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Biomedical subjects

C F Gilks

Publications and source records attributed to C F Gilks.

At least 55 records · Page 3Linked to original sources
PubMed1996

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cutaneous hypersensitivity reactions to thiacetazone, HIV infection and thiacetazone concentrations in plasma.

We have studied the relationship between the plasma concentration-time profile of thiacetazone over the 24 h between doses [AUC(0.24h)] and the incidence of cutaneous reactions among HIV-infected patients with tuberculosis in Kenya. Cutaneous reactions due to thiacetazone occurred in 4/14 [28.6%] HIV+ve patients compared with 3/47 [6.4%] HIV-ve patients [RR = 4.48, 95% CI-1.1 to 17.7], and all resolved on alternative therapy. Among the HIV+ve patients, those with cutaneous reactions had higher AUC(0.24h) values, although the difference was not significant. These results do not exclude pharmacokinetic change as being at least partly responsible for cutaneous reactions to TCZ in HIV+ve patients, and do not refute an immunological basis for the reaction. With regard to the operational use of TCZ in Africa, there is no indication that a modification of the dose will reduce the frequency of drug reactions.

Adolescent↗
PubMed1995

Disseminated Mycobacterium avium infection among HIV-infected patients in Kenya.

Previous studies from Africa have been unable to identify disseminated Mycobacterium avium complex (MAC) infection in patients with advanced human immunodeficiency virus (HIV) infection. We performed mycobacterial blood cultures and CD4 counts on 48 symptomatic adults with advanced HIV infection admitted to the hospital in Nairobi, Kenya over 4 weeks in 1992. Fourteen patients had mycobacteremia; these patients had significantly lower CD4 counts than the patients with negative cultures (14/mm3 vs. 85/mm3; p < 0.01). Three patients (6%) were bacteremic with M. avium (mean CD4 count, 10/mm3) and 11 (23%) were bacteremic with Mycobacterium tuberculosis complex (MTB) (mean CD4 count, 15/mm3). Thus, M. avium bacteremia was detected significantly less frequently in the study population than MTB bacteremia (p = 0.04). The minimum rate for HIV-associated disseminated M. avium infection in patients admitted to the hospital in Nairobi was estimated to be approximately 1%. Patients with mycobacteremia died or were discharged home sick before the diagnosis was made. Disseminated M. avium does occur in adults with advanced HIV infection in sub-Saharan Africa, but is less common than disseminated MTB.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Clonal relationships among bloodstream isolates of Escherichia coli.

The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at Boston, Mass., Long Beach, Calif., and Nairobi, Kenya, were determined by multilocus enzyme electrophoresis (MLEE), analysis of polymorphisms associated with the ribosomal operon (ribotyping), and serotyping. MLEE based on 20 enzymes resolved 101 electrophoretic types (ETs), forming five clusters; ribotyping resolved 56 distinct patterns concordant with the analysis by MLEE. The isolates at each study site formed a genetically diverse group and demonstrated similar clonal structures, with the same small subset of lineages accounting for the majority of isolates at each site. Moreover, two ribotypes accounted for approximately 30% of the isolates at each study site. One cluster contained the majority (65%) of isolates and, by direct comparison of the ETs and ribotypes of individual isolates, was genetically indistinguishable from the largest cluster for each of two other collections of E. coli causing pyelonephritis and neonatal meningitis (R. K. Selander, T. K. Korhonen, V. Väisänen-Rhen, P. H. Williams, P. E. Pattison, and D. A. Caugent, Infect. Immun. 52:213-222, 1986; M. Arthur, C. E. Johnson, R. H. Rubin, R. D. Arbeit, C. Campanelli, C. Kim, S. Steinbach, M. Agarwal, R. Wilkinson, and R. Goldstein, Infect. Immun. 57:303-313, 1989), thus defining a virulent set of lineages. The isolates within these virulent lineages typically carried DNA homologous to the adhesin operon pap or sfa and the hemolysin operon hly and expressed O1, O2, O4, O6, O18, O25, or O75 antigens. DNA homologous to pap was distributed among isolates of each major cluster, whereas hly was restricted to isolates of two clusters, typically detected in pap-positive strains, and sfa was restricted to isolates of one cluster, typically detected in pap- and hly-positive strains. The occurrence of pap-positive isolates in the same geographically and genetically divergent lineages suggests that this operon was acquired early in the radiation of E. coli, while hly and sfa were acquired subsequently, most likely by pap-positive and pap- and hly-positive precursors, respectively.

Adhesins, Escherichia coli↗
PubMed1995

Impaired natural immunity to pneumolysin during human immunodeficiency virus infection in the United States and Africa.

Human immunodeficiency virus (HIV) infection is associated with a significantly increased incidence of pneumococcal pneumonia and concomitant bacteremia. We hypothesized that the predisposition of HIV-infected patients to invasive pneumococcal infection may be related, in part, to an impaired immune response to the pneumococcal antigen pneumolysin (PLY) because PLY facilitates bacterial invasion. We measured serum anti-PLY antibodies in two separate populations of HIV-infected and HIV-seronegative controls, using both an enzyme-linked immunosorbent assay method and a functional assay of antibody inhibition of PLY-induced hemolysis and cytotoxicity. HIV-infected patients in the United States had significantly lower titers of anti-PLY antibodies by both methods than did seronegative control subjects. Moreover, HIV-infected patients in Kenya who later developed pneumococcal bacteremia also had significantly lower anti-PLY antibody levels at baseline compared with seronegative control subjects. We conclude that lower baseline levels of antibodies to PLY are associated with the higher incidence of bacteremic pneumococcal infections among HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Immune response following oral administration of cholera toxin B subunit to HIV-1-infected UK and Kenyan subjects.

OBJECTIVE: To determine the effect of HIV-1 infection on immunoglobulin (Ig) G and IgA antibody response and circulating antibody forming cell response to oral immunization with the B subunit of cholera toxin. DESIGN: Healthy UK volunteers, and HIV-1-positive UK and Kenyan volunteers at different clinical stages of HIV-1 infection received two oral immunizations. CD4+ T cells, serum beta 2-microglobulin and neopterin were measured as surrogate markers of disease stage, and correlated with immunization response. METHODS: Serum antitoxin IgG and IgA measured by enzyme-linked immunosorbent assay and antitoxin IgG, IgA and IgM antibody-forming cells detected by enzyme-linked immunospot assay at different times after two oral immunizations. RESULTS: UK HIV-positive volunteers (mean CD4+ T cell count, 52 x 10(6)/l) responded poorly to primary and booster immunization. HIV-infected Kenyans (752 x 10(6)/l CD4+ T cells) had a significant primary and booster antibody response, whereas those with a mean CD4+ T cell count 186 x 10(6)/l had an insignificant primary, but significant booster response. Two oral immunizations induced antibody responses in HIV-positive Kenyan groups (who may have prior immunity from exposure to environmental bacterial toxins) of similar or greater magnitude to healthy UK volunteers. CONCLUSIONS: Mucosal immunization may recall immune memory and be of benefit in early and moderately advanced clinical HIV disease. The findings have important clinical implications in that mucosally targeted vaccines are potentially useful in this group of patients.

Administration, Oral↗
PubMed1993

Evidence of previous infection with Mycobacterium avium-Mycobacterium intracellulare complex among healthy subjects: an international study of dominant mycobacterial skin test reactions.

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions of > or = 5 mm to one antigen that exceeded the reaction to the other by > or = 3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas.

Adult↗
PubMed1993

Prophylaxis for HIV-associated infections in the developing world.

Prophylaxis for specific HIV-associated infections has made a major difference in the industrialized world to patient survival and the quality of life. However, the HIV epidemic is spreading most rapidly in the poor developing world, where prophylaxis is neither currently used nor recommended. Streptococcus pneumoniae. Mycobacterium tuberculosis and non-typhi salmonellae are the pathogens responsible for much of the morbidity and mortality associated with HIV infection in the tropics. Because these problems often present relatively early in the course of the HIV disease, prophylaxis may be cost-effective and increase the years of productive life. Prevention of pneumococcal disease has not been considered a priority in the developing world. Penicillin chemoprophylaxis may be efficacious; immunization which is recommended for all HIV seropositive adults in the USA, has not been used. The importance of studies to test both efficacy and cost compared to benefit is discussed. The problem of HIV-associated tuberculosis is of major importance and several intervention studies are now in progress. The efficacy of chemoprophylaxis may be limited if the problem is largely acute infection rather than reactivated disease and if shown to be effective compliance will present a major operational difficulty. Systemic salmonellosis is greatly underdiagnosed but may be the leading cause of death. Recurrent infection can be prevented by chemoprophylaxis but this will be costly. The use of novel or currently unlicensed vaccines may eventually prove to be the most effective means of controlling the burden of disease and death caused by salmonellosis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya.

Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is a common complication of AIDS in the United States and other developing countries, but it is rare or absent in sub-Saharan Africa. To assess the comparative likelihood of exposure to MAC in these geographic areas, we used a standard protocol to culture 91 water samples from environmental sites and piped water supply systems in the United States, Finland, Zaire, and Kenya. MAC was isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%) samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and Kenya (P = 0.056). MAC was isolated from hospital water in the United States and Finland but not in hospital water in Zaire and Kenya. Serovar determinations showed that six of eight isolates from the United States were serovar 4 or 8. One MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest that exposure to MAC in water is likely in diverse areas of the world, but that the likelihood of human exposure to the organism in water may be slightly less in sub-Saharan Africa than in developed countries in the Northern Hemisphere.

AIDS-Related Opportunistic Infections↗
PubMed1992

The presentation and outcome of HIV-related disease in Nairobi.

The range of clinical presentations of HIV-related disease in Africa has not been adequately described, despite the fact that many hospitals have to rely heavily on clinical diagnosis. Six hundred adult medical patients seen in the Casualty Department of the main Government hospital in Nairobi were enrolled in a study of the presentation and outcome of HIV-related disease: 506 of these patients were admitted, of whom 19 per cent (95) were HIV seropositive. The remaining 94 were dealt with as outpatients: 11 percent (10) of these were seropositive. A history of prior treatment for sexually transmitted disease and, if male, being uncircumcised, were associated with being seropositive. Three presentations were strongly associated with HIV infection: acute fever with no focus except the gastrointestinal tract (enteric fever-like illness), acute cough with fever (community-acquired pneumonia) and chronic diarrhoea with wasting. The WHO clinical case definition (CCD) for AIDS missed a substantial amount of HIV-related morbidity (sensitivity 39 per cent) and misidentified many seronegative patients (positive predictive value 59 per cent). In comparison with the Centers for Disease Control surveillance definition for AIDS, the CCD was specific (91 per cent) and sensitive (79 per cent) but only had a positive predictive values of 30 per cent: the CCD may therefore be a poor surveillance tool for AIDS. Seropositive patients were much more likely to die than were seronegative patients (39 per cent vs. 15 per cent mortality). Enteric fever-like illness was the presentation which most commonly proved fatal. A wider spectrum of disease is associated with underlying HIV immunosuppression than has previously been described in Africa.

Acute Disease↗