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Results

Quantifying the influence of wind on mosquito flight and consequences for malaria transmission in southern Malawi 21 May 2018

Spatially targeting malaria control interventions in areas of high disease burden will become a more cost-effective and sustainable approach for national programmes in the era of elimination. To achieve this the geographical scale in which to implement control and identify the most likely sources and routes of infection are critical. Wind-assisted mosquito dispersal is an important, yet currently undervalued, source of information to track the spread of malaria and predict outbreaks. We will develop and apply a model, previously and successfully used to track the wind-borne spread of Bluetongue virus by midges, to predict the spread of malaria in a rural region of southern Malawi. The ‘spatial-temporal wind-outbreak trajectory simulation’ (SWOTS) model will use wind data, household infection status and insect flight parameters to determine the most likely source and route of infection during the rainy season. We will empirically validate the output from SWOTS using a simple mark-recapture field experiment to determine the influence of wind direction and speed on vector movement. This pilot project will determine the applicability of SWOTS as a risk assessment and disease preparedness tool for malaria in rural Africa and lay the foundations to extend to other transmission settings and vector-borne disease systems.

Amount: £94,334
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

PArtner-provided HIV Self-Testing and Linkage (PASTAL) in antenatal care clinics: methodology and delivery of an adaptive cluster-randomised trial in Blantyre, Malawi. 24 Nov 2014

HIV remains a global public health problem with 2.3 million new infections in 2012. Efforts to eliminate paediatric HIV have greatly strengthened HIV testing and counselling (HTC) services in African antenatal care clinics (ANC). HTC is a critical step towards HIV care and prevention, with couple-based testing especially valuable in ANC. In Malawi, >80% of pregnant women but only 15% of male partners undergo HTC. We have recently shown that self-testing (HIVST) is highly acceptable to men and can increase uptake of ART at population level. HIVST may need additional interventions to maximise uptake and subsequent HIV care/prevention services, such as financial incentives, or short messaging services. The wide range of potential interventions, and need for multiple direct comparisons pose methodological challenges in identifying optimal strategies. We propose to develop and apply novel methodologies to evaluate candidate interventions for male partner engagement for which current e vidence is promising but insufficient to proceed to Phase III trials. The broad objectives are to develop statistical methodology required to combine adaptive multi-arm multi-stage designs with cluster-randomized trial methodologies and to use these to identify most promising candidate interventions for encouraging HIVST with linkage by male partners of ANC attendees.

Amount: £235,231
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Malawi-Liverpool-Wellcome Trust Clinical Research Programme - supplementary award for Chikhwawa infrastructure improvements 27 May 2014

MLW is strategically placed to conduct high quality laboratory, clinical and epidemiological science relevant to health in sub-Saharan Africa. The programme is embedded within a rapidly growing medical school, co-located within the largest teaching hospital in Malawi with direct access to urban and rural populations. In the next 5 years, MLW research will increase fundamental understanding of disease mechanisms and burden, test novel interventions and ensure translation into health care. The cor e programme will ensure MLW delivers the following aims: (1) Pursuit of cutting-edge research focused on health problems with a high disease burden. Research management, mentorship, development of bioinformatics expertise, and clinical and diagnostic laboratory competencies, ensuring the highest quality. (2) Provision of a research training environment for clinicians, epidemiologists and laboratory scientists. Local research infrastructure, operational and financial systems, data manageme nt and research governance support. (3) Development of globally competitive research leaders. Moving towards local leadership, embedded within the University of Malawi College of Medicine, attracting further intermediate and senior Fellows, and encouraging re-entry of trained Malawian scientists. (4) Translation of scientific advances into human health improvements. Defining national and international research agendas through policy relevant evidence; policy committee membership; research synthesis workshops; and public engagement.

Amount: £160,976
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Institutional Strategic Support Fund FY2013/14 14 Oct 2013

Supported by ISSF funding, LSTM has offered a number of competitive challenge grants to LSTM based research projects in the general area of resistance (with a focus on drugs and insecticides – RDI). These projects will need to be completed within two years (Oct 2016).The research will focus on an area relevant to RDI, will involve PIs from more than one discipline (including external partnerships with NHS Trusts, other academic groups and industry partners), and will have the potential to generate data that can leverage further competitive research funding on completion. Funding: Renewal of Gates-funded IVCC and AWOL programmes, the latter with a major component using a novel mouse model for basic and translational research Reachout consortium. funded by EU to look at strengthening health systems through close-to-community services Cookstove project in Malawi funded by MRC MRC New Investigator Award – "Is targeting vascular remodelling by filarial parasites a viable anti-morbidity solution" CouNTDown programme for NTD implementation research funded by DFID (Adams, Reimer) Health Impact: Development of innovative ‘tiny target’ control systems for tsetse flies (Torr) Discovery of a previously unidentified reservoir of Schistosoma infection in pre-school children (Adams). Introduction of intermittent preventive therapy during pregnancy as a WHO policy recommendation (Terlouw). Development and validation of a human challenge model for Streptococcus pneumonia (Glennie). Development of new monitoring and evaluation systems for malaria surveillance (Terlouw) LSTM’s improving and rapidly growing media visibility and social media presence are beneficial in creating attention for our various PE initiatives

Amount: £500,000
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Improving neonatal health in remote rural areas in China and Vietnam. 25 Mar 2014

Newborn (first 4 weeks of life) health remains a significant problem in China and Vietnam, especially in rural areas where they are 3 to 4 times more likely to die than in more developed areas. Most newborns can be treated with cost-effective interventions at facility and community levels, which do not require high-level training or costly equipment. Achieving high coverage of these interventions in the poorest areas could reduce neonatal deaths by at least 70%. While NH practice guidelines exist in China and Vietnam at national and local levels to guide on appropriate care and treatment, a major problem is ineffective implementation of the guidelines. This development study will assess the feasibility of using a participatory problem-solving intervention with local health managers to improve NH guideline implementation. If feasible, it will inform the design of a full-scale study to evaluate the effectiveness of the intervention. In the full-scale study, the research team would support local health managers through problem-solving and planning workshops, mentoring and capacity development to (1) assess the effectiveness of current guidelines; (2) identify barriers to improved implementation relating to service delivery (e.g. workforce issues, transport, equipment and supplies) and service demand (limited by remote access and traditional beliefs); (3) develop feasible strategies within current resource constraints e.g. re-organising services and the workforce, and using suitable community engagement models to stimulate demand for improved services; and 4) develop appropriate methods to monitor impact and unintended consequences. To assess the intervention's feasibility in remote, rural China and Vietnam the development study must address 4 questions: 1. What are the current health service management practices and the degree of freedom for decision-making at different systems levels for improving NH outcomes? 2. What are the opportunities for developing or strengthening community actions to support improved NH outcomes? 3. What is the potential for monitoring NH outcomes and measuring cost-effectiveness of interventions at different health systems levels? 4. What is the feasibility for local managers to use a participatory problem-solving intervention to implement existing practice guidelines for improving NH outcomes covering community, primary and referral levels and what would be the best vehicle for the intervention? We plan to conduct desk-based reviews of NH practice guidelines, challenges of monitoring NH impact in remote areas and NH intervention cost-effectiveness, before holding a 2-day workshop in Beijing to refine our field work plan and data collection tools and conduct 3 national key informant interviews (KIIs). We will then collect data in Guizhou, China using 4 methods: (i) KIIs: community level representatives, local health service managers, frontline health workers and provincial level policy makers and senior health officials; (ii) focus group discussions: recent mothers and community members; (iii) document review of community action agreements and provincial/national policies and plans; (iv) observation of health management information systems (HMIS) and accounting systems. A smaller research team will repeat this data collection protocol in Tay Nguyen, Vietnam, before analysing the two country datasets. This will inform the design the full-scale study and facilitate stakeholder engagement. We will produce 3 outputs on monitoring NH services in remote areas; practicalities of monitoring NH in remote China and Vietnam; and national policy space and local decision making freedom to improve NH services. Three levels of stakeholders will benefit: local (health service managers and staff), national (policy makers in China's MCH centres and Vietnam's NH technical working group) and international (e.g. Unicef, WHO, PMNCH and implementation science groups like WHO-led Implementation Research Platform).

Amount: £22,882
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Improving the efficacy of malaria prevention in an insecticide resistant Africa 08 Dec 2015

Impressive reductions in malaria have occurred throughout sub-Saharan Africa over the past 12 years. However progress has not been geographically uniform and there are some high-burden countries where, despite good coverage with long lasting insecticide-treated nets (LLINs), the main preventative measure recommended by WHO, parasite prevalence rates and mortality from malaria remain obstinately high. Burkina Faso falls into this category. Despite two successful national LLIN distribution campaigns 60 % of children are persistently infected with malaria. Increased resistance to the pyrethroid insecticides used in LLINs and extensive transmission by mosquitoes biting outside the home, or at times when people are not protected by LLINs, are likely reducing the impact of LLINs but the relative importance of these poorly characterised vector factors, in relation to other human or health system factors has never been determined. This project will collect extensive empirical data and use models of malaria transmission to quantify the level of protection provided by LLINs in an insecticide resistant Africa. Via a detailed understanding of the factors limiting the efficacy of current tools we will identify the most cost effective, complementary interventions that would drive malaria transmission towards zero.

Amount: £1,704,931
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Optimising antimicrobial therapy for sepsis in Malawi 30 Sep 2016

Mortality from severe sepsis in Malawi is extremely high – 50% compared to 20-30% in high-income settings. Guidelines on optimal use of available therapies (antimicrobials, intravenous fluids and oxygen) are extrapolated from high-income settings and/or based on expert opinion. Data to inform acute care guidelines for Malawi and sub-Saharan Africa (SSA), are urgently needed. Data from SSA suggest sepsis is caused by diverse pathogens including M. tuberculosis, not covered by current empiric therapy, and I propose that broadening the spectrum of empiric antimicrobial chemotherapy may play a role in improving outcomes. Great care must be taken with such a strategy to minimise development of antimicrobial resistance (AMR). The epidemiology of this emerging threat is not well understood in Malawi, but longitudinal surveillance reveals an alarming increase in drug resistant infection. I propose to: Conduct a prospective case-cohort study of severe sepsis patients in Malawi to provide a detailed description of sepsis, including microbiological causes and determinants of poor outcome. Use deep sequencing to study survivors and describe acquisition and duration of carriage of resistant bacteria. Ultimately, this will guide antimicrobial strategies to achieve the twin aims of improving clinical outcomes while minimising the development of AMR in Malawi.

Amount: £396,007
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

When is enough, enough? Physiological responses to fluid resuscitation in sub-Saharan African adults with sepsis 23 May 2018

How are cardiovascular responses to intravenous fluid determined by causative pathogen, duration of illness and pre-existing cardiac disease in patients with sepsis in Malawi? Over 30 million people develop sepsis every year. The first six hours of treatment is critical, as in severe cases mortality is 25-50%, predominantly due to early cardiovascular compromise. In low income countries, intravenous fluids are used as primary supportive treatment. However, the three existing African trials describe higher mortality in those receiving higher fluid volumes, without any pathophysiological explanation. I will identify important mediators of treatment success in Africa examining biologically plausible candidates: 1) pathogen-specific effects; 2) sub-acute physiological compensation from late presentation; 3) existing cardiovascular pathology (related to rheumatic heart disease, HIV and hypertension). I will investigate cardiovascular dynamics in Malawian adults during sepsis resuscitation and unpick the causes of aberrant physiology by careful aetiological description, detailed cardiac and pulmonary ultrasound monitoring, and measures of tissue perfusion. I will investigate novel and existing mathematical models as predictors of specific adverse outcomes (pulmonary oedema, kidney injury, circulatory collapse), providing a theoretical underpinning for personalised fluid management, and the capacity to hypothesis-test alternative strategies for future clinical trials.

Amount: £813,093
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Enzyme inhibitors as a novel treatment for snake venom induced necrosis 31 May 2018

Snakebite is a neglected tropical disease that causes both systemic (~125,000 fatalities per annum) and local (up to 500,000 cases of long-term morbidity) toxicities. Snakebite therapy, known as antivenom, is highly ineffective at treating the local tissue destructive effects of snake venom, as antivenom antibodies are poor at crossing the blood-tissue barrier. In this project I will assess the validity of neutralising necrotic snake venoms with an alternative approach - enzyme inhibitors, which will target the toxin families (snake venom metalloproteinases and phospholipases A2) known to cause local tissue destruction. To do so, I will screen a range of small molecules that have been licensed as human medicines or demonstrated to be safe in clinical trials, to facilitate rapid translation. I will first use in-house, small-scale, biochemical assays to characterise the metalloproteinase and phospholipase activity of ten known necrotic venoms, before assessing the neutralising capability of the inhibitors in the same assays. Next, I will use matrigel as a substrate representing the basement membrane extracellular matrix for degradation based assessments. The results of these assays will identify the optimal combination of anti-necrosis enzyme inhibitors that can be taken forward into preclinical assessments of in vivo venom neutralisation in the future.

Malawi Liverpool Wellcome Trust Programme - Core Award 01 Jun 2017

We will achieve internationally excellent translational science to benefit human health with a focus on sub-Saharan Africa. MLW is built around excellent laboratories, strategically located in the largest hospital in Malawi, closely linked with the community and an integral part of the medical school. These relationships provide a valuable opportunity replicated in few centres in Africa to study major health issues spanning both community and hospital. We will manage two major Programmes: (1) Preventing death from severe infection, and (2) Transmission reduction in infectious diseases and continue to publish over 100 papers/year. Over the next 5 years, we will target clinical syndromes of sepsis, meningitis, diarrhoea and pneumonia with vaccine, behavioural and clinical management strategies. We will focus on transmission of HIV, TB and malaria with improved access to care, diagnosis and treatment. In addition, a Strategic Initiative will target selected high burden chronic diseases (lung impairment, stroke, blindness), particularly related to HIV. In partnership with the College of Medicine we will deliver Training that will attract, train and retain local and international senior scientists. Through our partnership with the Ministry of Health, our Policy Aims will ensure that our research is both relevant and applied to improve human health.

Amount: £25,084,066
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Developing a universal antivenom to treat snake venom-induced consumption coagulopathy 24 Feb 2016

Snakebite is a neglected tropical disease that causes ~100,000 deaths each year. Venom-induced consumption coagulopathy (VICC) is the most common, clinically important, pathology associated with snakebite. Existing antivenom treatments exhibit limited paraspecific efficacy, poor levels of antibody specificity and high incidences of adverse reactions. The aim of this project is to develop a single, pathology-specific, antivenom to be used throughout the world for treating venom-induced consumption coagulopathy caused by snakebite. The specific goals are: To identify the venom constituents that cause procoagulant bioactivities induced by different snake venoms To determine whether a panel of murine monoclonal antibodies can neutralise procoagulation irrespective of snake species To demonstrate proof of concept for humanising murine monoclonal antibodies specific to venom toxins To do so, I will first characterise the specific venom toxins found in different snake species that cause VICC using small-scale proteomics and biochemical assays. Next, I will design epitope-string immunogens to stimulate the production of antibodies specific to those toxins. I will then use a monoclonal antibody approach to generate a first of its kind, pathology specific, antivenom that will be validated pre-clinically for future worldwide use for treating VICC. Key words: snakebite, antivenom, protein, toxins, pathology, antibody

Amount: £817,821
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Accelerating malaria elimination efforts in the Sudano-Sahelian region of Africa: elucidation of factors driving transmission and unravelling the molecular basis of insecticide resistance in the major malaria vectors 22 Jun 2016

Malaria still devastates the tropical world; with a quarter of overall estimated mortality (~438,000 deaths) occurring in Nigeria alone. Achievement of 90% reduction in malaria cases and death by 2030 requires significant progress in control of the disease in Nigeria, and other neighbouring countries, such as Niger, Cameroon and Chad. The disease dynamics, i.e. composition and distribution of the malaria vectors, dynamics of malaria transmission and profiles of insecticides resistance and factors driving is poor characterised in the Sudano-Sahelian regions of these countries. Understanding the bionomics of the malaria vectors from these regions is indispensable to malaria control and elimination. To fill this important gap we intend to characterise the major malaria vectors from the Sudano-Sahelian regions of sub-Saharan Africa, to establish their contribution toward malaria transmission, and elucidate the features of insecticide resistance. Specifically, we aim to: 1- Establish the distribution of the major malaria vectors from Sudano-Sahelian region, their seasonality and vectorial capacity; 2- Characterise insecticide resistance and cross-resistance status of the mosquito populations, identify potential synergists and candidate resistance genes; 3- Identify the major genes responsible for metabolic resistance, and discover molecular markers of the resistance to detect and track it in the field.

Amount: £281,800
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

The Cooking and Pneumonia Study: a focus on food 25 Nov 2014

we will substantially enhance the food-focused aspects of this work. The work will be conducted in Chikhwawa, an area of Malawi greatly affected by food insecurity and where times of serious food shortage are within easy living memory. One of the most common serious adverse events reported among under 5 year olds in CAPS is malnutrition requiring hospitalization highlighting the ongoing impact of poor nutrition and food insecurity on the community we are working with. We will work with our Community Advisory Group leaders to identify two CAPS villages (one intervention and one control) and two households from each village to take part in some initial in depth inter-generational semi-structured discussions about cooking, food, health (pneumonia, gastroenteritis and nutrition particularly) and the environment. Following these discussions each household will be given a stills camera for 24 hours tocapture moments of interest/importance to them during the day with a follow upinterview the next day to capture the stories behind their pictures.

Ethical concerns for health professionals, media and the public in promoting adequate and safe blood transfusion services in Africa: a case study of Ghana and Zimbabwe. 21 May 2012

Ethical concerns abound in the area of providing effective blood transfusion services. In many parts of Africa, there are strong cultural and spiritual beliefs about blood. Blood transfusion services rely on donations from the general public and therefore the public view of blood and blood donation is absolutely critical. The media have a significant role to play in encouraging a healthy perception of the importance and safety of blood transfusion services, and this raises a series of ethical implications for journalists, health professionals and the public. Strong relationships and partnerships between blood transfusion centers and the media in Africa are vital. This research project in Ghana and Zimbabwe aims to explore the ethical concerns ofdifferent actors in relation to blood transfusion services and work to build stronger partnerships to improve donation rates of safe blood.

International Engagement Programme. 20 May 2011

We propose that MLW becomes more pro-active in engagement with local communities, organisations and government bodies. We plan to ensure that thereis full and free public access to information on our research and its findings. Over the next five years we will pursue a consolidated and better targeted communication agenda in partnership with the COM RSC.

Amount: £113,653
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Open access award. 20 Sep 2011

Not available

Amount: £30,000
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Study of carbamate and organophosphate resistance in Anopheles gambiae, the main malaria vector in West Africa. 23 Nov 2010

Increasingly carbamates and organophosphates insecticides are suggested as alternatives to pyrethroids due to the high resistance levels recorded to pyrethroids particularly in Anopheles gambiae s.s. from West Africa. The resistant to these insecticides is now challenged by the occurrence of a new duplicated allele (ace-1D). To preserve the effectiveness of vector control based on insecticides, it need to provide useful information on organophosphate and carbamate resistance. The development of improved tools to detect and monitor insecticides resistance mechanisms are a crucial need and that is the goal of this proposal. Here, we will: (i) Develp by 2013 diagnostic tools to detect the ace-1D allele in An. gambiae natural populations using news innovative molecular techniques. (ii) Monitor ace-1R and ace-1D frequencies in the field mosquitoes of seven West African countries up to 2014 by using current and developed diagnostic tools. (iii) Characterise the metabolic resistance mechan isms against carbamates/organophosphates using a newly developed An. gambiae whole genome Agilent array. If funded, this fellowship will necessary increase the research capacity of IRSP young research team which will esealy assist technically the NMCP in Benin. Futhermore this proposal will be a baseline for a strong collaboration between LSTM and IRSP.

Amount: £218,524
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

Wellcome Trust Clincal PhD Programme at the University of Liverpool: 'The IDEA study: intervention to address delays in equitable access to ART.' 13 Jul 2010

The research aims of this project are to understand the barriers to uptake of antiretroviral therapy (ART) among eligible HIV-infected adults in Malawi; and to investigate the effect of a Lay Health Worker (LHW)-provided educational and support intervention in improving access to ART. This research will be undertaken in two phases. Firstly we will undertake a cohort study of newly diagnosed HIV-positive adults in the primary health care system in Blantyre. Mixed quantitative and qualitative methods will be used. Uptake of ART in eligible participants; uptake of CD4 count sampling; collection of CD4 results; collection of cotrimoxazole preventative therapy; hospital illness episodes; and mortality will be assessed for four months following HIV diagnosis, with home-based tracing where necessary. Semi-structured in-depth interviews will be undertaken with participants both successful and unsuccessful in initiating ART to investigate pathways and barriers to accessing care. Positive-living people with HIV in Blantyre will be recruited as Lay Health Workers. LHWs will undergo a two-month participatory training programme, building upon findings from the cohort study and LHW's own experiences of care-seeking, to develop an educational and community support intervention. LHWs will be trained in providing the study intervention and in data collection procedures and Good Clinical Practice. All LHWs will receive a salary and transport in the form of a bicycle. In the second phase, we will conduct a randomised controlled trial to test the hypothesis that newly diagnosed HIV-positive adults receiving an intensive educational and support intervention provided by LHWs will be more successful at accessing ART compared to standard care.

Amount: £352,526
Funder: The Wellcome Trust
Recipient: Liverpool School of Tropical Medicine

"Captured Memories - Far East prisoner of war experiences over 60 years" to be held in October 2009 20 Oct 2009

To bring six ex-Far Eastern Prisoners of War (FEPOW) to LSTM to participate in a unique round-table discussion with clinical and research medical staff at LSTM. Some of the FEPOW, who are all in their late-80s - 90s, are ex-patients of the LSTM. The discussion, chaired by Professor Gill, will take place in front of an invited audience including medical staff of the school, medical students and a group of local 6th form pupils who are studying FEPOW history research as part of the LSTM oral history project. It will be recorded and added to the School's existing FEPOW oral history archive and also lodged with the Imperial War Museum's Sound Archive. The seminar is not open to the general public. Dr Sally Sheard, Senior Lecturer in Medical History at the University of Liverpool will be assisting in the organisation and running of the round table event. She has a wealth of experience in running witness seminars.