Attached are the Intro Editorial Overview article (Zumla 141-146) and one article (Reid et al p. S265-73 on TB/HIV control in prisons) among other article summaries below from the May 15th supplemental issue of J. Infect Dis. Supplement entitled “Tuberculosis and Tuberculosis/HIV/AIDS: Unanswered Questions and Controversies”. This is followed by recent summaries of TB/HIV articles classified into the several categories: 1) Scale up and Integrated Treatment of TB/HIV; 2) TB/HIV Testing, Diagnosis, Epidemological Issues and 3) Clinical/Treatment: CARE/CORMOBIDITIES, Immun…Misc. Below this are summaries of HIV related articles from the May 2012 issue of Int’l Journal of Tuberculosis and Lung Disease. Concluding this posting are summaries of HIV related articles from the Nov. 2011 issue of Int’l Journal of Tuberculosis and Lung Disease, which is now free access.
NOTE: Lserv posted at www.RobertMalow.org where you can use the search box to find current and prior Lserv content. Any questions concerning the Lserv (e.g. content that may be valuable to post, literature queries) should be directed to my graduate assistant, Jennifer Attonito at email@example.com. To subscribe or unsubscribe to this HIV Lserv, go to: http://listserv.fiu.edu/archives/hiv.html. Click “Join or Leave HIV.” Enter ‘Name’ and ‘Email Address’ (do not change any of the other settings on this page) then click ‘Join HIV’ button or the “Leave HIV (unsubscribe).
13) Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S141-6.
Eliminating Tuberculosis and Tuberculosis-HIV Co-Disease in the 21st Century: Key Perspectives, Controversies, Unresolved Issues, and Needs.
Zumla A, Atun R, Maeurer M, Kim PS, Jean-Philippe P, Hafner R, Schito M.
Department of Infection, Division of Infection and Immunity, University College London.
The Millennium Development Goal for tuberculosis control is “to halt the spread of TB by 2015 and begin to reverse the worldwide incidence” . The Stop TB Partnership targets include the following: (1) by 2015, reduce the global burden (prevalence and death rates) of tuberculosis by 50% relative to the global burden in 1990 (prevalence, <150/100 000 population; deaths, <15/100 000/y) and (2) by 2050, eliminate tuberculosis as a health threat (defined as a global tuberculosis incidence of <1 case/1 million population/y) [2, 3]. However, despite being declared a global emergency by the World Health Organization (WHO) in 1995 and ensuing major initiatives during the past 15 years , the global burden of tuberculosis, despite declining incidence, is higher today than at any other time in history.
Tuberculosis also remains one of the most important causes of death from an infectious disease . The WHO figures indicate that 8 million new cases occurred during 2010, with 45 million tuberculosis-related deaths . Since 2002, the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) has invested $14 billion in 150 countries to support large-scale prevention, treatment, and care programs against AIDS, tuberculosis, and malaria—more than half in Africa. It is worrisome to note that despite this recent investment, only half of the estimated total tuberculosis caseload is detected in the WHO Africa region, implying that more than half of active tuberculosis cases remain undetected and remain a source for continued transmission of Mycobacterium tuberculosis. Despite nearly 20 years of WHO-directed and coordinated activity and >12 years of multidrug-resistant (MDR) tuberculosis–specific activity, the response to the drug-resistant tuberculosis epidemic seems to be ineffectual, with projected rapid increase in the global incidence of MDR tuberculosis.
The emergence and spread of MDR tuberculosis, extensively …
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S147-58.
McNerney R, Maeurer M, Abubakar I, Marais B, McHugh TD, Ford N, Weyer K, Lawn S, Grobusch MP, Memish Z, Squire SB, Pantaleo G, Chakaya J, Casenghi M, Migliori GB, Mwaba P, Zijenah L, Hoelscher M, Cox H, Swaminathan S, Kim PS, Schito M, Harari A, Bates M, Schwank S, O’Grady J, Pletschette M, Ditui L, Atun R, Zumla A.
Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S159-68.
Nahid P, Kim PS, Evans CA, Alland D, Barer M, Diefenbach J, Ellner J, Hafner R, Hamilton CD, Iademarco MF, Ireton G, Kimerling ME, Lienhardt C, Mackenzie WR, Murray M, Perkins MD, Posey JE, Roberts T, Sizemore C, Stevens WS, Via L, Williams SD, Yew WW, Swindells S.
Division of Pulmonary and Critical Care Medicine, Department of Medicine at San Francisco General Hospital and Curry International Tuberculosis Center, University of California, San Francisco.
The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S169-80.
Opportunities and Challenges for Cost-Efficient Implementation of New Point-of-Care Diagnostics for HIV and Tuberculosis.
Schito M, Peter TF, Cavanaugh S, Piatek AS, Young GJ, Alexander H, Coggin W, Domingo GJ, Ellenberger D, Ermantraut E, Jani IV, Katamba A, Palamountain KM, Essajee S, Dowdy DW.
Division of AIDS, Henry M. Jackson Foundation for the Advancement of Military Medicine, National Institutes of Health, Bethesda, Maryland.
Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S181-90.
Palamountain KM, Baker J, Cowan EP, Essajee S, Mazzola LT, Metzler M, Schito M, Stevens WS, Young GJ, Domingo GJ.
Kellogg School of Management, Northwestern University, Evanston, Illinois.
In recent years, there has been significant investment from both the private and public sectors in the development of diagnostic technologies to meet the need for human immunodeficiency virus (HIV) and tuberculosis testing in low-resource settings. Future investments should ensure that the most appropriate technologies are adopted in settings where they will have a sustainable impact. Achieving these aims requires the involvement of many stakeholders, as their needs, operational constraints, and priorities are often distinct. Here, we discuss these considerations from different perspectives representing those of various stakeholders involved in the development, introduction, and implementation of diagnostic tests. We also discuss some opportunities to address these considerations.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S199-208.
Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.
Graham SM, Ahmed T, Amanullah F, Browning R, Cardenas V, Casenghi M, Cuevas LE, Gale M, Gie RP, Grzemska M, Handelsman E, Hatherill M, Hesseling AC, Jean-Philippe P, Kampmann B, Kabra SK, Lienhardt C, Lighter-Fisher J, Madhi S, Makhene M, Marais BJ, McNeeley DF, Menzies H, Mitchell C, Modi S, Mofenson L, Musoke P, Nachman S, Powell C, Rigaud M, Rouzier V, Starke JR, Swaminathan S, Wingfield C.
Centre for International Child Health, University of Melbourne Department of Paediatrics and Murdoch Childrens.
There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S209-15.
Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel.
Cuevas LE, Browning R, Bossuyt P, Casenghi M, Cotton MF, Cruz AT, Dodd LE, Drobniewski F, Gale M, Graham SM, Grzemska M, Heinrich N, Hesseling AC, Huebner R, Jean-Philippe P, Kabra SK, Kampmann B, Lewinsohn D, Li M, Lienhardt C, Mandalakas AM, Marais BJ, Menzies HJ, Montepiedra G, Mwansambo C, Oberhelman R, Palumbo P, Russek-Cohen E, Shapiro DE, Smith B, Soto-Castellares G, Starke JR, Swaminathan S, Wingfield C, Worrell C.
Child and Reproductive Health Group, Liverpool School of Tropical Medicine, United Kingdom.
Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children. In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S228-40.
Zumla A, Abubakar I, Raviglione M, Hoelscher M, Ditiu L, McHugh TD, Squire SB, Cox H, Ford N, McNerney R, Marais B, Grobusch M, Lawn SD, Migliori GB, Mwaba P, O’Grady J, Pletschette M, Ramsay A, Chakaya J, Schito M, Swaminathan S, Memish Z, Maeurer M, Atun R.
University College London, Centre for Clinical Microbiology, Division of Infection and Immunity, London.
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S241-9.
New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.
Lienhardt C, Raviglione M, Spigelman M, Hafner R, Jaramillo E, Hoelscher M, Zumla A, Gheuens J.
Stop TB Partnership.
For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients’ access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S250-7.
Phillips PP, Gillespie SH, Boeree M, Heinrich N, Aarnoutse R, McHugh T, Pletschette M, Lienhardt C, Hafner R, Mgone C, Zumla A, Nunn AJ, Hoelscher M.
Medical Research Council (MRC) Clinical Trials Unit, London, United Kingdom.
A growing number of new drugs for the treatment of tuberculosis are in clinical development. Confirmatory phase 3 trials are expensive and time-consuming and the question of whether one particular drug combination can be used to treat tuberculosis is less important from a public health perspective than the question of which are the shortest, simplest, most effective, and safest regimens. While preclinical and phase 1 studies provide some guidance in the selection of combinations for clinical evaluation, a large number of combinations will require phase 2 testing to ensure that only the best regimens advance to phase 3. The multi-arm multi-stage trial design is an example of a treatment selection-adaptive design where multiple experimental arms are each simultaneously compared with a common control and interim analyses allow for poor performing arms to be dropped early. Such designs, if designed and implemented correctly, require fewer patients, can be completed in a shorter time frame, and answer more relevant questions without any loss in statistical validity or scientific integrity. There are, however, practical issues that must be considered in applying this in tuberculosis treatment trials. More innovative trials designs should be considered to speed drug and regimen development for the treatment of tuberculosis.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S265-73.
Reid SE, Topp SM, Turnbull ER, Hatwiinda S, Harris JB, Maggard KR, Roberts ST, Krüüner A, Morse JC, Kapata N, Chisela C, Henostroza G.
Centre for Infectious Disease Research in Zambia, Lusaka.
Tuberculosis is one of the fastest-growing epidemics in prison populations in sub-Saharan Africa (SSA), constituting a threat to both inmates and the wider community. Various factors have contributed to the breakdown of tuberculosis control in prison facilities in SSA, including slow and insensitive diagnostics, failing prison infrastructure, inadequate funding, and weak prevention and treatment interventions for human immunodeficiency virus (HIV). In this article, we describe the challenges inherent in current approaches to tuberculosis control in prisons and consider the alternatives. We argue that although improved implementation of conventional tuberculosis control activities is necessary, considerable investment in a broader range of public health interventions, including infrastructure and staffing upgrades, cutting-edge tuberculosis diagnostics, and combination prevention for HIV, will be equally critical. This combination response to tuberculosis in prisons will be essential for tackling existing and nascent prison tuberculosis epidemics and will require high-level political support and financing.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S284-92.
Investing in improved performance of national tuberculosis programs reduces the tuberculosis burden: analysis of 22 high-burden countries, 2002-2009.
Akachi Y, Zumla A, Atun R.
Strategy, Performance and Evaluation Cluster, The Global Fund to Fight AIDS, Tuberculosis, and Malaria, Geneva, Switzerland.
Objective. To assess the impact of investment in national tuberculosis programs (NTPs) on NTP performance and tuberculosis burden in 22 high-burden countries, as determined by the World Health Organization (WHO).
Data Source/Study Setting. Estimates of annual tuberculosis burden and NTP performance indicators and control variables during 2002-2009 were obtained from the Organization for Economic Cooperation and Development, the WHO, the World Bank, and the Penn World Table for the 22 high-burden countries.
Study Design. Panel data analysis was performed using the outcome variables tuberculosis incidence, prevalence, and mortality and the key explanatory variables Partnership case detection rate and treatment success rate, controlling for gross domestic product per capita, population structure, and human immunodeficiency virus (HIV) prevalence.
Results. A $1 per capita (general population) higher NTP budget (including domestic and external sources) was associated with a 1.9% (95% confidence interval, .12%-3.6%) higher estimated case detection rate the following year for the 22 high-burden countries between 2002 and 2009. In the final models, which corrected for autocorrelation and heteroskedasticity, achieving the STOP TB Partnership case detection rate target of >70% was associated with significantly (P < .01) lower tuberculosis incidence, prevalence, and mortality the following year, even when controlling for general economic development and HIV prevalence as potential confounding variables.
Conclusions. Increased investment in NTPs was significantly associated with improved performance and with a downward trend in the tuberculosis burden in the 22 high-burden countries during 2002-2009.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S293-300. Epub 2012 Mar 22.
Controversies and unresolved issues in tuberculosis prevention and control: a low-burden-country perspective.
Abubakar I, Stagg HR, Cohen T, Mangtani P, Rodrigues LC, Pimpin L, Watson JM, Squire SB, Zumla A.
Respiratory Diseases Department, Health Protection Services Colindale, Health Protection Agency, London.
Despite declining incidence in most high-income countries, tuberculosis shows no signs of disappearing in the near future. Although surveillance data from most Western European countries show relatively stable declines in the rate of tuberculosis over the past several decades, some have reported either an increasing rate or a decelerating pace of reduction in recent years. The burden of disease now disproportionately affects high-risk groups such as migrants, homeless persons, and prisoners. In view of the concentration of cases in urban areas and high-risk deprived groups, interventions that may not be efficient when applied to the general population may be highly cost effective when targeted at high-risk groups. In this article, we examine some controversial elements of tuberculosis prevention and control in low-burden countries and recommend issues for further research. In particular, we assess current evidence on the duration of protection by BCG vaccine, the screening of migrants and hard-to-reach groups, and the use of preventive therapy for contacts of cases of infectious multidrug-resistant tuberculosis. This analysis is presented from the perspective of low-tuberculosis-burden, high-income countries attempting to eliminate tuberculosis.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S325-34.
Uhlin M, Andersson J, Zumla A, Maeurer M.
Center for Allogeneic Stem Cell Transplantation.
The continued spread of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant tuberculosis poses a major threat to global tuberculosis control. Treatment is complex and requires longer use of more-expensive, less effective, and toxic anti-tuberculosis drugs, which results in high morbidity and mortality. The poor treatment outcomes and the slow progress in the development and evaluation of new tuberculosis drugs have given rise to the development of adjunct immunotherapy. The host immune system is a critical factor both for containment and cure of Mycobacterium tuberculosis infection. Augmentation or dampening of proinflammatory responses can be of value in the treatment of individuals who have nonproductive M. tuberculosis infection with inflammation-induced tissue damage. The use of immunotherapy with interleukin 2, interferon γ, and interleukin 7 as an adjunct to drug treatment may improve success rates for treatment of MDR tuberculosis, shorten treatment time for drug-sensitive tuberculosis, and improve the immunity of individuals by enhancing M. tuberculosis elimination to prevent recurrence of disease. A broad range of immunological treatments, including cytokine treatment or cell-based therapy, is now available, although not all have been evaluated in humans. This review gives a critical overview of current adjunct immunotherapies for active tuberculosis, which are at various stages of development.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S340-6.
Tuberculosis and Tuberculosis/HIV/AIDS-Associated Mortality in Africa: The Urgent Need to Expand and Invest in Routine and Research Autopsies.
Mudenda V, Lucas S, Shibemba A, O’Grady J, Bates M, Kapata N, Schwank S, Mwaba P, Atun R, Hoelscher M, Maeurer M, Zumla A.
University of Zambia and University College London Medical School, (UNZA-UCLMS), Research and Training Project.
Frequently quoted statistics that tuberculosis and human immunodeficiency virus (HIV)/AIDS are the most important infectious causes of death in high-burden countries are based on clinical records, death certificates, and verbal autopsy studies. Causes of death ascertained through these methods are known to be grossly inaccurate. Most data from Africa on mortality and causes of death currently used by international agencies have come from verbal autopsy studies, which only provide inaccurate estimates of causes of death. Autopsy rates in most sub-Saharan African countries have declined over the years, and actual causes of deaths in the community and in hospitals in most sub-Saharan African countries remain unknown. The quality of cause-specific mortality statistics remains poor. The effect of various interventions to reduce mortality rates can only be evaluated accurately if cause-specific mortality data are available. Autopsy studies could have particular relevance to direct public health interventions, such as vaccination programs or preventive therapy, and could also allow for study of background levels of subclinical tuberculosis disease, Mycobacterium tuberculosis-HIV coinfection, and other infectious and noncommunicable diseases not yet clinically manifest. Autopsies performed soon after death may represent a unique opportunity to understand the pathogenesis of M. tuberculosis and the pathogenesis of early deaths after initiation of antiretroviral therapy. The few autopsies performed so far for research purposes have yielded invaluable information and insights into tuberculosis, HIV/AIDS, and other opportunistic infections. Accurate cause-specific mortality data are essential for prioritization of governmental and donor investments into health services to reduce morbidity and mortality from deadly infectious diseases such as tuberculosis and HIV/AIDS. There is an urgent need for reviving routine and research autopsies in sub-Saharan African countries.
J Infect Dis. May 15, 2012, Vol, 205, suppl 2 :S347-52. Epub 2012 Mar 22.
Kim PS, Makhene M, Sizemore C, Hafner R.
Division of AIDS.
Viewpoint Article: http://jid.oxfordjournals.org/content/205/suppl_2/S347.extract
Partially fueled by the human immunodeficiency virus (HIV) pandemic, tuberculosis is the second-leading cause of infectious diseases–associated mortality globally and the leading cause of death among those infected with HIV. In 2010, there were an estimated 8.8 million incident cases of tuberculosis and approximately 1.5 million deaths attributed to tuberculosis. Increased public heath efforts have been effective in decreasing the overall prevalence and mortality associated with this disease, but declines in incidence rates have been outpaced by global population growth, such that absolute incidence rates have not declined as fast as previously expected . Commensurate with increased public recognition of the importance of tuberculosis to global health in the mid-1990s, biomedical research for tuberculosis has increased both in the United States and internationally. Although tools to conduct modern biomedical research involving tuberculosis have only been available for a little over a decade, this research has resulted in several successes, including promising new vaccines to protect against tuberculosis in the highest-risk populations, diagnostic candidates to improve the accuracy and speed of diagnosing all forms of tuberculosis, and new drug candidates with the potential for improved treatment and chemoprevention for drug-sensitive and drug-resistant tuberculosis.
Despite these successes, many questions remain in all aspects of tuberculosis research, ranging from fundamental pathogenesis to programmatic implementation, and they are complicated by the complexity of the disease and its chronic nature. Compared with other infections, Mycobacterium tuberculosis infection does not elicit clinically relevant disease in the majority of subjects, and many who are infected carry asymptomatic, paucibacillary disease for decades. This complicates the definition and evaluation of early infection events and initial host responses and the characterization of infecting bacillary populations. The clinical definition of latent infection is limited to positive responses to injection of purified mycobacterial components (ie, the tuberculosis skin test) …
Kapata N, Chanda-Kapata P, Grobusch MP, O’Grady J, Schwank S, Bates M, Jansenn S, Mwinga A, Cobelens F, Mwaba P, Zumla A.
National TB and Leprosy Control Programme, Ministry of Health, Lusaka, Zambia; University of Zambia and University College London Medical School Research and Training Programme, Lusaka, Zambia…
Objective: To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade.
Methods: Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010.
Results: The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010.
Conclusions: The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).
J Acquir Immune Defic Syndr. 2012 Mar 6. [Epub ahead of print]
Integration of HIV and TB services results in improved TB treatment outcomes and earlier, prioritized ART initiation in a large urban HIV clinic in Uganda.
Hermans SM, Castelnuovo B, Katabira C, Mbidde P, Lange JM, Hoepelman AI, Coutinho A, Manabe YC.
Makerere University College of Health Sciences, Kampala, Uganda; University of Amsterdam, Amsterdam Institute for Global Health and Development, the Netherlands…
BACKGROUND: WHO recommends that treatment of TB in HIV-infected patients should be integrated with HIV care. In December 2008, a separate, outdoor integrated TB/HIV clinic was instituted for attendees of a large urban HIV clinic in Uganda. We sought to evaluate associated TB and HIV treatment outcomes.
METHODS: Routinely collected clinical, pharmacy and laboratory data was merged with TB clinic data for patients initiating TB treatment in 2009 and with TB register data for patients in 2007. TB treatment outcomes and (timing of) ART initiation in ART-naïve patients (overall and stratified by CD4+ T cell [CD4] count) in 2007 and 2009 were compared. Nosocomial transmission rates could not be assessed.
RESULTS: 346 patients were initiated on TB treatment in 2007 and 366 in 2009. Median CD4 counts at TB diagnosis did not differ. TB treatment cure or completion increased from 62% to 68%, death or default decreased from 33% to 25% (P<0.001). Fewer ART naïve TB patients were initiated on ART in 2009 versus 2007 (57% and 66%, P=0.031), but this decrease was only in patients with CD4 counts >250/mm (19% versus 48%, P=0.003). More patients were started on ART during TB treatment (94% versus 78%, P<0.001). Moreover, the majority were now initiated during intensive phase (60% versus 23%, P<0.001).
CONCLUSIONS: Integration of TB and HIV care has led to improved TB treatment outcomes and earlier, prioritized ART initiation. This supports roll-out of a fully integrated TB/HIV service delivery model throughout high-prevalence TB and HIV settings.
Trop Med Int Health. 2012 Mar 7. [Epub ahead of print]
Health system barriers to implementation of collaborative TB and HIV activities including prevention of mother to child transmission in South Africa.
Uwimana J, Jackson D, Hausler H, Zarowsky C.
School of Public Health, University of the Western Cape, Cape Town, South Africa TB/HIV Care Association, Cape Town, South Africa.
In South Africa, the control of TB and HIV co-infection remains a major challenge despite the availability of international and national guidelines for integration of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the provinces most affected by both TB and HIV, to identify and understand managers’ and community care workers’ (CCWs) perceptions of health systems barriers related to the implementation of collaborative TB/HIV activities, including prevention of mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews with health managers at provincial, district and facility level and with managers of NGOs involved in TB and HIV care, as well as six focus group discussions with CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on the process and the level of the implementation of policy directives on collaborative TB and HIV activities across all categories of respondents (i.e. province-, district-, facility- and community-based organizations). The majority of participants felt that the implementation of the policy was insufficiently consultative and that leadership and political will were lacking. The predominant themes related to health systems barriers include challenges related to structure and organisational culture; management, planning and power issues; unequal financing; and human resource capacity and regulatory problems notably relating to scope of practice of nurses and CCWs. Accelerated implementation of collaborative TB/HIV activities including PMTCT will require political will and leadership to address these health systems barriers.
Trop Med Int Health. 2012 Feb 1. [Epub ahead of print]
Training community care workers to provide comprehensive TB/HIV/PMTCT integrated care in KwaZulu-Natal: lessons learnt.
Uwimana J, Zarowsky C, Hausler H, Jackson D.
School of Public Health, University of the Western Cape, Cape Town, South Africa TB/HIV Care Association, Cape Town, South Africa.
Objective: To describe a participatory approach to implement and evaluate ways to integrate and train community care workers (CCWs) to enhance collaborative TB/HIV/PMTCT activities, and home-based HIV counseling and testing (HCT) at community level.
Methods: The intervention study was conducted in Sisonke, a rural district of KwaZulu Natal, South Africa. A baseline household (HH) survey was conducted in 11 villages. Six villages were randomly selected into intervention and control clusters. Training was provided first to CCWs from the intervention cluster (IC) followed by the control cluster (CC). Routine monthly data from CCWs were collected from March-December 2010. The data was subjected to bivariate tests.
Results: The baseline HH survey revealed that of 3012 HH members visited by CCWs in 2008, 21% were screened for TB symptoms, 7% were visited for TB adherence support and 2% for ART adherence, and 1.5% were counselled on infant feeding options. A total of 89 CCWs were trained. Data show that during the study period in IC, 684 adults were offered HCT by CCWs, 92% accepted HCT and tested and 7% tested HIV-positive and were referred to the clinic for further care. Of 3556 adults served in IC, 44% were screened for TB symptoms and 32% for symptoms of sexually transmitted infections (STIs) and 37% of children were traced as TB contact. Out of 6226 adults served in CC, 10% were screened for TB symptoms and 7% for STI symptoms. The differences in uptake of services between IC and CC were statistically significant (p<0.05).
Conclusion: The findings of this study suggest higher uptake of TB and STI symptoms screening, TB contact tracing and home based HCT in the intervention clusters. This study suggests that up-skilling CCWs could be one avenue to enhance TB/HIV case finding, TB contact tracing and linkages to care.
WHO policy on collaborative TB/HIV activities: guidelines for national programmes and other stakeholders
Authors: World Health Organization
Number of pages: 36
Publication date: 2012
These policy guidelines on collaborative TB/HIV activities are a compilation of existing WHO recommendations on HIV-related TB. They follow the same framework as the 2004 interim policy document, structuring the activities under three distinct objectives: establishing and strengthening mechanisms for integrated delivery of TB and HIV services; reducing the burden of TB among people living with HIV and initiating early antiretroviral therapy; and reducing the burden of HIV among people with presumptive TB (that is, people with signs and symptoms of TB or with suspected TB) and diagnosed TB.
2) TB/HIV Testing, Diagnosis, Epidemological Issues (e.g. prevalence, incidence, mortality) Article Summaries
Clin Dev Immunol. 2012;2012:842045. Epub 2012 Mar 14.
A systematic review of the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients.
Aljohaney A, Amjadi K, Alvarez GG.
Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
BACKGROUND: High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients.
OBJECTIVE: To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients.
METHODS: A literature search from 1950 to June 2011 in MEDLINE was conducted.
RESULTS: Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients.
CONCLUSIONS: Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB.
Int J Health Plann Manage. 2012 Mar 29. [Epub ahead of print]
A qualitative study of HIV testing and referral practices of private hospital doctors treating patients with TB in Chennai, India.
Miller R, Parkhurst JO, Peckham S, Singh RB.
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK. firstname.lastname@example.org.
OBJECTIVE: In India, 50%-80% of patients with tuberculosis (TB) seek private care. This study set out to explore HIV testing and referral practices of private hospital doctors treating patients with TB.
METHODS: Interviews were conducted with private hospital doctors (n = 15). Interviews covered HIV testing, linking HIV-positive patients with TB to HIV care, and coordination of care for co-infected patients.
RESULTS: Doctors did not routinely refer patients with TB to government HIV testing facilities as per national policy guidance. If deemed appropriate, then testing was conducted privately. Testing was more common when a facility guideline mandated testing or a public-private initiative for TB management was in place. Otherwise, testing was based on doctors’ judgement. Patients accustomed to private care who could not afford treatment were reportedly reluctant to shift to public facilities. A lack of communication between public and private doctors was found to undermine co-management.
CONCLUSIONS: In this sample, private provider practices were influenced by both the social and the health systems contexts in which they operated. An understanding of patient perceptions of HIV, private doctors concerns for retaining patients, and the contrasting philosophies of private medicine versus public health objectives was found to be critical to explain HIV testing and referral behaviours. The government has proposed to scale up HIV testing and treatment among patients with TB, yet operationalising this will require engagement with the realities of a large, diverse private sector. It will also require considering what role government policies can have on shaping private practice and how to potentially integrate public and private care.
BMC Infect Dis. 2012 Mar 15;12(1):57. [Epub ahead of print]
Factors associated with delayed diagnosis of tuberculosis in hospitalized patients in a high TB and HIV burden setting: a cross-sectional study.
Silva DR, Muller AM, de Tarso Roth Dalcin P.
Free HTML: http://www.biomedcentral.com/1471-2334/12/57
BACKGROUND: The most essential components of TB control are early diagnosis and adequate treatment. Delay in the diagnosis and treatment of tuberculosis may result in more extensive disease and more complications, increase severity of the disease and is associated with higher risk of mortality. The purpose of this study was to identify factors associated with delayed diagnosis of TB in hospitalized patients.
METHODS: We conducted a cross-sectional study in a general, tertiary care, university-affiliated hospital. Adult patients with TB that were hospitalized were identified retrospectively, and risk factors for delayed diagnosis were collected.
RESULTS: The median delay until diagnosis was 6 days (IQR: 2-12 days). One hundred and sixty six (54.4%) patients were diagnosed [less than or equal to] 6 days, and 139 (45.6%) > 6 days after admission. The main factors associated with diagnostic delay (> 6 days) were extra-pulmonary TB and negative sputum smear.
CONCLUSIONS: Although hospitalization permits a rapid management of the patient and favors a faster diagnosis, we found an unacceptable time delay before the diagnosis of pulmonary TB was made. Future studies should focus on attempt to explain the reasons of diagnostic retard in the patients with the characteristics related to delay in this study.
FEMS Immunol Med Microbiol. 2012 May 10. doi: 10.1111/j.1574-695X.2012.00987.x. [Epub ahead of print]
Mehta PK, Raj A, Singh N, Khuller GK.
Centre for Biotechnology, Maharshi Dayanand University, Rohtak-124001, Haryana, India.
During the last two decades, the resurgence of tuberculosis (TB) has been documented in both developed and developing nations and much of this increase in TB burden coincided with human immunodeficiency virus (HIV) epidemics. Since then, the disease pattern has changed with a higher incidence of extrapulmonary tuberculosis (EPTB) as well as disseminated TB. EPTB cases include TB lymphadenitis, pleural TB, TB meningitis, osteoarticular TB, genitourinary TB, abdominal TB, cutaneous TB, ocular TB, TB pericarditis and breast TB, although any organ can be involved. Diagnosis of EPTB can be baffling, compelling a high index of suspicion due to paucibacillary load in the biological specimens. A negative smear for acid-fast bacilli, lack of granulomas on histopathology and failure to culture Mycobacterium tuberculosis do not exclude the diagnosis of EPTB. Novel diagnostic modalities such as nucleic acid amplification (NAA) can be useful in varied forms of EPTB. This review is primarily focused on the diagnosis of several clinical forms of EPTB by polymerase chain reaction (PCR) using different gene targets.
Trop Med Int Health. 2012 May 11. doi: 10.1111/j.1365-3156.2012.03003.x. [Epub ahead of print]
Performance of the new WHO diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV prevalent settings: a multisite study in Uganda.
Alamo ST, Kunutsor S, Walley J, Thoulass J, Evans M, Muchuro S, Matovu A, Katabira E.
Reach Out Mbuya Parish HIV/AIDS Initiative, Kampala, Uganda …
Objective To compare the performance of the new WHO (2007) diagnostic algorithm for pulmonary tuberculosis (PTB) in high HIV prevalent settings (WHO07) to the WHO 2003 guidelines used by the Ugandan National Tuberculosis Program (UgWHO03). Methods A prospective observational cohort design was used at Reach Out Mbuya Parish HIV/AIDS Initiative, an urban slum community-based AIDS Service Organisation (ASO) and Kayunga Rural District Government Hospital. Newly diagnosed and enrolled HIV-infected patients were assessed for PTB. Research staff interviewed patients and staff and observed operational constraints. Results WHO07 reduced the time to diagnosis of smear-negative PTB with increased sensitivity compared with the UgWHO03 at both sites. Time to diagnosis of smear-negative PTB was significantly shorter at the urban ASO than at the rural ASO (12.4 vs. 28.5 days, P = 0.003). Diagnostic specificity and sensitivity [95% confidence intervals (CIs)] for smear-negative PTB were higher at the rural hospital compared with the urban ASO: [98% (93-100%) vs. 86% (77-92%), P = 0.001] and [95% (72-100%) vs. 90% (54-99%), P > 0.05], respectively. Common barriers to implementation of algorithms included failure by patients to attend follow-up appointments and poor adherence by healthcare workers to algorithms. Conclusion At both sites, WHO07 expedited diagnosis of smear-negative PTB with increased diagnostic accuracy compared with the UgWHO03. The WHO07 expedited diagnosis more at the urban ASO but with more diagnostic accuracy at the rural hospital. Barriers to implementation should be taken into account when operationalising these guidelines for TB diagnosis in resource-limited settings.
Number of pages: 76 Publication date: March 2012
Adopting electronic recording and reporting is not simply about choosing a piece of software: it is also about changing how people work. This is not a simple undertaking. This document introduces the key questions to be considered and illustrates what the questions, options and recommendations mean in practice by drawing on examples of recent experience from a variety of countries. It is an essential resource for all those planning to introduce electronic recording and reporting systems for TB care and control, or to enhance existing systems.
WHO guidelines on TB recording and reporting
BMC Infect Dis. 2012 May 4;12(1):107. [Epub ahead of print]
Kall MM, Coyne KM, Garrett NJ, Boyd AE, Ashcroft AT, Reeves I, Anderson J, Bothamley GH.
BACKGROUND: HIV and tuberculosis (TB) are commonly associated. Identifying latent and asymptomatic tuberculosis infection in HIV-positive patients is important in preventing death and morbidity associated with active TB.
METHODS: Cross-sectional study of one time use of an interferon-gamma release assay (T-SPOT.TB – immunospot) to detect tuberculosis infection in patients in an inner city HIV clinic with a large sub-Saharan population.
RESULTS: 542 patient samples from 520 patients who had disclosed no symptoms of TB were screened. Median follow-up was 35 months (range 27-69). More than half (55%) originated from countries with medium or high tuberculosis burden and 57% were women. Antiretroviral therapy was used by 67%; median CD4 count at test was 458 cells/ul. A negative test was found in 452 and an indeterminate results in 40 (7.4%) but neither were associated with a low CD4 count. A positive test was found in 50 individuals. All patients with positive tests were referred to the TB specialist, 47 (94%) had a chest radiograph and 46 (92%) attended the TB clinic. Two had culture-positive TB and a third individual with features of active TB was treated. 40 started and 38 completed preventive treatment. One patient who completed preventive treatment with isoniazid monotherapy subsequently developed isoniazid-resistant pulmonary tuberculosis. No patient with a negative test has developed TB.
CONCLUSIONS: The T-SPOT.TB test helped identify active TB in those without symptoms. There was a high completion rate for preventive treatment in those with a positive test result.
“It seems that the Health Ministry in India has decided to make tuberculosis a notifiable disease. “According to the proposal, the designated authority that would have to be informed about new TB cases are the district health officer/CMO of a district and the municipal health officer in a municipality” cites the Indian Express http://www.indianexpress.com/news/centre-to-make-tb-notifiable-disease/946595/
Eur Spine J. 2012 May 8. [Epub ahead of print]
Millet JP, Moreno A, Fina L, Del Baño L, Orcau A, de Olalla PG, Caylà JA.
Epidemiology Service, Public Health Agency of Barcelona, Barcelona, Spain, email@example.com.
Abstract/1st page image: http://www.springerlink.com/content/u4135771n6122717/
According to WHO estimates, in 2010 there were 8.8 million new cases of tuberculosis (TB) and 1.5 million deaths. TB has been classically associated with poverty, overcrowding and malnutrition. Low income countries and deprived areas, within big cities in developed countries, present the highest TB incidences and TB mortality rates. These are the settings where immigration, important social inequalities, HIV infection and drug or alcohol abuse may coexist, all factors strongly associated with TB. In spite of the political, economical, research and community efforts, TB remains a major global health problem worldwide. Moreover, in this new century, new challenges such as multidrug-resistance extension, migration to big cities and the new treatments with anti-tumour necrosis alpha factor for inflammatory diseases have emerged and threaten the decreasing trend in the global number of TB cases in the last years. We must also be aware about the impact that smoking and diabetes pandemics may be having on the incidence of TB. The existence of a good TB Prevention and Control Program is essential to fight against TB. The coordination among clinicians, microbiologists, epidemiologists and others, and the link between surveillance, control and research should always be a priority for a TB Program. Each city and country should define their needs according to the epidemiological situation. Local TB control programs will have to adapt to any new challenge that arises in order to respond to the needs of their population.
3) TB/HIV Clinical/Treatment: CARE/CORMOBIDITIES, Immun., Vaccine, Virol., Pathology, COST-EFFECTIVENESS, MISC RELATED ARTICLE SUMMARIES
AIDS Care. 2012 Apr 24. [Epub ahead of print]
Daftary A, Padayatchi N.
ICAP, Mailman School of Public Health , Columbia University , New York , NY.
There is a growing imperative to improve the coordination and collaboration of tuberculosis (TB) and HIV healthcare services in response to escalating rates of TB/HIV coinfection. Patient-specific challenges associated with the delivery of TB/HIV care have been minimally explored in this regard. As part of a larger study conducted in South Africa, this article highlights coinfected patients’ experiences with TB and HIV healthcare in light of their broader social environments. Qualitative, in-depth interviews were conducted with 40 adult, coinfected patients (24 women and 16 men) and eight key-informant healthcare workers at three urban/peri-urban, ambulatory, public health clinics in the high-burden province of KwaZulu-Natal. Transcribed interviews were analyzed under a modified grounded theory approach to capture subjective meanings of healthcare experience subsequent to patients’ codiagnosis with TB and HIV. Emerging analytic themes highlighted critical sociomedical constraints to TB/HIV care in relation to patients’ income and employment, eligibility for social assistance and antiretroviral treatment, fears around illness disclosure, social and material support, and treatment adherence. Patients’ healthcare experiences were bound by their poor access to essential resources, multiple life responsibilities, disparate gender roles, limits within the healthcare system, and the stigmatizing social symbolism of their illness. Overlapping social inequalities perpetuated coinfected patients’ experiences with stigma and collectively mediated their health decisions around disclosure, adherence, and retention in medical care. The study urges a contextualized understanding of the social challenges associated with TB/HIV healthcare and helps inform more patient-sensitive and socially responsive interventions against the co-epidemic.
J Community Health. 2012 Apr 4. [Epub ahead of print]
Severity of Outcomes Associated to Types of HIV Coinfection with TB and Malaria in a Setting Where the Three Pandemics Overlap.
Tshikuka Mulumba JG, Atua Matindii B, Kilauzi AL, Mengema B, Mafuta J, Eloko Eya Matangelo G, Mukongo Bulaïmu-Lukeba A, Jerry IL.
University School of Medical Technology (ISTM), Kinshasa XI, Democratic Republic of Congo, firstname.lastname@example.org.
Abstract/1st page image: http://www.springerlink.com/content/70h227351r41wj43/
The objectives of this study is to (1) characterize profiles of HIV coinfection with TB and malaria; (2) estimate the severity of outcome associated with each type of coinfection; (3) identify most severe coinfection type, and populations most affected. Data on 1,302 HIV/AIDS patients were collected from hospital record books for 2007 and 2008. Distribution patterns of types of HIV coinfection with TB and malaria were assessed among low and high SES (socioeconomic status) inpatients. Case fatality rate for each type of coinfection was estimated as the ratio of number of deaths associated with a specific type of coinfection over the number of cases, times 100. Case fatality rates were compared among coinfection types and between low and high SES inpatients. Four types of coinfections were identified: single-HIV, HIV-TB, HIV-malaria and HIV-TB-malaria. Single-HIV infection was the most prevalent, and predominant among high SES inpatients; HIV-TB was the second most prevalent, and predominant among low SES inpatients; HIV-malaria and HIV-TB-malaria coinfections were the least prevalent, they were relatively comparable between both SES groups. HIV-TB coinfection was the deadliest type of coinfection, followed by HIV-TB-malaria and HIV-malaria. Single-HIV infection was the least deadly of the four conditions. Aside from HIV-malaria, the proportion of fatalities associated with each coinfection type was higher among low SES inpatients when compared with high SES inpatients. HIV/AIDS treatment and care programs in communities with limited resources and high prevalence of malaria and TB should give priority attention to low socioeconomic status patients coinfected with TB to prevent unnecessary deaths among those living with HIV.
Cell. 2012 Mar 16;148(6):1271-83.
Goldberg DE, Siliciano RF, Jacobs WR Jr.
Department of Medicine and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO.
Although caused by vastly different pathogens, the world’s three most serious infectious diseases, tuberculosis, malaria, and HIV-1 infection, share the common problem of drug resistance. The pace of drug development has been very slow for tuberculosis and malaria and rapid for HIV-1. But for each disease, resistance to most drugs has appeared quickly after the introduction of the drug. Learning how to manage and prevent resistance is a major medical challenge that requires an understanding of the evolutionary dynamics of each pathogen. This Review summarizes the similarities and differences in the evolution of drug resistance for these three pathogens.
BMC Res Notes. 2012 Jan 26;5:67.
Kassa A, Jerene D, Assefa Y, Teka A, Aseffa A, Deribew A.
Ministry of Health, Addis Ababa, Ethiopia. email@example.com.
Free HTML: http://www.biomedcentral.com/1756-0500/5/67
BACKGROUND: Ethiopia has had mechanisms for TB/HIV collaborative activities since 2002. However, no published account has defined the role of these collaborative efforts in strengthening linkages between HIV and TB management units at the point-of-care level. Our objective was to assess the extent of linkages between the two programs at the patient management level at Zewditu Memorial Hospital in Addis Ababa, Ethiopia. Between January and December 2008, the registers of 241 TB patients were reviewed to determine the HIV testing rate, the treatment charts of 238 randomly selected patients were reviewed for providers’ compliance with evaluation criteria, and exit interviews were conducted with 309 TB/HIV co-infected clients to validate providers’ compliance.
RESULTS: From register review, it was determined that the HIV testing acceptance rate was 95%, and that 70% of patients received post-test counseling. A review of the patient chart revealed that of 51 patients with a complaint of cough, duration for cough was recorded in 35 (68.6%) cases and cough > 2 weeks was recorded in 25 (49.0%) cases. Seventy two percent (18 of 25) were linked for sputum microscopy. Linkage to cotrimoxazole prophylactic treatment was 81%, but only 47% of eligible patients were linked to isoniazid preventive therapy (IPT). Correct diagnosis was accomplished at a rate of 100% for smear positive pulmonary TB, 23% for smear negative pulmonary TB and 88% for extra pulmonary TB patients. Both chart review and exit interviews indicated that history of TB contact and cough > 2 weeks predicted TB disease.
CONCLUSION: The rates of HIV testing and linkage to cotrimoxazole prophylactic therapy were high. Improvement is needed in the areas of recording patient information, screening HIV positives for TB, initiation of IPT, referral, linkages, and TB diagnostic capacity.
New vaccines for the prevention of tuberculosis in human immunodeficiency virus infection [Perspectives]
Authors: von Reyn, C. F; Bakari, M.; Arbeit, R. D.; Lahey, T.; Ramadhani, A.; Egwaga, S.
The International Journal of Tuberculosis and Lung Disease, Volume 16, Number 6, 1 June 2012 , pp. 718-723(6)
The prevention of human immunodeficiency virus (HIV) associated tuberculosis (TB) remains challenging. Several vaccines against TB have advanced to clinical trials in patients with HIV infection. The DarDar Trial, a large, randomized, placebo-controlled efficacy trial conducted in Tanzania, has demonstrated that a multiple dose series of an inactivated whole cell mycobacterial vaccine is safe in HIV and can prevent HIV-associated TB in patients with childhood bacille Calmette-Guérin vaccination and CD4 counts of ≥200 cells/mm3. These developments offer promise that in the not too distant future immunization with an effective vaccine against TB can be added to other strategies for the prevention of HIV-associated TB. This expanded approach is referred to as the Five `I’s': intensified case finding, infection control, isoniazid preventive therapy (IPT), initiation of antiretroviral therapy (ART), and immunization against TB. We encourage additional studies of new TB vaccines in HIV, and propose a strategy to reduce the risk of TB by integrating IPT, ART and immunization into routine HIV care. At the time of HIV diagnosis, patients with CD4 counts of ≥200 cells/mm3 could receive immunization, IPT and, as appropriate, ART. In patients presenting with lower CD4 counts or already on ART, immunization could be initiated at CD4 counts of ≥200 cells/mm3 to add to the protection afforded by IPT and ART.
Outcomes of HIV-infected patients treated for recurrent tuberculosis with the standard retreatment regimen
McGreevy, J.1; Jean Juste, M. A.1; Severe, P.1; Collins, S.2; Koenig, S.3; Pape, J. W.4; Fitzgerald, D. W.2
The International Journal of Tuberculosis and Lung Disease, Volume 16, Number 6, 1 June 2012 , pp. 841-845(5)
SETTING: The Groupe Haitien d’Etude du Sarcome de Kaposi et des Infections Opportunistes (the GHESKIO AIDS and TB Center) in Port-au-Prince, Haiti.
OBJECTIVE: To measure the effectiveness of the standard TB retreatment regimen (2HRZES/1HRZE/5HRE) in human immunodeficiency virus (HIV) infected adults.
DESIGN: Cohort study.
RESULTS: Of 1318 HIV-infected patients with access to antiretroviral therapy following World Health Organization guidelines, 56 were diagnosed with recurrent pulmonary TB and retreated with the standard retreatment regimen: 10 patients (18%) died during retreatment, 3 (5%) defaulted, and 2 (4%) failed treatment. Forty-one patients (73%) achieved retreatment `success’ (cure, treatment completed). Of these, 8 (20%) died during follow-up, 5 (12%) were lost, and 5 (12%) had a second recurrence of TB. Only 26 (46%) of the 56 patients remained alive, in care, and TB-free after a median of 36 months of follow-up.
CONCLUSION: HIV-infected patients treated for recurrent TB with the standard retreatment regimen have high mortality and poor long-term outcomes.
DATE: 26 March 2012
Regulators are increasingly scrutinizing HIV and TB responses in South Africa’s mining sector, which could lead to the industry being hit where it hurts — the bottom line. Speaking to hundreds of mine workers and community members in the mining town of Carletonville on World TB Day, Deputy President Kgalema Motlanthe urged the mining industry to improve TB services by adopting the GeneXpert rapid TB test, upgrading health centres to allow for the treatment of drug-resistant TB, and by extending health services to those from surrounding communities and mines that may have limited access to healthcare. At the same event, Mineral Resources Minister Susan Shabangu announced that mining companies, whose HIV, TB and workplace safety policies are being audited by her department, will have to submit their policies as a prerequisite for renewing their mining licenses. As part of the deputy president’s call for all mine workers to be screened for TB and HIV in the next year, World TB Day celebrations were accompanied by HIV and TB screenings, during which at least 1,220 people were examined for TB and 260 people were tested for HIV. Before addressing the crowd, Motlanthe and Shabangu joined other officials, including Minister of Health Dr Aaron Motsoaledi and South African National AIDS Council deputy chairperson Mark Heywood at a community dialogue meeting with about 200 miners, who raised concerns like housing, compensation for their families if they should die, and unfair dismissal following TB diagnoses. Mark Heywood, who also heads the human rights organization, Section 27, encouraged miners to report such dismissals. “In South Africa it is illegal for anyone with HIV or TB to be dismissed or chased away from employment,” Heywood told IRIN/PlusNews. “We encourage any mineworker who has been dismissed because of TB or HIV to report it — to overcome TB we have to protect human rights.” As in many countries in southern and East Africa, South Afric a’s high TB incidence is fuelled by a high HIV prevalence. Although many people carry TB, only 10 percent will ever develop the active disease, but because of their compromised immune systems, people living with HIV are up to 37 times more likely to develop active TB…
Braz J Infect Dis. 2012 Apr;16(2):142-5.
Previous use of quinolones: a surrogate marker for first line anti-tuberculosis drugs resistance in HIV-infected patients?
Deutschendorf C, Goldani LZ, Santos RP.
Infectious Diseases Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, RS, Brazil.
OBJECTIVES: Drug resistant Mycobacterium tuberculosis causes much higher rates of treatment toxicity, failure or relapse, and mortality. We determined the drug resistant profile of Mycobacterium tuberculosis strains isolated from a population of HIV-infected patients in southern Brazil and studied the potential factors associated with resistance.
METHODS: We conducted a retrospective cohort study to determine the resistance profile of Mycobacterium tuberculosis isolated from HIV-infected patients and factors that could be associated with resistance from 2000 to 2005.
RESULTS: 236 patients were included in the study. Resistance to at least one drug was observed in 32 (14.6%) isolates, and multi-drug resistance was observed in 4 (1.82%) isolates. On multivariate analysis, previous use of tuberculostatics and quinolones were related to any first-line drug resistance.
CONCLUSIONS: In our study, previous quinolone use was significantly associated to first-line anti-TB drugs resistance. Multi-drug-resistant tuberculosis (MDR-TB) is a major problem worldwide, and we believe quinolones should be used with caution in settings where TB is endemic.
AIDS. 2012 Apr 26. [Epub ahead of print]
Pharmacokinetics of nevirapine in HIV-infected children under 3 years on rifampicin-based antituberculosis treatment.
Oudijk JM, McIlleron H, Mulenga V, Chintu C, Merry C, Walker AS, Cook A, Gibb DM, Burger DM.
Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Medical Centre Leeuwarden, Leeuwarden, The Netherlands; Department of Medicine, University of Cape Town, Cape Town, South Africa…
OBJECTIVE: There is an urgent need to optimise co-treatment for children with tuberculosis and HIV infection. We described nevirapine pharmacokinetics in Zambian children aged <3 years, co-treated with nevirapine, lamivudine and stavudine in fixed-dose-combination (using WHO weight bands) and rifampicin-based antituberculosis treatment.
DESIGN: Twenty-two children received antituberculosis and antiretroviral therapy (ART) concurrently for four weeks before pharmacokinetic sampling. Plasma nevirapine concentrations were determined in samples taken immediately before, and 1, 2 and 6 hours after an observed dose. Nevirapine pharmacokinetics were compared with those in 16 children aged <3 years without tuberculosis.
RESULTS: Twenty-two children were treated for HIV/TB co-infection, ten of whom were girls. One boy was excluded from analysis for non-adherence. The median age was 1.6 years (range: 0.7-3.2). Median weight was 8.0 kg (range: 5.1-10.5). The baseline CD4% was 13.1 (range: 3.9-43.6). Median pre-dose concentration of nevirapine was 2.93 mg/l (range: 1.06-11.4) and peak-concentration was 6.33 mg/l (range: 2.61-14.5). The nevirapine AUC up to 12 hours was estimated as 52.0 mg.h/l (range: 22.6-159.7) compared to 90.9 mg.h/l (range: 40.4-232.1) in children without tuberculosis (p < 0.001). Pre-dose concentrations of nevirapine were <3.0 mg/l in 11 children on tuberculosis treatment versus none of the 16 children without tuberculosis treatment (p = 0.001). AUC was 41% (95% CI: 23-54%) lower in children with tuberculosis than without tuberculosis (p < 0.001) after adjusting for dose/m2.
CONCLUSIONS: We found substantial reductions in nevirapine concentrations in young children receiving rifampicin. Further studies are needed to define the pharmacokinetics, safety and efficacy of adjusted doses of nevirapine-based ART in young children with tuberculosis.
PLoS One. 2012;7(4):e36001. Epub 2012 Apr 30.
The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis.
Pho MT, Swaminathan S, Kumarasamy N, Losina E, Ponnuraja C, Uhler LM, Scott CA, Mayer KH, Freedberg KA, Walensky RP.
Section of Hospital Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
Free HTML/Link to Free PDF: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036001
BACKGROUND: Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.
METHODS: We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).
RESULTS:Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.
CONCLUSIONS: Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.
Int J Tuberc Lung Dis. 2012 May;16(5):573-8.
Kumar A, Kumar AM, Gupta D, Kanchar A, Mohammed S, Srinath S, Tripathy S, Rajasekaran S, Chan PL, Swaminathan S, Dewan PK.
Central Tuberculosis Division, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India, New Delhi, India.
The Revised National Tuberculosis Control Programme (RNTCP) in India uses a fully intermittent thrice-weekly rifampicin-containing regimen for all tuberculosis (TB) patients, including those who are human immunodeficiency virus (HIV) infected, whereas the World Health Organization (WHO) recommends daily anti-tuberculosis treatment at least during the intensive phase. The WHO recommendation was based on the results of a meta-analysis demonstrating increased risk of recurrence and failure among HIV-infected TB patients receiving intermittent TB treatment compared to a daily regimen. Review of the primary evidence indicates limited, low-quality information on intermittency, mostly from observational studies in the pre-antiretroviral treatment (ART) era. Molecular epidemiology in India indicates that most of the recurrences and many of the failures result from exogenous re-infection, suggesting poor infection control and high transmission rather than poor regimen efficacy. Subsequently published studies have shown acceptable treatment outcomes among HIV-infected TB patients receiving intermittent anti-tuberculosis regimens with concomitant ART. Treatment outcomes among HIV-infected TB patients treated under programmatic conditions show low failure rates but high case fatality; death has been associated with lack of ART. The highest priority is therefore to reduce mortality by linking all HIV-infected TB patients to ART. While urgently seeking to reduce death rates among HIV-infected TB patients, given the poor evidence for change and operational advantages of an intermittent regimen, the RNTCP intends to collect the necessary evidence to inform national policy decisions through randomised clinical trials.
Int J Tuberc Lung Dis. 2012 May;16(5):569-70.
Marston BJ, De Cock KM.
Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Int J Tuberc Lung Dis. 2012 May;16(5):579-88. Epub 2012 Mar 7.
Microscopy compared to culture for the diagnosis of tuberculosis in induced sputum samples: a systematic review.
Hepple P, Ford N, McNerney R.
Manson Unit, Médecins Sans Frontières, London, UK; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
BACKGROUND: Resource-limited settings rely on sputum examination using microscopy to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and case detection rates are low. Sputum induction is proposed as a way to improve sample collection and enhance test sensitivity.
OBJECTIVE: To undertake a systematic review of studies comparing microscopy and culture sensitivity in induced sputum samples.
METHODS: We ran duplicate searches of databases (up to August 2011) and searchable websites of major human immunodeficiency virus (HIV) and TB conferences (up to November 2010) to identify studies comparing the performance of microscopy compared to culture on induced sputum samples, with culture as the reference standard.
RESULTS: A total of 23 studies met our inclusion criteria. The overall success of the induction was high, ranging from 76.4% (95%CI 68.5-83.2) to 100% (95%CI 98.5-100), while adverse events associated with sputum induction were infrequent and mild. The sensitivity of microscopy compared to culture ranged from 0% to 100%; only eight studies reported on the species of mycobacterium isolated in culture. Yield was generally higher for sputum induction compared to nasopharyngeal aspiration and gastric lavage, and compared equally well to bronchoalveolar lavage and physiotherapy.
DISCUSSION: Sputum induction increases TB case detection and is useful for people who are negative on spontaneous smear microscopy or unable to expectorate spontaneously. It is well-tolerated by children and adults, irrespective of HIV status, and can be used where culture is not available. The use of induced sputum samples with molecular tests, such as Xpert(®) MTB/RIF, warrants further investigation.
Int J Tuberc Lung Dis. 2012 May;16(5):615-7.
Klinkenberg E, van den Hof S, Tursynbayeva A, Kipruto H, Wahogo J, Pak S, Kutwa A, L’herminez R.
KNCV Tuberculosis Foundation, The Hague, The Netherlands; Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
In Kenya and Kazakhstan, integration of human immunodeficiency virus (HIV) testing results into the routine surveillance of multidrug-resistant tuberculosis (MDR-TB) proved feasible and useful. The integration process improved overall data quality and data validation capacity, and integrated data are a useful addition to routine cohort and treatment outcome data. Besides their importance for individual patient care, they provide trends on the association of MDR-TB and HIV in the routine programme setting. They also form a useful epidemiological basis for more specific studies, such as on nosocomial outbreaks. Whether the system itself is sensitive enough to monitor possible outbreaks needs further investigation.
Int J Tuberc Lung Dis. 2012 May;16(5):618-24.
Survival of HIV-infected patients after starting tuberculosis treatment: a prospective cohort study.
Maruza M, Albuquerque MF, Braga MC, Barbosa MT, Byington R, Coimbra I, Moura LV, Batista JD, Diniz GT, Miranda-Filho DB, Lacerda HR, Rodrigues LC, Ximenes RA.
Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
OBJECTIVES: To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment.
METHODS: A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated.
RESULTS: Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10 000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic.
CONCLUSIONS: The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.
Int J Tuberc Lung Dis. 2012 May;16(5):625-7.
Evaluation of integrated registers for tuberculosis and HIV surveillance in children, Ethiopia, 2007-2009.
Click ES, Feleke B, Pevzner E, Fantu R, Gadisa T, Assefa D, Melaku Z, Cain K, Menzies H.
Epidemic Intelligence Service, assigned to Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
In 2008, Ethiopia implemented tuberculosis (TB) treatment registers that included columns for recording human immunodeficiency virus (HIV) test results (integrated registers) to replace the previous system of separate TB and HIV registers (pre-integration registers). We compared the proportion of children with documented HIV rapid test results at eight hospitals before and after adopting the integrated registers. HIV status was more consistently documented in the integrated registers; however, HIV status for infants aged <18 months could not be assessed, as the registers did not capture results from polymerase chain reaction-based testing. Recording procedures should be revised to document age-appropriate HIV diagnostic results and ensure referral for appropriate care.
Int’l Journal of Tuberculosis and Lung Disease, Nov. 2011, which is now free access
Int J Tuberc Lung Dis. 2011 Nov;15(11):1421.
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PROFESSOR ANTHONY HARRIES, arguably one of the most prolific operational researchers in recent time, once quipped ‘what is needed is operational re- search on operational research’. Though meant as a light-hearted remark, the message is completely serious. The very same principles that apply to individual operational research (OR) efforts1—namely that a programme has well defined goals and objectives, that constraints or barriers to meeting those objectives are identified and that research questions are asked to address those constraints—also apply to the assessment of the broader body of OR at a national, regional and global level. However, the data necessary to conduct such analyses of OR at the programmatic level are not readily available…
Int J Tuberc Lung Dis. 2011 Nov;15(11):1426-35, i.
Building leadership capacity and future leaders in operational research in low-income countries: why and how?
Zachariah R, Reid T, Srinath S, Chakaya J, Legins K, Karunakara U, Harries AD.
Medical Department, Médecins Sans Frontières, Operational Centre Brussels, MSF-Luxembourg, Luxembourg. firstname.lastname@example.org
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Very limited operational research (OR) emerges from programme settings in low-income countries where the greatest burden of disease lies. The price paid for this void includes a lack of understanding of how health systems are actually functioning, not knowing what works and what does not, and an inability to propose adapted and innovative solutions to programme problems. We use the National Tuberculosis Control Programme as an example to advocate for strong programme-level leadership to steer OR and build viable relationships between programme managers, researchers and policy makers. We highlight the need to create a stimulating environment for conducting OR and identify some of the main practical challenges and enabling factors at programme level. We focus on the important role of an OR focal point within programmes and practical approaches to training that can deliver timely and quantifiable outputs. Finally, we emphasise the need to measure successful OR leadership development at programme level and we propose parameters by which this can be assessed. This paper 1) provides reasons why programmes should take the lead in coordinating and directing OR, 2) identifies the practical challenges and enabling factors for implementing, managing and sustaining OR and 3) proposes parameters for measuring successful leadership capacity development in OR.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1436-44, i.
The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis.
Harries AD, Lin Y, Satyanarayana S, Lönnroth K, Li L, Wilson N, Chauhan LS, Zachariah R, Baker MA, Jeon CY, Murray MB, Maher D, Bygbjerg IC, Enarson DA, Billo NE, Kapur A.
International Union Against Tuberculosis and Lung Disease, Paris, France; London School of Hygiene & Tropical Medicine, London, UK. email@example.com
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The prevalence of diabetes mellitus is increasing at a dramatic rate, and countries in Asia, particularly India and China, will bear the brunt of this epidemic. Persons with diabetes have a significantly increased risk of active tuberculosis (TB), which is two to three times higher than in persons without diabetes. In this article, we argue that the epidemiological interactions and the effects on clinical presentation and treatment resulting from the interaction between diabetes and TB are similar to those observed for human immunodeficiency virus (HIV) and TB. The lessons learned from approaches to reduce the dual burden of HIV and TB, and especially the modes of screening for the two diseases, can be adapted and applied to the screening, diagnosis, treatment and prevention of diabetes and TB. The new World Health Organization (WHO) and The Union Collaborative Framework for care and control of TB and diabetes has many similarities to the WHO Policy on Collaborative Activities to reduce the dual burden of TB and HIV, and aims to guide policy makers and implementers on how to move forward and combat this looming dual epidemic. The response to the growing HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated, despite clearly articulated warnings about the scale of the forthcoming problem. We must not make the same mistake with diabetes and TB. The Framework provides a template for action, and it is now up to donors, policy makers and implementers to apply the recommendations in the field and to ‘learn by doing’.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1445-54, i.
Couceiro L, Santana P, Nunes C.
Office of the High Commissioner for Health, Ministry of Health, Lisbon, Portugal. firstname.lastname@example.org
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Tuberculosis (TB) is a multidimensional disease, and interactions between individuals and groups are of extreme importance in its development. The aim of this study was to estimate the occurrence of pulmonary TB (PTB) to identify potential risk factors and to define high-risk areas in Portugal (2004-2006). The relevance of the common risk factors identified was evaluated at the national and local levels. Considering local public health at the municipality level, the main objective of this study was the support of local interventions, identifying local high-risk areas and the corresponding local risk factors. A complex statistical methodology based on correlation analysis, spatial clustering, risk maps and multivariate regression models was developed. The results showed that some areas were at higher risk of PTB than others due to high incidence of HIV/AIDS, incarceration, nonstandard (abnormal) and/or crowded accommodation, unemployment and immigrant populations. The majority of these areas showed increased TB incidence rates.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1461-7, i.
Álvarez JL, Kunst AE, Leinsalu M, Bopp M, Strand BH, Menvielle G, Lundberg O, Martikainen P, Deboosere P, Kalediene R, Artnik B, Mackenbach JP, Richardus JH.
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. email@example.com
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OBJECTIVE: To describe the magnitude of socioeconomic inequalities in tuberculosis (TB) mortality by level of education in male, female, urban and rural populations in several European countries.
DESIGN: Data were obtained from the Eurothine Project, covering 16 populations between 1990 and 2003. Age- and sex-standardised mortality rates, the relative index of inequality and the slope index of inequality were used to assess educational inequalities.
RESULTS: The number of TB deaths reported was 8530, with a death rate of 3 per 100 000 per year, of which 73% were males. Educational inequalities in TB mortality were present in all European populations. Inequalities in TB mortality were greater than in total mortality. Relative and absolute inequalities were large in Eastern European and Baltic countries but relatively small in Southern European countries and in Norway, Finland and Sweden. Inequalities in mortality were observed among both men and women, and in both rural and urban populations.
CONCLUSIONS: Socio-economic inequalities in TB mortality exist in all European countries. Firm political commitment is required to reduce inequalities in the social determinants of TB incidence. Targeted public health measures are called for to improve access to treatment of vulnerable groups and thereby reduce TB mortality.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1515-21, i.
Completion of isoniazid preventive therapy and survival in HIV-infected, TST-positive adults in Tanzania.
Kabali C, von Reyn CF, Brooks DR, Waddell R, Mtei L, Bakari M, Matee M, Pallangyo K, Arbeit RD, Horsburgh CR Jr.
Population Health Research Institute, Hamilton, Ontario, Canada. firstname.lastname@example.org
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SETTING: The World Health Organization recommends the use of isoniazid preventive therapy (IPT) for human immunodeficiency virus (HIV) infected patients with a positive tuberculin skin test (TST). However, due to concerns about the effectiveness of IPT in community health care settings and the development of drug resistance, these recommendations have not been widely implemented in countries where tuberculosis (TB) and HIV co-infection is common.
OBJECTIVE: To evaluate the effectiveness of IPT on survival and TB incidence among HIV-infected patients in Tanzania.
DESIGN: A cohort study nested within a randomized trial of HIV-infected adults with baseline CD4 counts of ≥ 200 cells/μ l was conducted to compare survival and incidence of active TB between TST-positive subjects who did or did not complete 6 months of IPT in the period 2001-2008.
RESULTS: Of 558 TST-positive subjects in the analytic cohort, 488 completed 6 months of IPT and 70 did not. Completers had a decrease in mortality compared to non-completers (HR 0.4, 95%CI 0.2-0.8). However, the protective effect of IPT on the incidence of active TB was non-significant (HR 0.6, 95%CI 0.3-1.3).
CONCLUSION: Completion of IPT is associated with increased survival in HIV-infected adults with CD4 counts ≥ 200 cells/μ l and a positive TST.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1522-7, i.
Nansera D, Graziano FM, Friedman DJ, Bobbs MK, Jones AN, Hansen KE.
Mbarara University of Science and Technology/Teaching Hospital, Mbarara, Uganda. email@example.com
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BACKGROUND: Vitamin D increases cathelicidin production, and might alter mortality due to tuberculosis (TB) in human immunodeficiency virus (HIV) coinfection. However, due to abundant sun exposure, vita min D levels might be excellent among Ugandans with HIV and TB.
METHODS: We measured 25(OH)D and calcium levels in 50 HIV-negative, 50 HIV-infected and 50 TB-HIV coinfected Ugandan adults.
RESULTS: Mean ± standard deviation 25(OH)D levels were 26 ± 7 ng/ml in HIV-negative, 28 ± 11 ng/ml in HIV-infected and 24 ± 11 ng/ml in TB-HIV co-infected adults (P > 0.05 all comparisons). Vitamin D deficiency (< 12 ng/ml) was present in 10% of the HIV-infected subjects, 12% of the TB-HIV co-infected and none of the healthy controls (P = 0.03 for healthy vs. TB, P > 0.05 for other comparisons); 20% of the healthy controls, 22% of the HIV-positive and 38% of the TB-HIV co-infected subjects (P = 0.047 for healthy vs. TB, P > 0.05 for other comparisons) had suboptimal vitamin D levels (< 20 ng/ml). No participant had hypercalcemia. Serum 25(OH)D levels correlated positively with body mass index (r = 0.22, P = 0.03) and serum calcium levels (r = 0.18, P = 0.03).
CONCLUSIONS: Ugandan HIV-infected adults with and without TB commonly had suboptimal vitamin D levels. Clinical trials are needed to evaluate the effect of vitamin D on health outcomes in HIV-infected patients with low vitamin D levels.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1528-34, i.
Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam.
Nguyen DT, Hung NQ, Giang LT, Dung NH, Lan NT, Lan NN, Yen NT, Bang ND, Ngoc DV, Trinh LT, Beasley RP, Ford CE, Hwang LY, Graviss EA.
University of Texas School of Public Health, Houston, Texas. firstname.lastname@example.org
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SETTING: District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam.
OBJECTIVE: To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam.
DESIGN: A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB).
RESULTS: The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance.
CONCLUSION: Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1535-9, i.
Evaluation of collaborative tuberculosis and human immunodeficiency virus activities in Phnom Penh, Cambodia.
Tsurugi Y, Eam KK, Eang MT, Uehara R, Nakamura Y, Murakami K, Sugiyama T, Yamada N, Ishikawa N.
The Research Institute of Tuberculosis, Tokyo, Japan. email@example.com
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SETTING: Phnom Penh, Cambodia.
OBJECTIVES: 1) To monitor the number of tuberculosis (TB) patients undergoing human immunodeficiency (HIV) testing during TB treatment and trends of referral of TB-HIV patients to HIV services following the appointment of TB-HIV coordinators in TB wards, and 2) to investigate factors that influence undesirable TB treatment outcomes.
DESIGN: Retrospective descriptive study based on a review of patient records and interviews with programme staff.
RESULTS: Eighty-six per cent of newly registered TB patients underwent HIV testing. Most of the TB-HIV patients were referred to HIV services. Using logistic regression analysis, the risk of an undesirable treatment outcome in extra-pulmonary TB was significantly lower than in smear-positive pulmonary TB. Interviews revealed that patients in poor clinical condition at the start of TB treatment or who faced social problems, such as homelessness or foreign nationality, were at considerable risk for undesirable TB treatment outcomes.
CONCLUSION: The appointment of TB-HIV coordinators to TB wards resulted in better HIV testing uptake and referral to HIV care and treatment services. To save TB-HIV patients’ lives, it is important to continue this kind of study over a longer term to monitor these activities and to identify high-risk patients.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1540-5, i.
Study of tuberculosis and AIDS stigma as barriers to tuberculosis treatment adherence using validated stigma scales.
Kipp AM, Pungrassami P, Stewart PW, Chongsuvivatwong V, Strauss RP, Van Rie A.
University of North Carolina, Chapel Hill, North Carolina. firstname.lastname@example.org
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BACKGROUND: Adherence to tuberculosis (TB) treatment is important for TB control. The effect of stigma on adherence has not been well quantified.
OBJECTIVE: To identify the effects of TB and acquired immune-deficiency syndrome (AIDS) stigma on missed doses during TB treatment.
DESIGN: Validated TB and AIDS stigma scales assessing perceived and experienced/felt stigma were administered in a prospective cohort of 459 TB patients at TB treatment initiation and after 2 months. Repeated measures and multivariable models estimated the effects of stigma on the rate of missed doses.
RESULTS: Fifty-six per cent of patients missed no doses, and associations between stigma and missed doses were minimal. Heterogeneity of effects was observed, how- ever, with higher experienced and felt TB stigma increasing missed doses among women (adjusted RR 1.22, 95%CI 1.10-1.34) and human immunodeficiency virus (HIV) co-infected patients (aRR 1.39, 95%CI 1.13-1.72). Experienced and felt AIDS stigma also increased missed doses among HIV co-infected patients (aRR 1.43, 95%CI 1.31-1.56).
CONCLUSION: Stigma has a minimal effect in this population with good adherence. Among women and HIV co-infected patients, however, experienced and felt stigma, and not perceived stigma, increased the rate of missed doses. Further research is needed to determine if stigma or coping interventions among these subgroups would improve adherence.
Int J Tuberc Lung Dis. 2011 Nov;15(11):1553-5, i.
Kurbatova EV, Gammino VM, Bayona J, Becerra M, Danilovitz M, Falzon D, Gelmanova I, Keshavjee S, Leimane V, Mitnick CD, Quelapio MI, Riekstina V, Taylor A, Viiklepp P, Zignol M, Cegielski JP.
US Centers for Disease Control and Prevention, Atlanta, GA EKurbatova@cdc.gov
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Monthly culture is usually recommended to monitor treatment of multidrug-resistant tuberculosis (MDR-TB). As mycobacterial laboratory capacity is limited in many settings, TB programs need evidence to decide whether monthly cultures are necessary compared to other approaches. We simulated three alternative monitoring strategies (culture every 2 or 3 months, and monthly smears alone) in a cohort of MDR-TB patients in Estonia, Latvia, Philippines, Russia and Peru from 2000 to 2004. This retrospective analysis illustrated that less frequent testing delays confirmation of bacteriological conversion. This would prolong intensive treatment, hospitalization and respiratory isolation, increasing cost and toxicity. After conversion, less frequent testing could delay diagnosis of possible treatment failure.