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E van der Ryst

Publications and source records attributed to E van der Ryst.

At least 19 recordsLinked to original sources

Progress in HIV vaccine research.

The relentless expansion of the HIV pandemic has demonstrated that the need for a vaccine is desperate. However, the development of an effective vaccine against HIV is a formidable challenge. It is likely that a successful vaccine will have to induce an immune response consisting of not only neutralizing antibodies targeted to conserved epitopes of the viral envelope and cytotoxic T-lymphocytes targeted to a variety of viral antigens, but also local mucosal immunity. Furthermore, a vaccine should induce broad-spectrum immunity covering all HIV subtypes. It is unlikely that a single vaccine will achieve all this, and a combination of vaccines will probably be necessary. Although no efficacious HIV vaccine is available yet, definite progress has been made. It was demonstrated that chimpanzees could be protected from both cell-free and cell-associated HIV challenge. Protection from mucosal challenge was also demonstrated in several studies and limited cross-protection between HIV subtypes was observed in several animal models. In spite of these successes, much remains to be done. Prototype vaccines studied to date have only induced short-lived immune responses and elicited no antibodies able to neutralize clinical isolates of HIV-1. Novel ways of producing HIV-1 envelope antigens may lead to improved antibody responses and raise the chances of a vaccine inducing long-term protective immunity.

AIDS Vaccines↗

HIV/AIDS-related knowledge, attitudes and practices among South African military recruits.

OBJECTIVES: To assess the level of HIV-related knowledge, as well as high-risk behaviour and attitudes towards HIV, in a group of South African National Defence Force (SANDF) recruits. DESIGN: Cross-sectional study. SETTING: Tempe military base in Bloemfontein. SUBJECTS: Three hundred and thirty-nine recruits from one company. OUTCOME MEASURES: HIV-related knowledge, attitudes and practices based on a self-administered questionnaire. RESULTS: All of the recruits were male, and most of them (81.4%) were black. The majority of recruits (98.5%) were between 18 and 24 years old. They had a good level of knowledge regarding HIV and AIDS, with more than 80% giving a correct response in most cases. However, several important misconceptions regarding HIV/AIDS and its transmission still exist. Furthermore, several recruits still practised high-risk behaviour, such as not using condoms with casual or new partners. Most obtained their knowledge regarding HIV/AIDS from schools (34.8%), health and social services (27.1%) and the printed media (17.7%), while only 5.2% stated that they learnt about HIV/AIDS from the SANDF education programmes. CONCLUSION: Efforts towards initiating behaviour changes in military recruits should be intensified, and if necessary education programmes should be adapted to facilitate achievement of this goal.

Adolescent↗

Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.

OBJECTIVES: Limited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5delta32, CCR5m303 and CCR2b-641 and the CXCR4 ligand gene variant SDF1-3'A. METHOD: Cross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent. RESULTS: The CCR5delta32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8% (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-641 allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3'A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians. CONCLUSIONS: These results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-641 gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

Alleles↗

Restriction fragment length polymorphism analysis for rapid gag subtype determination of human immunodeficiency virus type 1 in South Africa.

A rapid method for identification of human immunodeficiency virus Type 1 (HIV-1) gag subtypes was developed based on restriction fragment length polymorphism (RFLP) analysis of 400 or 650 bp long polymerase chain reaction (PCR) fragments encompassing the start of the p17 (400 bp) and part of the p24 (650bp) regions. The consensus sequences of subtypes A-D, the only subtypes identified in South Africa, were analyzed to detect restriction endonucleases which generate unique patterns for each subtype. Four restriction endonucleases were identified: AluI, AccI, SwaI and XmnI. Digestion of a 400 bp fragment with AluI allowed identification of subtype C. Samples not identified were then reamplified, and a 650 bp fragment digested with AccI to identify subtype B, followed by SwaI and XmnI to distinguish between subtypes A and D. This strategy was applied to 87 samples previously subtyped by either sequence analysis of the gag p17 region (n = 33); or heteroduplex mobility assay (HMA) based on the env gene (n = 75); or both (n = 21). Out of the 87 samples, RFLP identified two samples as subtype A, 28 as subtype B, 56 as subtype C and one as a subtype D virus. No discrepancies were found between RFLP gag subtypes and gag sequence subtypes demonstrating the reliability of this method. There was also no discordance between gag RFLP subtypes and env HMA subtypes, suggesting that there were no recombinant viruses detected relating to the genomic regions analyzed. RFLP is an effective technique for the rapid screening in an HIV epidemic of limited diversity, such as in South Africa.

DNA, Viral↗

Nutritional status of HIV-1 seropositive patients in the Free State Province of South Africa: anthropometric and dietary profile.

OBJECTIVE: To evaluate the nutritional intake and status of HIV-1 seropositive patients, as well as the relationship between malnutrition and disease stage. DESIGN: A cross-sectional study. SETTINGS: The Immunology Clinic at the Pelonomi Hospital in Bloemfontein, South Africa. SUBJECTS: Eighty-one HIV/AIDS patients in different stages of disease were recruited consecutively from January to May 1995. Eleven of these patients were followed in 1997. MAIN OUTCOME MEASURES: Anthropometric data including current weight, height, triceps skinfold thickness, mid-upper-arm circumference, body mass index and bone-free arm muscle area were collected. Nutrient intake was estimated using a diet history in combination with a standardised food frequency questionnaire. The patients were divided into 3 groups according to their CD4+ T cell counts. RESULTS: The men were leaner (BMI = 18.9) than the women (BMI = 22.7) and patients with a CD4+ T cell count < 200 (stage III) tended to have the lowest median values for all anthropometric measurements. More than half the patients had a low intake (< 67% of the recommended dietary allowances) of vitamin C, vitamin B6, vitamin D, vitamin A, calcium, iron and zinc. CONCLUSIONS: The results confirms that HIV/AIDS patients from this population are malnourished. There was, however, no association between disease stage and nutritional status. Nutritional supplementation of HIV/AIDS patients should be considered, as this might lead to improved immune function in these patients.

Acquired Immunodeficiency Syndrome↗

Correlation among total lymphocyte count, absolute CD4+ count, and CD4+ percentage in a group of HIV-1-infected South African patients.

Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of <200 cells/mm3, CD4+ percentage <20%, and CD4+ percentage <15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 x 10(9)/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of <200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.

Adolescent↗

Genital infection of female chimpanzees with human immunodeficiency virus type 1.

To develop an animal model for mucosal HIV-1 infection, adult chimpanzees were inoculated without trauma by depositing the virus inoculum at the entrance to the cervical canal with a rigid catheter to which flexible tubing was attached. By this procedure, persistent infections were established in some chimpanzees with various infectious doses of either cell-associated HIV-1LAI(IIIB) (peripheral blood mononuclear cells from an infected chimpanzee) or with cell-free HIV-1 strains representing subtypes B and E, but not with a subtype A strain. Although some animals did not become infected until after the second or third cervicovaginal exposure, one chimpanzee was clearly infected after one exposure by several criteria, including virus isolation, but this animal did not seroconvert. A second chimpanzee appeared to be resistant to infection despite repeated mucosal exposures at irregular intervals. However, lymphocytes from both of these animals exhibited low-level proliferative responses to HIV-1 but not SIV antigens. Despite these apparently abortive or latent infections, after exposure to HIV-1 by the intravenous route, both animals developed systemic infections and seroconverted. Overall, 8 of 10 chimpanzees were infected systemically after one to three cervicovaginal exposures to HIV-1LAI(IIIB). The results indicate that (1) HIV-1 productive infection of female chimpanzees by the cervicovaginal route generally requires more than one exposure, just as with humans; (2) low level infections without seroconversion can be established after mucosal exposure to HIV; and (3) vaccine efficacy studies involving a single virus challenge of immunized chimpanzees by the cervicovaginal route probably will not be possible.

Animals↗

Detection of Mycobacterium tuberculosis in serum samples using the polymerase chain reaction.

Conventional methods for the diagnosis of Mycobacterium tuberculosis infections have serious limitations. To determine whether amplification of M. tuberculosis DNA in serum by the polymerase chain reaction (PCR) might be a useful additional diagnostic tool, we tested 329 clinical specimens using primers specific for the IS6110 insertion sequence of the M. tuberculosis complex. The samples consisted of 30 serum samples from healthy controls, 114 serum samples from patients with diagnoses other than tuberculosis (including immunosuppressive disorders), 59 samples from patients with a clinical picture suggestive of tuberculosis, and 78 serum samples from patients with proven M. tuberculosis infection. Both serum, and representative samples from anatomical regions suspected of being infected, were collected from a further 48 patients for comparison with serum PCR. Serum PCR identified 72/78 (92%; 95% confidence interval CI: 84%-97%) patients with proven tuberculosis, and 49/59 (83%; 95% CI: 71%-92%) patients with suspected tuberculosis. In the group of patients with other diagnoses, 30/114 (26%; 95% CI: 18%-34%) tested positive, while none of the specimens from the healthy control group were positive (95% CI: 0%-12%). Serum PCR results also compared favourably with other clinical specimens obtained from the same patient. Serum PCR can, therefore, be a useful additional technique for the early diagnosis of M. tuberculosis infection, but it does not necessarily indicate active infection.

DNA Primers↗

Chronic lymphocytic leukaemia in the Bloemfontein academic hospitals.

OBJECTIVE: To study the clinical presentation, treatment and outcome of patients diagnosed with chronic lymphocytic leukaemia (CLL) in the Bloemfontein academic hospitals during the past 21 years. DESIGN: Descriptive, retrospective study of clinical records of all CLL patients diagnosed at the Haematology clinics of the Universitas and Pelonomi Hospitals in Bloemfontein from 1975 to 1996. METHODS: Age, sex and race distribution of CLL patients were analysed. The peripheral blood, bone marrow, clinical presentation and stage at time of diagnosis, were studied. Treatment modalities, response to treatment and survival of patients were also analysed. Categorical variables were summarised by frequencies and percentages, and numerical variables by means of percentiles. Subgroup comparisons were done by 95% confidence intervals (CI) for differences in percentages, medians or means. RESULTS: A total of 185 CLL patients were studied. There were more males (62.7%) than females and the mean age of the patients was 63 years (19 to 98 years). Eighty six percent of the patients were older than 50 years. Racial distribution was as follow: 106 White, 77 Black and two patients of mixed race. Black patients more often presented with advanced disease and higher lymphocyte counts. A response to therapy was noted for 118 (82.5%) of the 143 patients who received treatment. A complete remission or partial response was noted for 38 (32.2%) of the patients. CONCLUSIONS: The presentation of CLL in the Bloemfontein academic hospitals is similar to what is seen world-wide. This is the first study describing CLL in a large number of Black patients and demonstrates that although Black patients presented more often at a younger age and had high risk disease, their clinical course and progression according to stage, also correlated with what is described in the literature.

Adult↗

Nutritional status of HIV-1 seropositive patients in the Free State Province of South Africa--laboratory parameters.

OBJECTIVE: To evaluate the nutritional status of HIV-1 seropositive patients with regards to laboratory parameters; the correlation between nutrient intake and actual values of nutrients, as well as the relationship between malnutrition and disease progression. DESIGN: A cross sectional study. SETTING: The Immunology Clinic at the Pelonomi Hospital in Bloemfontein, South Africa. SUBJECTS: 90 HIV/AIDS patients in different stages of disease were recruited consecutively from January to May 1995. Sixteen patients were followed up in 1997. MAIN OUTCOME MEASURES: The patients were divided into three groups according to their CD4+ T-cell counts, and blood levels of protein, albumin, cholesterol, ferritin, vitamin B12, magnesium, and phosphorus, as well as several micronutrients including vitamin E, vitamin C, beta-carotene and retinol which were determined using standard methods. These values were compared with the normal reference values used in the laboratory, and we tried to correlate these parameters with disease stage, as well as recorded nutrient intake in a subgroup of 35 patients. RESULTS: Abnormal values for several parameters, including plasma-retinol and serum-protein were found, but no correlation between more advanced disease and micronutrient deficiencies could be demonstrated. CONCLUSIONS: HIV/AIDS patients from this population are deficient in several micronutrients, and for some patients this is mirrored by a low intake. Multivitamin/anti-oxidant supplementation of HIV/AIDS patients should be considered, as this could lead to improved immune function in these patients.

Adolescent↗

Hairy cell leukaemia in the Bloemfontein academic hospitals.

OBJECTIVES: To study the clinical presentation, treatment and outcome of patients diagnosed with hairy cell leukaemia (HCL) in the Bloemfontein Academic Hospitals during the past 21 years. DESIGN: Retrospective study. All HCL patients diagnosed from 1975 to 1996. SETTING: Haematology clinics of the Universitas and Pelonomi Hospitals in Bloemfontein. SUBJECTS: All HCL patients diagnosed from 1975 to 1996. MAIN OUTCOME MEASURES: To determine the clinical and demographic profile, as well as response to treatment, of HCL patients in this region. RESULTS: A total of 16 HCL patients were studied. There were more males (13) than females and the mean age of the patients was 58 years (35 to 82 year; SD14.8). No Black patients were diagnosed. The patients mostly presented with a cytopenia and splenomegaly was present in 12 of the 14 patients for which spleen size was noted. All of the patients had a splenectomy and six were also treated with 2'-deoxycoformycin (Pentostatin). All six of the patient showed a response to treatment with this purine analogue. CONCLUSIONS: The presentation of HCL in the Bloemfontein academic hospitals is similar to what is seen world-wide. However, to evaluate the durability of the response to treatment with the purine analogues. Long term follow up is needed.

Adult↗

Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus.

To evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-1[IIIB(LAI)] gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1[IIIB(LAI)]-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1[IIIB(LAI)] of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1[MN] antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1[DH12], a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1[DH12], and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1[IIIB(LAI)] or HIV-1[MN] did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1[DH12].

AIDS Vaccines↗