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Biomedical subjects

G Biberfeld

Publications and source records attributed to G Biberfeld.

At least 73 records · Page 4Linked to original sources
PubMed1997

Protection of human immunodeficiency virus type 2-exposed seronegative macaques from mucosal simian immunodeficiency virus transmission.

At present it is not known which form of immunity would be most effective against infection with human immunodeficiency virus (HIV). To evaluate the possible role of cellular immunity, we examined whether four HIV type 2-exposed but seronegative macaques developed cellular immune responses and determined whether these exposed macaques were resistant to mucosal transmission of simian immunodeficiency virus (SIV). Following intrarectal challenge with SIV, 2 monkeys were protected against detectable SIV replication and another showed suppressed viral replication compared to 14 persistently infected controls. The two protected monkeys demonstrated SIV-specific cytotoxic T lymphocytes before as well as after SIV challenge. Here we provide evidence that activation of the cell-mediated arm of the immune system only, without antibody formation, can control SIV replication in macaques. The results imply that vaccines that stimulate a strong and broad cellular immune response could prevent mucosal HIV transmission.

Animals↗
PubMed1997

Increased prevalence of HIV-2 infection in hospitalized patients with severe bacterial diseases in Guinea-Bissau.

We studied the association between HIV-2 infection and bacterial pneumonia, sepsis or pyomyositis, as well as the influence of HIV-2 infection on the clinical outcome in patients with these bacterial infections. A total of 201 consecutive hospitalized patients were included at the Simao Mendes National Hospital in Bissau, Guinea-Bissau. Age- and sex-matched controls were selected from an ongoing census in a semi-urban area of Bissau. Among 201 cases with such bacterial infection the prevalence of HIV-1 was 5.4%, HIV-2, 27.9%, and both HIV-1 and HIV-2 reactivity 6.4%. Among controls, the corresponding prevalence rates were significantly lower, 1.5%, 9.0% and 1.0%, respectively. A total of 140, 31 and 30 cases of pneumonia, sepsis and pyomyositis were included, and the differences in prevalence of HIV-2 compared with the controls also remained significant for each diagnosis separately. Lymphocyte subsets were determined in 93 consecutive patients, and the CD4 cell counts and CD4/CD8 lymphocyte ratios were markedly suppressed in the HIV-2-seropositive group. Due to excess mortality in the seropositive groups with sepsis (75.0%) and pyomyositis (25.0%), the mortality during hospitalization was significantly higher among HIV-2 infected compared to HIV-negative patients. Among cases of pneumonia the mortality was low in the HIV-2-seropositive (2.9%) as well as in the HIV-seronegative (3.4%) group.

Adult↗
PubMed1996

A new method for measuring lymphoproliferation at the single-cell level in whole blood cultures by flow cytometry.

A simple and reproducible method is described for the measurement of proliferative responses to mitogens and antigens. Whole blood (WB) cultures are used and separation procedures are not necessary. Proliferative responses are monitored as development of lymphoblasts determined by flow cytometry (FC). Lymphocytes and lymphoblasts were shown to be exclusively selectable from mixed cell populations of WB by their light scatter profile on FC analysis. More than 90% of the lymphoblasts identified by FC were replicating DNA as determined by incorporation of the thymidine analogue 2-bromo-5-deoxyuridine. The WB/FC technique can be combined with triple immunofluorescence which was illustrated by determining subsets of lymphoblasts developing following stimulation with various mitogens and antigens. The new method was compared with the conventional method (peripheral blood mononuclear cell culture and proliferation measured by detection of DNA synthesis). The reproducibility of the methods were not different. The antigen-induced responses recorded by both methods correlated, but with significantly higher stimulation indices obtained by WB/FC. The latter procedure was also technically easier to perform and less time-consuming.

Cell Culture Techniques↗
PubMed1996

Evaluation of the FACScount, TRAx CD4 and Dynabeads methods for CD4 lymphocyte determination.

A study to evaluate the performance of the FACScount, TRAx CD4 and Dynabeads methods for the determination of CD4+ T lymphocyte subset levels was conducted in Tanzania as part of a World Health Organization (WHO) collaborative multicenter field evaluation of alternative methodologies for the enumeration of CD4+ T lymphocytes. The objective was to compare the performance of these alternative methods in a developing country setting, against that of flow cytometry as the reference standard. T lymphocyte subset levels were determined in 91 HIV seronegative and 98 HIV-1 seropositive adults using the three alternative methods. CD4+ and CD8+ T lymphocyte counts were determined by all methods except for TRAx CD4 enzyme linked immunosorbent assay (ELISA) which measures CD4+ T lymphocyte levels only. Linear regression analysis was done to correlate the counts obtained by the alternative methods to those obtained by flow cytometry. The overall correlation coefficients of FACScount and Dynabeads CD4+ and CD8+ T lymphocyte counts with those of flow cytometry were high (r > 0.9). A lower correlation (r = 0.631) was obtained when TRAx CD4+ ELISA counts were compared to those of the reference method. These results show that two of these alternative methodologies are suitable for the determination of CD4+ and CD8+ T lymphocyte counts with the use of African blood samples. Since the methods are simpler and cheaper than flow cytometry, they provide an alternative option for the enumeration of T lymphocyte subsets in laboratories with limited facilities.

Adult↗
PubMed1996

Performance of a modified HIV-1 p24 antigen assay for early diagnosis of HIV-1 infection in infants and prediction of mother-to-infant transmission of HIV-1 in Dar es Salaam, Tanzania.

The aim of this study was to determine the utility of an amplified human immunodeficiency virus type 1 (HIV-1) p24 antigen (ag) assay using heated plasma or serum samples for the early diagnosis of HIV-1 infection in infants and for the prediction of the risk of mother-to-infant (MTI) transmission of HIV-1 in Dar es Salaam, Tanzania. The study included 125 samples from 76 infants positive for HIV-1 DNA by the polymerase chain reaction (PCR), 106 samples from 101 PCR-negative infants and 116 and 160 samples from seropositive and seronegative mothers, respectively. Samples were boiled to dissociate immune complexes and tested for HIV-1 p24 ag using a p24 ag amplification assay. Reactive samples were confirmed by a neutralization assay. Altogether, 123 of 125 samples from 76 PCR-positive infants were positive for p24 ag (sensitivity = 98.7%). HIV-1 p24 ag was found in all 18 samples collected at 1-8 weeks, in 35 of 36 samples collected at 9-26 weeks, in all 40 samples collected at 27-52 weeks, and in 30 of 31 samples collected > 52 weeks after birth. Detection of HIV-1 p24 ag was significantly more common in transmitting mothers (12 of 29, 41.4%) than in nontransmitting mothers (nine of 87, 10.3%) (p < 0.001). Among mothers with p24 antigenemia, the vertical transmission rate was significantly higher (12 of 21, 57%) than in mothers without p24 antigenemia (17 of 95, 18%) (p < 0.001). All samples from 101 PCR-negative children and 160 seronegative mothers were negative for p24 ag (specificity = 100%). We conclude that using heated plasma or serum increases the sensitivity of the p24 ag assay significantly. This modified simple test may be sufficient for the early diagnosis of HIV-1 infection in infants in settings with limited laboratory facilities. It is also useful for prediction of the risk of MTI transmission of HIV-1.

Biomarkers↗
PubMed1996

Protection against mucosal SIVsm challenge in macaques infected with a chimeric SIV that expresses HIV type 1 envelope.

In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge. Four cynomolgus monkeys were inoculated intravenously with SHIV-4. Virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of SHIV. All monkeys developed neutralizing antibodies to HIV-1 and high antibody titers to HIV-1 envelope glycoproteins. In contrast, no neutralizing antibodies to SIVsm were detected and cross-reacting antibodies to SIV envelope glycoproteins were demonstrable in low titers. Nine to 12 months after the SHIV inoculation the four monkeys and six naive control monkeys were challenged intrarectally with 10 monkey infectious doses of macaque cell-grown SIVsm. After a follow-up period of 1 year, two of four SHIV-infected monkeys were completely protected against SIVsm infection as shown by repeated negative virus isolations and negative polymerase chain reaction for SIV envelope DNA. One naive monkey that received blood from the two protected monkeys showed no signs of infection. The remaining two SHIV-infected monkeys showed an initial infection on challenge with SIVsm, but viral replication was thereafter suppressed. Cytotoxic T lymphocytes to SIV Nef and RT were demonstrable in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SIV infection. All six control animals yielded virus repeatedly after SIVsm challenge and three of them showed declining CD4 cell counts. Thus, infection with SHIV expressing HIV-1 envelope could induce cross-protection against mucosal SIVsm challenge.

Acquired Immunodeficiency Syndrome↗
PubMed1996

SIV infection of monkey spleen cells including follicular dendritic cells in different stages of disease.

Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes, and macrophages from SIVsm-inoculated cynomolgus monkeys (Macaca fascicularis) at different stages of disease were compared for latent and productive SIV infection. Analysis of FDCs by in situ hybridization, electron microscopy, and coculture assays indicated that comparatively high levels of virus were associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR results revealed that the levels for SIVpol DNA did not correlate with the level of env mRNA in the various cell subsets, suggesting differences in latency. Limiting dilution assays for spliced env mRNA showed a 10-100-fold higher amount of env mRNA in FDCs than in other spleen cell subsets early during SIV infection. At late stages of disease, the number of productively infected FDCs significantly decreased in parallel with a marked reduction of the FDC network and follicular involution. Our findings indicate that destruction of FDCs probably reflects a cytopathic effect of SIV and/or the activity of specific antiviral cytotoxic T lymphocytes.

Animals↗
PubMed1996

Nested PCR assays with novel primers yield greater sensitivity to Tanzanian HIV-1 samples than a commercial PCR detection kit.

To investigate the efficacy of the SK431/SK145 primer pair and two nested primer assays in amplifying African HIV-1 samples, a total of 35 Tanzanian PBMC samples were examined. These were assayed by two HIV-1 specific nested in-house PCR assays and a commercial HIV-1 PCR kit (GeneAmp) using SK431/SK145 as the primer pair. One of the nested PCR assays has been evaluated previously (old assay), whereas the modified assay was constructed from the HIV-1 sequence alignment released in August 1993. The modified nested primer assay showed increased sensitivity in the gag and env regions compared to the old nested primer assay. However, both the old and the modified nested primer assays displayed higher sensitivity for the detection of Tanzanian HIV-1 proviruses than the GeneAmp assay. When two regions were used (gag and env) as targets for the amplification, the modified nested primer assay detected 97.1% (34/35) of the proteinase K lysed samples, compared to 68.6% (24/35) using the SK431/SK145 primer pair (P < 0.01**). The results indicate that the SK431/SK145 primer pair may be less suitable when HIV-1 samples from Africa are analysed. The results also show that continuous modification of primer sequences can improve and maintain high sensitivity for the detection of highly divergent HIV-1 strains.

DNA Primers↗
PubMed1996

Pulmonary tuberculosis in Guinea-Bissau: clinical and bacteriological findings, human immunodeficiency virus status and short term survival of hospitalized patients.

OBJECTIVE: To study tuberculosis patients in Guinea-Bissau with regard to clinical findings, bacteriologically verified diagnosis, human immunodeficiency virus (HIV) status and short term survival. DESIGN: 763 consecutive patients referred to the tuberculosis clinic with pulmonary symptoms underwent clinical examination and Ziehl-Neelsen sputum microscopy. Sputum for culture of mycobacteria on Löwenstein-Jensen medium was collected from all hospitalized patients, who were also screened by enzyme linked immunosorbent assay for the presence of HIV-1 and HIV-2 antibodies. HIV-positivity was confirmed by Western blot. RESULTS: 350 patients were diagnosed with tuberculosis and hospitalized. Adequate sputum samples were obtained from 301 patients, of whom 184 (61%) were positive on direct microscopy and the remaining 116 patients were diagnosed from clinical findings. Mycobacterium tuberculosis was cultured from 184 patients and M. avium in 16 patients, whereas in 101 patients the culture was negative. HIV-1 antibodies were found in 3.0%, HIV-2 antibodies in 16.4%, and dual infections in 2.0%. These figures, however, did not differ significantly from those of randomly selected age and sex matched controls. The prevalence of HIV-antibodies was statistically as common in patients with culture verified tuberculosis as in patients with clinically defined tuberculosis. Clinical acquired immunodeficiency syndrome was commonly diagnosed (80/301 patients) but significantly more often in HIV-positive, culture-positive tuberculosis patients, as were weight loss and lymphadenopathy. There was no statistical difference in short-time survival rate between the various patient groups. CONCLUSION: The diagnostic criteria applied, which are generally used in developing countries, identified most patients with pulmonary tuberculosis; however, a substantial number of patients are treated for tuberculosis without definite diagnostic criteria. The prevalence of HIV-infection was high but statistically no significant difference was demonstrated between the patient groups, controls and patients hospitalized for diseases other than tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Immunogenicity and protective efficacy of a human immunodeficiency virus type 2 recombinant canarypox (ALVAC) vaccine candidate in cynomolgus monkeys.

The efficacy of a recombinant human immunodeficiency virus (HIV) type 2 canarypox (ALVAC HIV-2) vaccine candidate given alone or in combination with HIV-2 envelope gp125 or HIV-2 V3 synthetic peptides was investigated in 14 cynomolgus monkeys. High antibody titers to HIV-2 gp125 were demonstrated in monkeys given booster immunizations with gp125. Neutralizing antibody titers were low (< or = 20) in all monkeys except 2. Significant lymphocyte proliferative responses to killed HIV-2 virions were observed in monkeys given booster immunizations with gp125. HIV-2-specific cytotoxic T lymphocytes were demonstrated prior to viral challenge in 3 of 12 monkeys. After challenge with homologous cell-free HIV-2 propagated in monkey cells, 4 of 10 monkeys immunized with ALVAC HIV-2 plus HIV-2 gp125 or V3 peptides were protected, as determined by negative virus isolation and polymerase chain reaction for viral DNA. Four monkeys immunized with ALVAC HIV-2 alone were not protected. All 12 control monkeys became infected. There was no correlation between the immunologic parameters studied and protection against infection in the vaccinated monkeys.

AIDS Vaccines↗
PubMed1996

Immunohaematological findings in healthy and HIV-1 infected adults in Dar es Salaam, Tanzania.

In order to assess the prognostic value of lymphocyte subsets and immune activation markers in HIV-1 infected Tanzanian patients, peripheral white blood cell(WBC) count, total lymphocytes, CD4+ and CD8+ T-lymphocytes and Beta-2 microglobulin (B-2M) concentrations were determined among healthy HIV-1 seronegative Tanzanian blood donors and in infected Tanzania individuals in different clinical stages of HIV-1 infection. CD4+ T-lymphocytes, CD8+ T-lymphocyte percentages, CD4:CD8 lymphocyte ratios and the concentrations of B-2M were strongly correlated with the clinical stages of HIV-1 infection. These results suggest that B-2M could be a useful prognostic marker in HIV-1 infection in settings where T-lymphocyte subset determinations cannot be done.

Adult↗
PubMed1996

High frequency of sexually transmitted diseases among pregnant women in Dar es Salaam, Tanzania: need for intervention.

In order to determine the prevalence and characteristics of sexually transmitted diseases (STDs) in pregnant women (PW) attending a primary health care antenatal clinic (ANC) in metropolitan Dar es Salaam, Tanzania, a randomly selected sample of PW in their second or third trimesters were invited to participate at their first visit. They were interviewed using a questionnaire and underwent genital examination. Genital swabs were obtained for microscopy and/or culture isolation of Candida albicans, Trichomonas vaginalis, and Neisseria gonorrhoeae. Blood specimens were also obtained for serological testing for syphilis and for antibodies to the human immunodeficiency virus (HIV). A total of 777 PW aged 14 to 40 years were seen. Parities ranged from 0 to 10. Prevalence of syphilis, trichomoniasis, gonorrhoea and HIV infection were 4.0%, 22.7%, 3.6% and 15.2%, respectively. At least one acute STD (excluding HIV infection) was found in 32.8% of the PW. The prevalence of multiple STDs (excluding HIV infection) was higher in teenagers (45.3%, 77/170) than in PW in other age groups (29.2%, 177/607) (p < 0.001). The prevalence of HIV infection in teenage PW was 10.0%. Most STDs were least prevalent in PW who were married monogamously. Of the 732 PW who had one or more genital infections (including infection with Candida species), 669 (91.4%) had one or more genital complaints. However, most of the genital complaints were not disease specific. Since this study has shown that the prevalences of acute STDs were high in PW, especially in teenagers, it is recommended that all PW in Tanzania should be screened for STDs syndromically including the use of appropriate clinical and laboratory examination whenever possible.

Adolescent↗
PubMed1995

HIV-1, HIV-2, HTLV-I/II and Treponema pallidum infections: incidence, prevalence, and HIV-2-associated mortality in an occupational cohort in Guinea-Bissau.

The prevalence and incidence of human immunodeficiency virus types 1 and 2 (HIV-1, HIV-2), human T-lymphotropic virus types I and II (HTLV-I/II), and syphilitic infections and the association between these infections were determined in a cohort of police officers in Guinea-Bissau. Between January 1990 and December 1992, 1,384 subjects (1,241 men and 143 women) were included in the study; and of the first 879 tested, 561 were tested at least for a second time. The overall seroprevalence of HIV-1 was 0.4%, of HIV-2 11.6%, and of HTLV I/II 4.4%. Three individuals (0.2%) were seropositive for both HIV-1 and HIV-2. Women had a significantly higher prevalence of HIV-2 infection than men (16.8% and 11.0%, respectively, p < 0.05). Serologic evidence of previous syphilis was present in 12.1% and was significantly more common in men (12.7%) than in women (7.0%) (p < 0.05). There was a significant association between the prevalence of HIV-2 and HTLV-I/II infection (p < 0.05). The annual incidence of HIV-1 was 0.7%, of HIV-2 1.6%, of HTLV I/II 0.4%, and of syphilis 1.7%. There was no association between the incidence of the various infections. The death rate (per 100 person-years) was significantly higher among HIV-2-infected individuals (2.7%) than among HIV-negative individuals (0.5%) (relative risk = 5.1; 95% confidence interval, 2.1-12.2; p < 0.001). HIV-related symptoms were more frequent among the HIV-2-positive individuals who died compared with the seronegative individuals who died (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗