Correspondence
3
4
Fu LC, Guo XB, Wang WL, et al. An exploration on the dosage and treatment course of dihydroartemisinin for falciparum malaria. Trad Chin Drug Res Clin Pharm 1996; 7: 17–18. Ferreira PE, Culleton R, Gil JP, Meshnick SR. Artemisinin resistance in Plasmodium falciparum: what is it really? Trends Parasitol 2013; 29: 318–20.
Stratified infection medicine: a call to arms Human susceptibility to infectious disease is strongly heritable.1 In the past decade, genetic studies have found more than 30 common genetic variants that have profound effects on susceptibility to infection, course of disease, and response to treatment.2 A major challenge for infectious disease medicine in the next decade will be making use of this knowledge to benefit patients. Stratification of patients, by customising management according to their genotypes, makes little impact on clinical treatment of infectious disease. We are aware of only one example—hepatitis C virus infection— in which this new paradigm has been exploited. In infection with hepatitis C virus genotype 1, a single nucleotide polymorphism in the IFNL3 gene is associated with a sustained virological response to treatment, and this can be clinically tested to predict response to therapy.3 By contrast, oncologists successfully and routinely apply knowledge of both patient’s and tumour’s genotypes to allocate patients to ever-smaller groups for whom optimum therapeutic strategies have been found. For example, HER2positive breast cancer responds to trastuzumab, and lung cancers carrying EGFR mutations respond to oral EGFR tyrosine kinase inhibitors. Several single nucleotide polymorphisms associated with infectious disease phenotypes could have implications for clinical practice.
www.thelancet.com/infection Vol 14 June 2014
The IFNL3 mutation associated with hepatitis C virus is also associated with the severity and frequency of reactivation of orofacial herpes simplex virus type 1 infection,4 which highlights two major concepts: first, that there are genetic variants that confer susceptibility to multiple pathogens; and second, that there are likely to be genotype-determined comorbidities that have not yet been observed and reported. Influenza A virus is a pathogen of global importance and a genetic polymorphism in IFITM3 is strongly associated with risk of severe influenza in human beings.5 If the clinical impact of this mutation can be quantified, and genotyping can be made both rapid and cost effective, then patients at high risk of life-threatening disease could be identified early and treated aggressively. The mortality associated with infective endocarditis is substantial and surgery can be lifesaving, but current guidelines recognise that indications for surgery are not supported by strong evidence. Staphylococcus aureus is the most common pathogen causing infective endocarditis and a single nucleotide polymorphism in the platelet glycoprotein GP1b receptor has been associated with increased risk of septic emboli in S aureus infective endocarditis.6 If confirmed by clinical studies, this finding could help stratify patients with S aureus infective endocarditis by providing an indication for early surgery in carriers of the risk allele, so reducing embolic complications in these patients. A better understanding of infectionassociated host genetic variation and the detection of novel biomarkers associated with the course of disease clearly have the potential to influence the clinical management of patients with infectious diseases. As well as continuing to apply genomic methods to important infections, there is a strong and timely need in infectious
disease medicine to translate the results of these new genomic studies into clinical practice. In their Comment in The Lancet Infectious Diseases, Jake Dunning and colleagues7 make the case for opensource cooperation to stimulate clinical research of infectious diseases. Such an approach will be especially important if we are to understand fully how genes affect the susceptibility of people to infectious diseases. To accomplish this, worldwide cooperation will be essential, and clinicians and scientists will have to embrace new ways of working together.7 Only through new strategies such as this can we meet the huge challenges, in both high-income and low-income countries, posed by soaring health-care costs, multidrug resistant pathogens, and emerging infections. We declare no competing interests.
*Clark D Russell, Samantha J Griffiths, J Kenneth Baillie, Juergen Haas [email protected] Division of Pathway Medicine, University of Edinburgh, The Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK (CDR, SJG, JH); and The Roslin Institute, University of Edinburgh, Midlothian, UK (JKB) 1
2
3
4
5
6
7
Sørensen TI, Nielsen GG, Andersen PK, et al. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 1988; 318: 727–32. Chapman SJ, Hill AV. Human genetic susceptibility to infectious disease. Nat Rev Genet 2012; 13: 175–88. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399–401. Griffiths SJ, Koegl M, Boutell C, et al. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication. PLoS Pathog 2013; 9: e1003514. Everitt AR, Clare S, Pertel T, et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 2012; 484: 519–23. Daga S, Shepherd JG, Hung RK, et al. GPIb VNTR C/C genotype may predict embolic events in infective endocarditis. J Heart Valve Dis 2013; 22: 133–41. Dunning JW, Merson L, Rohde GG, et al. Open source clinical science for emerging infections. Lancet Infect Dis 2014; 14: 8–9.
451
3
4
Fu LC, Guo XB, Wang WL, et al. An exploration on the dosage and treatment course of dihydroartemisinin for falciparum malaria. Trad Chin Drug Res Clin Pharm 1996; 7: 17–18. Ferreira PE, Culleton R, Gil JP, Meshnick SR. Artemisinin resistance in Plasmodium falciparum: what is it really? Trends Parasitol 2013; 29: 318–20.
Stratified infection medicine: a call to arms Human susceptibility to infectious disease is strongly heritable.1 In the past decade, genetic studies have found more than 30 common genetic variants that have profound effects on susceptibility to infection, course of disease, and response to treatment.2 A major challenge for infectious disease medicine in the next decade will be making use of this knowledge to benefit patients. Stratification of patients, by customising management according to their genotypes, makes little impact on clinical treatment of infectious disease. We are aware of only one example—hepatitis C virus infection— in which this new paradigm has been exploited. In infection with hepatitis C virus genotype 1, a single nucleotide polymorphism in the IFNL3 gene is associated with a sustained virological response to treatment, and this can be clinically tested to predict response to therapy.3 By contrast, oncologists successfully and routinely apply knowledge of both patient’s and tumour’s genotypes to allocate patients to ever-smaller groups for whom optimum therapeutic strategies have been found. For example, HER2positive breast cancer responds to trastuzumab, and lung cancers carrying EGFR mutations respond to oral EGFR tyrosine kinase inhibitors. Several single nucleotide polymorphisms associated with infectious disease phenotypes could have implications for clinical practice.
www.thelancet.com/infection Vol 14 June 2014
The IFNL3 mutation associated with hepatitis C virus is also associated with the severity and frequency of reactivation of orofacial herpes simplex virus type 1 infection,4 which highlights two major concepts: first, that there are genetic variants that confer susceptibility to multiple pathogens; and second, that there are likely to be genotype-determined comorbidities that have not yet been observed and reported. Influenza A virus is a pathogen of global importance and a genetic polymorphism in IFITM3 is strongly associated with risk of severe influenza in human beings.5 If the clinical impact of this mutation can be quantified, and genotyping can be made both rapid and cost effective, then patients at high risk of life-threatening disease could be identified early and treated aggressively. The mortality associated with infective endocarditis is substantial and surgery can be lifesaving, but current guidelines recognise that indications for surgery are not supported by strong evidence. Staphylococcus aureus is the most common pathogen causing infective endocarditis and a single nucleotide polymorphism in the platelet glycoprotein GP1b receptor has been associated with increased risk of septic emboli in S aureus infective endocarditis.6 If confirmed by clinical studies, this finding could help stratify patients with S aureus infective endocarditis by providing an indication for early surgery in carriers of the risk allele, so reducing embolic complications in these patients. A better understanding of infectionassociated host genetic variation and the detection of novel biomarkers associated with the course of disease clearly have the potential to influence the clinical management of patients with infectious diseases. As well as continuing to apply genomic methods to important infections, there is a strong and timely need in infectious
disease medicine to translate the results of these new genomic studies into clinical practice. In their Comment in The Lancet Infectious Diseases, Jake Dunning and colleagues7 make the case for opensource cooperation to stimulate clinical research of infectious diseases. Such an approach will be especially important if we are to understand fully how genes affect the susceptibility of people to infectious diseases. To accomplish this, worldwide cooperation will be essential, and clinicians and scientists will have to embrace new ways of working together.7 Only through new strategies such as this can we meet the huge challenges, in both high-income and low-income countries, posed by soaring health-care costs, multidrug resistant pathogens, and emerging infections. We declare no competing interests.
*Clark D Russell, Samantha J Griffiths, J Kenneth Baillie, Juergen Haas [email protected] Division of Pathway Medicine, University of Edinburgh, The Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK (CDR, SJG, JH); and The Roslin Institute, University of Edinburgh, Midlothian, UK (JKB) 1
2
3
4
5
6
7
Sørensen TI, Nielsen GG, Andersen PK, et al. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med 1988; 318: 727–32. Chapman SJ, Hill AV. Human genetic susceptibility to infectious disease. Nat Rev Genet 2012; 13: 175–88. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399–401. Griffiths SJ, Koegl M, Boutell C, et al. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication. PLoS Pathog 2013; 9: e1003514. Everitt AR, Clare S, Pertel T, et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 2012; 484: 519–23. Daga S, Shepherd JG, Hung RK, et al. GPIb VNTR C/C genotype may predict embolic events in infective endocarditis. J Heart Valve Dis 2013; 22: 133–41. Dunning JW, Merson L, Rohde GG, et al. Open source clinical science for emerging infections. Lancet Infect Dis 2014; 14: 8–9.
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