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A comprehensive body of research into the effectiveness, cost and distribution of long-lasting insecticidal nets (LLINs) by LSHTM has made a major contribution to the reduction of malaria-related mortality between 2008 and 2013, especially among children in Africa. The research formed the basis of a radically altered strategic approach to combating malaria by WHO and other agencies, and led to the roll-out of malaria campaigns based around LLINs in several African countries. LSHTM research into the technology of LLINs, which also contributed to these developments, is described in a separate case study.
LSHTM researchers carried out the initial trials of intermittent preventive treatment in infants (IPTi), a strategy to improve malaria control in very young children. LSHTM staff were active in setting up and running a dedicated research consortium which developed and executed a research agenda to provide data to inform policy. School staff presented evidence to a series of WHO policy-making meetings which in 2009 recommended that IPTi should be included as part of routine malaria control. This policy, which has been adopted in one country and discussed by eight others, has the potential to benefit hundreds of millions of lives.
A substantial programme of research carried out by LSHTM has provided evidence for a major shift of strategy and progress in global efforts to eliminate malaria. As a result, WHO now recommends a policy designed to ensure medically-treated individuals are non-infectious to mosquitoes. In addition, drug development partnerships such as the Medicines for Malaria Venture now include transmission interruption in the target product profiles for new medicines. Several countries have made strategic decisions for the prevention of malaria transmission on the basis of the research, and the senior investigators act as advisers to international anti-malaria initiatives.
Research in West Africa by LSHTM and partners has shown that monthly treatment with effective antimalarial drugs during the rainy season provides children with a very high degree of personal protection against malaria, can be delivered on a large scale by community health workers at moderate cost, and with no serious side-effects. Based on this research, WHO now recommends that children living in Sahel areas where malaria is a major problem should receive such `seasonal malaria chemoprevention' (SMC) with sulfadoxine-pyrimethamine plus amodiaquine. Ten countries have incorporated SMC into their strategic plans for malaria control.
Malaria kills around 650,000 children a year but can be prevented by killing the mosquito vectors. As mosquitoes become resistant to insecticides the prevention measures can become ineffective. Research at the Liverpool School of Tropical Medicine (LSTM) led by Professor Hemingway FRS has been instrumental in the development of current World Health Organisation (WHO) guidelines to manage resistance, and has led to improved resistance diagnostics and novel monitoring software to integrate entomological and human health outcomes. LSTM's research led to the creation of the Innovative Vector Control Consortium (IVCC) which was established as an independent Product Development Partnership (PDP) in 2008. New, longer lasting formulations of insecticides developed by IVCC are now in operational use, and several novel public health insecticides are under development.
Research carried out by LSHTM made a fundamental contribution to the creation of the Affordable Medicines Facility — malaria (AMFm), a financing mechanism initiated to improve access to effective antimalarials through subsidies and price negotiations with drug manufacturers. Drawing on LSHTM research showing the importance of the private sector in supplying antimalarial medicines, the scheme was proposed by the US Institute of Medicine (IOM) and piloted in Kenya and Tanzania. After its 2009 launch, a subsequent evaluation by LSHTM and others using LSHTM methodological innovations led to AMFm's integration into ongoing funding streams.
Malaria in Africa, traditionally diagnosed from fever symptoms, has been massively overdiagnosed, and other causes of fever missed. This research demonstrated the magnitude of overdiagnosis, undertook trials of rapid diagnostic tests, identified alternative bacterial diagnoses, completed economic appraisals and studied prescriber behaviour. The research underpinned a major change in policy by WHO (2010), substantial investments by the Global Fund to fight HIV, TB and Malaria (GFATM), and changed clinical practice, to direct antimalarials to malaria patients only. In one country alone, 516,576 courses of inappropriate artemisinin-based combination therapy (ACT) were averted, worth in excess of $1m.
Research at LSHTM has been central to the introduction of the Hib vaccine in developing countries. School staff were involved in the 1990s Gambia Hib vaccine trial, which demonstrated the impact of Hib vaccine on pneumonia. Through their work on the subsequent Hib Initiative, their research was instrumental in speeding up evidence-based decision-making for Hib vaccine introduction in a number of countries, mainly in Asia and Africa. The project has been an outstanding success, with Hib vaccine now introduced into 71 of the 73 countries eligible for GAVI Alliance support.
Miltefosine is the first oral drug to be developed for the treatment of leishmaniasis, a worldwide parasitic infection with up to 12m cases. Also developed as a cancer drug, miltefosine was identified and tested for leishmaniasis therapy at LSHTM and has been added to WHO's essential medicines list as a result of subsequent clinical trials. It has been widely used for the treatment of visceral leishmaniasis (VL) in India, Nepal and Bangladesh, and for the cutaneous form of the disease in Latin America. Phase III and IV clinical trials of combination therapies including miltefosine have been carried out in India.
Work by LSHTM researchers has led to a greater understanding of Plasmodium malaria parasite species and contributed new methodologies for diagnosis. As a result, patients with the uncommon species P. knowlesi and many hundreds with P. ovale spp. have been correctly diagnosed by polymerase chain reaction (PCR), and the rapid detection of parasite DNA is revolutionising clinical trial design. The work has led to the successful commercialisation of a low-cost, easy-to-use malaria testing kit for use in developing countries. Through media outputs and further research, the work has taken awareness of the issues surrounding malaria diagnostics to an international audience.