I. D. Rusen

Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

FIDELIS—Innovative Approaches to Increasing Global Case Detection of Tuberculosis

Tuberculosis was declared a global public health emergency in 1993. In 2003, only 45% of the worlds estimated new smear-positive tuberculosis cases were detected-well below the 70% global case detection target set by the World Health Organization. The FIDELIS (Fund for Innovative DOTS Expansion Through Local Initiatives to Stop TB) initiative is a new global disease control initiative that has been developed to rapidly assess and implement innovative approaches to increase tuberculosis case detection. To date, 32 projects have been approved-covering approximately 378 million people in 13 countries-24 (75%) of which are in the worlds 6 highest-burden countries. A wide range of target populations and interventions have been incorporated into successful FIDELIS projects. The FIDELIS initiative may serve as a model to discover best practices to address other urgent global public health problems.

Treatment Delay Among Tuberculosis Patients in Tanzania: Data from the FIDELIS Initiative.

BackgroundSeveral FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP) during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on treatment delay and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB) patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis.MethodsTreatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study.ResultsWe included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays.ConclusionIn this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had a 25% longer median delay.

Poverty and lung health

The International Union Against Tuberculosis and Lung Disease (The Union) held its 40th World Conference on Lung Health in Cancun, Mexico, between 3 and 7 December 2009. It was attended by over 2000 delegates from 104 countries around the world. The conference featured four stimulating plenary sessions and an extensive selection of scientific symposia. A total of 1125 abstracts were also presented from five broad categories: clinical trials and TB basic science, clinical research for treatment and care, epidemiology, education, advocacy and social issues, and policy and program implementation. In addition, the conference was preceded by a series of well-attended postgraduate courses and workshops.

Capacity Building in Operational Research: More than One Way to Slice the Cake.

The importance of programmatically relevant operational research (OR) as a key driver to strengthen public health activities is well recognized (1). Moreover, building capacity of health workers from high-disease burden countries to independently conduct OR on priority issues within their health services is accepted as an essential component of public health programs. However, the approach taken in building local OR capacity varies widely between training initiatives. Program managers and those responsible for planning OR training activities may thus be left asking themselves what the best approach is for their own setting? The Union-MSF model is the training model adopted by the Structured Operational Research and Training Initiative (SORT IT), a global partnership led by the Special Program for Research and Training in Tropical Diseases at the World Health Organization (2). It has set the standard for hands-on, milestone-based training with an emphasis on tangible outputs – marked largely by the submission of research papers to peer-reviewed scientific journals. The success of this approach is undeniable as evidenced by the research outputs: by March 31, 2015, there had been 247 papers submitted to peer-review journals from 20 completed OR courses of which 208 (84%) were in press or published. The involvement in SORT IT has further established the standardization and quality of this training. To date, most of the research conducted under SORT IT has been retrospective analyses of routinely collected data. SORT IT partners are now planning expansion into more complex, prospective operational, and implementation research using mixed quantitative and qualitative methods. The International Union Against Tuberculosis and Lung Disease (The Union)-implemented TREAT TB project has undertaken several OR training activities within the multi-year research initiative (3). Several India-based trainings within this Initiative have followed very closely the SORT IT approach. TREAT TB has also supported training in South Africa, again adopting modular, hands-on approaches to research protocol development and implementation. However, the South Africa training program (Operational Research Assistance Project) included participants from both health services and academic settings, who were linked in pairs to jointly undertake a research project. Once again, the development and submission of a research paper related to a priority issue within their health service was a key output of the effort. More recently, TREAT TB has developed a virtual training program for OR. Utilizing a combination of synchronous (online learning together simultaneously) and asynchronous approaches, the program attempted to increase access to OR training while allowing participants to remain in their communities and workplaces. A small group of participants was selected for the pilot course. Four participants (out of six initiating the training) completed the training and presented their findings at an international scientific conference in 2014. Publication of their research manuscripts is pending. A country-based OR training program in Ethiopia was jointly conducted by international and local partners over a 2-year period beginning in 2012. Again utilizing modular training techniques, the Ethiopian Operational Research Initiative implemented a team approach to the research development and implementation phase. Teams usually consisted of four people representing the regional health bureau (RHB), the regional laboratory, a health facility and a local university. The research topics selected were based on a national OR priority setting exercise to ensure the relevance of the research undertaken. Successful outputs of the research effort included presentations in a symposium at an international conference and publication of a special supplement of a peer-reviewed journal comprising the research outputs from the initial wave of participants (4). These highlighted training initiatives were not without challenges. Hurdles in securing ethics approval locally and unexpected barriers to access data during the research implementation phase were among the “real-life” research issues faced by participants in the programs. The availability of experienced mentors within the course faculty offered timely support and, in most instances, practical solutions to overcome these challenges. The overall success of these varied OR training efforts suggests a range of approaches might attain the desired goal of building a larger pool of health workers able to independently undertake locally relevant OR leading to improved health services. While the experiences highlighted were focused on participants from low-to middle-income settings, the approach taken is likely equally applicable to public health workers of all backgrounds. Ongoing evaluation of OR training initiatives is essential to better delineate the ideal package for a given setting. Important components to be evaluated to direct future training initiatives include: the role of online/virtual training methods, the minimum duration of training required to transfer the necessary research knowledge and skills, the scope of research methods, and approaches appropriate for training different levels of health workers. Nonetheless, in advance of further evaluations, common factors that appear to form the basis of a successful research training program include: clear, time-based milestones for each stage of the research process, a strong mentorship component and concrete research outputs – namely a successfully completed research manuscript that is considered of sufficient quality to warrant submission to a national or international peer-reviewed journal. In addition to these core components for all OR trainings, we recommend an expansion of OR training content to include advanced research methods in the form of specialized training on qualitative research methods, health economics and how to conduct systematic reviews with meta-analyses among others, along with further evaluation of these efforts. Additionally, moving forward, an emphasis on assessment of the impact of OR on program practice and policy will be an increasingly important consideration in gaging the success of research training efforts. Ministries of Health and other stakeholders keen on increasing local capacity for OR, yet concerned about selecting a single, “correct” approach, may be reassured that a variety of approaches tailored to their local setting may deliver the ultimate goal of strengthened public health programs, provided the essential components are not overlooked.

The International Union Against Tuberculosis and Lung Disease: past, present and future

The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organization involved in the fight against tuberculosis. This review documents the history and structure of The Union up to 2009, and describes the achievements that have taken place in the field of tuberculosis and lung health. The progress made in tackling the major killer (pneumonia) of children less than 5 years of age, the barrier to affordable essential asthma medicines, the complex issue of tobacco control, the move into the realm of HIV and AIDS, and new ideas and activities around the increasingly important domain of operational research are described and discussed. Finally, as with many institutions that have seen a rapid phase of growth, expansion and decentralisation to regional offices around the world, the review highlights the internal strategic initiative that aims to fine-tune the organisational structure, clarify lines of authority, create more efficient business, human resource and financial systems and revise, where necessary, The Unions guiding mission, vision and values for the future.

RUSEN AND ENARSON RESPOND

We appreciate Lauer and Birn’s interest in our article. However, many of the concerns they raise are speculative and are not consistent with the operational reality of FIDELIS. First, the authors question the local nature of the FIDELIS projects and suggest that FIDELIS is most accessible to organizations affiliated with developed countries. In fact, the projects approved to date are truly local in nature; internationally associated nongovernmental organizations and academic institutions have been awarded only 7 of 32 projects approved in rounds 1 through 4. Second, Lauer and Birn wonder whether the members of the “existing TB control structure” who are charged with evaluating proposals will endorse innovative ideas. Our experience indicates that this concern is unfounded; innovative approaches are routinely approved by the proposal review committee. Recently approved activities such as mobilizing students to identify persons suspected of having tuberculosis or enlisting religious leaders to speak about tuberculosis at the mosque after Friday prayer can hardly be considered “existing standardized strategies.” Third, the authors question the focus on cost-effectiveness within the FIDELIS initiative. We agree that cost should be only one of several factors considered in evaluating potential tuberculosis control interventions. In an ideal world, costs would not be a consideration at all. However, to be competitive with other health priorities in need of funding and to ensure that successful interventions can be scaled up,1 FIDELIS projects must be able to show that they can produce results at a reasonable cost. Several FIDELIS projects have demonstrated that interventions can successfully target those with limited access to health services and still be cost-effective. Furthermore, the figure of US

Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.

80 per outcome is for additional costs related to the proposed innovative intervention, not including the routine costs of the existing program. Fourth, Lauer and Birn question the advisability of the 1-year funding cycle. We agree that the time frame for implementation is short and challenging. However, the innovative ideas funded by FIDELIS are being implemented in the context of ongoing public health programs and should not require extensive preparation or infrastructure. Furthermore, many projects have been able to meet this timeline and either obtain a second year of funding or incorporate successful activities into other country funding mechanisms. Of 32 projects in rounds 1 through 4, 11 have been awarded phase 2 funding and at least 4 other phase 1 projects have been able to continue their activities with funds obtained through other sources. FIDELIS is a relatively new initiative. We are continually examining our practices and procedures to reach our goals, and we welcome constructive input.