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      "title_narrative":["Engaging Partners in Childbirth for Prevention of Mother-To-Child Transmission of HIV (EPiC-pMTCT): preliminary work for a randomised controlled trial"],
      "description_narrative":["HIV is a major public health problem, and a major route of transmission is Mother-To-Child Transmission (MTCT) which accounts for about 10% of the national HIV burden in African countries. Prevention of this mode of transmission (pMTCT) is a key element in global HIV prevention and the World Health Organisation has recommended that pMTCT of HIV infection should be prioritized in sub-Saharan Africa. Evidence-based interventions to reduce MTCT are available in many maternity units in Africa, but their uptake is poor. The barriers to uptake are closely linked with the role of the male partners in perinatal care of the woman. It is known that men are the primary decision makers in many African countries where pMTCT is offered.  Studies show that women are more likely to (a) undergo HIV testing, (b) disclose their HIV status to their husband, (c) adhere to treatment during pregnancy (d) deliver in a pMTCT facility and, (e) comply with infant feeding recommendations if their partners are engaged in the pMTCT programme. While male participation has a potentially positive impact on the uptake of pMTCT interventions, initiatives to prevent mother-to-child HIV transmission in sub-Saharan Africa have focused overwhelmingly on women, to the unintended exclusion of their male partners. The actual impact of male involvement is unknown, as there is a lack of quantitative data on the benefits and effectiveness of male partner engagement. A recent Cochrane meta-analysis found only one eligible study that assessed the effectiveness of male involvement in improving women's uptake of pMTCT services, and that study only focused on one part of the perinatal pMTCT cascade. While male involvement holds promise for improving uptake of pMTCT interventions, further rigorous evaluation and implementation research is needed.  Efforts in this direction must, however, begin by addressing conceptual and methodological issues in the study and implementation of male partner involvement in pMTCT. A uniform definition of male participation in pMTCT programmes does not exist, and there are no standardized measures or reliable indicators of male involvement. Also needed is a reconceptualisation of the role of men in pMTCT. It has been argued that to maximize the health outcomes of pMTCT programs, men should not be seen as simply \"facilitating factors\" that enable women to access health-care services, but be recognized as a constituent part of reproductive health policy and practice.  Also, efforts to include male partners in HIV prevention for women have focused primarily on engaging men to support their female partners in adopting a prevention strategy, without also offering broader consideration for men's own health needs or of a social agenda aimed at promoting greater sex equality.  In a future study we propose to undertake a randomised controlled trial to assess a multi-component family-centred intervention. The hypothesis for the trial is that implementation of the intervention would result in improved uptake of pMTCT programmes in the intervention arm compared with the control arm. Before embarking on the trial, we propose to undertake development work (the current study) that will devise a programme of engagement of partners (i.e. the multi-component EPiC-pMTCT intervention) based on evidence in the literature and qualitative data from this study, and also assess the feasibility of conducting the cluster randomised controlled trial. The results from this development work will also inform the selection of centres that will participate in the proposed trial if it is deemed feasible.  The outputs from this research will comprise a synthesis of the evidence on barriers to male engagement in pMTCT, an analysis of the perspectives of men, women, health professionals and policy makers on male engagement, an intervention package, and a report on the feasibility of collecting the data required for the trial.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Unveiling the protein landscape of the African trypanosome cell surface and chasing down potential targets for therapeutic intervention"],
      "description_narrative":["Neglected tropical diseases are a diverse group of diseases that thrive mainly among the poorest of the world's populations. Three of the World Health Organisation's 10 most significant neglected tropical diseases - African trypanosomiasis (also known as sleeping sickness), leishmaniasis, and Chagas' disease - are caused by closely-related single-celled parasites. Human infection with African trypanosomes is brought about when an infected tsetse fly takes a blood meal. Without treatment the disease progresses through general ill health to coma and death. Current drugs in use against trypanosomes are old, toxic and failing due to emergence of resistance. Urgent new research is needed to identify potential new therapeutic options.  An unusual aspect of African trypanosomes is that they multiply in the human blood in full view of the body's defence systems. They do this by periodically changing their cell surface to escape recognition by the host. However, many molecules on the parasite surface perform essential functions and cannot be changed. Trypanosomes place these in a special, protected domain on the cell surface. Identifying surface-exposed invariant molecules and understanding how this protective segregation is maintained are of major scientific interest, as well as of practical utility in uncovering ways in which trypanosomes may be vulnerable to new therapies.  Using a combinatorial approach funded by the MRC, I have previously identified the composition of the African trypanosome cell surface. I now aim to exploit this knowledge to single out those invariant surface molecules that are essential to the survival of the parasite during infection. For this, I propose to harness some of the power of modern DNA sequencing technologies to test which cell surface genes, when silenced, cause the parasite to die inside the host. A similar method will be used to identify not only cell surface genes, but any genes that the parasite uses to maintain the cell surface organisation, which is so critical to escaping the host immune attack.   Finally, I propose to test those surface-exposed molecules for their potential as vaccines. My pilot experiments show that I can use genetically-modified parasite to screen for molecules on the parasite surface that are accessible to the immune system. I propose to develop this assay and test the most promising candidates in an animal model of human disease. The proposed work will increase our understanding of the fundamental biology of a significant human parasite, and also, by exposing essential surface molecules, provide the first steps in developing new treatments.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Mathematical modelling and spatial data analysis to inform TB care and control strategies in high TB incidence settings"],
      "description_narrative":["9.0 million people developed tuberculosis (TB) in 2013, with 1.5 million dying. Detecting TB disease at an early stage minimises the harm it causes to a person's health, and reduces the number of other people whom they infect. In richer countries with little TB, anyone who has had extended contact with someone with TB is likely to be tested. Poorer countries with much higher rates of TB mostly rely on people going to health centres themselves when they have symptoms of TB. Screening the general population for TB results in cases being detected earlier, but is too expensive to be widely used in high-TB countries. Developing a better understanding of the spatial distribution of TB will enable screening to be targeted at areas where it will have the greatest effect.  I will look at TB in four settings with moderate or high levels of TB: Blantyre city, Malawi; Karonga district, Malawi; Zambia; and Western Cape Province, South Africa. There are three main questions I will explore:  1) I will identify areas within the four settings where rates of TB are highest, and determine what characteristics of areas are associated with high levels of TB. For instance, TB is often concentrated in the poorest, most crowded areas of cities, and/or in areas with high rates of HIV.  2) Most TB screening programs use one of two approaches: offering quick and convenient screening at a set location (which may change on a regular basis), or screening people at their own homes (either because they live with someone who has been diagnosed with TB, or because screening is being offered to all households in an area). In the former case, uptake of screening is likely to be highest amongst people living close to a screening location, and drop off as the distance increases. Very little is known about how quickly screening rates drop off with distance however, or how quickly levels of undiagnosed TB increase again after a screening program has stopped. I will investigate these questions using data from a completed trial of two intervention strategies in Zambia and South Africa.   3) It is possible that data on the household locations of people diagnosed with TB can be used to develop more cost-effective interventions against TB. At the moment, the World Health Organization recommends testing all people who live in the same house as a TB patient. Testing people in their neighbourhood may also be beneficial however, for two reasons. Firstly, M. tb. (the bacteria that causes most TB disease) is infectious and the patient may therefore have transmitted M. tb. to or caught M. tb. from someone who lives nearby. Secondly, certain factors such as HIV or malnutrition increase the odds of someone having TB, and these factors are often locally clustered. I will use data from the settings listed above (which include the dates and household locations of all people diagnosed with TB) to estimate the number of TB cases that could have been detected earlier if neighbourhood screening had been carried out. I will see if cost-effectiveness can be improved by only screening the neighbourhoods of patients with certain characteristics, for instance HIV positive cases. Finally, I will use computer simulations to estimate the number of new TB cases that could be prevented by screening.  The planned research will give us a much better understanding of how the distribution of TB varies within high-TB cities and districts. It also will improve our knowledge of how current interventions against TB work at a small scale, and will suggest new interventions that can be used to reduce TB in resource poor settings.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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