Translational Medicine

Dr Janjira Thaipadungpanit from our MORU unit in Bangkok, Thailand, tells us about her research on molecular diagnosis and bacterial genotyping A molecular microbiologist, Dr Janjira’s research focusses on using bacterial typing based on genome to confirm which disease is present in a patient. She aims to develop a single whole genome sequence type test using mutliple-PCR assays that can determine from a single sample of blood what bacteria or viruses are present in a patient’s blood – thereby speeding up diagnosis and potentially saving lives in resource-limited settings. Head of Molecular Microbiology at MORU, Dr Janjira Thaipadungpanit’s research interests include the molecular epidemiology of leptospirosis and melioidosis using multilocus sequence typing or genome data and molecular diagnosis to identify the causes of acute febrile illness and sepsis in patients.

Dr Markus Winterbert from our MORU unit in Bangkok, Thailand, tells us about his research on biomarkers for tropical diseases Having a background in malaria physiology and biochemistry, Markus Winterberg’s research focus is on the interaction between host, pathogen and drug, the metabolism of antimalarial drugs and discovering biomarkers for tropical diseases. Markus aims to use these biomarkers to develop non-invasive, field-based rapid diagnostic tests for tropical diseases that quickly identify pathogens, thereby improving diagnostics and the treatment of patients. Dr Markus Winterberg is Head of Laboratory and a Principal Investigator in MORU’s Department of Clinical Pharmacology. The key aspect of his research is ‘trop-med-omics’, the application of mass spectrometry-based bioanalysis in tropical medicine, particularly using proteomics and metabolomics to identify a disease in a patient.

Premjit Amornchai from our MORU unit in Bangkok, Thailand, tells us about her work as biosafety level 3 lab manager and microbioogy safety officer To prevent relapse or reinfection, melioidosis requires a specific and prolonged treatment. Melioidosis is endemic at least 45 countries, but greatly under-reported, with a microbiological culture required to confirm diagnosis. This can take 2-7 days. In Thailand, up to 40 percent of hospital admitted melioidosis patients die. Premjit works with MORU researchers who have produced a rapid diagnostic test that aims to improve both diagnosis and public awareness of melioidosis. Microbiologist Premjit Amornchai heads MORU’s Bio-Safety Level (BSL) 3 Laboratory in Bangkok, Thailand. Safety is very important for Premjit. The BSL3 Lab handles several dangerous materials, most notably, Burkholderia pseudomallei, a highly pathogenic bacterium commonly found in soil and water in Southeast Asia and northern Australia. The pathogen causes the difficult to diagnose, deadly bacterial infection melioidosis.

Professor Bob Snow from our KEMRI-Wellcome programme in Nairobi, Kenya, tells us how his research brings together epidemiological profiles and government policies to maximise malaria control programmes in Africa Quality data is vital to design better malaria control programmes. This project helps various African countries gather epidemiological evidence to better control malaria. Professor Bob Snow showed how sub-regional, evidence-based platforms can effectively change malaria treatment policies. Professor Bob Snow has developed a large programme of work on the phenotype of malaria disease, its relationship to parasite exposure and its wider public health burden. Technical advisor to the Kenyan Government (and member of a number of international malaria advisory panels), Professor Snow provides the bridge between basic malaria epidemiology and malaria control policy in the region. Malaria control in Africa.

Dr Lorenz von Seidlein from our MORU unit in Bangkok, Thailand, tells us about his research on malaria elimination in the Greater Mekong sub-region Multidrug resistant P. falciparum malaria is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for artemisinin combination therapies, the main falciparum malaria medicines. A further spread from Myanmar to India then sub-Saharan Africa would be a global public health disaster. TME seeks the best ways to eliminate drug-resistant malaria, using both technical solutions and novel ways that engage entire communities. Dr Lorenz von Seidlein coordinates MORU’s Targeted Malaria Elimination (TME) study, which seeks to eliminate artemisinin resistant falciparum malaria by treating entire communities that have significant levels of subclinical malaria parasite infections and transmission with the antimalarial Dihydroartemisinin-piperaquine (DHA-PIP).

Dr Olga Tosas-Auguet from our unit in Kenya tells us about her research on mapping bacterial antibiotic resistance Dr Olga Tosas-Auguet aims to develop ad evaluate a new approach to large scale surveillance of bacterial antibiotic resistance in low income settings. This approach can then be taken forward to a testing stage, initially in partnership with an emerging network of policy makers and healthcare practitioners in Africa. Resistance to antibiotics is a growing issue worldwide. Mapping where the resistance is as well as its distribution and diversity is hampered by the lack of laboratory facilities in many parts of the world. New technologies allow the characterisation of whole pathogen communities, giving us clues where multi-drug resistant organisms come from. This can help set up a better public health perspective surveillance.

David Dance from our LOMWRU unit in Laos tells us about his research on bacterial infections in Laos, particularly melioidosis David Dance is a Clinical Microbiologist supporting the work of LOMWRU (Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit) on bacterial infections of importance to public health in Laos. He is particularly interested in all aspects of melioidosis (Burkholderia pseudomallei) infection, especially gaining a greater understanding of the global distribution of the disease and the environmental factors that underpin its distribution. Laos is seing a growing number of melioidosis, a bacterial infection caused by a bacterium that lived in the environment. Meliolidosis is a disease greatly under-recognised and treatment is specific, making it a major threat to farmers in developing countries. A better understanding of the prevalence of this infection and how it spreads allows us to better target prevention and treatment.

Dr Gail Carson is Head of ISARIC Coordinating Centre (International Severe Acute Respiratory and Emerging Infection Consortium), a network of networks established in 2011 to ensure a rapid research response to outbreaks of pandemic potential. A quick and efficient response to an outbreak requires strong central communication and coordination. Information needs to be shared quickly and then fed into patient care and policy. A wider approach, cutting across disciplines and specialities, helps limit the number of infected people and the impact on the economy.

Professor Frank Smithuis is the director of MOCRU, Myanmar Oxford Clinical Research Unit. MOCRU involves a network of 6 clinics and 650 community health workers in remote areas. Up until now, Myanmar has spent little on heathcare and receive little assistance from rich countries. Prevention is difficult, which leaves diagnosis and treatment. MOCRU has set up a network of community health workers, trained and supplied with diagnostics and treatments, to help improve access to healthcare for remote communities.

Dr Georgina Humphreys coordinates the WorldWide Antimalarial Resistance Network (WWARN) study groups by encouraging partner engagement and managing the data curation and development of publications. WWARN is a network of research that analyses pooled data of numerous clinical trials. The sheer size of those data sets allows study groups to answer questions that couldn't be asked of a normal size clinical trial, such as the efficacy of an anti-malarial drug on malnourished or severely anaemic children. This research helps design policies to maintain the efficacy of current anti-malaria drugs, currently threatened by growing resistance.

Dr Claire Palles studies whole genome sequencing data and targeted analyses with the aim of discovering genetic variants that affect susceptibility to colorectal cancer and Barrett’s oesophagus. The gastrointestinal track is responsible for more cancers than any other system. A condition called Barrett's oesophagus, characterised by a change in the cells lining the oesophagus, can lead to oesophageal adenocarcinoma. Only few people with Barrett's oesophagus will go on to develop cancer, and genome sequencing studies aim to identify genetic risk factors and therefore better target high-risk patients.

LOMWRU researchers conduct clinical research to help improve global, regional and Lao public health. They focus on infectious diseases, and also investigate diseases of nutrition and poverty. Poor quality medicines are a serious threat to our health. Falsified medicines and substandards medicines are a problem for all countries, but particularly for low and middle income countries where we see, for example, a large epidemic of fake anti-malarial drugs. Globally, better medicine regulatory authorities will help improve the quality of our medicines.

Director of OUCRU-Nepal, Dr Buddha Basnyat studies high altitude illness as well as undifferentiated febrile illness in the tropics, both common but neglected problems in Nepal. High altitude illness can be prevented by a simple rule: don't go too high, too fast. Drugs can also be used, and Dr Basnyat showed that a much lower dose of Diamox, a commonly used drug, is as effective. His research also focusses on the effect of high altitude on pilgrims, an older, poorer and more vulnerable population.

Professor Kevin Baird leads our Eijkman-Oxford Clinical Research Unit (EOCRU) in Jakarta, Indonesia. Delivering health care in Indonesia is a challenge, made more difficult by the geography and distances. Our EOCRU unit specialises in clinical trials on tropical infections, particularly Plasmodium vivax malaria. Current treatments with primaquine are effective but very toxic for patients with G6PD deficiency. Better point of care diagnostics can help us treat all patients safely.

Professor Peter Simmonds studies the epidemiology, evolution and emergence of a wide range of human pathogenic viruses. RNA viruses are major pathogens that represent the majority of new viruses emerging over time. They are particularly good at evading the host's response to infection. A better understanding of the interaction between virus and host can lead to a better control of viral infections. Recent discoveries on viral genome composition and structure might allow us to manipulate this interaction and generate new, safer vaccines.

Dr Mehul Dhorda heads the Asia Regional Centre of the WorldWide Antimalarial Resistance Network (WWARN). Artemisinin resistance is firmly established in many parts of Southeast Asia and threatens the lives of millions of people. To improve regional intelligence and aid containment efforts, Dr Dhorda promotes the collection of high quality data on malaria drug resistance. His research aims to simplify and harmonise data, securely store results and analyse comparative or collective pooled analyses.

Professor Ben Cooper from MORU in Thailand uses mathematical modelling and statistical techniques to help understand the dynamics of infectious disease and evaluate potential control measures. Antibiotic resistance is one of today's major global health problems. Mathematical models help us answer what if questions and evaluate the impact of specific interventions such as hands hygiene on the spread of bacterial drug resistance. Effective solutions are then translated into policy changes or changes in practice at national or international level.

Dr Richard Maude's work combines clinical studies, descriptive epidemiology and mathematical modelling of malaria in South and Southeast Asia. Malaria epidemiology focuses on two main challenges to malaria elimination: antimalarial drug resistance and the movement of people that are spreading the malaria parasite. Travel surveys and cellphone records, combined with population parasite genetics help predict the spread of malaria and of drug resistance. Close coordination with all groups and agencies involved is crucial to malaria surveillance and elimination strategies.

Naomi’s work focuses on supporting researchers to collect, clean and store research data. PRESERVING EVIDENCE FOR THE FUTURE Research is only as good as the evidence it generates, and data management is a critical part of this process since it supports findings. High quality data must be preserved for long term use and available to the research community. Ultimately, data is not about numbers, but about people's lives and health.

Dr Kesinee Chotivanich's laboratory provides facilities and resources to researchers, students, and collaborators who are interested in tropical diseases, with the aim to improve patients’ care. More effective diagnosis and treatments are needed to reduce the morbidity and mortality affecting malaria patients. Researchers at the Malaria Laboratory at MORU study the pathophysiology of the disease, and test new compound drugs for anti-malarial activity. In the context of growing artemisinin resistance, this research will have a global impact.

The Cambodia Oxford Medical Research Unit (COMRU) is based in Siem Reap, northern Cambodia, which remains one of the poorest countries in South East Asia with extremely limited health services. PNEUMONIA IN CAMBODIA Infectious diseases are prevalent in Cambodia, a country that is struggling with poor infrastructure. Streptococcus pneumoniae causes the most severe form of pneumonia and is now targeted by the pneumococcal conjugate vaccine. Dr Paul Turner is studying the effect of this vaccine in field conditions in SE Asia, as well as other direct applications such as the evaluation of a new diagnostic test for Typhoid and interventions to reduce the burden of infections acquired within hospitals.

Dr Direk Limmathurotsakul's research focuses on the epidemiology of melioidosis, a bacterial infection caused by Burkholderia pseudomallei. Melioidosis is endemic in at least 45 countries, but greatly under-reported. Up to 50% of cases seen in hospital die. Our researchers at MORU have produced a rapid diagnostic test that aims to improve both diagnosis and public awareness. Better coordination between researchers and policy makers is needed to face upcoming emerging infectious diseases.

Dr Claudia Turner heads the clinical research program at the Cambodia Oxford Medical Research Unit (COMRU), in collaboration with the Angkor Hospital for Children. Whereas children mortality has dramatically decreased over the past 15 years, almost half the remaining mortality still occurs during the first 4 weeks of age. Neonatology, or care of newborns, doesn't need to be difficult or expensive. Low cost intervertions involving communities, such as keeping babies warm, save lives.

Dr Chris Paton studies the use of open-source Electronic Health Records (EHR) software, online learning and mobile technology to improve healthcare delivery in low-resource settings. LEARNING HEALTH SYSTEM In a learning health system, health care providers use electronic health records to identify problems, implement local solutions and check if the solutions are effective. Health informatics, or the use of IT in healthcare, needs to find innovative solutions for low income settings, such as the use of open-source softwares and mobile technology. This approach has been used to deliver training to rural healthcare workers in Kenya.

With 390 million infections occuring each year, dengue is the most important mosquito-borne viral infection, and no vaccine is currently available. DENGUE The majority of people infected with the dengue virus experience a flu-like febrile illness, but in a small proportion of patients, particularly children, the virus causes the blood vessels to become leaky which can induce shock and lead to death. Improved diagnosis and understanding of the disease process enable better outcomes for patients with severe dengue.

There is a great need for better treatments for malaria and for a preventative malaria vaccine. SPACIAL EPIDEMIOLOGY & VACCINES Understanding the variation of malaria risk between houses, villages or region, and how malaria is transmitted in and around that variability helps develop better malaria control programmes and use their resources more wisely. Since malaria control tools are becoming less effective with time, progress in vaccine design is essential.

Men who have sex with men (MSM) are a stigmatised group in Africa, but a predominant actor in the transmission of HIV. Professor Eduard Sanders is interested in putting together public health interventions to reduce HIV transmission in vulnerable populations, facilitating the early diagnosis of acute HIV infections and preventing its further spread. He also researches bacterial sexually transmitted infections in high risk populations, and HIV-1 early treatment trials.

Chorea-Acanthocytosis: ChAc is a rare progressive neurological disorder caused by mutations in a very complex gene. Dr Antonio Velayos-Baeza is interested in two main projects: Chorea-acanthocytosis (ChAc), a rare autosomal-recessive disorder that is characterised by progressive neurodegeneration and red cell acanthocytosis (spiky red blood cells), and Developmental dyslexia, the most common of the childhood learning disorders.

In pregnant women, severe malaria is responsible for high maternal mortality, and uncomplicated malaria results in in high morbidity. Professor Rose McGready works on the treatment and epidemiology of uncomplicated malaria in pregnancy. Pregnant women are particularly vulnerable as pregnancy reduces the immunity to malaria, increasing the susceptibility to malaria infection and the risk of illness, severe anaemia and death. For the unborn child, maternal malaria increases the risk of spontaneous abortion, stillbirth, premature delivery and low birth weight - a leading cause of child mortality.

Resistance to drugs in bacteria can be aquired by swapping genes between individual bacteria. Computer programs developed by Dr Iqbal enable doctors to predict which antibiotics will be met with drug resistance, enabling the selection of the right drug. BIOINFORMATICS & PATHOGEN GENOMICS Dr Zamin Iqbal studies the DNA of bacteria and parasites, and compares the genomes of individual pathogens to track the spread of antibiotic resistance. Pathogens accumulate small genetic changes over time, and by tracking these changes, it is possible to map the spread of an infection. This enables better surveillance of pathogen evolution, within a host, within a hospital and across the world.

Computational and stastistical methods help us understand evolution as well as genetic disease. Professor Gerton Lunter is interested in investigating the processes of evolution and biology using computational methods. His focus is on sequencing data; Professor Lunter develops methods to investigate evolutionary questions in population genetics.

Melioidosis is a neglected tropical disease, and a major infectious killer in South East Asia. Melioidosis particularly affects people with diabetes. Dr Susanna Dunachie works on tropical diseases such as melioidosis, scrub typhus and vivax malaria. Melioidosis is a bacterial disease that results in pneumonia, liver and splenic abscesses and septic shock. The disease can reactivate after a latent period and is inherently resistant to many standard antibiotics. People continue to die around the world from this infection for which there is no vaccine. Understanding the disease is therefore crucial.

Over 250 Institutions participate in the effort of sharing data on the efficacy of antimalarial drugs, which involves standardising and re-analysing data. Professor Philippe Guérin is Director of the WorldWide Antimalarial Resistance Network (WWARN). The best lines of defence against malaria are avoidance of mosquito bites and effective drug therapy. WWARN tracks the emergence of antimalarial drug resistance to ensure that anyone affected by malaria receives effective and safe drug treatment.

Identifying and addressing ethical issues are key to the success of any clinical trials, particularly when working with vulnerable populations. Dr Phaik Yeong Cheah leads the Department of Bioethics & Engagement at the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand. She is particularly interested in ethical issues in community engagement, data sharing, consent and assent in paediatric research.

In settings with high level of poverty and over-stretched health services, researchers have even greater responsibilities to the communities and study participants. SOCIAL AND BEHAVIOURAL RESEARCH A social scientist and public health researcher based in Kenya, Professor Vicki Marsh aims to understand and strenghten policies based on social and ethical aspects of international collaborations. Improving communications between researchers and the patients and local communities is not only ethically important; it can also lead to better research.

Artemisinins are very poweful tools in the treatment of malaria, and the emerging loss of their activity has the potential to create a major public health problem. MALARIA TREATMENT Dr Charlie Woodrow is based at MORU in Bangkok, Thailand, where he coordinates clinical and laboratory studies on resistance to artemisinins. Bringing together diverse datasets of clinical, in vitro and molecular data has helped better understand the emerging resistance, particularly in Myanmar.

Too high a dose can result in toxicity and side-effects, too low a dose can cause the illness to come back and at worse develop resistance. Professor Joel Tarning is Head of Clinical Pharmacology in our MORU Unit in Bangkok, Thailand. He's working towards drug dose-optimisation using novel pharmacometric modelling approaches. He is particularly interested in antimalarial treatments for children and pregnant women.

Economics and health are interlinked in many ways, as seen in the vicious cycle between poverty and ill health. Dr Yoel Lubell leads the economic team at the MORU Mathematical and Economic Modelling Group, based in Bangkok, Thailand. His research focuses on the evaluation of diagnostics, treatments and vaccines for infectious diseases, with the aim of providing guidance on malaria elimination and control of artemisinin resistance in the Mekong region.

Dr Christiane Dolecek speaks about the research on enteric fever she conducted in Vietman and Nepal. Dr Christiane Dolecek's clinical research focuses on tropical diseases, in particular enteric fever and malaria. She has led enteric fever clinical trials in Vietnam and Nepal with the aim to systematically assess the current WHO recommendations as well as new treatment options.

Professor Peter Horby is Senior Clinical Research Fellow. His research focusses on epidemic diseases such as Ebola and bird flu, and crosses the disciplines of basic science, medical science and public health. Influenza, SARS & Ebola Research on emerging infectious diseases can only be conducted during outbreaks. Although virology has improved, a well calibrated and effective public health response is often lacking. Epidemiological and clinical research as well as mathematical modelling will give us answers during the epidemics and help us provide better diagnostics and better treatments.

Microbiology in Thailand Acurately diagnosing infections is particularly challenging in tropical environments. Researchers at the Mahidol Oxford Tropical Medicine Research Unit (MORU) are working to develop effective and practical means of diagnosing and treating malaria and other neglected tropical diseases, such as dengue fever. The development of rapid tests for dengue, similar to pregnancy tests, allow rapid and acurate diagnostics in the field.

Infectious diseases in South East Asia The Mahidol Oxford Tropical Medicine Research Unit (MORU) is a collaboration between the University of Oxford and Mahidol University, and was established with the Wellcome Trust in 1979. MORU aims to fight the infectious tropical diseases affecting rural communities in Asia and elsewhere in the developing world. MORU's malaria research aims to directly improve the treatment of the disease globally. It's researchers focus on the treatment of severe malaria, the spread of antimalarial drug resistance, and the pathophysiology of falciparum and vivax malaria. These studies are used to formulate novel adjuvant therapies, and have been translated into recommendations for the use of artemisinin based combination therapies.

Daniel Paris: Rickettsial Disease Rickettsial diseases such as scrub typhus are important causes of fever in southeast Asia especially in rural communities. Discovered quite recently and not big killers, these diseases are among the most under-reported and under-diagnosed illnesses that are both treatable and preventable. Rickettsial studies at he Mahidol Oxford Tropical Medicine Research Unit (MORU) focus on the epidemiology and incidence of the disease using hospital-based fever studies in Thailand and Laos. Our research unit has developed highly improved acute diagnosis of rickettsial illness. MORU also has ongoing studies to determine the pathophysiological mechanisms of scrub typhus infection.

Between research and humanitarian Professor François Nosten's work concentrates on infectious diseases at the Thai-Burma border. The main focus of his research is on malaria, especially malaria in pregnant women and emerging drug resistance of malaria parasites.

Novel light microscopy techniques allow us to track single viruses. From a virus centric approach, we can now study interactions between the host and the virus. In the case of HIV, we could demonstrate that the virus might enter the cell through endocytosis. A better understanding of virus-cell interactions will ultimately help us test and develop new drugs and vaccines.

DNA replication and Cancer The process of DNA replication is complex, and mistakes can lead to genome instability. Surveillance systems are not always successful which results in mutations that have the potential to inactivate genes or change their activity. This can lead to cancer, and many chemotherapeutic drugs are designed to disrupt DNA replication. A better understanding of these mechanisms can help us develop new drugs with reduced side effects.

Over the past decade, data-driven science has produced enormous sets of data. The convergence of statistics and computer science, in the field known as machine learning, provide the means to understand these large datasets. Ultimately, machine learning algorithms will be develop into clinical decision making support systems.

Tuberculous Meningitis Professor Guy Thwaites is trying to improve outcomes for patients with tuberculous meningitis, the most severe form of tuberculosis. 100, 000 people a year get tuberculous meningitis and without treatment 100% of people with the disease will die.

Innate immune system Professor Alison Simmons is interested in the molecular aspects of innate immune recognition, the primitive arm of the immune system that defends the host from infection by other organisms in a non-specific manner. Defects in the innate immune system can result in difficulty clearing infections but also in inflammation.

Structure of viruses Professor David Stuart studies the structure of viruses at the molecular level. His work is particularly interested in virus-receptor interaction and the basic puzzles of virus assembly and he uses structural biology to answer these questions.