Biomedical subjects

Gavin J Churchyard

Publications and source records attributed to Gavin J Churchyard.

8 recordsLinked to original sources

PubMed2005

Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study.

CONTEXT: Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials, but implementation has been limited and there are no data on effectiveness under routine conditions. OBJECTIVE: To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions. DESIGN, SETTING, AND PARTICIPANTS: Randomized intervention study with a novel incremental recruitment design. Between 1999 and 2001 (before antiretroviral therapy was available), 1655 HIV-infected male employees of a South African gold-mining company (median age, 37 years) were enrolled in the study. Median follow-up was 22.1 months. INTERVENTION: Employees were invited in random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self-administered for 6 months among attendees with no evidence of active tuberculosis. MAIN OUTCOME MEASURE: Incidence of tuberculosis (including both first and recurrent episodes) during the periods before and after clinic enrollment. RESULTS: A total of 1016 of 1655 men included in the analysis attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men eligible to start primary isoniazid preventive therapy did so. The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years, respectively (incidence rate ratio [IRR] after adjustment for calendar period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable analysis adjusting for calendar period, age, and silicosis grade, the tuberculosis IRR for clinic enrollment was 0.62 (95% CI, 0.43-0.89). In a further analysis excluding individuals with a history of tuberculosis (and, hence, ineligible for isoniazid preventive therapy), the adjusted IRR for clinic enrollment was 0.54 (95% CI, 0.35-0.83). CONCLUSIONS: Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38% overall and by 46% among individuals with no history of tuberculosis prior to the study. Tuberculosis incidence remained high despite isoniazid preventive therapy, and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2004

Does tuberculosis increase HIV load?

BACKGROUND: The effect that tuberculosis (TB) has on human immunodeficiency virus (HIV) disease progression is not clearly understood. METHODS: In an observational cohort study of HIV-infected adults in South Africa, baseline and final HIV load were compared between individuals who experienced an episode of TB (n=30) during follow-up and control subjects (n=56) matched by baseline CD4 cell count and follow-up time; linear regression modeling was used to control for confounding. RESULTS: Mean HIV load was higher in the TB group than in the non-TB control group for both baseline (4.73 vs. 4.24 log(10) copies/mL; P=.003) and final values (5.02 vs. 4.34 log(10) copies/mL; P<.001). After adjustment for baseline HIV load and World Health Organization HIV stage, the difference in final HIV load was 0.24 log(10) copies/mL (95% confidence interval, -0.01 to 0.50 log(10) copies/mL; P=.06). CONCLUSIONS: Poor prognosis for HIV-infected individuals after TB may be due to preexisting high HIV load rather than to the TB event itself. An episode of TB was associated with a small adjusted increase in HIV load at the end of the study--an increase that would not be regarded as clinically significant in an individual but could have some effect on HIV disease progression or HIV transmission at the population level. Prevention of TB is important for the reduction of HIV-related morbidity and mortality; however, antiretroviral therapy is required to have a major effect on survival in individuals with HIV disease.

AIDS-Related Opportunistic Infections↗

PubMed2004

Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners.

We hypothesized that rapid presentation may be a general feature of tuberculosis (TB) associated with human immunodeficiency virus (HIV) that limits the impact of HIV on the point prevalence of TB. To investigate this, we performed a cross-sectional HIV and TB disease survey with retrospective and prospective follow-up. HIV prevalence among 1,773 systematically recruited miners was 27%. TB incidence was much more strongly HIV associated (incidence rate ratio, 5.5; 95% confidence interval [CI], 3.5-8.6) than the point prevalence of undiagnosed TB disease (odds ratio, 1.7; 95% CI, 0.9-3.3). For smear-positive TB, 7 of 9 (78%) prevalent cases were HIV negative, and point prevalence was nonsignificantly lower in miners who were HIV positive (odds ratio, 0.8; 95% CI, 0.1-4.2). The calculated mean duration of smear positivity before diagnosis (point prevalence/incidence) was substantially shorter for HIV-positive than HIV-negative TB patients (0.17 and 1.15 years, respectively; ratio, 0.15; 95% CI, 0.00-0.73). HIV has considerably less impact on the point prevalence of TB disease than on TB incidence, probably because rapid disease progression increases presentation and case-finding rates. The difference in mean duration of smear positivity was particularly marked and, if generalizable, will have major implications for TB control prospects in high HIV prevalence areas.

Adolescent↗

PubMed2003

Stable incidence rates of tuberculosis (TB) among human immunodeficiency virus (HIV)-negative South African gold miners during a decade of epidemic HIV-associated TB.

During the last decade, annual tuberculosis (TB) case-notification rates increased 4-fold, to >4000 cases/100000 person-years, in the study workforce, among whom prevalence of human immunodeficiency virus (HIV) was 30% in 2000. Three separate cohort studies, totalling 6454 HIV-negative participants, were combined and analyzed for time trends. Observed incidence of TB varied between 962 (1991-1994) and 1589 (1999-2000) cases/100000 person-years (P=.17, test for trend). There was, however, a progressive increase in age, and, for each period, older age was associated with increased incidence rates of TB (P<.001). Having adjusted for age differences, there was no significant association between incidence of TB and calendar period (P=.81, test for trend). Relative to 1991-1994, multivariate-adjusted incidence-rate ratios were 0.94, for 1995-1997, 0.96, for 1998-1999, and 1.05, for 1999-2000. Preventing a secondary epidemic of TB among HIV-negative individuals may be achievable with conventional means, even in settings with a high burden of HIV-associated TB.

AIDS-Related Opportunistic Infections↗

PubMed2003

Efficacy of secondary isoniazid preventive therapy among HIV-infected Southern Africans: time to change policy?

OBJECTIVE: To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among gold miners working in South Africa. DESIGN: An observational study. SETTING: Health service providing comprehensive care for gold miners. METHODS: The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort (n = 338) had received secondary preventive therapy with isoniazid (IPT) and the other had not (n = 221). RESULTS: The overall incidence of recurrent TB was reduced by 55% among men who received IPT compared with those who did not (incidence rates 8.6 and 19.1 per 100 person-years, respectively; incidence rate ratio, 0.45; 95% confidence interval 0.26-0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 cell count and age. The number of person-years of IPT required to prevent one case of recurrent TB among individuals with a CD4 cell count < 200 x 106 cells/l, and > or = 200 x 106 cells/l was 5 and 19, respectively. CONCLUSION: Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 cell counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high.

Adult↗

PubMed2003

HIV infection and chronic chest disease as risk factors for bacterial pneumonia: a case-control study.

OBJECTIVES: To investigate risk factors for severe acute pneumonia in South African gold miners. DESIGN AND METHODS: An inclusive case-control study drawn from a predefined cohort of 4762 miners of known HIV status. Cases were defined by hospital admission meeting the clinical and radiological case definitions for pneumonia during 1998. Controls were randomly selected from the starting cohort. Considered risk factors were: HIV infection, smoking, age, occupation, previous tuberculosis, and chronic premorbid chest disease caused by post-tuberculous lung disease or silicosis (International Labour Office grades 1/0 and above) defined from routine screening radiographs taken before the start of the study. RESULTS: There were 109 cases and 400 controls. HIV infection [odds ratio (OR) 31.6], previous tuberculosis (OR 2.4), and an abnormal premorbid radiograph (OR 2.8) were each significantly more prevalent in cases than controls, whereas other variables were not. On multivariate analysis, HIV infection [OR 30.7, 95% confidence interval (CI) 12.1-78.1] and an abnormal premorbid radiograph (OR 2.3, 95% CI 1.1-4.8) remained significant risk factors. Median CD4 cell counts in HIV-positive cases with and without abnormal premorbid radiographs were 185 and 162 x 106/l, making confounding between chronic chest disease and the extent of immunocompromise an unlikely explanation for this association. CONCLUSION: HIV infection and an abnormal premorbid chest radiograph are both strong risk factors for pneumonia in miners. Pre-existing chronic chest disease may be an important risk factor for HIV-associated pneumonia in other populations, and if so, is an additional indication for considering antibiotic prophylaxis in HIV-positive individuals.

Adult↗

PubMed2002

Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus.

A cohort of 1792 human immunodeficiency virus (HIV)-positive and 2970 HIV-negative South African miners was observed for 12 months starting in February 1998. All-cause hospitalizations and deaths were significantly associated with HIV infection (respective unadjusted incidence rate ratios, 2.9 and 9.2; respective 95% confidence intervals, 2.5-3.4 and 5.5-16.0). Tuberculosis (TB), bacterial pneumonia, cryptococcosis, and trauma were the major causes of admission for HIV-positive patients, whereas Pneumocystis carinii pneumonia was an uncommon cause (respective admission rates, 8.5, 6.9, 2.2, 6.0, and 0.53 admissions per 100 person-years). Enteritis, bronchitis, urinary tract infections, and soft-tissue infections were also significantly associated with HIV infection. Cryptococcosis caused 44% of deaths among HIV-positive patients. Trauma was the main hazard for HIV-negative men, causing 42% of admissions and 60% of deaths. A broad range of infectious conditions is significantly associated with HIV infection in South African miners. Identification and implementation of effective prophylactic regimens are urgently needed.

Adult↗

PubMed2002

Polymorphisms in the tumor necrosis factor-alpha gene promoter may predispose to severe silicosis in black South African miners.

Susceptibility to silicosis is in part genetically determined. Polymorphisms in the promoter region of tumor necrosis factor (TNF)-alpha, a cytokine with a central role in the pathophysiology of silicosis, have been associated with predisposition to several infectious and inflammatory diseases. Polymorphisms at positions -308, -238, and -376 in the TNF-alpha promoter region were compared in nine patients with severe silicosis with International Labour Office (ILO) grade 3 nodularity, 112 patients with less severe silicosis (ILO grades 1/1 to 2/2), and 120 black South African gold miners without silicosis (ILO grades 0/0) in an age-frequency-matched case- control study. There were no significant differences between miners with less severe silicosis and controls at any loci in the TNF-alpha promoter region, but miners with severe silicosis were significantly more likely than controls to have -238A (33% versus 6%, Fisher's exact p value = 0.022) and -376A (33% versus 5%, Fisher's exact p value = 0.016). These alleles were in linkage disequilibrium (p < 0.001), and so were not independent. The association remained significant (Fisher's exact p values = 0.011 and 0.011, respectively) when analysis was limited to the majority tribe (Basotho), which included all subjects with severe silicosis. Subjects with severe silicosis were also significantly more likely to have the -308A allele (Fisher's exact p value = 0.034), but this result was confounded by ethnicity and was not significant within Basotho tribe members (Fisher's exact p value = 0.15). TNF-alpha promoter polymorphisms are associated with severe, but not less severe, silicosis in this population. A predominant effect on disease severity, rather than on disease frequency, appears to be a general feature of promoter polymorphism in diseases in which TNF-alpha has a critical role.

Adult↗