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Biomedical subjects

G Biberfeld

Publications and source records attributed to G Biberfeld.

At least 109 records · Page 6Linked to original sources
PubMed1993

A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau.

OBJECTIVES: To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN: A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING: Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS: Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS: Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION: Vertical transmission of HIV-2 appears to be rare.

Child, Preschool↗
PubMed1992

A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.

High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.

Animals↗
PubMed1992

Malignant lymphoma associated with human AIDS and with SIV-induced immunodeficiency in macaques.

Malignant lymphomas associated with human (HIV) and simian (SIV) immunodeficiency virus infections are reviewed and compared. Recent observation of a high frequency of lymphomas in a series of cynomolgus macaques, highly immunodeficient after infection with SIVsm(smm3) are described. In addition to the increased frequency in human and monkey AIDS, SIV and HIV lymphomas share several important features. Clinically and by histology they present as aggressive high-grade malignant tumors with a predilection for extranodal growth in viscera, skin, central nervous system, testis, and retroorbitally. Most malignant lymphomas are of B-cell origin. AIDS lymphomas in humans are heterogeneous with regard to Epstein-Barr virus (EBV) association. Similarly, most lymphomas in monkeys experimentally infected with SIV tested to date were shown to be associated with an EBV-like simian herpes virus. These observations point to the possibility of using SIV-immunodeficient macaques for study of EBV and other oncogenic and immunosuppressive factors in AIDS-associated lymphomagenesis.

AIDS-Related Complex↗
PubMed1992

Clinical features and predictive markers of disease progression in cynomolgus monkeys experimentally infected with simian immunodeficiency virus.

OBJECTIVE: To study the pathogenicity of simian immunodeficiency virus (SIVsm) in cynomolgus monkeys in order to establish an animal model for human AIDS. METHODS: Thirty-three cynomolgus monkeys were monitored for more than 2 years following experimental infection with SIVsm. RESULTS: All the macaques became SIV-infected, as demonstrated by virus recovery from peripheral blood lymphocytes and by the appearance of viral antibodies. SIVsm was found to be pathogenic, killing 29 out of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high-grade malignant and of B-cell origin. Disease progression was associated with low CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag antibodies and development of systemic giant cell disease in 55% of the monkeys. CONCLUSIONS: There are many similarities between SIVsm-induced AIDS in cynomolgus monkeys and human AIDS with regard to clinical, virological, immunological and pathological manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1992

High HIV seroprevalence and increased HIV-associated mortality among hospitalized patients with deep bacterial infections in Dar es Salaam, Tanzania.

OBJECTIVES: To correlate deep bacterial infections with HIV infection and evaluate the influence of HIV on clinical picture and outcome in patients with meningitis, pneumonia or pyomyositis. DESIGN: Case-control comparison of HIV seroprevalence between patients and an age- and sex-matched control group in a prospective cross-sectional study of hospitalized patients. PARTICIPANTS: One hundred and sixty-five patients admitted to hospital with either purulent meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from orthopaedic/trauma wards. SETTING: University Hospital, Dar es Salaam, Tanzania. OUTCOME MEASURES: Differences in HIV seroprevalence and mortality. RESULTS: Of 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with 13 (17%) in the control group (P = 0.345). Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (P = 0.013). Ten out of 19 (53%) HIV-seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028). Of patients with pneumococcal meningitis, five out of six (83%) seropositives died, compared with two out of 12 (17%) seronegatives (P = 0.013). Fifteen out of 45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%) in the control group (P = 0.001). There was no difference in mortality between seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (P less than 0.0001). Eighteen out of 25 (72%) seropositive patients with pyomyositis fulfilled the World Health Organization (WHO) clinical case definition for AIDS. Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis. CONCLUSIONS: These results show a strong association between pyomyositis, pneumonia and HIV infection. They also indicate an increased mortality associated with HIV infection in patients with pyogenic meningitis, especially pneumococcal meningitis. Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system.

AIDS-Related Opportunistic Infections↗
PubMed1992

Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau.

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS].

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Alternative confirmatory strategies in HIV-1 antibody testing.

Alternatives to confirmation of human immunodeficiency virus (HIV)-1 seropositivity by Western blot analysis were evaluated retrospectively using combinations of six anti-HIV-1 screening assays, including four enzyme-linked immunosorbent assays (ELISA) and two simple tests (a rapid dot immunoassay and an agglutination assay), according to an algorithm where sera are first screened by one assay and those repeatedly reactive on this assay are tested repeatedly by a second assay. Two panels of sera collected in Dar es Salaam, Tanzania, were used. Panel 1 was composed of 1,465 consecutive blood donor sera of which 99 (6.8%) were confirmed HIV-1 antibody positive, and panel 2 was composed of sera from 396 consecutively admitted patients at two medical wards of which 116 (29.3%) were confirmed HIV-1 antibody positive. Sera reactive on any of the six screening assays were also tested by a confirmatory Western blot assay. The sensitivity of the assays at the initial valid testing were as follows: Abbott 99.5%, Behring 99.5%, Organon 97.7%, Wellcozyme 100%, HIV CHEK-1 95.8%, and Serodia 95.8%. After repeat testing of sera that initially gave false-negative results all assays showed 100% sensitivity except HIV CHEK-1 (98.6%). The specificities after repeat testing were between 99.6 and 99.9% for all assays except for the Behring ELISA (98.1%). Several combinations of screening assays were found to give the same diagnostic accuracy as the screening assay followed by Western blot analysis. We conclude that an alternative confirmatory strategy can be fully satisfactory for some testing purposes.

Agglutination Tests↗
PubMed1992

Improved detection of HIV-2 DNA in clinical samples using a nested primer-based polymerase chain reaction.

A two-step polymerase chain reaction (PCR), with four double (nested) primer pairs, used for the detection of HIV-2 in clinical samples is described. With these four nested primer pairs we could detect HIV-2 DNA in 17 of 17 virus isolates and in blood mononuclear cell samples from 31 of 37 (83.7%) seropositive individuals after ethidium bromide staining of the amplified DNA. The nested primer PCR was also compared with a single primer pair-based PCR followed by hybridization. The sensitivities of the two methods were almost equal, but the nested primer PCR offered obvious technical advantages.

Adolescent↗
PubMed1991

Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys.

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.

Animals↗
PubMed1991

Vaccine protection against HIV-2 infection in cynomolgus monkeys.

The aim of this study was to determine if protection against an infectious human immunodeficiency virus type 2 (HIV-2) challenge could be obtained in cynomolgus macaques by active immunization using whole killed virus vaccine. Four monkeys were immunized with killed HIV-2SBL-6669, two of them with five intramuscular (im) injections of viral preparation containing 100 or 300 micrograms protein emulsified in incomplete Freund's adjuvant (IFA) and the two remaining received four im injections of 25-50 micrograms viral protein in iscoms. Each of the four vaccinated cynomolgus monkeys, along with four unvaccinated controls, were challenged intravenously two weeks after the last booster with approximately 100 animal infectious doses (ID50) of live HIV-2SBL-6669. All four immunized monkeys developed antibodies to HIV-2 envelope and core proteins before challenge exposure to HIV-2, but only the two animals vaccinated with virus in IFA developed detectable neutralizing antibodies. The two monkeys immunized with killed virus in IFA have shown no evidence of infection nine months after challenge with live virus. When blood and lymph node cells from these animals were transfused into naive cynomolgus monkeys, the recipients remained free of infection. In contrast, virus was recovered repeatedly in all nonimmunized animals and in the two animals immunized with iscom-associated viral antigens, which had a low content of envelope gp125 antigen. The demonstration of vaccine-induced protection against HIV-2 in a nonhuman primate raises hope for effective immunization against HIV infections in humans as well.

Animals↗
PubMed1991

Comparison of linear antigenic sites in the envelope proteins of human immunodeficiency virus (HIV) type 2 and type 1.

The occurrence of dominant linear antigenic sites in the envelope glycoproteins of human immunodeficiency virus type 2 (HIV-2) was evaluated. Twenty-five peptides representing different regions of HIV-2, strain SBL-6669, were synthesized. For comparison the corresponding peptides of HIV-1, strain BRU, were also prepared. The peptides were tested in enzyme-linked immunosorbent assay (ELISA) with human sera from individuals with proven HIV-1 or HIV-2 infection and simian sera from animals infected with HIV-2 or simian immunodeficiency virus of sooty mangabay monkey origin (SIVsm). Four major antigenic regions were identified. Peptides representing parts or the whole V3 (neutralizing loop) region and an additional stretch of amino acids located at the carboxy terminal of this region showed considerable reactivity. This reaction was predominantly type specific, but some heterotypic reactivity was also seen. Peptides representing the carboxy terminal 21 amino acids of the V3 region of the type-related viruses HIV-2 and SIVsm allowed selective identification of strain-specific antibodies. A second major antigenic region was found close to the carboxy terminal end of the large glycoproteins. This region was cross-reactive between the two types. The two additional dominating antigenic regions were located in the amino terminal region of the transmembrane glycoprotein. One region has previously been shown to be a uniquely antigenic type-specific site. The other region was also type-specific, but was identified only in HIV-2, amino acids Glu634-Lys649. Excellent facilities are available for the design of not only type-unique site-specific serological tests but potentially also type-cross-reactive and strain-specific assays.

Animals↗
PubMed1991

HIV-2 infection in hospitalized patients in Bissau, Guinea-Bissau.

During 11 months in 1989-1990, 1009 consecutive hospitalized adult patients admitted to the medical wards of the National Hospital in Bissau were interviewed, examined clinically, and tested for antibodies to HIV-1 and HIV-2. The prevalence of HIV-2 infection was 20.4% (206 out of 1009) and of HIV-2-associated AIDS 4.4% (44 out of 1009). HIV-2 infection was more frequent in women (25%, 110 out of 440) than in men (16.9%, 96 out of 569). HIV-1 infection was diagnosed in one patient only, and one patient (with AIDS) had reactivity to both HIV-1 and HIV-2. Among HIV-2-seropositive patients, AIDS was demonstrated in 21.3% and AIDS-related symptoms (not fulfilling the AIDS criteria) in 19.4%. The frequency of AIDS-associated symptoms was significantly higher in HIV-2-seropositive patients than in seronegative patients. The clinical profile of the HIV-2-associated AIDS cases was very similar to that described in HIV-1-associated AIDS cases in Africa. Seven out of 51 patients fulfilling the clinical criteria for AIDS were HIV-seronegative. The World Health Organization (WHO) clinical case definition for AIDS in Africa had a specificity of 99% and a positive predictive value of 86%. Tuberculosis was more common in HIV-2-seropositive patients (6.3%) than in HIV-2-seronegative patients (2.2%). A history of blood transfusion was a significant risk factor for HIV-2 infection. HIV-2 infection and AIDS are public health problems in Guinea-Bissau.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A capture enzyme immunoassay for detection of HIV-2/SIV antigen.

An antigen capture enzyme immunoassay was developed for the demonstration of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV). The assay (HIV-2 CE) has a sensitivity of approximately 250 pg/ml of HIV-2/SIV antigen. The HIV-2 CE was 4-16 times more sensitive than the Abbott HIV-1 antigen assay for detection of HIV-2/SIV antigen in cell culture supernatant. The sensitivity for detection of HIV-2/SIV antigen in serum or plasma was 98.5% in the HIV-2 CE and 95.5% in the Abbott HIV-1 antigen assay. The specificity of the HIV-2 CE was 99.2% (one false positive among 119 negative sera) whereas the Abbott assay was 100% specific. The HIV-2 CE detected antigen in supernatants from cultures of peripheral blood mononuclear cells of macaque monkeys infected with HIV-2 or SIV about 1 week before a reverse transcriptase (RT) microassay was positive and remained positive for at least 1 week after the RT assay had become negative. Three cultures from persistently infected monkeys were positive only in the HIV-2 CE, reflecting a higher sensitivity compared to the RT microassay. Thus, the HIV-2 CE was more sensitive than the Abbott HIV-1 antigen assay for detection of HIV-2/SIV antigen in culture supernatants as well as in serum/plasma. Furthermore, the HIV-2 CE showed a higher sensitivity than the RT microassay for detection of HIV-2/SIV in cell culture supernatants.

Animals↗