This study uses a case study approach to examine the development of a massive open online course (MOOC) on intervention and implementation research in infectious diseases of poverty for learners in ...low- and middle-income countries (LMICs). Implementation research (IR) seeks to understand and address barriers to effective implementation of health interventions, strategies, and policies. In recent years, IR has attracted increased interest, and corresponding demand for training, however, current training opportunities are not easily accessible to learners in LMICs. In 2017, the MOOC was introduced to a diverse range of learners to enhance access to training materials and has been offered yearly since. Findings are based on the experiences of the MOOC working group which included developers and facilitators, and on interpretations of data such as forum discussion activity and Facebook posts. The use of material from local contexts and in local languages, and professional facilitation of discussion forums was identified by the working group to be key considerations in developing the MOOC. Other findings include the importance of using clear instructions and preparing discussion questions to stimulate learner engagement. These findings add to the limited knowledge of MOOCs developed for LMICs and are of value to others developing professional development MOOCs in LMIC health contexts.
Introduction A theory of change is a visual representation of the pathway by which a programme anticipates it will achieve its goal. It usually starts with discussions around the goal and works ...backwards through outcomes and outputs to activities. Methods We used a theory of change to improve coherence across three research entities at the WHO. Part of the remit of all three entities is to strengthen capacity in low-income and middle-income countries for implementation research. Results Representatives from the three entities were able to formulate a joint goal for strengthening capacity in implementation research. They identified three pathways by which this could be achieved: (a) conducting implementation research, (b) strengthening implementation research systems and (c) using implementation research for public health priorities. Conclusion The process of developing the theory of change and the logic framework it created, provided a means to track progress towards the goal and to guide improvements in programmes within their lifetime. The process we used to develop the theory of change and the pathways to achieve the joint goal are adaptable and could be used by other organisations that also aim to strengthen research capacity. This would lead to more coherence, better translation of research findings into decision-making and ultimately improvements in public health.
Women's global health leadership in LMICs Liu, Ewen; Iwelunmor, Juliet; Gabagaya, Grace ...
The Lancet global health,
September 2019, 2019-09-00, 20190901, Volume:
7, Issue:
9
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
TNF is an essential player in infections with Leishmania major, contributing to the control of the inflammatory lesion and, to a lesser degree, to parasite killing. However, the relative contribution ...of the soluble and transmembrane forms of TNF in these processes is unknown. To investigate the role of transmembrane TNF (mTNF) in the control of L. major infections, mTNF-knock-in (mTNFΔ/Δ) mice, which express functional mTNF but do not release soluble TNF, were infected with L. major, and the development of the inflammatory lesion and the immune response was compared to that occurring in L. major-infected TNF⁻/⁻ and wild-type mice. mTNFΔ/Δ mice controlled the infection and resolved their inflammatory lesion as well as wild-type mice, a process associated with the early clearance of neutrophils at the site of parasite infection. In contrast, L. major-infected TNF⁻/⁻ mice developed non-healing lesions, characterized by an elevated presence of neutrophils at the site of infection and partial control of parasite number within the lesions. Altogether, the results presented here demonstrate that mTNF, in absence of soluble TNF, is sufficient to control infection due to L. major, enabling the regulation of inflammation, and the optimal killing of Leishmania parasites at the site of infection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, ...neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (MPhi) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of MPhi. Extent of neutrophil apoptosis positively correlated with the number of MPhi added. This process was strictly dependent on TNF because MPhi from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using MPhi derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with MPhi was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate MPhi-induced apoptosis of neutrophils, but BALB/c MPhi were not as potent as C57BL/6 MPhi in this induction. Our results emphasize the importance of MPhi-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation.
Susceptibility and development of Th2 cells in BALB/c mice infected with Leishmania major result from early IL-4 production by Vbeta4Valpha8 CD4+ T cells in response to the Leishmania homolog of ...mammalian RACK1 Ag. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. We further showed that transfer of 10(7) BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10(7) control BALB/c spleen cells were resistant to infection with L. major and developed a Th1 response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.
Introduction In the 1970s, very few international programmes provided support to strengthen tropical disease research capacity and most research for the diseases prevalent in low- and middle-income ...countries (LMICs) was done by scientists and institutions in advanced industrialised countries. ...at different times in TDR's history there have been competitive grants exclusively targeting low-income countries to help them increase their capacities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mice from the majority of inbred strains are resistant to infection by
Leishmania major, an obligate intracellular protozoan parasite of macrophages in the mammalian host. In contrast, mice from BALB ...strains are unable to control infection and develop progressive disease. In this model of infection, genetically determined resistance and susceptibility have been clearly shown to result from the appearance of parasite-specific CD4
+ T helper 1 or T helper 2 cells, respectively. This murine model of infection is considered as one of the best experimental systems for the study of the mechanisms operating in vivo at the initiation of polarised T helper 1 and T helper 2 cell maturation. Among the several factors influencing Th cell development, cytokines themselves critically regulate this process. The results accumulated during the last years have clarified some aspects of the role played by cytokines in Th cell differentiation. They are providing critical information that may ultimately lead to the rational devise of means by which to tailor immune responses to the effector functions that are most efficient in preventing and/or controlling infections with pathogens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Capacity development for clinical research is held back by a lack of recognition for the skills acquired through involvement in clinical trials and in other varied types of global health research ...studies. Although some competency frameworks and associated recognised career pathways exist for different clinical research roles, they mostly apply to a single role or study setting. Our experience supports the need for an integrated approach, looking at the many roles in parallel and at all types of clinical research beyond trials. Here, we propose a single, flexible framework which is applicable to the full global health research team, and can be used for recognising staff by highlighting acquired skills and possible progression between various roles. It can also illuminate where capacity needs strengthening and contribute to raising research engagement. Through systematic analysis of existing competency frameworks and current job descriptions covering 11 distinct, broad clinical research roles, we identified and defined 50 key competencies required by the team as a whole and throughout the study life cycle. The competencies are relevant and adaptable to studies that differ in design, geographical location or disease, and fall in five main areas—(1) Ethics, Quality and Risk Management; (2) Study and Site Management; (3) Research Operations; (4) Scientific Thinking; and (5) Professional Skills. A pilot framework and implementation tools are now available online and in paper format. They have the potential to be a new mechanism for enabling research skills development and career progression for all staff engaged in clinical research globally.
The essential role of cytokines in parasitic diseases has been emphasised since the in vivo description of the importance of T helper 1 (Th1) and T helper 2 (Th2) CD4+ T cell responses in resistance ...and susceptibility to infection with L. major in mice. Th1 cells produced IL-2, IFN-γ and Lymphotoxin T (LT) and Th2 cells produce IL-4, IL-5 and IL-13. In this model of infection the correlation between on the one hand resistance to infection and the development of a Th1 response and on the other hand susceptibility and Th2 cell development allowed the identification of the mechanisms directing the differentiation of CD4+ T cell precursors towards either Th1 type or Th2 type responses. Cytokines are the crucial inducer of functional CD4+ T cell subset differentiation during infection with L. major. IL-12 and IFN-γ direct the differentiation of Th1 response and IL-4 of a Th2 response. In susceptible mice, careful analysis of IL-4 production during the first days of infection has shown that the IL-4 produced as a result of a very early burst of IL-4 mRNA expression (16 hours) plays a essential role in the maturation of a Th2 CD4+ T cell response by rendering the CD4+ T cell precursors unresponsive to IL-12. Activation of a restricted population of CD4+ T cells expressing the Vβ4 Vα8 TCR heterodimer after recognition of a single antigen, the LACK (Leishmania Activated c Kinase) antigen, resulted in this rapid production of IL-4 required for the subsequent CD4+ T cell differentiation. Thus, tolerization of these cells might contribute a strategy for preventing infection with L. major.
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