PubMed Health⌕ Search

Biomedical subjects

R E Chaisson

Publications and source records attributed to R E Chaisson.

At least 19 recordsLinked to original sources

Establishing a workplace antiretroviral therapy programme in South Africa.

Ways to expand access to antiretroviral treatment (ART) in low income settings are being sought. We describe an HIV care programme including ART in an industrial setting in South Africa. The programme uses guidelines derived from local and international best practice. The training component aims to build capacity among health care staff. Nurses and doctors are supported by experienced HIV clinicians through telephone consultation and site visits. Patients undergo a three-stage counselling procedure prior to starting ART. Drug regimens and monitoring are standardised and prophylaxis against opportunistic infections (isoniazid and cotrimoxazole) is offered routinely. Laboratory and pharmacy services, using named-patient dispensing, are centralized. The programme is designed to ensure that data on clinical and economic outcomes will be available for programme evaluation. Between November 2002-December 2004, ART delivery has been established at 70 ART workplace ART sites. The sites range from 200 to 12000 employees, and from small occupational health clinics and general practitioner rooms to larger hospital clinics. During this period, 2456 patients began ART. Of those on treatment for at least three months, 1728 (78%) have been retained on the programme and only 38 (1.7%) patients have failed the first-line ART regimen. This model for delivery of ART is feasible and successful in an industrial setting. The model may be generalizable to other employment health services in settings of high HIV prevalence, and as a model for implementing ART in other types of health-care settings.

Anti-HIV Agents↗

The cost-effectiveness of DOTS in urban Brazil.

SETTING: Rio de Janeiro, Brazil, is a middle-income setting with an estimated 1% adult human immunodeficiency virus (HIV) seroprevalence. OBJECTIVE: To examine the cost-effectiveness of DOTS in Rio de Janeiro. DESIGN: Cost-effectiveness analysis based on cost data and an epidemiological model based on programmatic outcomes from the Health Department in Rio de Janeiro, cost data from the retail market sector and epidemiological data from published studies. RESULTS: The 10-year cost of a tuberculosis program treating a population of 262 000 based on self-administered therapy (SAT) was estimated to be $580 271 compared to $1047 886 for DOTS. The largest portion of the DOTS budget was for staff costs and costs incurred by patients, both at 28%. For SAT, the largest percentage of the budget was allocated to medication costs, at 34%. Upgrading from SAT to DOTS averted 1558 cases of tuberculosis (TB, uncertainty range [UR] 1418-1704) and 143 TB deaths (UR 131-155). The incremental cost effectiveness ratio (ICER) for DOTS was $300 per case averted (UR $289-$312) and $3270 per death averted (UR $3123-$3435). In terms of disability adjusted life years (DALYs), DOTS saved 5426 DALYs (UR 4908-5961). The ICER for DOTS was $86 per DALY saved (UR $74-$100). CONCLUSIONS: DOTS is a highly cost-effective intervention in Brazil.

Antitubercular Agents↗

Delayed tuberculosis diagnosis and tuberculosis transmission.

SETTING: Tuberculosis (TB) patients and their close contacts reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. OBJECTIVES: A recent prospective study found that 49% of pulmonary TB patients had total treatment delays > or = 90 days. This cohort was analyzed to determine the association between total treatment delay and TB transmission. DESIGN: TB patient data were collected as part of a prospective cohort study; contact data were collected from local health departments. RESULTS: Close contacts of 54 US-born patients (n = 310) and those of 70 foreign-born cases (n = 393) received tuberculin skin tests (TSTs). Among contacts of US-born patients with a total treatment delay of > or = 90 days, 40% had positive TSTs vs. 24% contacts of patients with shorter delays (aOR 2.34; P = 0.03). Other patient factors associated with TST positivity among contacts of US-born cases were black race (aOR 3.03; P = 0.05), sputum smear positive for AFB (aOR 3.29; P = 0.01) and chest radiograph with cavitation (aOR 3.11; P = 0.01). No associations were observed between foreign-born patients and risk of TST positivity among their contacts. CONCLUSION: Among US-born patients, delay in TB diagnosis is associated with greater transmission of infection to contacts and could be used independently of other index patient factors to identify contacts at greatest risk of TB infection.

Contact Tracing↗

Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors.

SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population.

Adult↗

Improvements in treatment success rates with directly observed therapy in Rio de Janeiro City.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To evaluate the effect of directly observed therapy (DOT) on treatment success, by comparing the treatment success rates between patients treated under DOT with those who received self-administered therapy (SAT). DESIGN: A longitudinal study in a cohort of tuberculosis (TB) patients. Of 9929 new pulmonary TB cases, 1190 (12%) were treated under DOT and 8739 (88%) under SAT. All patients received a three-drug regimen consisting of rifampicin (RMP), isoniazid (INH) and pyrazinamide for 2 months followed by 4 months of RMP and INH. RESULTS: Patients under DOT were more likely to convert to sputum-negative at the end of the second month than those treated under SAT (86.3% vs. 61.9%, P < 0.001). DOT alone was significantly associated with successful treatment (OR 1.6, 95%CI 1.37-1.86, P < 0.001), even when controlled by sex, age and positive smear or culture at enrollment (OR 1.56, 95%CI 1.33-1.82, P < 0.001). CONCLUSION: This pilot DOTS implementation phase showed that DOT is highly effective and feasible in a large urban centre of a developing country.

Adult↗

Diagnostic yield of peripheral lymph node needle-core biopsies in HIV-infected adults with suspected smear-negative tuberculosis.

Significant lymphadenopathy in human immunodeficiency virus (HIV) infected adults in developing countries is usually caused by tuberculosis. We studied the safety and diagnostic yield of needle-core biopsies, under local anaesthetic, of enlarged lymph nodes in 26 HIV-infected adults presenting with suspected tuberculosis who were sputum smear-negative. Biopsy samples were sent for histology and mycobacterial culture. Induced sputum, urine and blood were also sent for mycobacterial culture. The procedure was well tolerated. A definitive diagnosis was made on initial needle-core biopsy in 22 subjects (85%) and in two of three subjects who underwent a second needle-core biopsy. Tuberculosis was the final diagnosis in 24 subjects (92%).

AIDS-Related Opportunistic Infections↗

Impact of empiric antibiotics and chest radiograph on delays in the diagnosis of tuberculosis.

SETTING: Maryland Department of Health and Mental Hygiene, Division of Tuberculosis (TB) Control. OBJECTIVES: To assess the implications of antibiotic treatment of presumed community-acquired pneumonia (CAP) on delays in the diagnosis of TB, and to assess the frequency with which chest radiographs (CXRs) were utilized before a diagnosis of pneumonia or pulmonary TB was made. DESIGN: A nested case-control study within a prospective study conducted to assess factors associated with delays in the diagnosis of TB. RESULTS: Cases (n = 85; 54%) were patients who received antibiotics for non-TB diagnoses/indications prior to TB diagnosis, and controls (n = 73; 46%) were patients who had initially received TB therapy. Median health care delay for cases was 39 days vs. 15 days (P < 0.01) for controls. Median antibiotic delay was similar among all antibiotic classes. Of 54 patients who did not have a CXR at their first health care visit, 41 (79%) received empiric antibiotics, compared to 44/105 (42%) who had a CXR (P < 0.01). Only 31/54 (57%) patients initially diagnosed with CAP had a CXR at the time of diagnosis. CONCLUSION: More widespread use of CXR when diagnosing CAP should reduce delays in diagnosing TB, and the unnecessary use of antibiotics.

Adult↗

Latent tuberculosis infection among undergraduate medical students in Rio de Janeiro State, Brazil.

SETTING: Five medical schools in three cities with different tuberculosis (TB) incidence rates in Rio de Janeiro State, Brazil. OBJECTIVE: To estimate prevalence of and associated factors for latent tuberculosis infection (LTBI) among medical students. DESIGN: A cross-sectional survey was conducted among undergraduate students in pre-clinical, early and late clinical years from schools in cities with low (28/100,000), intermediate (63/100,000) and high (114/100,000) TB incidence rates. Information on socio-demographic profile, previous BCG vaccination, potential TB exposure, co-morbidity and use of respiratory protective masks was obtained. A tuberculin skin test (TST) was performed using the Mantoux technique by an experienced professional. A positive TST, defined as induration > or = 10 mm, was considered LTBI. RESULTS: LTBI prevalence was 6.9% (95%CI 5.4-8.6). In multivariate analysis, male sex (adjusted odds ratio [aOR] 1.8; 95% CI 1.1-3.0), late clinical years (aOR 1.9; 95% CI 1.01-3.5), intermediate TB incidence (aOR 4.3; 95% CI 1.3-14.6) and high TB incidence in the city of medical school (aOR 5.1; 95% CI 1.6-16.8) were significantly associated with LTBI. CONCLUSIONS: The higher prevalence of LTBI in late clinical years suggests that medical students are at increased risk for nosocomial Mycobacterium tuberculosis infection. The implementation of a TB control program may be necessary in medical schools, particularly in cities with higher TB incidence.

Adult↗

Patient and health care system delays in pulmonary tuberculosis diagnosis in a low-incidence state.

SETTING: Tuberculosis (TB) patients reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. OBJECTIVE: To determine the extent of delayed diagnosis of TB and to assess patient and provider factors associated with delays. DESIGN: A prospective cohort study. RESULTS: Median patient, health care and total delays were 32, 26 and 89 days, respectively, for 158 patients. Non-white (relative hazard [RH] 0.62; 95% CI 0.39-0.98) and less educated (RH 0.43; 95% CI 0.26-0.72) patients had longer patient delays. English-speaking patients (RH 0.40; 95% CI 0.24-0.68) had increased health care delays, as did patients who received a diagnosis of a respiratory illness and non-TB antibiotics (RH 0.69; 95% CI 0.49-0.96) prior to a TB diagnosis. Patients first presenting to a private physician (51 days) rather than a hospital emergency room (18 days; RH 1.87; 95% CI 1.05-3.33) or public health clinic (10 days; RH 1.79; 95% CI 1.21-2.63) had longer health care delays. When a TB diagnostic tool (chest radiograph or AFB culture) was utilized, a more rapid diagnosis of TB was made. CONCLUSION: Education of the patient population about TB symptoms might reduce delays. Increased physician awareness of the current epidemiology of TB and better use of available diagnostic tools will reduce delays and may reduce TB transmission.

Female↗

Active case finding of tuberculosis: historical perspective and future prospects.

Despite a history of remarkable scientific achievements in microbiology and therapeutics, tuberculosis (TB) continues to pose an extraordinary threat to human health. Case finding and treatment of TB disease are the principal means of controlling transmission and reducing incidence. This review presents a historical perspective of active case finding (ACF) of TB, detailing case detection strategies that have been used over the last century. This review is divided into the following sections: mass radiography, house-to-house surveys, out-patient case detection, enhanced case finding, high-risk populations and cost-effectiveness. The report concludes with a discussion and recommendations for future case finding strategies. Understanding the strengths and weaknesses of these methods will help inform and shape ACF as a TB control policy in the twenty-first century.

Communicable Disease Control↗

Feasibility and acceptability of a specialist clinical service for HIV-infected mineworkers in South Africa.

Occupational settings offer an ideal opportunity to provide preventive health services for HIV-infected workers. A specialized clinic was established in a mining hospital in the Free State, South Africa, with the primary aim of delivering preventive therapy such as isoniazid to those at high risk of tuberculosis (individuals with HIV infection or silicosis), and cotrimoxazole to those at highest risk for opportunistic infections. The clinic design has taken regard of the importance of minimizing stigma, protecting confidentiality, monitoring potential side effects, supporting adherence and identification of prophylaxis failure. The clinic opened in April 1999 and, by August 2001, 1773 patients had attended at least once; 1762 are HIV-infected and 11 have silicosis. Of those with HIV infection, most were asymptomatic at their first visit. The clinic has achieved high acceptability: 99% of persons who were actively recruited to the service agreed to attend. The number still attending after a median of 13 months from recruitment was 1,270 (72%) and only 48 (2.7%) have declined continued attendance. Most losses were due to termination of employment unrelated to a medical condition. The clinic has already been successfully replicated in two other regions of the mining health service in South Africa and provides a model for workplace HIV clinical services that could be used for implementation of further interventions such as antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.

Adult↗

TB treatment: as simple as DOT?

Treatment completion continues to be an unmet challenge in tuberculosis (TB) control worldwide. Since the introduction of DOTS by the World Health Organization in 1993, directly observed therapy (DOT) has been promoted as the centerpiece of the strategy. The results of three randomized controlled studies designed to evaluate the effects of DOT on treatment completion, and carried out in South Africa, Thailand and Pakistan, showed conflicting results. It is doubtful that any of the studies provided valid measures of the effectiveness of DOT. Each study operationalized DOT in ways that did not match the study definition and failed to account for additional study interventions in their analyses. Given the evidence, there is no one factor that is 'the' answer to the challenge of TB treatment completion.

Directly Observed Therapy↗

HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy.

OBJECTIVE: To determine if HIV-1 RNA and CD4 lymphocyte thresholds for the initiation of highly active antiretroviral therapy (HAART) are associated with clinical response to therapy. DESIGN: Observational cohort study. SETTING: Johns Hopkins Hospital HIV Clinic. PATIENTS: HIV-infected adults. INTERVENTION: Patients initiating HAART (n = 530) were compared with concurrent patients who did not receive HAART (n = 484). MAIN OUTCOME MEASURE: Progression to a new AIDS-defining illness or death. RESULTS: The average duration of follow-up for the cohort was 22 months. HAART resulted in decreased disease progression among persons with fewer than, but not more than, 200 x 10(6) CD4 lymphocytes/l prior to treatment. Among persons receiving HAART, plasma HIV-1 RNA level prior to therapy was not associated with HIV disease progression within CD4 T-lymphocyte count strata. In a Cox multivariate proportional hazards model that adjusted for age, sex, race, prior opportunistic infection, and CD4 T lymphocytes, < or = 200 x 10(6) CD4 lymphocytes/l was the strongest predictor of disease progression. HIV-1 RNA level prior to starting HAART of < 5000 copies/ml, 5001-55 000 copies/ml, or > 55 000 copies/ml was not associated with disease progression on therapy, particularly among persons with > 200 x 10(6) CD4 lymphocytes/l. There was no sex difference in disease progression on treatment. CONCLUSIONS: Our data suggest that current guidelines for initiating HAART should place greater emphasis on CD4 lymphocyte than HIV-1 RNA level for both men and women. Further longitudinal follow-up will be needed to better ascertain whether HAART initiated at > 200 x 10(6) CD4 lymphocytes/l is effective in slowing disease progression.

Adolescent↗

Transmission of Mycobacterium tuberculosis through casual contact with an infectious case.

BACKGROUND: An ongoing restriction fragment length polymorphism study of Mycobacterium tuberculosis isolates from tuberculosis cases showed an identical 12-band IS6110 pattern unique to 3 unrelated patients (Patients A-C) diagnosed as having tuberculosis within a 9-month period. METHODS: In an attempt to identify epidemiologic links between the 3 patients, we performed site visits to the retail business work site of patient A and conducted detailed interviews with all 3 patients and their contacts. RESULTS: Patient B had visited patient A's work site 3 times during patient A's infectious period, spending no more than 15 minutes each time. Patient C visited patient A's work site on 6 to 10 occasions during this period for no more than 45 minutes at any one time. There were no other epidemiologic links between these 3 cases other than the contact at the store. Contact investigation identified 4 tuberculin skin test conversions among 8 (50%) of patient A's coworkers, 6 positive tests among 15 household contacts (40%), and 8 positive tests among 16 identified customers who were casual contacts (50%). Patient B and patient C were most likely infected by patient A during one of their brief visits to patient A's work site. CONCLUSIONS: These data demonstrate that some tuberculosis is spread through casual contact not normally pursued in traditional contact investigations and that, in certain situations, M tuberculosis can be transmitted despite minimal duration of exposure. In addition, this outbreak emphasizes the importance of DNA fingerprinting data for identifying unusual transmission in unexpected settings.

Adult↗

Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz.

OBJECTIVE: To compare the effectiveness of initial highly active antiretroviral therapy with either: a single protease inhibitor (PI); ritonavir (RTV)/saquinavir (SQV); or efavirenz (EFV) plus nucleoside reverse transcriptase inhibitors. DESIGN: Cohort study. SETTING: Urban HIV clinic. PATIENTS: Five-hundred and forty-five HIV-1-infected individuals with minimal antiretroviral exposure who started combination therapy with > or = 3 antiretroviral drugs and > or = 1 NRTI to which they had not previously been exposed (single PI, 416; RTV/SQV, 68; EFV, 61). MAIN OUTCOME MEASURES: HIV-1 RNA < 400 copies/ml within 8 months of starting therapy; time to HIV-1 RNA rebound to > 1000 copies/ml in the subset of patients achieving initial viral suppression; change in CD4 cell count from baseline within 12 months of starting therapy. RESULTS: By intent-to-treat analysis, initial viral suppression was achieved by 72% of patients in the EFV group, compared to 49% in the single PI group (P = 0.001) and 51% in the RTV/SQV group (P = 0.019). Among patients who achieved initial viral suppression, time to viral rebound was similar in the three groups. Durable viral suppression (> or = 3 consecutive HIV-1 RNA levels < 400 copies/ml for > 6 months) was achieved by 53% of patients in the EFV group, 26% in the single PI group, and 29% in the RTV/SQV group (P < 0.05 for both comparisons with EFV). The median CD4 cell count increase was 139 x 10(6) cells/l, and was similar in the three groups. CONCLUSIONS: In agreement with a recent clinical trial, use of initial EFV-based combination antiretroviral therapy was associated with higher rates of viral suppression than PI-based therapy in a clinical cohort.

Adult↗

Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses.

Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.

Case-Control Studies↗