Improving understanding of disease control implementation research through a mooc with participants from low- and middle-income countries: Evaluating participant reactions and learning.

The Special Programme for Research and Training in Tropical Diseases developed a massive open online course (MOOC) on implementation research with a focus on infectious diseases of poverty (IDPs) to reinforce the explanation of implementation research concepts through real case studies. The target MOOC participant group included public health officers, researchers and students. By reshaping institutions and building resilience in communities and systems, implementation research will allow progress towards universal health coverage and sustainable development goals.

Diversifying Implementation Science: A Global Perspective.

We present a joint global perspective about the urgent need to diversify the loci of knowledge creation and sharing in global implementation science. We underscore the imperative of addressing implementation research questions relevant to practitioners, policy makers, and researchers from low- and middle-income countries.

Benefits and barriers in a clinical research competency development scheme for low- and middle-income countries.

Background: The EDCTP-TDR Clinical Research and Development Fellowship (CRDF) scheme has offered one-year clinical research training placements for early- and mid-career researchers from LMIC since 1999.

Objective: Using the results of a 2018 external evaluation of the CRDF, the current article aims to identify the principal benefits for the main stakeholders of the CRDF scheme as well as the main barriers to accessing these benefits.

Method: Data analysis was derived from an external evaluation of the CRDF scheme.

Strengthening the core health research capacity of national health systems helps build country resilience to epidemics: a cross-sectional survey.

 TDR, The Special Programme for Research and Training hosted at the World Health Organization, has long supported Low- and Middle-Income Countries in strengthening research capacity through three training programmes: the Postgraduate Training Scheme (PGTS), the Clinical Research and Development Fellowship (CRDF), and the Structured Operational Research Training InitiaTive (SORT IT). In the advent of the COVID-19 pandemic, we assessed whether those trained through these programmes were involved in the COVID-19 response and if so, in which area(s) of the emergency response they were applying their skills. From the records for each training programme, we identified the individuals who had completed training during the relevant timespan of each programme: 1999-2018 for the CRDF scheme, 2015-2020 for PGTS, and 2009-2019 for SORT-IT.

Developing a framework of core competencies in implementation research for low/middle-income countries.

The field of implementation research (IR) is growing. However, there are no recognised IR core competencies in low/middle-income countries (LMICs), nor consistent curriculum across IR training programs globally. The goal of this effort is to develop a framework of IR core competencies for training programs in LMICs.

Tracking the career development of scientists in low- and middle-income countries trained through TDR's research capacity strengthening programmes: Learning from monitoring and impact evaluation.

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation.

Operational and implementation research within Global Fund to Fight AIDS, Tuberculosis and Malaria grants: a situation analysis in six countries.

Background: Operational/implementation research (OR/IR) is a key activity to improve disease control programme performance. We assessed the extent to which malaria and tuberculosis (TB) grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria ("Global Fund") include support for OR/IR, and discuss the implications of the current Global Fund operating mechanisms for OR/IR support.

Methods: The situation analysis focussed on malaria and TB, while HIV was excluded.

Developing the ethics of implementation research in health.

Implementation research (IR) is growing in recognition as an important generator of practical knowledge that can be translated into health policy. With its aim to answer questions about how to improve access to interventions that have been shown to work but have not reached many of the people who could benefit from them, IR involves a range of particular ethical considerations that have not yet been comprehensively covered in international guidelines on health research ethics. The fundamental ethical principles governing clinical research apply equally in IR, but the application of these principles may differ depending on the IR question, context, and the nature of the proposed intervention.

Efficacy and Safety of 'Fixed Dose' versus 'Loose' Drug Regimens for Treatment of Pulmonary Tuberculosis in Two High TB-Burden African Countries: A Randomized Controlled Trial.

Background: There are limited data on the performance of the use of fixed-dose combination (FDC) TB drugs when used under programmatic settings in high TB-endemic countries. We evaluated the efficacy and safety of FDC versus loose formulation (LF) TB treatment regimens for treatment of pulmonary TB (PTB) in the context of actual medical practice in prevailing conditions within programmatic settings in five sites in two high TB-burden African countries.

Methods: A two-arm, single-blind, randomized clinical trial comparing FDCs with separate LFs involving 1000 adults newly diagnosed with culture positive PTB was conducted at five sites in two African countries between 2007 and 2011.

Research Capacity Strengthening in Low and Middle Income Countries - An Evaluation of the WHO/TDR Career Development Fellowship Programme.

Between August 2012 and April 2013 the Career Development Fellowship programme of the Special Programme for Research and Training in Tropical Diseases (World Health Organization) underwent an external evaluation to assess its past performance and determine recommendations for future programme development and continuous performance improvement. The programme provides a year-long training experience for qualified researchers from low and middle income countries at pharmaceutical companies or product development partnerships. Independent evaluators from the Swiss Tropical and Public Health Institute and the Barcelona Institute for Global Health used a results-based methodology to review the programme.

Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial.

Background: WHO guidelines recommend early initiation of antiretroviral therapy (ART) irrespective of CD4 cell count for all patients with tuberculosis who also have HIV, but evidence supporting this approach is poor quality. We assessed the effect of timing of ART initiation on tuberculosis treatment outcomes for HIV-positive patients with CD4 counts of 220 cells per μL or more.

Methods: We did this randomised, placebo-controlled trial between Jan 1, 2008, and April 31, 2013 at 26 treatment centres in South Africa, Tanzania, Uganda, and Zambia.

Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12).

Biomarkers for tuberculosis disease activity, cure, and relapse.

New drugs, vaccines, and other therapies will be required to realise the goal of global tuberculosis elimination or control. This Review covers the important role biomarkers can have in accelerating drug development by providing validated surrogate endpoints that can bring enhanced statistical power to small short studies. Candidate biomarkers should differentiate people with active tuberculosis from healthy individuals, normalise with therapy, and reproducibly predict clinical outcomes in diverse patient populations.

Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities.

Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering.