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Optimizing the Protection of Research Participants and Personnel in HIV-Related Research Where TB Is Prevalent

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Abstract

Tuberculosis (TB) is a leading cause of death among persons with HIV globally. HIV-related research in TB endemic areas raises some unique and important ethical issues in infection control related to protecting both research participants and personnel. To address such concerns, this article provides practical guidance to help research teams develop strategies to prevent TB transmission in studies involving persons with HIV in TB endemic settings.

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... 22 The use of N95 respirators with annual fit testing is effective in preventing nosocomial infections. 30 Fit testing for respirators is critical to ensure adequate respiratory protection for HCWs 26 31 and can help staff correctly use respirators and protect the wearer from inhalation hazards. 32 However, most of the respirators sold in China are designed according to specifications set by a panel of the US Los Alamos National Laboratory, which are based on facial features more typical of adults in Western countries. ...
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Objectives Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Design Cross-sectional survey using observation and interviews. Setting All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Primary and secondary outcome measures Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. Results The TB-designated hospitals treated a median of 3030 outpatients (IQR 764–7094) and 279 patients with confirmed TB (IQR 154–459) annually, and 160 patients with TB (IQR 79–426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. Conclusions TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission rates of patients with TB.
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In many settings, the dedication of healthcare workers (HCWs) to the treatment of tuberculosis exposes them to serious risks. Current ethical considerations related to tuberculosis prevention in HCWs involve the threat posed by comorbidities, issues of power and space, the implications of intersectoral collaborations, (de)professionalization, just remuneration, the duty to care, and involvement in research. Emerging ethical considerations include mandatory vaccination and the use of geolocalization services and information technologies. The following exploration of these various ethical considerations demonstrates that the language of ethics can fruitfully be deployed to shed new light on policies that have repercussions on the lives of HCWs in underresourced settings. The language of ethics can help responsible parties get a clearer sense of what they owe HCWs, particularly when these individuals are poorly compensated, and it shows that it is essential that HCWs' contribution be acknowledged through a shared commitment to alleviate ethically problematic aspects of the environments within which they provide care. For this reason, there is a strong case for the community of bioethicists to continue to take greater interest both in the micro-level (eg, patient-provider interactions) and macro-level (eg, injustices that occur as a result of the world order) issues that put HCWs working in areas with high tuberculosis prevalence in ethically untenable positions. Ultimately, appropriate responses to the various ethical considerations explored here must vary based on the setting, but, as this article shows, they require thoughtful reflection and courageous action on the part of governments, policy makers, and managers responsible for national responses to the tuberculosis epidemic. © 2016 The Author. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
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In sub Saharan Africa, the cocktail of many advanced HIV-infected susceptible hosts, poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing (DST) have resulted in HIV-infected individuals being disproportionately represented in Multi drug resistant Tuberculosis (MDR-TB) cases. The prevailing application of the WHO re-treatment protocol indiscriminately to all re-treatment cases sets the stage for an increase in mortality and MDR-TB nosocomial transmission. A comprehensive search was performed of the Cochrane Infectious Diseases Group Specialized Register and Medline database including the bibliographies of the retrieved reference. The TB diagnosis paradigm which for decades relied on smear sputum and culture is likely to change with the advent of the point-of-care diagnostic, Xpert MTB/RIF assay. Until the new DST infrastructure is available, along with clinical trials for both, current and new approaches to retreatment TB in areas heavily affected by HIV and TB, there are cost effective administrative, environmental, and protective measures that may be immediately instituted. The severe lack of infection control practices in sub Saharan Africa may jeopardise the recent strides in MDR-TB management. Cost effective infection control measures must be immediately implemented, otherwise the development of further drug resistance may offset recent strides in MDR-TB management. Indiscriminate use of the WHO standardized retreatment protocol can lead to nosocomial transmission of MDR-TB by: -Precluding early diagnosis and prompt separation of patients who experienced treatment failure category and thereby more likely to have MDR-TB. -Leaving patients from the treatment failure category in health establishments on ineffective standard retreatment regimen until the DST results are known. -targeting only patients who have had prior TB therapy, new severely debilitated TB patients having primary unrecognized MDR-TB may continue spreading resistant organisms.
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Background: Several interventions for tuberculosis (TB) control have been recommended by the World Health Organization (WHO) over the past decade. These include isoniazid preventive therapy (IPT) for HIV-infected individuals and household contacts of infectious TB patients, diagnostic algorithms for rule-in or rule-out of smear-negative pulmonary TB, and programmatic treatment for multidrug-resistant TB. There is no systematically collected data on the type of evidence that is publicly available to guide the scale-up of these interventions in low- and middle-income countries. We investigated the availability of published evidence on their effectiveness, delivery, and cost-effectiveness that policy makers need for scaling-up these interventions at country level. Methods and findings: PubMed, Web of Science, EMBASE, and several regional databases were searched for studies published from 1 January 1990 through 31 March 2012 that assessed health outcomes, delivery aspects, or cost-effectiveness for any of these interventions in low- or middle-income countries. Selected studies were evaluated for their objective(s), design, geographical and institutional setting, and generalizability. Studies reporting health outcomes were categorized as primarily addressing efficacy or effectiveness of the intervention. These criteria were used to draw landscapes of published research. We identified 59 studies on IPT in HIV infection, 14 on IPT in household contacts, 44 on rule-in diagnosis, 19 on rule-out diagnosis, and 72 on second-line treatment. Comparative effectiveness studies were relatively few (n = 9) and limited to South America and sub-Saharan Africa for IPT in HIV-infection, absent for IPT in household contacts, and rare for second-line treatment (n = 3). Evaluations of diagnostic and screening algorithms were more frequent (n = 19) but geographically clustered and mainly of non-comparative design. Fifty-four studies evaluated ways of delivering these interventions, and nine addressed their cost-effectiveness. Conclusions: There are substantial gaps in published evidence for scale-up for five WHO-recommended TB interventions settings at country level, which for many countries possibly precludes program-wide implementation of these interventions. There is a strong need for rigorous operational research studies to be carried out in programmatic settings to inform on best use of existing and new interventions in TB control.
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Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. We sought to quantify the efficacy of surgical face masks when worn by patients with multidrug-resistant TB (MDR-TB). Over 3 months, 17 patients with pulmonary MDR-TB occupied an MDR-TB ward in South Africa and wore face masks on alternate days. Ward air was exhausted to two identical chambers, each housing 90 pathogen-free guinea pigs that breathed ward air either when patients wore surgical face masks (intervention group) or when patients did not wear masks (control group). Efficacy was based on differences in guinea pig infections in each chamber. Sixty-nine of 90 control guinea pigs (76.6%; 95% confidence interval [CI], 68-85%) became infected, compared with 36 of 90 intervention guinea pigs (40%; 95% CI, 31-51%), representing a 56% (95% CI, 33-70.5%) decreased risk of TB transmission when patients used masks. Surgical face masks on patients with MDR-TB significantly reduced transmission and offer an adjunct measure for reducing TB transmission from infectious patients.
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Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa. Room ventilation was assessed (CO₂ gas tracer technique) in 4 rooms where roof turbines and air-intake grates were installed, across three scenarios: turbine, grate and window closed, only window open, and only turbine and grate open, with concurrent wind speed measurement. 332 measurements were conducted over 24 months. For all 4 rooms combined, median air changes per hour (ACH) increased with wind speed quartiles across all scenarios. Higher median ACH were recorded with open roof turbines and grates, compared to open windows across all wind speed quartiles. Ventilation with open turbine and grate exceeded WHO-recommended levels (60 Litres/second/patient) for 95% or more of measurements in 3 of the 4 rooms; 47% in the remaining room, where wind speeds were lower and a smaller diameter turbine was installed. High room ventilation rates, meeting recommended thresholds, may be achieved using wind-driven roof turbines and grates, even at low wind speeds. Roof turbines and air-intake grates are not easily closed by staff, allowing continued ventilation through colder periods. This simple, low-cost technology represents an important addition to our tools for TB infection control.
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The importance of infection control (IC) in health care settings with tuberculosis (TB) patients has been highlighted by recent health care-associated outbreaks in South Africa. To conduct operational evaluations of IC in drug-resistant TB settings at a national level. A cross-sectional descriptive study was conducted from June to September 2009 in all multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) facilities in South Africa. Structured interviews with key informants were completed, along with observation of IC practices. Health care workers (HCWs) were asked to complete an anonymous knowledge, attitudes and practices (KAP) questionnaire. Multilevel modeling was used to take into consideration the relationship between center and HCW level variables. Twenty-four M(X)DR-TB facilities (100%) were enrolled. Facility infrastructure and staff adherence to IC recommendations were highly varied between facilities. Key informant interviews were incongruent with direct observation of practices in all settings. A total of 499 HCWs were enrolled in the KAP evaluation. Higher level of clinical training was associated with greater IC knowledge (P < 0.001), more appropriate attitudes (P < 0.001) and less time spent with coughing patients (P < 0.001). IC practices were poor across all disciplines. These findings demonstrate a clear need to improve and standardize IC infrastructure in drug-resistant TB settings in South Africa.
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Antiretroviral therapy (ART) has been remarkably effective in ameliorating Human Immunodeficiency Virus (HIV)-associated morbidity and mortality. The rapid decline in viral load during ART also presents an opportunity to develop a "treatment as prevention" strategy in order to reduce HIV transmission at a population level. Modelling exercises have demonstrated that for this strategy to be effective, early initiation of ART with high coverage of the HIV-infected population will be required. The HIV epidemic has fueled a resurgence of tuberculosis (TB) particularly in sub- Saharan Africa and widespread early initiation of ART could also impact this epidemic via several mechanisms. The proportion of patients with low CD4 cell counts who are at high risk of TB disease from progression of both latent and new TB infection would be greatly reduced. Entry into a life-long ART program provides an ongoing opportunity for intensified TB case finding among the HIV-infected population. Regular screening for HIV infection also presents an opportunity for intensified TB case finding in the general population. The combined effect of reduced progression of infection to disease and intensified case finding could reduce the overall prevalence of infectious TB, thereby further decreasing TB transmission. In addition, decreasing prevalence of HIV infection would reduce the TB-susceptible pool within the population. The 'test and treat' strategy therefore has potential to reduce the TB risk at both an individual and a population level. In this paper we explore the expected "TB dividend" of wider access to ART and also explore the potential of the "test and treat" strategy to impact on TB transmission, particularly in the heavily burdened setting of sub- Saharan Africa.
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Introduction: The risk of tuberculosis (TB) in healthcare workers (HCWs) is related to its incidence in the general population, and increased by the specific risk as a professional group. The prevalence of latent tuberculosis infection (LTBI) in HCWs in Portugal using the tuberculin skin test (TST) and the interferon-γ release assays (IGRA) was analyzed over a five-year period. Methods: A screening programme for LTBI in HCWs was conducted, with clinical evaluations, TST, IGRA, and chest radiography. Putative risk factors for LTBI were assessed by a standardised questionnaire. Results: Between September 2005 and June 2009, 5,414 HCWs were screened. The prevalence of LTBI was 55.2% and 25.9% using a TST ≥ 10 mm or an IGRA test result (QuantiFERON-TB Gold In-Tube) INF-γ ≥0.35 IU/mL as a criterion for LTBI, respectively. In 53 HCWs active TB was diagnosed. The number of HCWs with newly detected active TB decreased from 19 in the first year to 6 in 2008. Risk assessment was poorly related to TST diameter. However, physicians (1.7%) and nurses (1.0%) had the highest rates of active TB. Conclusions: LTBI and TB burden among HCWs in Portugal is high. The screening of these professionals to identify HCWs with LTBI is essential in order to offer preventive chemotherapy to those with a high risk of future progression to disease. Systematic screening had a positive impact on the rate of active TB in HCWs either by early case detection or by increasing the awareness of HCWs and therefore the precautions taken by them.
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Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform.
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Unrecognized transmission is a major contributor to ongoing TB epidemics in high-burden, resource-constrained settings. Limitations in diagnosis, treatment, and infection control in health-care and community settings allow for continued transmission of drug-sensitive and drug-resistant TB, particularly in regions of high HIV prevalence. Health-care facilities are common sites of TB transmission. Improved implementation of infection control practices appropriate for the local setting and in combination, has been associated with reduced transmission. Community settings account for the majority of TB transmission and deserve increased focus. Strengthening and intensifying existing high-yield strategies, including household contact tracing, can reduce onward TB transmission. Recent studies documenting high transmission risk community sites and strategies for community-based intensive case finding hold promise for feasible, effective transmission reduction. Infection control in community settings has been neglected and requires urgent attention. Developing and implementing improved strategies for decreasing transmission to children, within prisons and of drug-resistant TB are needed.
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This issue contains nine papers on the subject of upper-room ultraviolet germicidal irradiation (UVGI) for control of hazards to health from airborne bio-aerosols. These contributions originated from a two-day "Symposium on Upper Room UVGI - Toward International Application Guidelines" held in December, 2011 at the Harvard School of Public Health, the conclusion of a year-long, interdisciplinary research and training program on this issue, sponsored by Fogarty International. Not all of the presentations at that symposium resulted in papers, and the purpose of this instruction and overview is to put the presentations into a broader context, with comments on areas discussed, but not captured in the papers. This article is protected by copyright. All rights reserved.
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According to a growing consensus among biomedical researchers, community engagement can improve the ethics and outcomes of clinical trials. Although successful efforts to develop community engagement practices in HIV/AIDS research have been reported, little attention has been given to engagement with the community in tuberculosis research. This article aims to draw attention to some existing community engagement initiatives in tuberculosis research and to resources that might help tuberculosis researchers to establish and implement community engagement programmes for their trials. One of these resources-the good participatory practice guidelines for tuberculosis drug trials-offers a conceptual framework and practical guidance for community engagement in tuberculosis research. To build momentum and to improve community engagement, lessons need to be shared, and formal assessment strategies for community engagement initiatives need to be developed. To build successfully on the promising activities described in this personal view, research funders and sponsors should show leadership in allocation of resources for the implementation and assessment of community engagement programmes in tuberculosis trials.
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Background: Effective infection control measures are essential to reduce tuberculosis (TB) transmission in domestic, workplace, and health care settings. Acceptability of infection control measures is key to patient adherence. Methods: We used a prospective questionnaire study to determine knowledge and acceptability of potential patient-specific TB infection control measures in a rural South African community. Fifty adult TB suspects were interviewed at investigation, and 50 newly diagnosed TB patients were interviewed at the start and at the end of TB treatment. Results: TB patients and TB suspects had similar knowledge of infection control measures at baseline. Fifty-seven percent of all participants reported knowing the cause of TB, but only 25% correctly identified microbial etiology. Basic cough hygiene was accepted by 98% of participants. Most participants (89%) accepted wearing of face masks in health facilities, but only 42% of TB suspects and 66% of TB patients (P = .016) would accept wearing face masks at home. Only 68% of participants accepted separate cohorting in health facilities and avoidance of co-sleeping with uninfected household members. At the end of treatment, TB patients demonstrated increased knowledge of TB and increased acceptability of certain household infection control measures. Conclusion: Acceptability of patient-specific infection control measures within households increases with acquired knowledge of TB. National control programs should maximize early TB education to improve adherence to infection control measures.
Article
This study investigated the disinfection efficacy of the upper-room ultraviolet germicidal irradiation (UR-UVGI) system with ceiling fans. The investigation used the steady-state Computational Fluid Dynamics (CFD) simulations to solve the rotation of ceiling fan with a rotating reference frame. Two ambient air exchange rates, 2 ACH and 6 ACH (air changes per hour), and four downward fan rotational speeds, 0 rpm, 80 rpm, 150 rpm, and 235 rpm were considered. Additionally, the passive scalar concentration simulations incorporated ultraviolet (UV) dose by two methods: one based on the total exposure time and average UV fluence rate, and another based on SVE3* (New Scale for Ventilation Efficiency 3), originally defined to evaluate the mean age of the air from an air supply opening. Overall, the CFD results enabled the evaluation of UR-UVGI disinfection efficacy using different indices, including the fraction of remaining microorganisms, equivalent air exchange rate, UR-UVGI effectiveness, and tuberculosis infection probability by the Wells-Riley equation. The results indicated that air exchange rate was the decisive factor for determining UR-UVGI performance in disinfecting indoor air. Using a ceiling fan could also improve the performance in general. Furthermore, the results clarified the mechanism for the ceiling fan to influence UR-UVGI disinfection efficacy. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.
Article
Objectives: Given the imperative to scale up integrated tuberculosis (TB) and HIV services in settings where both are of major public health importance, we aimed to synthesise knowledge concerning implementation of TB/HIV service integration. Methods: Systematic review of studies describing a strategy to facilitate TB and HIV service integration, searching 15 bibliographic databases including Medline, Embase and the Cochrane library; and relevant conference abstracts. Results: Sixty-three of 1936 peer-reviewed articles and 70 of 170 abstracts met our inclusion criteria. We identified five models: entry via TB service, with referral for HIV testing and care; entry via TB service, on-site HIV testing, and referral for HIV care; entry via HIV service with referral for TB screening and treatment; entry via HIV service, on-site TB screening, and referral for TB diagnosis and treatment; and TB and HIV services provided at a single facility. Referral-based models are most easily implemented, but referral failure is a key risk. Closer integration requires more staff training and additional infrastructure (e.g. private space for HIV counselling; integrated records). Infection control is a major concern. More integrated models hold potential efficiencies from both provider and user perspective. Most papers report 'outcomes' (e.g. proportion of TB patients tested for HIV); few report downstream 'impacts' such as outcomes of TB treatment or antiretroviral therapy. Very few studies address the perspectives of service users or staff, or costs or cost-effectiveness. Conclusions: While scaling up integrated services, robust comparisons of the impacts of different models are needed using standardised outcome measures.
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Five in-patient and out-patient tuberculosis (TB) care facilities in two regions of Russia. To identify barriers and motivators to the use of infection control measures among Russian TB health care workers. In this qualitative study, a convenience sample of 96 health care workers (HCWs) was used to generate 15 homogeneous focus groups, consisting of physicians, nurses, and laboratory or support staff. Barriers and motivators related to knowledge, attitudes and beliefs, and practices were identified. The three main barriers were 1) knowledge deficits, including the belief that TB was transmitted by dust, linens and eating utensils; 2) negative attitudes related to the discomfort of respirators; and 3) practices with respect to quality and care of respirators. Education and training, fear of infecting loved ones, and fear of punishment were the main motivators. Our results point to the need for evaluation of current educational programs. Positive health promotion messages that appeal to fear might also be successful in promoting TB infection control. Individualized rewards based on personal motivators or group rewards that build on collectivist theory could be explored.
Article
Initiation of antiretroviral therapy (ART) and the 3I's are strategies to prevent HIV-associated tuberculosis (TB). We describe factors associated with undiagnosed TB among HIV-infected patients attending an HIV clinic in South Africa and discuss implications for the 3 Is. Convenience sample of HIV clinic attendees. HIV-infected participants were assessed for TB using a symptom screen, sputum-smear microscopy, sputum and blood mycobacterial culture, fine needle aspiration of enlarged lymph nodes, and chest radiography. Four hundred twenty-two participants were enrolled. The median age and CD4+ T-cell count were 37 years [interquartile range (IQR): 31-44 years] and 215 cells per microliter (IQR: 107-347 cells/μL). Forty-seven percent had been on ART for a median duration of 8 months (IQR: 3.3-22.8 months). Three hundred sixty-one participants (85.6%) reported TB symptoms. Twenty-seven participants (6.4%) met criteria for bacteriologically confirmed TB and 50 (11.6%) for any form of TB. Bacteriologically confirmed TB was associated with CD4+ T-cell counts ≤100 cells per microliter (odds ratio: 5.05, 95% confidence interval: 1.69 to 15.12) when compared with CD4+ T-cell counts >200 cells per microliter and hemoglobin {hemoglobin < 10 g/dL [odds ratio 3.12 (95% confidence interval: 1.26 to 7.72)]}. Undiagnosed TB among HIV-infected ambulatory patients was associated with low CD4+ T-cell counts regardless of ART status. TB screening algorithms which include CD4+ T-cell count and hemoglobin testing may be an effective way to identify HIV-infected clinic attendees at highest risk of undiagnosed TB. Isoniazid preventive therapy and TB infection control are essential for reducing occurrence of HIV-associated TB even after ART initiation.
Article
Tuberculosis causes >1.7 million deaths worldwide each year and is frequently transmitted in hospitals. Outbreaks of multidrug-resistant tuberculosis have led to illness and death among health care workers (HCWs) in many countries. Some countries, such as the United States, implemented occupational health policies that substantially reduced tuberculosis rates among HCWs. Inadequate tuberculosis infection control in China may contribute to its high burden of tuberculosis and multidrug-resistant tuberculosis, which are both the second highest worldwide. Occupational health policies in China for tuberculosis control can be strengthened.We reviewed the development and content of tuberculosis infection control policies in the United States and China. Sources included published academic literature, Chinese Ministry of Health policies, US government agency reports, legal databases, personal observations of hospitals, review of internet discussion sites, and discussions with HCWs and health care and law experts.In the United States, slow acceptance of the tuberculosis problem in HCWs resulted in decades of inaction. Tuberculosis infection control policies, based mostly on expert opinion, were implemented only after tuberculosis resurged in the 1980s. Effective evidence-based policies were developed only after multiple cycles of policy implementation, evaluation and revision. These policies have now substantially reduced occupational tuberculosis. In China, tuberculosis has not been formally recognized as an occupational disease, and data regarding the burden in HCWs are sparse. Vagueness of current labour laws and suboptimal alignment of infection control authority and expertise result in varied and sometimes absent protection of HCWs against tuberculosis. Formal evaluations of occupational tuberculosis policies have not been reported.By collecting data on its current HCW tuberculosis burden and infection control practices, refining policies, continually evaluating its policies based on accumulated evidence and rapidly identifying unsuspected tuberculosis cases, China can develop a more comprehensive strategy to ensure the health of HCWs and reduce transmission of tuberculosis and multidrug-resistant tuberculosis.
Article
The global burden of tuberculosis (TB) demands that research be undertaken. The vulnerability of the populations most at risk for TB demands that such research be subject to ethical review to protect their rights and interests. In this brief article we cannot review the vast and important literature bearing on the ethics of clinical and epidemiological research and public health surveillance. Instead, we have focused on three questions that have been at the center of discussion and debate and which have special relevance for TB. First, we examine a question that has special bearing when wealthy nations or international organizations carry out research in poor countries: what does justice require in the post trial period? Second, we examine the question of how the principles of consent and confidentiality may require modification in record-based epidemiological research. Third, we look at the challenges posed by public health surveillance, which in many cases requires case reporting by clinicians to public health agencies. By way of conclusion, we take note of the centrality of enhancing the institutional capacities for ethical review of research in poor nations.
Article
Antiretroviral therapy (ART) has the potential to prevent human immunodeficiency virus (HIV) transmission by reducing the concentration of HIV in blood and genital secretions. Indeed, mathematical models with favorable assumptions suggest the potential of ART to stop the spread of HIV infection. Empirical results from ecological and population-based studies and from several short-term observational studies involving HIV status-discordant heterosexual couples suggest that ART reduces the rate of HIV transmission. A multinational, randomized, controlled trial (National Institutes of Health HPTN052) examining the reliability and durability of ART as prevention of transmission in HIV status-discordant couples is under way. The latter and other studies also consider sexual risk-taking behavior and transmission of HIV-resistant variants when ART is used as prevention. Early HIV detection and treatment (ie, test and treat) are being considered as an important prevention strategy. In this article, we review the data supporting the use of ART to prevent HIV transmission and critically examine the public health implications of this strategy.
Article
The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa. Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk. Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR)=6.2/100 person-years; 95% CI 5.5-7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2-8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4-6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4-7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02-7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR)=0.36; 95% CI 0.25-0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR=0.11; 95% CI 0.02-0.78). Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.
Article
An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. During 1985--1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was accompanied by a rise in multidrug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin. In addition, virtually untreatable strains of M. tuberculosis are emerging globally. Extensively drug-resistant (XDR) TB is defined as MDR TB that also is resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (amikacin, kanamycin, or capreomycin). XDR TB has been identified in all regions of the world, including the United States. In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era. In January 1992, CDC convened a Federal TB Task Force to draft an action plan to improve prevention and control of drug-resistant TB in the United States (CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992;41([No. RR-11]). In November 2006, CDC reconvened the Task Force to draft an updated action plan to address the issue of MDR TB and XDR TB. Task Force members were divided into nine response areas and charged with articulating the most pressing problems, identifying barriers to improvement, and recommending specific action steps to improve prevention and control of XDR TB within their respective areas. Although the first priority of the Federal TB Task Force convened in 2006 was to delineate objectives and action steps to address MDR TB and XDR TB domestically, members recognized the necessity for TB experts in the United States to work with the international community to help strengthen TB control efforts globally. TB represents a substantial public health problem in low- and middle-income countries, many of which might benefit from assistance by the United States. In addition, the global TB epidemic directly affects the United States because the majority of all cases of TB and 80% of cases of MDR TB reported in the United States occur among foreign-born persons. For these reasons, the Action Plan also outlines potential steps that U.S. government agencies can take to help solve global XDR TB problems. Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible, to treat or prevent. The recommendations provided in this report include specific action steps and new activities that will require additional funding and a renewed commitment by government and nongovernment organizations involved in domestic and international TB control efforts to be implemented effectively. The Federal TB Task Force will coordinate activities of various federal agencies and partner with state and local health departments, nonprofit and TB advocacy organizations in implementing this plan to control and prevent XDR TB in the United States and to contribute to global efforts in the fight against this emerging public health crisis.
Article
The conduct of biomedical studies is guided by statements of internationally recognised principles of human rights. The first principle of the Nuremberg Code was the centrality of voluntary participation of subjects with informed consent. All prevalence surveys should be reviewed by the appropriate ethics review committees. Each potential survey participant should be adequately informed of the aims, methods and sources of funding of the survey, any possible conflicts of interest, the institutional affiliations of the researchers, the anticipated benefits and potential risks of the study, and any discomfort it may entail. Attention should be paid to safety in each component of the survey. Test procedures that require particular attention are chest radiography (CXR) and bacteriological examination. Quality assurance should be applied to all aspects of research and, in particular, to any measurements undertaken, including CXR assessments, laboratory examinations and questionnaire and data management. Furthermore, to ensure comparability of data from different surveys, it is important to apply the same survey design and methodology and to use the same reporting format.
Article
In 1995 the National Institute for Occupational Safety and Health issued new rules for personal respirators. All nine new respirator categories are authorized in health care facilities for the prevention of the transmission of tuberculosis (TB). The new N95 respirator category is the most frequently used for this purpose. Data are presented on their efficiency for collecting TB-size bacteria and their potential for reaerosolizing collected bacteria. All measurements of bacterial penetration were performed with dynamic aerosol size spectrometers at flow conditions corresponding to normal wear and respirator certification conditions. The reaerosolization tests were performed at conditions ranging from normal breathing to violent coughing or sneezing. The tested N95 respirators collected 0.1 to 0.3 microm particles with efficiencies of 95% or higher, as specified by the regulations. TB-size bacteria of 0.8 microm and larger, however, were collected with 99.5% or higher efficiencies; that is, the penetration of these bacteria through the filter material was 0.5% or less, much less than the required maximum penetration of 5% for the smaller particle sizes. No bacteria were reaerosolized during normal exhalation. Some reaerosolization (0.1% or less) was observed only at low humidity and extremely high air flow through the respirator, corresponding to violent coughing or sneezing. The filter materials of N95 respirators provide good protection against TB bacteria. Thus, a significant number of bacteria can enter the respirator-wearer's breathing space only through spaces where the respirator inadequately seals to the wearer's face. Reentrainment and reaerosolization of mycobacteria is not a problem when normal work practices are observed in health care facilities.
Article
Clinicians need to decide whether to begin empiric therapy for patients who are suspected of having tuberculosis (TB) but have negative sputum smear results. Culture results may take weeks, and delaying treatment may allow further transmission of disease. Study objective: To identify the clinical, demographic, and radiographic characteristics that identify smear-negative patients who have TB, and to create a TB prediction rule. Retrospective chart review. University-affiliated public hospital in San Francisco, CA, between 1993 and 1998. Forty-seven patients with TB and 141 control patients who were hospitalized with a suspicion of pulmonary TB; all had negative sputum smear results. Measurements and results: Demographic, clinical, and radiographic variables were determined by chart review. In multivariate analysis, a positive tuberculin skin test result (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.0 to 11.9) was independently associated with an increased risk of a positive TB culture finding. A radiographic pattern not typical of pulmonary tuberculosis (OR, 0.3; 95% CI, 0.1 to 0.7) and expectoration with cough (OR, 0.3; 95% CI, 0.1 to 0.6) were predictive of a decreased risk. An interaction between HIV seropositivity and mediastinal lymphadenopathy on the chest radiograph was also associated with a positive TB culture result (OR, 7.2; 95% CI, 1.4 to 36.0). The TB prediction score (TPS) was created with widely ranging likelihood ratios that could affect the posterior probability of TB by 30-fold. The TPS put into context with the overall prevalence of TB in a given area may help clinicians decide if a patient with negative sputum smear results should start empiric antituberculous therapy or wait for culture results. These results need prospective validation.
Article
To describe the integration of tuberculosis screening into the activities of an HIV voluntary counselling and testing (VCT) centre in a country with endemic tuberculosis. An HIV VCT centre in Port au Prince, Haiti. All patients presenting for HIV VCT who reported cough received same-day evaluation for active tuberculosis. Of the 1327 adults presenting to the centre for the first time between January and April 1997, 263 (20%) reported cough and of these 241 (92%) were evaluated. Of the 241 patients evaluated for cough, 76 (32%) were diagnosed with pulmonary tuberculosis. Of the 76 patients diagnosed with pulmonary tuberculosis, 28 (37%) had a positive smear for acid-fast bacilli (AFB), 14 (18%) had a negative AFB smear but a positive sputum culture for Mycobacterium tuberculosis, and 34 (45%) had culture-negative tuberculosis. Also, 31 out of 241 (13%) VCT clients evaluated for cough were diagnosed with bacterial pneumonia. This report confirms that in areas with a high HIV and tuberculosis prevalence, a high proportion of VCT clients have active pulmonary tuberculosis. The integration of tuberculosis screening offers several benefits, including the diagnosis and treatment of large numbers of individuals with tuberculosis, a decreased risk of nosocomial tuberculosis transmission, and the opportunity to provide tuberculosis prophylaxis to HIV-positive patients in whom tuberculosis has been excluded. Future studies are needed to determine the cost-effectiveness of integrated tuberculosis and HIV VCT services, and whether integration should be recommended in all countries with high HIV and tuberculosis rates.
Article
Tuberculosis (TB) is the most common opportunistic infection among persons with human immunodeficiency virus or the acquired immune-deficiency syndrome (HIV/AIDS). Isoniazid preventive therapy (IPT) effectively treats latent TB infection (LTBI) and prevents progression to active TB. To analyse the costs and cost-effectiveness of tuberculin skin testing (TST) prior to offering IPT. We implemented a program for LTBI screening and IPT using TST for persons with HIV at a voluntary counseling and testing (VCT) center in Kampala, Uganda. Cost-effectiveness analyses using Markov methods were adopted to compare strategies of using and not using TST before offering IPT. The program enrolled 7073 persons with HIV. Based on the prevalence of LTBI in the population, 34/100 HIV-infected patients would benefit from IPT. The results showed that 28% of LTBI patients would be treated using the TST strategy, and 40% would be treated with a non-TST strategy. Compared to no intervention, the estimated incremental cost of identifying and providing IPT using TST was dollars 211 per patient; the incremental cost using a non-TST strategy was dollars 768 per patient. At a large VCT center in Uganda, the inclusion of TST to identify the HIV-infected persons who will most benefit from IPT is cost-effective.
Article
The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa. We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs. From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains. MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.
Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings [serial online] Available at: http://www.cdc.gov/mmwr/pdf/rr/ rr5417.pdf Available at: resources/ pmtct-care/docs/focused-monitoring-tool.pdf
  • Disease Centers
  • Control
  • Prevention
Centers for Disease Control and Prevention. Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings [serial online]. 2005. Available at: http://www.cdc.gov/mmwr/pdf/rr/ rr5417.pdf. Accessed August 1, 2013. 26. Centers for Disease Control and Prevention. TB Infection Control Monitoring and Evaluation Tool [serial online]. 2010. Available at: resources/ pmtct-care/docs/focused-monitoring-tool.pdf. Accessed August 1, 2013.
Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control
  • T Kufa
  • V Mngomezulu
  • S Charalambous
Kufa T, Mngomezulu V, Charalambous S, et al. Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control. J Acquir Immune Defic Syndr. 2012; 60:e22-e28. [PubMed: 22627184]
Centers for Disease Control and Prevention. TB Infection Control Monitoring and Evaluation Tool [serial online
  • Disease Centers For
  • Prevention Control
Centers for Disease Control and Prevention. Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings [serial online]. 2005. Available at: http://www.cdc.gov/mmwr/pdf/rr/ rr5417.pdf. Accessed August 1, 2013. 26. Centers for Disease Control and Prevention. TB Infection Control Monitoring and Evaluation Tool [serial online]. 2010. Available at: resources/ pmtct-care/docs/focused-monitoring-tool.pdf. Accessed August 1, 2013.
Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings
Guidelines for Preventing Transmission of Mycobacterium tuberculosis in Health-Care Settings. Centers for Disease Control and Prevention; 2005. [serial online] [August 1, 2013]
. Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control.
  • Kufa