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

Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients

BACKGROUND: Electronic monitoring (EM) is used increasingly to measure medication non-adherence. Unbiased EM assessment requires fulfillment of assumptions. The purpose of this study was to determine assumptions needed for internal and external validity of EM measurement. To test internal validity, we examined if (1) EM equipment functioned correctly, (2) if all EM bottle openings corresponded to actual drug intake, and (3) if EM did not influence a patient's normal adherence behavior. To assess external validity, we examined if there were indications that using EM affected the sample representativeness. METHODS: We used data from the Supporting Medication Adherence in Renal Transplantation (SMART) study, which included 250 adult renal transplant patients whose adherence to immunosuppressive drugs was measured during 3 months with the Medication Event Monitoring System (MEMS). Internal validity was determined by assessing the prevalence of nonfunctioning EM systems, the prevalence of patient-reported discrepancies between cap openings and actual intakes (using contemporaneous notes and interview at the end of the study), and by exploring whether adherence was initially uncharacteristically high and decreased over time (an indication of a possible EM intervention effect). Sample representativeness was examined by screening for differences between participants and non-participants or drop outs on non-adherence. RESULTS: Our analysis revealed that some assumptions were not fulfilled: 1) one cap malfunctioned (0.4%), 2) self-reported mismatches between bottle openings and actual drug intake occurred in 62% of the patients (n = 155), and 3) adherence decreased over the first 5 weeks of the monitoring, indicating that EM had a waning intervention effect. CONCLUSION: The validity assumptions presented in this article should be checked in future studies using EM as a measure of medication non-adherence

Addressing challenges in the production and analysis of illumina sequencing data

Advances in DNA sequencing technologies have made it possible to generate large amounts of sequence data very rapidly and at substantially lower cost than capillary sequencing. These new technologies have specific characteristics and limitations that require either consideration during project design, or which must be addressed during data analysis. Specialist skills, both at the laboratory and the computational stages of project design and analysis, are crucial to the generation of high quality data from these new platforms. The Illumina sequencers (including the Genome Analyzers I/II/IIe/IIx and the new HiScan and HiSeq) represent a widely used platform providing parallel readout of several hundred million immobilized sequences using fluorescent-dye reversible-terminator chemistry. Sequencing library quality, sample handling, instrument settings and sequencing chemistry have a strong impact on sequencing run quality. The presence of adapter chimeras and adapter sequences at the end of short-insert molecules, as well as increased error rates and short read lengths complicate many computational analyses. We discuss here some of the factors that influence the frequency and severity of these problems and provide solutions for circumventing these. Further, we present a set of general principles for good analysis practice that enable problems with sequencing runs to be identified and dealt with

Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis

The visceral leishmaniasis (VL) is a disease potentially fatal if not diagnosed and treated opportunely. This article presents the results of the study on the manifestations identified at the time of the clinical suspicion of the VL cases. This study was conducted in Belo Horizonte, the capital of the State of Minas Gerais, located in southeastern Brazil. This study is both timely and substantive because the Belo Horizonte is an area of transmission of VL, with one of the highest VL-death proportions of Brazil. The patients with higher risk of death had at least one of the following characteristics: ≥60 years, weakness, HIV co-infection, bleeding, jaundice and other associated infections. During the period 2002–2009, 8% to 22% of the patients with VL progressed to death in Belo Horizonte, whilst the proportion in the country was much lower and varied between 5% and 9%. This study has identified vulnerable patients who are at higher risk of death from VL and who would benefit from early predictive evaluation of the prognostic. Hence, the knowledge regarding the factors associated with death may contribute for clinical management and for reduction of deaths from VL

An evaluation of factors associated with taking and responding positive to the tuberculin skin test in individuals with HIV/AIDS

<p>Abstract</p> <p>Background</p> <p>The tuberculin skin test (TST) is still the standard test for detecting latent infection by <it>M tuberculosis </it>(LTBI). Given that the Brazilian Health Ministry recommends that the treatment of latent tuberculosis (LTBI) should be guided by the TST results, the present study sets out to describe the coverage of administering the TST in people living with HIV at two referral health centers in the city of Recife, where TST is offered to all patients. In addition, factors associated with the non-application of the test and with positive TST results were also analyzed.</p> <p>Methods</p> <p>A cross-sectional study was carried out with HIV patients, aged 18 years or over, attending outpatient clinics at the Correia Picanço Hospital/SES/PE and the Oswaldo Cruz/UPE University Hospital, who had been recommended to take the TST, in the period between November 2007 and February 2010. Univariate and multivariate logistic regression analyses were carried out to establish associations between the dependent variable - taking the TST (yes/no), at a first stage analysis, and the independent variables, followed by a second stage analysis considering a positive TST as the dependent variable. The odds ratio was calculated as the measure of association and the confidence interval (CI) at 95% as the measure of accuracy of the estimate.</p> <p>Results</p> <p>Of the 2,290 patients recruited, 1087 (47.5%) took the TST. Of the 1,087 patients who took the tuberculin skin test, the prevalence of TST ≥ 5 mm was 21.6% among patients with CD4 ≥ 200 and 9.49% among those with CD4 < 200 (p = 0.002). The patients most likely not to take the test were: men, people aged under 39 years, people with low educational levels and crack users. The risk for not taking the TST was statiscally different for health service. Patients who presented better immunity (CD4 ≥ 200) were more than two and a half times more likely to test positive that those with higher levels of immunodeficiency (CD4 < 200).</p> <p>Conclusions</p> <p>Considering that the TST is recommended by the Brazilian health authorities, coverage for taking the test was very low. The most serious implication of this is that LTBI treatment was not carried out for the unidentified TST-positive patients, who may consequently go on to develop TB and eventually die.</p

Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

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 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

Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumoniae carriage isolates among HIV-infected mineworkers in South Africa.

OBJECTIVES: To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa. METHODS: In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing. RESULTS: Among 856 participants (854 male, median age 41.5years, median CD4 290cells/mm(3)), 294 (34.3%) were receiving cotrimoxazole prophylaxis. Overall, 75/856 (8.8%) carried S. pneumoniae; among those taking vs. not taking cotrimoxazole, 8.2% vs. 9.1% were carriers. Risk factors for pneumococcal carriage were living with a child (adjusted OR 2.12, 95% CI 1.06-4.62) and recent hospitalisation (adjusted OR 1.80; 95% CI 0.98-3.30). Among participants not taking cotrimoxazole, the prevalence of carriage was higher in individuals with lower CD4 counts. Comparing participants taking cotrimoxazole vs. not, 60.9% vs. 22.4% (p=0.001) isolates were non-susceptible to cotrimoxazole and 30.4% vs. 8.2% were non-susceptible to penicillin (p=0.014). Thirty three/72 (45.8%) isolates were paediatric serotypes/groups. Nasopharyngeal compared with oropharyngeal swabs had higher sensitivity in detecting carriage (53/75, 70.7% vs. 31/75, 41.3%), and adding oropharyngeal sampling increased detection from 6.2% to 8.8%. CONCLUSIONS: Non-susceptibility to cotrimoxazole and penicillin was more common among isolates from participants taking cotrimoxazole prophylaxis. Surveillance for antimicrobial susceptibility is important where prophylaxis is used. Treatment for pneumococcal disease should take into account a higher risk of non-susceptibility to antibiotics amongst individuals taking cotrimoxazole prophylaxis