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T Corrah

Publications and source records attributed to T Corrah.

51 records · Page 3Linked to original sources

HIV type 2 proviral load measured by quantitative polymerase chain reaction correlates with CD4+ lymphopenia in HIV type 2-infected individuals.

The efficiency of detection of 2 sets of primer pairs from putatively conserved regions of the human immunodeficiency virus type 2 (HIV-2) genome were assessed in 86 seropositive individuals from The Gambia by nested polymerase chain reaction (PCR). HIV-2 long terminal repeat (LTR) target sequences were detected in DNA extracted from peripheral blood mononuclear cells (PBMCs) in 84 of 86 (97%) individuals whereas HIV-2 integrase (pol) gene sequences were detected in 39 of 41 (95%) individuals. The use of LTR target sequences and recombinant Pfu DNA polymerase, rather than Taq polymerase, in a modified secondary amplification reaction mediated the incorporation of 35S-labeled nucleotides in a quantitative radiometric assay. This sensitive assay was used to quantify HIV-2 proviral DNA in clinical samples and compared well with estimations by limiting end-point dilution of target molecules. A linear response between counts and the number of copies amplified from serial dilutions of pROD10 plasmid DNA (3-2000 copies) yielded a standard curve to allow extrapolation to clinical data. Increased levels of HIV-2 proviral DNA, expressed as copies per 10(5) CD4-positive lymphocytes, were associated with declining CD4 count in 63 adult patients (Spearman rank correlation, r = -0.71, n = 63, p < 0.001) and with the occurrence of HIV-related clinical disease. Kruskall-Wallis analysis of variance analysis showed the mean proviral copy number (log10) to be significantly different between groups (p < 0.001) where CD4 counts were grouped as < 200/mm3 (3.4 +/- 1.05 copies), 200-500/mm3 (2.84 +/- 0.93 copies), and > 500/mm3 (1.88 +/- 0.43 copies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

HIV-2-infected patients survive longer than HIV-1-infected patients.

OBJECTIVE: To compare survival of patients infected with HIV-1 and HIV-2. DESIGN: Longitudinal follow-up of 175 HIV-1- and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. METHODS: Survival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. RESULTS: The overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (CI), 0.49-0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% CI, 0.43-0.94), and for three strata of beta 2-microglobulin levels 0.60 (95% CI, 0.42-0.84). CONCLUSION: Mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

A longitudinal study of per cent agalactosyl IgG in tuberculosis patients receiving chemotherapy, with or without immunotherapy.

An increased percentage of circulating IgG molecules that lack galactose from the oligosaccharides on the CH2 domain correlates with disease severity in tuberculosis, rheumatoid arthritis and Crohn's disease. We have recently observed that a single injection of 10(9) autoclaved Mycobacterium vaccae given to tuberculosis patients 7 days after the initiation of chemotherapy causes accelerated clinical improvement, and clearance of bacilli from the sputum. We now show that this immunotherapy also causes rapid loss of agalactosyl IgG, detectable within 14-21 days, whereas chemotherapy alone causes agalactosyl IgG to rise further for up to 2 months. There is simultaneous inhibition of the antibody response to lipoarabinomannan, and transient enhancement of the tuberculin skin-test response. These findings are compatible with a shift from antibody production towards increased cell-mediated immunity. The ideal treatment for tuberculosis would supplement a truncated course of chemotherapy with an immunotherapeutic preparation able to down-regulate the Koch phenomenon and replace it with an efficiently bactericidal mechanism. We tentatively postulate that a fall in per cent agalactosyl IgG [%Gal(0)] in tuberculosis patients may be a marker of such a change.

Adolescent↗

Immunological responses of Gambians in relation to clinical stage of HIV-2 disease.

This study describes a broad spectrum of cellular and antibody-mediated immune responses found in 28 asymptomatic and 37 symptomatic Gambian patients with HIV-2 infection. It shows that these responses vary according to the stage of infection as described by three clinical staging systems. The first system was a local one based on the signs used for the WHO Bangui clinical definition of AIDS, the second, suggested by WHO, was based on a performance scale, and the third was that used by the Centre for Disease Control. Asymptomatic patients had significantly lower mean CD4 counts, lymphoproliferative and interferon-gamma (IFN-gamma) responses and lower IgG and IgM antibody responses to keyhole limpet haemocyanin (KLH) than controls. These measurements and the size of the skin test reaction to purified protein derivative (PPD) or Candida antigen declined significantly according to the stage of infection. Mean values of the serological markers beta 2-microglobulin and neopterin and antibody titres to Epstein-Barr virus capsid antigen (EBVCA) rose significantly according to severity of disease. The Gambian or WHO clinical staging systems, which are easy and cheap to apply, may serve as an alternative to sophisticated and expensive immunological measurements when trying to stage disease and predict prognosis.

Adult↗

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus type 2 (HIV2).

In the mid 1980's a second human retrovirus, capable of causing the acquired immunodeficiency syndrome (AIDS), was isolated from patients of West African origin. This virus, now called human immunodeficiency virus type 2 (HIV2), was found to be distinct from human immunodeficiency virus type 1 (HIV1) but closely related to simian immunodeficiency viruses (SIV). Although the genomes of HIV1 and HIV2 are similar there are significant differences in nucleotide and amino acid sequences, most marked with the envelope genes and proteins. Both viruses, however, bind to the same CD4 cellular receptor. HIV2 is largely confined to West Africa where it is the dominant HIV, though patients infected with HIV2 have been described in Europe and America. Its transmission, clinical features and immunological effects are similar to those associated with HIV1 infection. However, there is some suggestion that the incubation period from infection to clinical disease may be longer than with HIV1 and that HIV2 may be less pathogenic. Patients with sera that react with both HIV1 and HIV2 antigens have been described, but it is unclear whether this represents serological cross reactivity or true double virus infection. Testing for HIV2 antibodies may become increasingly necessary in HIV2 non-endemic areas.

Acquired Immunodeficiency Syndrome↗

Biological and molecular variability of human immunodeficiency virus type 2 isolates from The Gambia.

Seven new human immunodeficiency virus type 2 (HIV-2) isolates (CBL-20 to CBL-26) from The Gambia were characterized. Their cytopathogenicity and growth in vitro correlated with the severity of clinical disease. CBL-22 was highly sensitive to neutralization by HIV-2 sera and was cross-neutralized by some HIV-1 sera. These findings, the differing sizes of envelope glycoproteins of individual isolates, and the sequence analysis of amplified regions of the viral DNAs show that these HIV-2 isolates from one geographical region in West Africa exhibit biological and genome variability comparable to that observed for HIV-1.

Adult↗

Helicobacter pylori in Gambian children with chronic diarrhoea and malnutrition.

Infection with Helicobacter pylori (formerly Campylobacter pylori) was studied by measuring antibody titres to H pylori in Gambian children. Serological evidence of infection was found in 12 of 82 (15%) infants aged less than 20 months; this increased to 62 of 135 (46%) in those aged 40-60 months. Positive serology was found in 41 of 77 (53%) infants with chronic diarrhoea and malnutrition (mean age 19 months, range 5-36) compared with 18 of 70 (26%) of age matched healthy controls and nearly a quarter (12/49, 24%) of age matched undernourished (marasmic) subjects. These data show that infection with H pylori is common in the Gambia and that in infancy this infection is associated with chronic diarrhoea and malnutrition.

Adult↗

Knowledge of AIDS, use of condoms and results of counselling subjects with asymptomatic HIV2 infection in The Gambia.

A questionnaire administered to subjects seen during a serological survey in The Gambia revealed that knowledge of AIDS and HIV infection was limited. Males, those with a secondary education and people who lived in urban areas had a better understanding but only 17% of women seen in rural areas had any knowledge of the condition. Only 8% of the subjects seen had used condoms in the preceding 12 months; during this time half of them had done so on less than five occasions. Subjects with a secondary education were more likely to have used condoms. A counsellor met 31 asymptomatic seropositive subjects identified during this survey on two occasions. In the majority, the information given caused anxiety rather than modification of behaviour and, at the time of the second interview, only one subject had discussed the situation with the partner and begun using condoms. Some of the cultural factors which may affect the outcome of counselling in an African society are discussed in the light of these findings.

Acquired Immunodeficiency Syndrome↗

Envelope cross-reactivity in Western blot for HIV-1 and HIV-2 may not indicate dual infection.

Serological identification of infection with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) by western blot alone may not be sufficient to diagnose dual infection. Extensive cross-reactions (eg, to envelope glycoprotein antibody) are seen on heterologous western blots. The use of other techniques, in this case competitive enzyme-linked immunosorbent assays, indicates that blot patterns previously thought to demonstrate simultaneous dual infections should be interpreted with caution.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8.

OBJECTIVES: To investigate the distribution of Kaposi's sarcoma (KS) cases in patients with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) infection in the Gambia; to document the prevalence of human herpesvirus 8 (HHV-8) infection in various population groups in the Gambia. STUDY DESIGN/METHODS: A retrospective analysis of KS cases in hospital records at the Medical Research Council (MRC) hospital was performed, along with a cross-sectional survey of HHV-8 prevalence in hospital-based and community-based study population with polymerase chain reaction (PCR) and serologic assays. RESULTS: After adjusting for gender and CD% at the first visit, HIV-1-positive patients were 12.4 times more likely to have KS than were HIV-2-positive patients. The prevalence of antibodies to HHV-8 and the HHV-8 genome was high in both HIV-1-positive and HIV-2-positive patients without KS. The prevalence of antibodies was also high in pregnant women who were HIV-1-positive, HIV-2-positive, or HIV-negative (73%, 83%, and 79%, respectively). CONCLUSIONS: HHV-8 infection is widespread in the Gambia. In addition to immunosuppression and HHV-8 infection, other cofactors specifically related to HIV-1 rather than HIV-2 appear to be involved in the development of KS.

AIDS-Related Opportunistic Infections↗

Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection.

OBJECTIVES: To elucidate why the virulence of HIV-1 and HIV-2 infections differ in West African populations. STUDY DESIGN/METHOD: Peripheral blood plasma virion RNA and cellular proviral DNA levels were measured in a cross-section of 59 HIV-1 and 49 HIV-2 singly infected individuals representing all stages of infection in The Gambia, West Africa. Novel reverse transcriptase polymerase chain reaction (RT-PCR) assays specific and sensitive for virus quantification of non-clade B HIV-1 and HIV-2 infections were used. RESULTS: HIV-1 and HIV-2 proviral and plasma RNA levels were inversely correlated with CD4+ count for both infections with cellular proviral load similar at each stage of infection. Critically, up to three-fourths of HIV-2-infected individuals with high CD4 percentages (> 28%) had undetectable (< 500 copies/mL) levels of peripheral blood HIV-2 RNA in contrast to HIV-1-infected individuals who had readily detectable plasma virus at all stages of infection (P < .0001). Plasma RNA levels were similar in the intermediate and end stages of infection, indicating similar replication potential for both viruses. In the cross-section of HIV-1- and HIV-2-infected patients studied, the data indicate a wider dynamic range of HIV-2 RNA in vivo compared with HIV-1. DISCUSSION: Low levels of HIV-2 replication and virion expression characterize individuals with high CD4+ lymphocyte counts, suggesting that a very different dynamic equilibrium exists between virus and host for HIV-2 compared with HIV-1. By analogy with HIV-1, our data implicate a considerably lower turnover of HIV-2 virion RNA in vivo with a markedly reduced production of infectious genomes in individuals during the subclinical phase of infection. CONCLUSION: The lower levels of virion expression of HIV-2 infections in vivo are compatible with observed differences in the natural history of HIV-1 and HIV-2 infections, relating to overall differences in the pathogenesis and disease progression of the two infections.

Acquired Immunodeficiency Syndrome↗