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MOLECULAR & MEDICAL
LABORATORY,
CLINICAL AND
FIELD STUDIES
OF MALARIA AND
OTHER TROPICAL
INFECTIOUS
BY COMBINING
LABORATORY
INVESTIGATIONS WITH
STUDIES IN THE FIELD,
WE AIM TO HAVE A
MAJOR IMPACT ON
MALARIA AND OTHER
TROPICAL INFECTIOUS DISEASE:
THE BIGGER PICTURE
The Molecular and Medical Parasitology Group at Our laboratory studies are rooted in the realities of Left: Malaria parasite St George's University of London, led by Professor malaria treatment and control. We are continuing within an infected red blood cel .
Sanjeev Krishna, is notable for the breadth of its to characterise PfATP6, to shed light on possible research interests. Our ultimate aim is to improve the mechanisms of drug resistance (and how they might diagnosis, treatment and control of tropical parasitic be overcome). Our previous work also identified an diseases, including malaria – responsible for the important mechanism responsible for resistance to deaths of nearly a mil ion children a year – and sleeping other commonly used antimalarial drugs – amplification sickness (African trypanosomiasis). of the pfmdr1 gene.
A core focus of our work are ‘transporter proteins' Furthermore, field studies are core to our work. We have of the malaria parasite, which move key molecules been involved in numerous clinical trials of antimalarial into and out of the cel . These transporters are of treatments, particularly in Africa, helping to establish fundamental importance to the biology of the parasite, treatment regimes tailored to local needs. Thanks to and they may also be important drug targets. We have our longstanding col aboration with Peter Kremsner in generated evidence that one transporter, known as Tübingen, we have particularly strong links with Gabon. PfATP6, is a target of artemisinins – the most widely Other clinical studies have focused on the used class of antimalarial drug. In addition, a glucose consequences of malaria infection. Our main interests transporter, PfHT, could be an important target for have been around harmful build up of lactate in the drug development.
bloodstream and fluid balance, providing important Our laboratory studies are based on expression of evidence to guide treatment. transporters in artificial systems, which enable us to study their function systematical y. As well as a conventional frog egg expression system, we have recently introduced a more flexible and powerful yeast platform.
Molecular & Medical Parasitology Group WE ARE WORKING TO
CREATE A DEVICE THAT
CAN NOT ONLY DETECT
THE MALARIA PARASITE
BUT ALSO IDENTIFY
ITS DRUG RESISTANCE
PROFILE – SO PATIENTS
CAN BE GIVEN
‘PERSONALISED' DRUG
TREATMENTS.
A timeline of the group's major
discoveries and achievements
identification of PfATP6 as PfATP6 expressed in yeast artemisinin target lactic adiosis described PfHT validated as drug target Nanomal field trials begin cation ATPases identified isolation of PfHT fluid depletion in C. difficile simplified artesunate regime pfmdr1 amplification With Professor Phil Butcher at St George's, we are also Above: Professor working with QuantuMDx to adapt the technology for Sanjeev Krishna (left) A third major area of interest is diagnostics. Effective and members of the TB, in a £1m project funded by the UK Government's treatment of infectious diseases is often hampered Molecular and Medical Technology Strategy Board. The technology is also being by the lack of diagnostic tools – clinical symptoms are Parasitology Group.
applied to sexual y transmitted infgections, through rarely specific enough to permit accurate diagnosis the MRC-funded eSTI2 consortium, led by Tariz Sadiq.
and referral to centralised facilities is slow, inefficient and expensive.
We have worked for several years on new technological Policy and advocacy
approaches to underpin diagnostics for diseases such As well as these laboratory and clinical studies, as tuberculosis and African trypanosomiasis (sleeping we also contribute to policy-making and advocacy sickness). Recently, we were awarded €5.2m/£4m EU for tropical infectious diseases. Professor Krishna funding to lead an international consortium, Nanomal, has been an advisor to multiple international bodies, developing a smartphone-like diagnostic for malaria, including the World Health Organisation. He has sat drawing on innovative ‘lab-on-a-chip' technologies on advisory committees for the WHO, and major developed by project partners QuantuMDx. international funders including the US National With our understanding of malaria infection and drug Institutes of Health, the UK's Wel come Trust and resistance, we are working with QuantuMDx and others. He is an advisor to the Foundation for Innovative academic partners – Peter Kremsner in Tübingen and New Diagnostics (FIND), a not-for-profit organisation Pedro Gil at the Karolinska Institute in Stockholm – promoting the development of new diagnostic tools for to create a device that can not only detect the malaria resource-poor countries. He also has strong industrial parasite but also identify its drug resistance profile contacts, and has acted as scientific advisor to several – so patients can be given the most appropriate large pharmaceutical companies and biotech firms. ‘personalised' drug treatments. Molecular & Medical Parasitology Group BY UNDERSTANDING
THEIR UNIQUE BIOLOGY,
WE MAY BE ABLE TO
IDENTIFY NEW WAYS
TO COMBAT MALARIA
PARASITES. OUR
RESEARCH FOCUSES
ON THEIR DISTINCTIVE
TRANSPORTER
TRANSPORTERS: EXPLOITING
PARASITE BIOLOGY
The artemisinin target

Above: Malaria parasites in the mosquito gut. Left: Molecular models PfATP6 is the likely target of artemisinin antimalarials.
of artemisinin.
Derived from extracts of the sweet wormwood plant, artemisinin-based antimalarial drugs are recommended for use global y; several hundred mil ion doses are given every year. Yet they were developed without any clear idea of their molecular target. In 2003, we identified PfATP6 as the likely target for artemisinin, and since then have generated more evidence in support of our initial findings. The unusual chemical structure of artemisinin resembles that of a Knowing the identity of the artemisinin target is extremely calcium pump inhibitor, thapsigargin. This led us to suggest that important. It will provide a way to identify mechanisms of artemisinin might also act on a calcium pump. The malaria parasite resistance, should they arise, and possibly to monitor for genetic genome codes for only one such pump, PfATP6. When expressed changes associated with resistance. It will also support the in frog eggs, PfATP6 was strongly and specifical y inhibited development of new therapeutics that bypass these mechanisms by artemisinin. Furthermore, there was very good agreement of resistance.
between the degree of inhibition of PfATP6 by different artemisinin Although a spontaneous genetic change in PfATP6 associated derivatives and their parasite-killing abilities.
with altered sensitivity to artemisinin has been identified, the We later showed that a single amino acid change in the likely significance of genetic variation is difficult to assess, as numerous inhibitor-binding region of PfATP6 could dramatical y reduce natural variants of PfATP6 exist. The yeast system now provides us inhibition by artemisinin.
with a tool to examine the functional significance of such variants, particularly their susceptibility to artemisinins.
PfATP6 may not be the only target of artemisinin. Nevertheless, we have recently shown that PfATP6 is essential to parasite Eckstein-Ludwig U et al. Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003;424(6951):957–61.
survival, and have confirmed our initial findings in studies of PfATP6 expressed in yeast cel s. Significantly, variants associated Uhlemann AC et al. A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol. 2005;12(7):628–9.
with reduced artemisinin sensitivity in the field were less sensitive Pulcini S et al. Expression in yeast links field polymorphisms in PfATP6 to in to artemisinin inhibition in this assay.
vitro artemisinin resistance and identifies new inhibitor classes. J Infect Dis. Molecular & Medical Parasitology Group Blocking glucose uptake
A key parasite sugar transporter could be an important
Donec nisl sapien, target for new antimalarial drugs.
feugiat vitae dolor Psuscipit, non pretium With resistance always likely to be a problem, new antimalarial purus fringilla. Curabitur drugs are constantly needed. The malaria parasite relies on a key tristique tincidunt sugar transporter, PfHT, to take up glucose, and selective inhibitors lectus, tincidunt mollis urna viverra vel.
of PfHT are highly effective at killing parasites – pinpointing the transporter as an attractive drug target.
Although their metabolism is complex and incompletely understood, malaria parasites rely on a continuous supply of glucose from the host. This is taken up by a single sugar transporter, PfHT. In theory, As a further demonstration of the validity of PfHT as a drug target, blocking this transporter should therefore starve the parasite of its we were unable to eliminate the pfht gene – suggesting that loss energy source.
of PfHT is incompatible with parasite survival. To explore the potential of PfHT as a drug target, we expressed Our results indicate that PfHT is a highly attractive drug target for the transporter in our frog egg system. It efficiently transported all human malarias. Although compound 3361 is not well suited to glucose, and uptake could be readily inhibited by glucose drug development, smal molecule inhibitors of PfHT could provide analogues. Importantly, these analogues had no significant effect valuable tools in the fight to eliminate the malaria parasite.
on host glucose transporters. One of the most potent inhibitors, Joet T et al. Validation of the hexose transporter of Plasmodium falciparum as a compound 3361, killed cultured malaria parasites and significantly novel drug target. Proc Natl Acad Sci USA. 2003;100(13):7476–9.
inhibited the growth of P. berghei parasites in a mouse model Slavic K et al. Use of a selective inhibitor to define the chemotherapeutic potential of the plasmodial hexose transporter in different stages of the parasite's life cycle. Antimicrob Agents Chemother. 2011;55(6):2824–30. A further advantage of targeting PfHT is that glucose uptake is Slavic K et al. Life cycle studies of the hexose transporter of Plasmodium species vital at multiple stages of the parasite life cycle. Indeed, compound and genetic validation of their essentiality. Mol Microbiol. 2010;75(6):1402–13.
3361 inhibited liver-stage parasite development, when parasites multiply asexual y, and could also block transmission of the parasite to its mosquito vector.
A drug resistance marker
A technological advance helped to identify a critical

Molecular methods factor in the development of resistance to commonly
have provided a way to used antimalarials.
monitor for resistance to antimalarial drugs.
The antimalarial drug mefloquine was introduced into Thailand in 1984. Within six years, it was rendered near useless by the development of drug resistance. By adapting methods of DNA amplification, we were able to show that drug resistance was caused primarily by duplication of a specific parasite gene, pfmdr1, coding for a drug transporter protein. This test has gone on to be used by the Worldwide Antimalarial Resistance Network (WWARN) to monitor for emerging drug resistance.
Initial attempts to identify the causes of mefloquine resistance threw up conflicting results. As well as mutations affecting Our approach has been widely adopted to track the emergence individual proteins, resistance could reflect duplications of genes of drug resistance. Global y, it formed part of the WWARN toolkit such as pfmdr1, a relative of which renders some tumours resistant for monitoring drug resistance. Notably, pfmdr1 expansion is to anticancer drugs. In the early 2000s, however, assaying not yet a major factor in Africa, but this situation could change increases in gene copy number was not straightforward.
with increased antimalarial use, emphasising the need for active We developed a new technique, based on the polymerase chain reaction (PCR), to detect copy number changes in pfmdr1. With Price RN et al. Mefloquine resistance in Plasmodium falciparum and increased col eagues in Thailand and elsewhere, we then analysed more pfmdr1 gene copy number. Lancet. 2004;364(9432):438–47.
than 600 samples from malaria patients, looking for changes to Sidhu AB et al. Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and genes associated with drug resistance and pfmdr1 copy number artemisinin. J Infect Dis. 2006;194(4):528–35.
changes. The latter proved the most common cause of resistance to mefloquine (as well as reduced sensitivity to newly introduced combination treatments of mefloquine and artesunate).
With David Fidock in New York, we also showed that genetical y modifying parasites to lower pfmdr1 copy number increased their sensitivity to mefloquine and a range of other antimalarials.
Molecular & Medical Parasitology Group FIELD STUDIES ARE
ESSENTIAL FOR
THE IMPACT OF
MALARIA PARASITE
INFECTION AND THE
BEST APPROACHES
CLINICAL MALARIA
A practical guide to antimalarial use

Rigorous clinical trials have helped to establish the most
appropriate treatment regimes for children with malaria.
Young children are at particular risk The development of artemisinin-based drugs provided a much- needed boost to the antimalarial armamentarium. Drug treatment has the twin aims not just of treating individuals but also of preventing the spread of parasites, cal ing for careful design of drug regimes, routes of drug delivery and an awareness of how drugs are metabolised in the body. We have been involved in numerous international clinical trials that have shaped global antimalarial policy and national practice. Children are at particular risk of malaria. Severely ill children may be unable to take antimalarial drugs by mouth and, in areas of poor health infrastructure, injection of drugs may not be practical. In Ghana, we showed that that intrarectal administration of still delivering the same quantity of drug – was no worse than the artesunate was a suitable alternative, and later contributed to a standard five-dose regime. A simplified regime would be more landmark international trial showing that intrarectal artesunate convenient for patients and offer significant cost savings. was safe and effective in severe malaria. Krishna S et al. Bioavailability and preliminary clinical efficacy of intrarectal artesunate in Ghanaian children with moderate malaria. Antimicrob Agents We have also led other studies in Ghana and Gabon examining different treatment regimes for children. Fol owing work Gomes MF et al. Pre-referral rectal artesunate to prevent death and disability in establishing the feasibility of intramuscular injection of quinine severe malaria: a placebo-control ed trial. Lancet. 2009;373(9663):557–66.
for severe malaria, we went on to show that this route of Nealon C et al. Intramuscular bioavailability and clinical efficacy of artesunate administration was also suitable for artesunate, and also that in Gabonese children with severe malaria. Antimicrob Agents Chemother. amodiaquine–artesunate combination treatment was effective for uncomplicated malaria. Adjuik M et al. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. With Peter Kremsner and col eagues in the Severe Malaria In African Children network, we also recently showed that a Kremsner PG et al. A simplified intravenous artesunate regimen for severe malaria. simplified artesunate regime – three doses instead of five, while J Infect Dis. 2012;205(2):312–9.
Molecular & Medical Parasitology Group Treating dehydration in malaria
Although mild dehydration is sometimes seen in childhood
malaria, it does not appear to be a major factor in disease,
arguing against use of rapid rehydration.
malaria treatment.
Most childhood deaths from malaria occur within the first 24 hours of hospitalisation. One factor suggested to be a risk factor for severe malaria is excessive fluid loss, leading some to propose rapid rehydration for severely ill infants. Our studies in Gabon, however, found no evidence that severe malaria was associated with excessive fluid loss.
Determining body fluid levels experimental y is difficult, and many studies have assessed dehydration through clinical proxy measures. We used careful experimental methods to measure body fluids in children with severe and moderate malaria, and also validated a relatively simple method of determining fluid levels by measuring the flow of small electrical currents between hands and feet.
We found that severe malaria was typical y associated with mild dehydration, but found no evidence that the severity of symptoms was linked to the degree of dehydration. Hence our results suggested it was unlikely that fluid loss was contributing More work is needed to ful y understand the impact of malaria significantly to disease processes. Gradual fluid replacement was parasite infection on the body. In particular, there remains an sufficient to normalise patients within 12 hours. We could also urgent need to understand the basis of lactic acidosis and how find no evidence that body fluid volumes were associated with it can best be addressed. high blood lactate levels, a known risk factor for severe disease.
Planche T et al. Assessment of volume depletion in children with malaria. PLoS Med. Given the potential dangers of rapid rehydration, we therefore Jarvis JN et al. Lactic acidosis in Gabonese children with severe malaria is unrelated argued that it was not warranted in treatment of severely il to dehydration. Clin Infect Dis. 2006;42(12):1719–25.
children with malaria. Unfortunately, the FEAST clinical trial run to assess rapid rehydration had to be terminated early when it was found to be increasing the risk of death.
P. knowlesi: an emerging threat
The ‘fifth malaria parasite', Plasmodium knowlesi may become
more significant as control of other species improves.

Plasmodium knowlesi is principal y a parasite of macaques, but since the early 2000s it has become clear that it can also natural y infect humans. With col eagues in Malaysia, we have been uncovering more about the disease caused by this parasite and how it can best be treated.
P. knowlesi has emerged as a significant threat in Malaysia and in other parts of South-East Asia – in some locations accounting for the majority of malaria cases. About one in ten patients experience severe, potential y fatal disease. Worryingly, there are signs that P. knowlesi infections are rising in areas where human With little known about treatment, we have also explored the Plasmodium knowlesi is emerging as an malaria is being brought under control.
sensitivity of P. knowlesi to currently used antimalarial drugs. While the parasite is highly sensitive to artemisinins, it is Working with Dr Balbir Singh, Dr Janet Cox-Singh and col eagues surprisingly insensitive to mefloquine – arguing against its use in pathogen in parts at the University Malaysia Sarawak, we have been characterising of South-East Asia.
P. knowlesi infections.
this emerging infection and comparing it with ‘conventional' Willmann M et al. Laboratory markers of disease severity in Plasmodium knowlesi human malarias. As well as carrying out the first post-mortem infection: a case control study. Malar J. 2012;11:363.
of a knowlesi malaria patient, we have shown that parasite and Cox-Singh J et al. Anti-inflammatory cytokines predominate in acute human platelet counts are a convenient and reasonably accurate way to Plasmodium knowlesi infections. PLoS One. 2011;6(6):e20541.
identify patients at risk of severe disease. We have also found Fatih FA et al. Susceptibility of human Plasmodium knowlesi infections to anti- that the inflammatory immune response to P. knowlesi parasites malarials. Malar J. 2013;12(1):425.
differs significantly from that seen in P. falciparum infections – comparisons that may reveal factors linked to disease severity. Molecular & Medical Parasitology Group ACCURATE AND
AFFORDABLE
DIAGNOSTICS WILL BE
CRITICAL TO EFFECTIVE
HEALTHCARE IN THE
RAPID DETECTION
OF PARASITE INFECTIONS
Towards practical diagnostics

It remains technically challenging to develop accurate
Above: A prototype and affordable diagnostics suitable for use in the
malaria handheld Accurate diagnosis of infectious disease is important both for Left: Clinical assessment of treatment of individual patients but also, more general y, for a young girl with monitoring the prevalence and spread of disease. Unfortunately, sleeping sickness.
clinical symptoms alone are rarely sufficient to al ow unambiguous identification of a causative organism, while culture-based or other methods of identification usual y require referral to central facilities – which is slow, inefficient and expensive. We have a long-standing interest in diagnostics, for diseases such as African trypanosomiasis (sleeping sickness), tuberculosis and malaria.
To be of practical value, diagnostics must be both highly sensitive We have also used our diagnostics expertise closer to home. (detecting an infectious agent whenever it is present) and specific Our evaluation of diagnostic tests for the important microbial (not generating ‘false positives' – positive results when an pathogen Clostridium difficile, for example, revealed significant organism is not actual y present). These can be highly chal enging issues in the way the results of commercial y available diagnostic criteria to fulfill. Furthermore, for use in the developing world, tools were being interpreted, and recommended a screening an additional set of criteria are important, such as ease of use, approach overcoming these drawbacks. reliability, affordability, robustness and the practicalities of use in Papadopoulos MC et al. A novel and accurate diagnostic test for human African In the past we have explored the potential of proteomics-based Agranoff D et al. Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum. Lancet. 2006;368(9540):1012–21.
approaches – analysis of characteristic peptide fragments – for trypanosomiasis and TB. Recently, DNA-based methods Planche T et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis. 2008;8(12):777–84.
combined with nanotechnology sensors have emerged as a highly promising approach, as in our Nanomal consortium (see right). With Professor Phil Butcher at St George's, we are also working with Nanomal's technology partners, QuantuMDx, to develop an affordable DNA-based diagnostic for TB.
Molecular & Medical Parasitology Group THE CHALLENGE IS TO DEVELOP A
SIMPLE DEVICE THAT HEALTHCARE
WORKERS IN DEVELOPING
COUNTRIES CAN USE TO IDENTIFY
THE PRESENCE OF MALARIA
PARASITES WITHIN 15 MINUTES.
A ‘lab-on-a-chip' device could revolutionise the diagnosis
QuantuMDx has developed miniaturised technology that enables Above: DNA-based of malaria and the assessment of drug resistance.
methods may al ow complex genetic manipulations to be carried out on devices the rapid identification size of smartphones. From a blood sample, specific parasite Malaria is difficult to diagnose from symptoms alone, and of infections in DNA sequences are amplified. These amplified sequences are identifying malaria parasites in blood samples is a specialist and developing world detected by nanowire sensors, which relay a simple reading to time-consuming task. Hence patients may not get antimalarial the user indicating the presence of malaria parasites. In addition, drugs when they need them, or are given them when they do the device also incorporates DNA sequencing capacity, which can not actual y have the disease. Furthermore, even if they do have be used to probe for changes in DNA sequences associated with malaria, there is currently no way of knowing which drugs patients resistance to antimalarial drugs.
are likely to respond to. This may all change through the work of the Nanomal consortium.
The device is designed to be a point-of-care diagnostic, providing results while a patient waits for treatment. But it will also Led from St George's University of London, the Nanomal generate results important to wider surveil ance of disease and consortium has received €5.2m/£4m EU funding to develop drug resistance. Potential y, digital data generated by the device a simple, affordable point-of-care diagnostic for malaria. could be transmitted to central data stores for col ation and The consortium combines the expertise in malaria treatment and diagnosis in St George's and in the laboratories of our col aborators – Peter Kremsner at Tübingen University and EU Framework Programme 7 (FP7) funding for Nanomal was Pedro Gil at the Karolinska Institute – with the innovative awarded in 2012. We hope to begin the first field tests of nanotechnological applications being developed at QuantuMDx, a prototype devices in 2014. biotech company based in Newcastle upon Tyne.
The chal enge is to develop a simple device that healthcare workers in developing countries can use to identify the presence of malaria parasites within 15 minutes. In addition, the device needs to identify the species of parasite present and its likely responsiveness to different antimalarial drugs – so patients can be given the most appropriate treatment.
Molecular & Medical Parasitology Group OUR FUTURE AIMS
ARE TO CONTINUE
WORKING ON MULTIPLE
FRONTS TO TACKLE THE
SCOURGE OF MALARIA
AND OTHER TROPICAL
PARASITIC DISEASES,
ROOTED IN THE
REALITIES OF DISEASE
AS IT IS ACTUALLY
FORWARD LOOK
Tropical parasitic diseases remain a major source of Similarly, we plan to continue our work on PfHT, il -health and death in developing countries. Nearly a potential y important new target for antimalarial a mil ion children still die of malaria every year, and development. One advantage of our new yeast diseases such as sleeping sickness remain difficult expression platform is the ability to conduct high- to diagnose and treat, affecting the lives of mil ions throughput screens to identify potential inhibitors, of the poorest people on the planet. Even when and hence new leads for drug development. effective therapies are available, the emergence of drug Our clinical studies will continue in Gabon, where we resistance ensures that there is always a need for new are aim to minimise the burden of disease through a medicines. Recent signs that malaria parasites may multifaceted approach encompassing policy advice have reduced sensitivity to artemisinins, for example, as well as clinical studies to test new classes of are a cause for genuine concern.
antimalarial drugs. Such work would also benefit Parasite transporters remain at the core of our from the introduction of new diagnostic tools.
laboratory studies. Our new yeast expression system Indeed, diagnostic development will remain a key provides us with a powerful platform for analysing the focus. Field trials will be used to test prototype properties of transporters such as PfATP6. This wil devices developed through the Nanomal consortium. enable us to find out more about its interactions with If successful, we will work to refine the technology and artemisinins, and about the functional consequences of identify ways in which they can be deployed in the field to natural y occurring genetic variations and new mutations support treatment, control programmes and surveil ance that may affect these interactions. These studies for drug resistance. We will also be working with our could provide important clues to the development St George's col eagues on similar diagnostic tools for TB. of resistance to artemisinins and how they might be overcome, or how PfATP6 could be targeted in Through these and other routes we hope to have a major impact on the diagnosis, treatment and control of malaria and other major parasitic diseases of the tropics. 10 Molecular & Medical Parasitology Group
NEARLY A MILLION CHILDREN
STILL DIE OF MALARIA
EVERY YEAR, AND TROPICAL
DISEASES REMAIN DIFFICULT
TO DIAGNOSE AND TREAT,
AFFECTING THE LIVES OF
MILLIONS OF THE POOREST
PEOPLE ON THE PLANET.
From malaria to cancer
Above: Professor Sanjeev Krishna and members of the Molecular and Medical Artemisinins may have multiple medical benefits –
Parasitology Group.
including in cancer.
Artemisinins were original y isolated from the sweet wormwood plant, long used in the Chinese herbal remedy Qinghaosu. As wel as their antimalarial properties, they have been shown to have multiple other potential y beneficial activities – leading to some suggestions they could become the ‘new aspirin', another plant-derived product with a host of beneficial effects.
One possible application of artemisinins is in treatment of cancer. Many groups have established that artemisinins have activity on cancer cel s. We have contributed to one study on a synthetic derivate of artemisin, artemisone, finding significant activity on a range of cancer cel s lines. Artemisone was also able to enhance the anticancer effects of other commonly used anticancer agents.
These and other results argue that further clinical studies of artemisinins in cancer are justified. Gravett AM et al. In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents. Cancer Chemother Pharmacol. Molecular & Medical Parasitology Group Molecular and Medical Parasitology Group St George's, University of London Cranmer Terrace London SW17 0RE, UK T: +44 (0)208 725 5836 E: s.krishna@sgul.ac.uk W: www.tropmed.ac.uk Main funders: Wel come Trust, Medical Research Council, European Union, National Institutes of Health, Medicines for Malaria Venture. Acknowledgements:Photography: Gary Knight, Noel Murphy.
Text: Ian Jones (Jinja Publishing Ltd)Design: Jag Matharu (Thin Air Productions Ltd)

Source: http://www.tropmed.ac.uk/blog/mmpg-brochure-130214.pdf

Doi:10.3402/meo.v20.27097

Medical Education Online æ A study to enhance medical students' professionaldecision-making, using teaching interventions oncommon medications Jane Wilcockand Janet Strivens2 1Faculty of Health and Life Sciences, Institute of Learning and Teaching, School of Medicine,University of Liverpool, Liverpool, UK; 2Educational Developer, Centre for Lifelong Learning,University of Liverpool, Liverpool, UK

Exp_stat_rivaroxaban_07_2013.indd

Die Zeitschrift der Ärztinnen und Ärzte Management von Notfällen und Blutungen Autoren: Univ.-Prof. Dr. Marianne Brodmann, Priv.-Doz. Dr. Benjamin Dieplinger, Univ.-Prof. Dr. Hans Domanovits, Univ.-Prof. Dr. Sabine Eichinger-Hasenauer, Univ.-Prof. Dr. Dietmar Fries, Prim. Univ.-Prof. Dr. Reinhold Függer, OA Dr. Manfred Gütl, Univ.-Doz. Dr. Hans-Peter Haring, Univ.-Prof. Dr. Michael Hiesmayr, Univ.-Prof. Dr. Paul A. Kyrle, Prim. Univ.-Prof. Dr. Wilfried Lang, Univ.-Doz. Dr. Stefan Marlovits, Univ.-Prof. Dr. Erich Minar, OA Dr. Peter Perger, Univ.-Prof. Dr. Peter Quehenberger, Univ.-Prof. Dr. Martin Schillinger, Priv.-Doz. Dr. Barbara Steinlechner, OA Dr. Wolfgang Sturm.