Contribution of reinfection to recurrent tuberculosis in South African gold miners.

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.

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.

Screening for tuberculosis prior to isoniazid preventive therapy among HIV-infected gold miners in South Africa.

SETTING: Human immunodeficiency virus (HIV) clinic for employees of a gold mine, Free State, South Africa. OBJECTIVE: To evaluate the process of screening for active tuberculosis (TB) prior to commencing TB preventive therapy in HIV-infected individuals. DESIGN: Cross-sectional study comparing performance of various combinations of screening tests for TB against a gold standard diagnosis of TB based on symptoms, chest radiograph (CXR), sputum microscopy and culture. RESULTS: Of 899 individuals, 44 (4.9%) had TB. The most sensitive symptom combination (59.1%) was any of night sweats, new or worsening cough or reported weight loss; measured weight loss > 5% or abnormal CXR increased sensitivity to 90.9%. Sputum microscopy did not increase sensitivity further, but including World Health Organization HIV clinical staging or CD4 count did. As the specificity of all these combinations was low, many individuals required further investigation to rule out TB. TB prevalence was high (11.7%) among individuals with a CD4 count < 200/mm3. CONCLUSION: CXR greatly increased the sensitivity of screening for TB in this population. Sputum microscopy conferred no additional benefit among asymptomatic patients with a normal CXR. The high prevalence of TB amongst those with a low CD4 count underlines the importance of screening for active TB prior to commencing TB preventive therapy, and before antiretroviral therapy.

Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the Environmental Exposure Unit (EEU).

The Environmental Exposure Unit, an indoor pollen challenge system to test anti-allergic medications, was used to compare the onset and duration of action and the efficacy of levocetirizine and desloratadine, two recently developed H1-antagonists. In this double-blind, placebo-controlled, parallel-group study, qualified subjects were randomised to once-daily levocetirizine 5 mg (n = 141), desloratadine 5 mg (n = 140) or placebo (n = 92) and exposed to ragweed pollen on two consecutive days (7 h and 6 h). Symptoms were self-rated every 30 min. On both days, levocetirizine produced a greater improvement in the major symptom complex score (primary efficacy variable) than desloratadine (p = 0.015); both were better than placebo (p < 0.001). Levocetirizine acted earlier (1 h vs. 3 h) and produced greater symptom relief at 24 h than desloratadine (p = 0.003). Levocetirizine also alleviated nasal obstruction better than desloratadine (p = 0.007) on day 1; and better than placebo (p = 0.014) after the second dose on day 2, which was not observed with desloratadine. Levocetirizine and desloratadine were safe and well tolerated.

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.

Attitudes to HIV voluntary counselling and testing among mineworkers in South Africa: will availability of antiretroviral therapy encourage testing?

We conducted a study to identify attitudes that influence uptake of HIV voluntary counselling and testing (VCT) amongst gold mine workers in South Africa; 105 healthy men were interviewed. The level of basic knowledge of HIV was high, but reported awareness of the extent of HIV infection in the workforce and perceived personal risk of HIV infection was low. Health issues were considered the most important indication for HIV testing and one-third had been tested. Fear of testing positive for HIV and the potential consequences, particularly stigmatization, disease and death, were the major identified barriers to VCT. Half of the participants felt workplace education programmes needed to be improved to promote VCT access. Twenty-six per cent became more favourably inclined towards HIV testing in response to information on improvements that have been made to the confidentiality and convenience of the company's VCT service. Only 14% then indicated that they would be more likely to access VCT if antiretroviral therapy became available. A vigorous community education programme is essential if the introduction of ART is to be effective in promoting uptake of VCT.

Use of UNAIDS tools to evaluate HIV voluntary counselling and testing services for mineworkers in South Africa.

HIV voluntary counselling and testing (VCT) is now an integral part of many HIV care and control programmes. However, very little work has been done to assess the quality of VCT services. An evaluation of VCT services for mineworkers in Welkom, South Africa was conducted to assess client and counsellor satisfaction, the quality of the services and to identify barriers to uptake of VCT. A cross-sectional survey was carried out using tools developed by UNAIDS, consisting of semi-structured interviews and observation of counselling sessions. Twenty-two nurse counsellors and six community volunteers were interviewed. Twenty-four counselling sessions were observed and 24 client exit interviews were conducted. Although nine of the 22 nurse counsellors had only in-service rather than formal training for HIV counselling whereas all community volunteers had been formally trained, nurse counsellors demonstrated better interpersonal skills than did community volunteers. Both clients and counsellors identified fear of a positive result as a major barrier to HIV testing. Clients also raised concerns about confidentiality. UNAIDS evaluation tools were a feasible and an acceptable method of assessing VCT in this operational setting. The study identified areas where training needs to be strengthened and suggested ways of improving the services, and changes to the service have now been implemented in line with these recommendations.

Subacute pulmonary granulomatous schistosomiasis: high resolution CT appearances--another cause of the halo sign.

A case of probable acute granulomatous pulmonary schistosomiasis is described with multiple focal opacities on chest radiography and widespread, but predominantly peribronchovascular, nodules with ground-glass halos on high resolution CT (HRCT). The HRCT appearances in early schistosomiasis have not been described previously. Although the features are not diagnostic and may be seen in other conditions, in the appropriate clinical context they may suggest pulmonary involvement in schistosomiasis. The features of pulmonary schistosomiasis in the different stages of infection are discussed. Pulmonary involvement should be suspected in patients with even minor respiratory symptoms when there is a history of exposure to fresh water in endemic areas.

Quality of life indices may be predictive of placebo and medication response to treatment for allergic rhinitis.

BACKGROUND: Quality of life (QOL) is known to be an important clinical endpoint in determining medication efficacy; however, the predictive value of QOL indices for response to medication or placebo has not been tested. OBJECTIVE: To determine whether a correlation between measures of QOL and response to medication/placebo exists in an evaluation of budesonide for allergic rhinitis. METHODS: Two hundred nine participants completed the 36-item short-form health QOL survey at screening for entry into a study examining the onset of action of budesonide in an allergen challenge system. During the treatment phase, symptom assessments were recorded hourly after dosing of double-blind medication. Participants were determined to be responders or nonresponders to study medication. A responder was defined as a participant who rated medication effectiveness as fair to excellent with regard to symptom relief, for three consecutive hourly assessments during the study day or one whose total symptom score decreased by > or =25% for three consecutive hourly assessments. Baseline QOL scores were compared between responders and nonresponders. RESULTS: Differences were noted among responders and nonresponders on the basis of whether budesonide or placebo was received. Ratings of general health perception, pain, physical function, and role limitation due to physical health were significantly lower among participants who responded to placebo, compared with placebo nonresponders. In addition, the overall physical health and 36-item short-form health survey averages were significantly lower. Differences between responders and nonresponders to budesonide did not reach statistical significance. CONCLUSIONS: Lower baseline QOL scores were associated with a clinically significant response to placebo in a trial of treatment for allergic rhinitis. QOL may be a factor in participant response to medication in clinical studies and, hence, a predictor of outcome.

Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with seasonal allergic rhinitis: confirmation of a test system.

BACKGROUND: The environmental exposure unit (EEU) is an instrument designed to determine onset of action of antiallergic treatment. Confirmation of test results would be useful in defining its role. OBJECTIVE: This study was intended to confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU using an identical protocol design (randomized, double-blind, parallel-group comparison having the same symptom scoring system, endpoints, and statistical analyses), thus demonstrating reproducibility of studies conducted in the EEU. METHODS: Onset of action and symptom relief with once-daily cetirizine 10 mg, loratadine 10 mg, and placebo (n = 120 each group) were evaluated replicating a previous study design. Subjects meeting inclusion and exclusion criteria and qualifying symptom scores were randomized to 2 days' exposure (6 to 7 hours daily) with treatment. Changes in total and major symptom complex (TSC, MSC) scores based on 14 symptoms evaluated at 30-minute intervals served as primary efficacy variables. RESULTS: Onset of action again was earlier with cetirizine (at 1 hour, P < or = 0.001) versus loratadine (at 3 hours, P < or = 0.01). Cetirizine produced a 25.4% least-square mean reduction in TSC scores overall versus an 11.2% decrease with loratadine (P = 0.006) and a 4.8% increase with placebo (P < 0.001); loratadine and placebo were also significantly different (P = 0.002). Similar changes were also noted in MSC scores. Cetirizine consistently reduced TSC and MSC scores after the first dose versus placebo (P < or = 0.001) and at most time points versus loratadine (P < or = 0.05). Adverse events were reported in 1.7% of patients in each active-treatment group and in 2.5% on placebo. CONCLUSIONS: Cetirizine acted earlier and was more effective than loratadine or placebo in reducing symptoms of seasonal allergic rhinitis in subjects undergoing a controlled pollen challenge, replicating results from an earlier, identically designed study, demonstrating reproducibility of these assessments by the EEU.

Hypersensitivity reactions following laminaria placement.

Laminaria tents are commonly placed intracervically prior to elective termination of pregnancy. Three women, each of whom had undergone at least one previous abortion in which a laminaria was utilized, developed hypersensitivity reactions following laminaria placement. The reactions included urticaria, angioedema and respiratory distress. All responded to removal of the laminaria and administration of either diphenhydramine, prednisone, inhaled bronchodilators or subcutaneous epinephrine. One of the women subsequently underwent skin testing and was positive to laminaria. Patients undergoing laminaria placement may manifest a Type I reaction, IgE-mediated sensitivity. Providers should counsel patients with histories of multiple previous laminaria insertions about this possibility, have alternative methods of cervical dilation available, and be able to promptly recognize and treat reactions when they occur.

Prevention and treatment of malaria in UK travellers.

With around 2500 new cases of malaria being reported each year and more than a million UK residents visiting malaria endemic countries, there has never been a greater need for effective prevention and treatment. The latest information on malaria management is outlined below.

Onset of action of intranasal budesonide (Rhinocort aqua) in seasonal allergic rhinitis studied in a controlled exposure model.

BACKGROUND: Intranasal budesonide aqueous nasal spray (BANS) is recognized as an efficacious treatment for seasonal allergic rhinitis (SAR), but the time to onset of action is not known. OBJECTIVE: The primary objective was to evaluate the time at which the onset of action of BANS in the symptomatic relief of seasonal allergic rhinitis becomes evident within 12 hours after a single dose in a controlled ragweed pollen exposure setting. METHODS: The study was of a double-blind, randomized, parallel-group design, testing BANS (64 microgram and 256 microgram) and placebo on ragweed-sensitive subjects with symptoms for at least 1 year by using a controlled pollen challenge system (Environmental Exposure Unit). The efficacy variables were the combined nasal score (the sum of blocked nose, runny nose, and sneezing-itchy nose), individual nasal symptoms, overall evaluation of treatment efficacy reported by participants on diaries, and peak nasal inspiratory flow (PNIF). RESULTS: A total of 217 participants were treated with BANS or placebo. At 7 to 12 hours, BANS was better than placebo in reducing combined nasal and blocked nose symptoms. For PNIF, the time to onset of action was shortest for 256 microgram of BANS relative to placebo (3 hours, P =.003). BANS 64 microgram was better than placebo in reducing the individual scores of blocked nose, runny nose, and sneezing-itchy nose from 3 to 5 hours after administration. Treatment efficacy was higher for those receiving BANS compared with placebo starting at 5 hours. All treatments were well tolerated, and no specific adverse events occurred. CONCLUSIONS: The onset of action of intranasal BANS was 7 hours according to combined nasal and blocked nose symptom scores. Evidence of earlier response was observed at 3 hours for runny nose and PNIF.

Environmental exposure unit: a system to test anti-allergic treatment.

LEARNING OBJECTIVES: Reading this article will enable readers to recognize the Environmental Exposure Unit (EEU), its historic development and its current role as a system to test anti-allergic treatment; to recognize clinical relevance of this test system and its relationship with other pollen challenge methods of evaluation of anti-allergic medication; and, to recognize variables associated with standard clinical studies of anti-allergic medication. Readers will review four studies of antihistamines tested in the Environmental Exposure Unit, three studies on nasal corticosteroids, one on topical eye drops and one on immunotherapy conducted in the EEU. DATA SOURCES: The EEU has been in operation since 1985 preceded by a prototype challenge system to assess respiratory effects of urea formaldehyde foam insulation. A number of studies on the onset of action and efficacy of different antihistamines and nasal corticosteroids as well as other treatments have been completed producing accurate and consistent results influenced to some extent by study designs. STUDY SELECTION: Studies of commonly used antihistamines and nasal corticosteroids are discussed in detail and represent several of the studies undertaken to date in the EEU. RESULTS: Controlled ragweed pollen exposure using the EEU has shown that some antihistamines demonstrate an onset of action within 30 minutes while others have taken up to 3 hours to produce significant effect. Nasal corticosteroids evidenced the onset of clinical improvement at 5 to 6 hours with significance over placebo between 6 and 12 hours depending on dose. CONCLUSION: The EEU is an effective pollen delivery system that accurately and consistently determines the onset of action and efficacy of anti-allergic treatment in large groups of subjects. It eliminates variables associated with various other methods of evaluation of these medications but does not supplant the need for such evaluations.

Impact on quality of life during an allergen challenge research trial.

BACKGROUND: Quality of life (QOL) issues resulting from participation in an allergy research trial, or indeed any clinical trial, is not documented in the medical literature. OBJECTIVE: To determine whether participating in a trial where allergic symptoms are induced has a significant impact on subjects' QOL, and to quantify extent and duration. METHODS: Subjects were recruited from a trial utilizing a controlled allergen environment to assess anti-allergic medications. A QOL survey (consisting of the Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ] & the SF-36) was completed at screening, on study day, and approximately 2 weeks post-study. Follow-up was sought from subjects' whose QOL was significantly worse than baseline. RESULTS: Of 219 trial participants, 206 completed both screening and study surveys; 141 returned at least one follow-up survey; and 136 constructed the final dataset. Mean overall scores at follow-up via RQLQ were significantly better than screening (P < .001). Significant decreases in QOL from baseline on study day occurred in social function on the SF-36 (P = .026) and in domains of sleep (P = .019), non-nasal symptoms (P = .05), ocular symptoms (P < .001), and nasal symptoms (P < .001) on the RQLQ. Average post-study follow-up was 17.1 days (range = 5 to 55 days). CONCLUSION: Subjects participating in a trial involving allergic symptom induction experienced a decrease of QOL in parameters specific to rhinoconjunctivitis and social function. Subjects' QOL returned to or improved over baseline within 2 1/2 weeks. Positive QOL findings are important to studies where symptoms are induced and also have relevance to standard Phase 3 drug trials.

A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed?

The precise amount of epinephrine needed to reverse severe symptomatology due to an anaphylactic reaction is unknown. We tried to determine how frequently more than one injection of epinephrine is required to treat an anaphylactic reaction. A retrospective review of patient charts with anaphylactic reactions requiring epinephrine, in response to inhalant allergen and hymenoptera venom immunotherapy as well as live hymenoptera stings, examined type of reaction; number, doses, and timing of epinephrine administered; and ancillary treatment. A total of 105 anaphylactic reaction events of varying severity (Ring's classification) were recorded (54--Grade I, 29--Grade II, 18--Grade III, 0--Grade IV, 4--unknown). The median epinephrine dose administered was 0.3 cc (range 0.1 to 0.8 cc, 1:1000). The timing of the first epinephrine injection was < or = 5 minutes in 27, 6-10 minutes in 13, 11-30 minutes in 16, < or = 30 minutes in 32, 31-60 minutes in 12, and > 60 minutes in five epinephrine treated patients. Overall, 38 patients (35.5%; CI95, 26.4-44.6%) required > 1 epinephrine injection. Of these, 11 experienced Grade I (11/54-20.3%; CI95, 9.6-31.0%), 12--Grade II (12/29-41.5%, CI95, 23.5-59.3%), and 13--Grade III (13/18-72.2%, CI95, 51.5-92.9%); reactivity was unknown in 2 patients. Forty-four patients also received an antihistamine, 10 received corticosteroids, and 30 received both medications and/or other ancillary therapy. A significant number of patients (> 35%) with anaphylactic reactions received greater than one epinephrine dose to manage events for the three classes of severity. Patients at risk for anaphylaxis and their caregivers need to recognize that more than one dose of epinephrine may be required for treatment of anaphylaxis.

Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit.

BACKGROUND: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer once-daily selective H1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: To better characterize the efficacy and onset of action of cetirizine in a more controlled but clinically relevant setting, this agent was compared with loratadine and placebo in patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an environmental exposure unit (EEU). METHODS: This was a double-blind, randomized, parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six exposures), and those with qualifying symptom scores were randomized to controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg cetirizine (n = 67), 10 mg loratadine (n = 67), or placebo (n = 68). The mean ragweed pollen level was 3480 +/- 350 grains/m3 (standard deviation). The primary efficacy variables were the total symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated every half hour in the EEU throughout the study. RESULTS: Cetirizine produced a 36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo (p < or = 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7% with loratadine and 6.7% with placebo (p < or = 0.01). Onset of action as assessed by reductions in TSC and MSC scores versus placebo was evident within 1 hour with cetirizine (p < or = 0.02) and 3 hours with loratadine (p < or = 0.03). The incidence of treatment-related side effects was similar among groups, with headache reported most commonly in each group. CONCLUSION: Cetirizine is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing controlled pollen challenge.

A comparison of triamcinolone acetonide nasal aerosol spray and fluticasone propionate aqueous solution spray in the treatment of spring allergic rhinitis.

BACKGROUND: Many nasal corticosteroids with different potencies and formulations are available, but they have all been proven safe and effective. The clinical relevance, if any, of these differences is not yet completely established. OBJECTIVE: We sought to compare the efficacy, safety, and patients' acceptance of triamcinolone acetonide aerosol spray and fluticasone propionate aqueous solution in the treatment of spring allergic rhinitis. METHODS: After a drug-free baseline evaluation, patients with rhinitis were randomized to receive either a triamcinolone aerosol spray of 110 microg in each nostril once daily (n = 117) or a fluticasone solution spray of 100 microg in each nostril once daily (n = 116) in a single-blind, parallel-group study. The Rhinitis Index Score (sum of scores of symptoms on a scale from 0 to 3) was evaluated daily, in the morning before drug administration, for 21 days. The efficacy of each treatment was assessed by the mean reduction from baseline in the Rhinitis Index Score and in individual symptom scores. Patients' acceptance of the study drugs was also monitored by a daily questionnaire. RESULTS: Reductions of the Rhinitis Index Score (mean +/- SEM) were 4.20 +/- 0.21 and 4.60 +/- 0.21 for triamcinolone and fluticasone, respectively (p = 0.23). There were no statistically significant differences between the drugs in the reduction of any of the individual symptoms. Patients expressed statistically significant differences between the drugs regarding acceptance; different properties of the aerosol and the solution were appreciated differently. CONCLUSIONS: This study shows that triamcinolone acetonide aerosol and fluticasone propionate solution sprays are both clinically equally effective, safe, and well tolerated for the treatment of spring pollen allergic rhinitis.