determined in the emergency room of a teaching hospital. Of 909 patients, 19% had at least one infection; 7.8% had HCV, 6.9% HBV, 3.3% HIV, and 2.8% HTLV I/II. The probability that a healthcare worker would have an accident with an infected patient and seroconvert was 4.99 to 24.9 per 100,000 venipunctures for HBV, 5.6 to 8.4 for HCV, and 0.12-0.16 for HIV in our emergency room.
Circumsporozoite (CS) antibodies have been shown to be reliable indicators of malaria transmission in endemic areas. Their prevalence in travelers can indicate the degree of exposure to plasmodial infection. Two hundred sixty-two short-term travelers to Kenya were recruited to a prospective study to determine the incidence of CS antibody conversion. All travelers were receiving malaria chemoprophylaxis. Serum samples were drawn before departure and 4-6 weeks after their return to Germany. Sera from 310 volunteers who did not leave Germany served as controls. Serum specimens from 13 (4.96%) of the 262 travelers were found to be positive after return. None of the travelers developed symptoms of clinical malaria or antibodies against the blood stages of Plasmodium falciparum. All 310 control samples tested negative. These data demonstrate a considerable risk of malaria transmission for short-term travelers to East Africa.
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In a prospective open-label study, 41 male subjects received nelfinavir, zidovudine, and lamivudine stratified as either: early stage (ES; negative/indeterminate Western blot; n = 19) or late stage (LS; positive Western blot; n = 22) primary HIV-1 infection. Despite higher median baseline HIV-1 RNA levels and lower CD4(+) cell numbers in the ES subjects, a significantly greater decline in viral load (-3.46 vs. -2.83 log(10) copies/ml; p = 0.023) and increase in CD4(+) cell number (+85 vs. +41 cells/month increase, p = 0.01) were observed over the first 3 months of therapy such that both groups had comparable results at 1 year. The proportion with HIV-1 RNA < 50 copies/mL at 1 year was similar (9 of 19 ES subjects and 11 of 22 LS subjects by intention-to-treat analysis). Memory CD4(+) cell numbers, and activated CD4(+) percentages, were also significantly improved in ES subjects. Despite poorer prognostic markers at baseline ES subjects achieved responses similar to those of LS subjects after 1 year of treatment.
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A patient who presented with late stage HIV-associated diseases could not be diagnosed by commercial ELISA tests and a Western blot. However, we could amplify proviral DNA of HIV-1. We found a novel GPGGMI motif in the V3 loop, a novel insertion of a proline in the C3 region, and persistent deletion of two amino acids in the vif gene. The patient had been treated with HAART after diagnosis. Forty months after the first amplification of HIV-1 DNA, anti-HIV-1 antibody was confirmed by ELISA and Western blot and, thus, we amplified and sequenced HIV-1 full sequences. Interestingly, the sequence at the TATAA box was TAAAA, although full sequences were not CRF01_AE. The major differences in the level of the HIV-1 gene between the seronegative and seropositive states were changes at the glycosylation site (NXT) next to the inserted proline and many resistance mutations including M184V to antiretroviral drugs occurred. This is the first report on HIV-1 full sequences isolated from seronegative AIDS patients infected with subtype B in Korea.
A prospective study of 1,198 individuals who seroconverted to human immunodeficiency virus (HIV) was conducted to estimate the incidence and determinants of herpes zoster and to determine whether herpes zoster can accelerate the progression to AIDS. Herpes zoster was diagnosed for 48 individuals (4%). After adjusting for the CD4 cell count, individuals acquiring HIV infection through sexual contact were more likely to have herpes zoster than were injection drug users (relative hazard, 1.50). The crude relative hazard of AIDS for individuals who had herpes zoster compared with those without herpes zoster was 2.44; the adjusted relative hazard was 1.08. After adjusting for the CD4 cell count, fever was the only specific characteristic of herpes zoster that was significantly associated with a more rapid progression to AIDS (relative hazard, 6.52). Data suggest that herpes zoster occurs more frequently in individuals acquiring HIV infection through sexual transmission. There was no evidence that herpes zoster per se is an independent cofactor of progression of HIV disease, although febrile episodes of herpes zoster may predict a faster progression to AIDS.
To evaluate the consequences of receiving human immunodeficiency virus type 1 (HIV-1)-seropositive blood, 90 HIV-1-seronegative recipients of HIV-1-seropositive blood (case patients) and 90 HIV-1-seronegative recipients of HIV-1-seronegative blood, matched for age, sex, number of transfusions, diagnosis, and severity of illness (controls), were followed for 12 months after transfusion at Mama Yemo Hospital in Kinshasa, Zaire. Of case patients and controls, 72% were children transfused for anemia caused by malaria. Of the 46 case patients case patients alive 6 months after transfusion and for whom HIV-1 serologic results were obtained, 44 (96%) had seroconverted. Significantly more case patients (47%) than controls (16%) died within 1 year after transfusion (P less than .001). In the first 3 months after transfusion, fatigue, diarrhea, fever, cough, pruritus, pallor, oral candidiasis, polyadenopathy, hepatosplenomegaly, and rhinorrhea were observed more often among seroconverters than controls (P less than .04). Six percent of case patients and no controls had developed clinical AIDS after 12 months of follow-up. These findings underscore the urgent need for appropriate HIV screening facilities in transfusion centers worldwide.
Routine military screening identified human immunodeficiency virus (HIV) infection in an asymptomatic dentist who had three prior negative antibody tests. A look-back investigation evaluated the provider and the practice and provided notification, counseling, and HIV testing for patients. Test results were linked to dental procedures categorized by levels of invasiveness. Of 1631 patients tested, all were negative for antibody to HIV. Analysis of 12,164 procedures on 876 patients determined 20.5% of patients had procedures from the highest stratum of invasiveness; 42% had only low-risk exposure. Stratification of the degree of invasive exposure and clinical evaluation of disease stage in the infected health care worker are important in look-back investigations. The early stage of disease in the provider, the adherence to infection control precautions, and the low percentage of invasive procedures may have contributed to the lack of transmission. These results are consistent with current assessment that risk of transmission of HIV during invasive medical procedures is low.
V3 loop sequences were compared from 5 human immunodeficiency virus type 1 (HIV-1)-infected patients over time. Three patients remained asymptomatic and 2 became symptomatic with large decrease in CD4 cell counts. The patient isolates were previously evaluated for phenotypic and antigenic properties and had different sensitivities to serum neutralization and changes in phenotype. This study showed a number of amino acid changes for the 2 symptomatic patients, each of whom progressed to AIDS during the study. The only amino acid substitution consistently associated with reduced CD4 cell counts, cytopathic effect, and progression to AIDS was Arg at position 11. Specific amino acid changes could not be correlated with increasing serum neutralization resistance or cytotropism changes. Increased loop charge was associated with a switch from macrophage to T cell tropism and a decrease in the number of CD4 cells. The study shows the importance of naturally occurring mutations in the V3 loop in controlling the biologic properties of HIV-1.
Exposure to Coxsackie B virus or other enteroviruses prenatally or in childhood increases the risk for later manifestation of insulin-dependent diabetes mellitus (IDDM). The occurrence of enterovirus infections was analyzed in 23 initially nondiabetic and islet cell antibody (ICA)-negative siblings of IDDM patients who converted to ICA positivity during a prospective follow-up study. Increases in enterovirus antibody levels, documented by heavy chain-capture RIA and EIA techniques, were significantly more frequent in sample intervals in which ICA first appeared (18/23, 78%) than in other sample intervals in these siblings (30/92, 33%; P < .001) or all sample intervals in 97 ICA-negative control siblings (117/403, 29%; P < .001). The children who converted to ICA positivity during an enterovirus infection more often had the high-risk HLA-DQB1 genotype than did children who were constantly ICA-negative (P < .01). The results suggest that enteroviruses may be important in the induction of a beta cell damaging process long before the clinical manifestation of IDDM.
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