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T Corrah

Publications and source records attributed to T Corrah.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ex vivo analysis of cytotoxic T lymphocytes to measles antigens during infection and after vaccination in Gambian children.

The study of cytotoxic T cell responses to measles antigens during infection and after vaccination may provide insight into the immunopathology of the infection. It will also provide a knowledge of the immunity conferred by wild or attenuated virus, which will help in the design of new vaccines. Direct cytotoxic T cell responses, which did not require in vitro restimulation, were measured from peripheral blood by a standard 51Cr-release assay in 35 patients with acute measles, using HLA class I matched allogeneic B cells as targets. 77% showed specific responses to measles fusion protein, 69% to the hemagglutinin, and 50% to the nucleoprotein. These responses, which were related to severity of disease and history of previous vaccination, had waned by 14-24 wk after measles when memory responses to the same antigens could be elicited by restimulation in 71% of the 13 patients tested. A similar pattern followed vaccination: direct cytotoxic responses to fusion and hemagglutinin proteins were shown in 70% of the 20 children tested while 50% responded to the nucleoprotein. These responses, which were mediated by both CD8(+) and CD4(+) cells, faded over 6 wk when memory responses could be restimulated. Thus, a vigorous cytotoxic T lymphocyte response to fusion, hemagglutinin, and nucleoproteins is important in both natural and vaccine-induced immunity to measles.

Adolescent↗
PubMed1998

Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans.

BACKGROUND: Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. In mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in tuberculosis is unknown. We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa. METHODS: Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded. RESULTS: Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95 percent confidence interval, 1.86 to 9.12; chi-square= 14.58; P<0.001). CONCLUSIONS: Genetic variation in NRAMP1 affects susceptibility to tuberculosis in West Africans.

Adult↗
PubMed1998

Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis.

SETTING: A study of tuberculosis cases and healthy blood donor controls from the Western Region of The Gambia, West Africa. OBJECTIVE: To investigate the potential role of candidate gene polymorphisms in host susceptibility to tuberculosis. DESIGN: Single base change polymorphisms in interleukin 1 beta (IL1 beta), interleukin 10 (IL10) and fucosyltransferase-2 (FUT-2), microsatellite polymorphisms in interleukin 1 alpha (IL1 alpha) and IL10 and a minisatellite polymorphism in interleukin 1 receptor antagonist (IL1RA) were typed in over 400 tuberculosis cases and 400 healthy blood donor controls. RESULTS: IL1 gene cluster polymorphisms (IL1RA and possibly IL1 alpha) showed marginally significant association with tuberculosis. In particular IL1RA allele 2 heterozygotes were less frequent among tuberculosis cases than controls (P = 0.03). IL1 beta, IL10 and FUT-2 polymorphisms were not associated with tuberculosis. CONCLUSION: Genetic susceptibility to tuberculosis among Gambians may be partly determined by genes in the IL1 gene cluster on chromosome 2. Further association studies will be required on other population groups to confirm whether these results are of biological significance.

Adult↗
PubMed1998

Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans.

We retrospectively studied MBP genotypes in patients with malaria, tuberculosis (TB), and persistent hepatitis B virus (HBV) carriage, in clinics and hospitals in The Gambia. Children under 10 years with cerebral malaria and/or severe malarial anaemia, were compared with children with symptomatic, mild malaria, and controls of the same age and ethnicity. Adult TB cases with smear-positive pulmonary TB were compared with healthy blood donors from the same ethnic groups. Malaria cases and controls were tested for hepatitis B core antibody (anti-HBc) and surface antigen (HBsAg). TB patients were tested for HIV antibodies. Genotyping used sequence-specific oligonucleotide analysis to identify MBP variant alleles. Overall, 46% (944/2041) of patients and controls were homozygous for the wild-type MBP allele, 45% (922/2041) were carriers of a single variant allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor heterozygotes for MBP variants were at increased risk of clinical malaria, persistent HBV carriage or TB. The most common mutation in Africans, the codon 57 variant allele, was weakly associated with resistance to TB (221/794 in TB cases and 276/844 in controls, p = 0.037). MBP deficiency is not a significant risk factor for persistent HBV, severe malaria nor pulmonary TB in West Africa.

Adult↗
PubMed1998

Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia.

BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality in young children in the developing world. The recent development of pneumococcal polysaccharide/protein conjugate vaccines may make possible prevention of this infection. However, little is known about the epidemiology of invasive pneumococcal disease in children in the developing world. OBJECTIVES: To determine the incidence and epidemiologic features of invasive pneumococcal disease in children resident in a semiurban area of The Gambia. METHOD: The study was part of a large trial of an Haemophilus influenzae type b vaccine that recruited 42 848 children at the age of 2 months during the period March, 1993, to October, 1995. Follow-up of study children continued until December 31, 1995; therefore the first children to enter the trial were followed for 2.5 years and the last for just a few months. During the period of surveillance, 2256 children were investigated for possible invasive pneumococcal disease when they presented to a hospital or health center. RESULTS: We detected 110 cases of pneumococcal disease. Pneumonia was the most common form of invasive pneumococcal disease observed (75.5% of patients). The incidence of pneumococcal disease was 224 [95% confidence interval (CI) 171, 277] per 100,000 child years among children ages 2 to 11 months, 139 (95% CI 93, 184) per 100,000 among children ages 12 to 23 months and 82 (95% CI 21, 143) per 100,000 among children ages 24 to 35 months. Pneumococci of serogroups 14, 6, 5, 23, 19, 46 and 2 were isolated most frequently. Susceptibility to pneumococcal disease was not increased significantly among Haemophilus influenzae type b-vaccinated children. CONCLUSIONS: The pneumococcus is a major cause of bacterial infection in The Gambia. A proposed nine-valent pneumococcal conjugate vaccine for developing countries containing conjugates of serogroups 1, 4, 5, 6, 9, 14, 18, 19 and 23 would cover 74% of cases of invasive pneumococcal disease in children resident in the Western Region of The Gambia.

Bacterial Capsules↗
PubMed1998

Cytotoxic T cells from human immunodeficiency virus type 2-infected patients frequently cross-react with different human immunodeficiency virus type 1 clades.

Knowledge of immune mechanisms responsible for the cross-protection between highly divergent viruses such as human immunodeficiency virus type 1 (HIV-1) and HIV-2 may contribute to an understanding of whether virus variability may be overcome in the design of vaccine candidates which are broadly protective across the HIV subtypes. We demonstrate that despite the significant difference in virus amino acid sequence, the majority of HIV-2-infected individuals with different HLA molecules possess a dominant cytotoxic T-cell response which is able to recognize HIV-1 Gag protein. Furthermore, HLA-B5801-positive subjects show broad cross-recognition of HIV-1 subtypes since they mounted a T-cell response that tolerated extensive amino acid substitutions within HLA-B5801-restricted HIV-1 and HIV-2 epitopes. These results suggests that HLA-B5801-positive HIV-2-infected individuals have an enhanced ability to react with HIV-1 that could play a role in cross-protection.

Cells, Cultured↗
PubMed1998

The role of cytotoxic T-cells in HIV infection.

HIV-specific cytotoxic T lymphocytes (CTL) are believed to play a major role in controlling virus levels through the asymptomatic period of HIV infection. For the rational design of an HIV vaccine, we need to know whether protective immunity can ever develop following HIV exposure in people who remain uninfected. We have detected HIV-specific CTL in 5/6 repeatedly exposed, persistently seronegative female sex-workers in The Gambia. Their CTL, repeatedly detected over two years, recognise epitopes presented by HLA-B35 which are cross-reactive between HIV-1 & HIV-2, suggesting they could have been primed first by HIV-2 exposure and subsequently boosted by exposure to HIV-1. Using previously identified clade B HIV-1 epitope peptides, we have now detected HIV-specific CTL in 6/15 highly exposed and apparently HIV-resistant Kenyan prostitutes, predominantly towards epitopes highly conserved between B and the Kenyan A & D clades of HIV-1. This CTL activity towards conserved virus epitopes may represent protective immunity to HIV generated in response to repeated exposure, and prophylactic HIV vaccines should aim to generate similar CTL responses.

Cells, Cultured↗
PubMed1997

Rate of decline of percentage CD4+ cells is faster in HIV-1 than in HIV-2 infection.

Increasing evidence suggests that the pathogenesis of HIV-1 is different from that of HIV-2. Thus, we have measured, longitudinally at various times over a median follow-up of 2.1 years, the percentage CD4+ cells of 94 patients infected with HIV-1 and 164 patients infected with HIV-2. The pattern of decline of CD4% over time was linear for patients with either infection. Multilevel statistical modeling techniques showed that after stratifying for HIV status, the rate of decline of CD4% was faster among patients who died than among those who survived (difference in rate of decline = 2.34% CD4+ cells/year; p = 0.0002). After stratifying for survival status, the rate of decline was faster and less variable among patients infected with HIV-1 than among patients infected with HIV-2 (difference in rate of decline = 1.12% CD4+ cells/year; p = 0.05). The proportion of patients who showed no fall in CD4+ cells was higher in HIV-2 than in HIV-1 infection (p = 0.026). These data suggest fundamental differences between the two infections, with HIV-1 being more pathogenic resulting in a faster and more homogeneous rate of decline than HIV-2. In HIV-2 infection, disease in many patients progresses slowly, but in some the advance is just as fast as that in HIV-1 infection. The reasons for this marked heterogeneity need elucidation to understand the disease and to target therapeutic interventions against HIV-2 in those most at risk.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Increasing prevalence of penicillinase-producing Neisseria gonorrhoeae and the emergence of high-level, plasmid-mediated tetracycline resistance among gonococcal isolates in The Gambia.

One hundred and three strains of Neisseria gonorrhoeae isolated from a periurban STD clinic in The Gambia were studied for antimicrobial susceptibility, plasmid profile, and serogroup using standard procedures. Seventy-nine (77%) were penicillinase producers (PPNG) and fully resistant to penicillin (MIC > or = 8 mg/l). One isolate showed chromosomally induced resistance to penicillin (MIC 2 mg/l). None of the isolates was sensitive to tetracycline; 16 (16%) showed intermediate resistance (MICs 1-8 mg/l) and 87 (84%) showed high-level plasmid-mediated resistance (TRNG) (MICs > 10 mg/l). This is the first report of TRNG in The Gambia. Only 6 (6%) strains were fully sensitive to trimethoprim-sulphamethoxazole (MIC < 8 mg/l); 78 (76%) showed intermediate level resistance (MICs 8-16 mg/l) and 19 (18%) were fully resistant (MIC > 32 mg/l). Indications of an increase in MIC to ciprofloxacin and ceftriaxone were found in 6 (6%) and 1 (1%) strains, respectively, although all remained fully sensitive (MICs 0.004-0.03 mg/l and 0.001-0.015 mg/l). All PPNG and TRNG strains carried the 3.2 MDa and 25.2 MDa plasmids, respectively. All isolates carried the 2.6 MDa cryptic plasmid and 9 (3 PPNG and 6 non-PPNG) carried the 24.5 MDa conjugative plasmid. Forty-four (43%) strains were typed group W1, 58 (56%) W11/111 and 1 had cross-reacting antigens. Because PPNG are frequently encountered and high-level TRNG is now prevalent, the newer cephalosporins and quinolones must now be considered as first-line drugs for the treatment of gonorrhoea in The Gambia.

Anti-Bacterial Agents↗
PubMed1996

Haemophilus influenzae type b disease in the western region of The Gambia: background surveillance for a vaccine efficacy trial.

In preparation for a field trial of an Haemophilus influenzae type b conjugate vaccine in the Western Region of The Gambia, a 3-year prospective study was undertaken to determine the incidence of Hib disease and the vaccination status of affected children. One hundred and eighty-two children with invasive Hib disease were found; 141 (77%) had meningitis, 31 (17%) pneumonia and 10 (6%) other forms of invasive disease. The estimated annual incidence rates for all invasive Hib diseases were 274 and 73 per 100,000 in children aged < 1 and < 5 years, respectively. For meningitis, the rate was 222 per 100,000 per year in children aged < 1 year. Children with meningitis were significantly younger than those with pneumonia (median age 7 months, interquartile range [IQR] 5-9, vs 12 months, IQR 6-15 (P = 0.002)) and younger than those with other forms of Hib disease. Of 142 children for whom vaccination status was known, 18 had received no DPT, 36 had received one, 40 had received two and 48 had received three doses. This study confirmed the high incidence of systemic Hib disease among Gambian children and the need to vaccinate at an early age. It provided the background epidemiological data required for the successful planning of an Hib vaccine trial which is now in progress.

Age Distribution↗
PubMed1995

HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women.

A crucial requirement in the rational design of a prophylactic vaccine against the human immunodeficiency virus (HIV) is to establish whether or not protective immunity can occur following natural infection. The immune response to HIV infection is characterized by very vigorous HIV-specific cytotoxic T-lymphocyte (CTL) activity. We have identified four HIV-1 and HIV-2 cross-reactive peptide epitopes, presented to CTL from HIV-infected Gambians by HLA-B35 (the most common Gambian class I HLA molecule). These peptides were used to elicit HIV-specific CTLs from three out of six repeatedly exposed but HIV-seronegative female prostitutes with HLA-B35. These women remain seronegative with no evidence of HIV infection by polymerase chain reaction or viral culture. Their CTL activity may represent protective immunity against HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load.

OBJECTIVES: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load. METHODS: Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2CBL-22 chronically infected C8166 cell line. A biotinylated primer was used to capture the 35S dATP-incorporated secondary PCR product in a quantitative radiometric assay. RESULTS: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r = -0.625, P = 0.003 and r = -0.674, P = 0.001, respectively). CONCLUSION: HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.

Acquired Immunodeficiency Syndrome↗