- Email: [email protected]
Behavioural research to inform understanding of hepatitis C resistance
Correspondence
research.1 More studies are needed to confirm whether immunological assessment could help to diminish sepsis incidence in patients who are at risk. Such studies should be regarded as an additional priority in the proposed roadmap. We declare no competing interests.
*Jesús F Bermejo-Martin, David Andaluz-Ojeda, Raquel Almansa, Jose María Eiros, Eduardo Tamayo [email protected] Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL & IECSCYL, 47005 Valladolid, Spain (JFB-M, DA-O, RA, JME, ET); Servicio de Medicina Intensiva, Hospital Clínico Universitario de Valladolid, SACYL, Valladolid, Spain (DA-O); and Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Valladolid, Spain (ET) 1
2
3
4
5
Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15: 581–614. Henriksen DP, Pottegård A, Laursen CB, et al. Risk factors for hospitalization due to communityacquired sepsis—a population-based casecontrol study. PLoS One 2015; 10: e0124838. Cajander S, Bäckman A, Tina E, Strålin K, Söderquist B, Källman J. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Crit Care 2013; 17: R223. Tamayo E, Almansa R, Carrasco E, et al. Quantification of IgM molecular response by droplet digital PCR as a potential tool for the early diagnosis of sepsis. Crit Care 2014; 18: 433. Andaluz-Ojeda D, Iglesias V, Bobillo F, et al. Early natural killer cell counts in blood predict mortality in severe sepsis. Crit Care 2011; 15: R243.
In the Commission on sepsis by Jonathan Cohen and colleagues, 1 we were especially interested in the section on the global and regional epidemiology of sepsis, since we believe this is an area of great need for further studies. Although the authors argued that existing ways to measure sepsis incidence seem inadequate and fraught with difficulties resulting from problems with detection, documentation, and coding of the complication even in high-income countries, they did not provide a way forward to try to address this important information gap.1 1260
Importantly, most studies of sepsis epidemiology focused on intensive-care units and emergency departments, whereas it is increasingly apparent that the disease is even more prevalent and perhaps claim more lives on general hospital wards.2,3 We successfully piloted last year a new approach to try to address some of these problems. We formed a partnership with the Cardiff University Research Society (CUReS) and collaborated with medical students to undertake a 24-h point-prevalence study of sepsis and severe sepsis in four acute hospitals in Wales. 2% of patients present on the day in the participating hospitals had sepsis or severe sepsis, with a 90-day mortality of 35%. 4 The feasibility study highlighted the advantages of data collection by medical students, as they could provide the necessary manpower and clinical insight without the possible bias of the clinical teams, who are often under pressure to meet process measure targets and patient needs.4 However, the paper-based data collection process was cumbersome and prone to errors. To overcome this problem, CUReS developed the Welsh Digital Data Collection platform using Android tablet devices alongside a highly functional, yet free and opensource software package known as Open Data Kit. This software package is already a widely used and proven application for clinical data collection and provides a flexible way to obtain complex sets of data.5 The security features implemented include the ability to encrypt all data collected from the point of collection until the end of the study using the RSA-2048 protocol to satisfy data protection concerns. We believe our approach of collaboration with medical students and use of low-cost but high-fidelity technology can be easily replicated on an international scale and could provide a viable alternative to conventional clinical trial approaches
to measure the incidence of sepsis on general wards. We declare no competing interests. TS and GE were supported by the UK National Institute of Social and Health Care Research Allied Health and Social Care Clinical Research Fellowship. TS is also supported by the Cwm Taf University Health Board.
*Tamas Szakmany, Gemma Ellis, Ben Sharif, Robert M Lundin, Judith E Hall szakmanyt1@cardiff.ac.uk Department of Anaesthesia, Intensive Care and Pain Medicine, Cardiff University, Cardiff, CF14 4XN, UK 1
2
3
4
5
Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15: 581–614. Vincent J-L, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34: 344–53. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 2013; 41: 1167–74. Szakmany T, Ellis G, Lundin RM, et al. Sepsis in Wales on the general wards: results of a feasibility pilot. Br J Anaesth 2015; 114: 1000–01. Raja A, Tridane A, Gaffar A, Lindquist T, Pribadi K. Android and ODK based data collection framework to aid in epidemiological analysis. Online J Public Health Inform 2014; 5: 228.
Behavioural research to inform understanding of hepatitis C resistance Michael Mina and colleagues’ Review1 of the genetic and immunological determinants of hepatitis C virus (HCV) resistance among highly exposed but seronegative (HESN) individuals complements behavioural research with people who inject drugs (PWID). Epidemiological research has shown that some individuals remain uninfected despite reporting risk factors such as sharing of injecting equipment with people known to be HCV positive.2 This finding increased our interest in developing a qualitative research programme to more clearly understand how and why some PWID can avoid HCV infection. In our study of HCV-uninfected PWID from a well characterised cohort in Melbourne, Australia, we sought to identify factors affecting avoidance
www.thelancet.com/infection Vol 15 November 2015
Correspondence
of HCV infection in settings with high infection prevalence.3 We qualitatively interviewed 28 participants who had been injecting drugs for 5 years or more, and asked them to reflect on practices, tactics, and strategies that they believed to have protected them from infection. Results showed that individual injection practices remain important in restricting HCV transmission. Several strategies and tactics were implemented to avoid infection—eg, planning the purchase and use of drugs ahead of time, specific injection techniques to avoid blood exposure, injecting alone or injecting with others known to be HCV negative, and avoidance of drug withdrawal.4 However, participants also reported occasions of sharing injecting equipment. Narratives highlighted that sociospatial environments, and the social relations and practices implicit within networks of injectors, increase the likelihood of HCV transmission. Features of sociospatial environments identified as potentially protective included small, bounded networks (ie, home-based rather than street-based networks of injectors) and social processes and actions such as trust, serostatus negotiation, shared safer injecting norms, and collective confinement of injection (and equipment sharing) within the network. Because effective HCV vaccines are still in early stages of development and individuals are unlikely to know whether they have protective immunity, we should continue to focus on behavioural interventions to prevent HCV transmission. Our understanding of networks of injectors shows that these networks have a central role in both increasing and potentially blocking HCV transmission.5 Our findings support the conclusions of epidemiological research2 that sociospatial environments and network relations and practices, above and beyond individual injection practices, are key to
understanding transmission dynamics and possible prevention interventions for HCV. Further research with longterm HCV-negative PWID can inform the development of multicomponent prevention interventions that take into account individual practices and the sociospatial environments in which injection takes place. We declare no competing interests.
*Peter Higgs, Robyn Dwyer, Shelley Cogger, Margaret Hellard, Lisa Maher [email protected] National Drug Research Institute, Faculty of Health Sciences, Curtin University, Fitzroy, VIC 3065, Australia (PH, RD); Burnet Institute, Melbourne, VIC, Australia (SC, MH); and Kirby Institute, University of New South Wales Australia, Kensington, NSW, Australia (LM) 1
2
3
4 5
Mina MM, Luciani F, Cameron B, et al. Resistance to hepatitis C virus: potential genetic and immunological determinants. Lancet Infect Dis 2015; 15: 451–60. Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis 2011; 204: 74–83. Sacks-Davis R, Aitken CK, Higgs P, et al. High rates of hepatitis C virus reinfection and spontaneous clearance of reinfection in people who inject drugs: a prospective cohort study. PLoS One 2013; 8: e80216. Higgs P. WHACK 31—Emerging Trends Vol 2 (Melbourne), 2013: 12–14. Aitken C, Lewis J, Hocking J, Bowden S, Hellard M. Does information about IDU’s injecting networks predict exposure to the hepatitis C virus? Hepat Mon 2009; 9: 17–23.
Hepatitis C prevalence among people who inject drugs in Hungary Data have been published in Hungary,1 showing that between 2011 and 2014, prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) rose from 24% to 49% in the country, from 34% to 61% in the capital city Budapest, and from 10% to 33% outside Budapest (figure). Additionally, in March and May, 2014, two incident cases of HIV were detected among PWIDs. Since around 2010, the number of new psychoactive substances
www.thelancet.com/infection Vol 15 November 2015
(NPS; also known as designer drugs or legal highs) in Europe has almost exponentially increased. 2 NPS have overwhelmingly replaced traditional drugs, such as cannabis, amphetamines, and heroin, in Hungary. Injection of NPS is associated with a very high number of daily injecting episodes (on average six times a day) and a high prevalence of syringe sharing and reuse. Spread of NPS among PWID, therefore, created a strong demand for harm reduction, which was unmet by harm reduction services in Hungary. For example, owing to ongoing fierce political attacks and related scarcity of government funding, the two largest needle exchange programmes in Hungary were forced to close down in the second half of 2014, effectively halving the number of free syringes available for PWID. The HIV epidemics that occurred in 2011 in Romania and Greece among PWID were preceded by a shift from heroin and amphetamines to injectable NPS and a related increase in injecting frequency and syringe sharing 3—similar to the present situation in Hungary. The number of distributed syringes per PWID was about ten in Greece and about 50 in Romania during the years before the HIV outbreaks4—this number is 39 in Hungary now, which is far lower than the minimum of 100 recommended by WHO. Mathematical models describing the spread of HIV and HCV among PWID show that the probability of an HIV epidemic is low when HCV prevalence is under 35%, but above this threshold, the potential for an HIV outbreak substantially increases.5 Doubling of HCV prevalence among PWIDs in Hungary in the past few years to much above this threshold suggests that the probability of an HIV outbreak might now be very real—potentially ending an era of near-zero HIV prevalence among PWID in the country. We declare no competing interests.
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research.1 More studies are needed to confirm whether immunological assessment could help to diminish sepsis incidence in patients who are at risk. Such studies should be regarded as an additional priority in the proposed roadmap. We declare no competing interests.
*Jesús F Bermejo-Martin, David Andaluz-Ojeda, Raquel Almansa, Jose María Eiros, Eduardo Tamayo [email protected] Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL & IECSCYL, 47005 Valladolid, Spain (JFB-M, DA-O, RA, JME, ET); Servicio de Medicina Intensiva, Hospital Clínico Universitario de Valladolid, SACYL, Valladolid, Spain (DA-O); and Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Valladolid, Spain (ET) 1
2
3
4
5
Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15: 581–614. Henriksen DP, Pottegård A, Laursen CB, et al. Risk factors for hospitalization due to communityacquired sepsis—a population-based casecontrol study. PLoS One 2015; 10: e0124838. Cajander S, Bäckman A, Tina E, Strålin K, Söderquist B, Källman J. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Crit Care 2013; 17: R223. Tamayo E, Almansa R, Carrasco E, et al. Quantification of IgM molecular response by droplet digital PCR as a potential tool for the early diagnosis of sepsis. Crit Care 2014; 18: 433. Andaluz-Ojeda D, Iglesias V, Bobillo F, et al. Early natural killer cell counts in blood predict mortality in severe sepsis. Crit Care 2011; 15: R243.
In the Commission on sepsis by Jonathan Cohen and colleagues, 1 we were especially interested in the section on the global and regional epidemiology of sepsis, since we believe this is an area of great need for further studies. Although the authors argued that existing ways to measure sepsis incidence seem inadequate and fraught with difficulties resulting from problems with detection, documentation, and coding of the complication even in high-income countries, they did not provide a way forward to try to address this important information gap.1 1260
Importantly, most studies of sepsis epidemiology focused on intensive-care units and emergency departments, whereas it is increasingly apparent that the disease is even more prevalent and perhaps claim more lives on general hospital wards.2,3 We successfully piloted last year a new approach to try to address some of these problems. We formed a partnership with the Cardiff University Research Society (CUReS) and collaborated with medical students to undertake a 24-h point-prevalence study of sepsis and severe sepsis in four acute hospitals in Wales. 2% of patients present on the day in the participating hospitals had sepsis or severe sepsis, with a 90-day mortality of 35%. 4 The feasibility study highlighted the advantages of data collection by medical students, as they could provide the necessary manpower and clinical insight without the possible bias of the clinical teams, who are often under pressure to meet process measure targets and patient needs.4 However, the paper-based data collection process was cumbersome and prone to errors. To overcome this problem, CUReS developed the Welsh Digital Data Collection platform using Android tablet devices alongside a highly functional, yet free and opensource software package known as Open Data Kit. This software package is already a widely used and proven application for clinical data collection and provides a flexible way to obtain complex sets of data.5 The security features implemented include the ability to encrypt all data collected from the point of collection until the end of the study using the RSA-2048 protocol to satisfy data protection concerns. We believe our approach of collaboration with medical students and use of low-cost but high-fidelity technology can be easily replicated on an international scale and could provide a viable alternative to conventional clinical trial approaches
to measure the incidence of sepsis on general wards. We declare no competing interests. TS and GE were supported by the UK National Institute of Social and Health Care Research Allied Health and Social Care Clinical Research Fellowship. TS is also supported by the Cwm Taf University Health Board.
*Tamas Szakmany, Gemma Ellis, Ben Sharif, Robert M Lundin, Judith E Hall szakmanyt1@cardiff.ac.uk Department of Anaesthesia, Intensive Care and Pain Medicine, Cardiff University, Cardiff, CF14 4XN, UK 1
2
3
4
5
Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15: 581–614. Vincent J-L, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34: 344–53. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 2013; 41: 1167–74. Szakmany T, Ellis G, Lundin RM, et al. Sepsis in Wales on the general wards: results of a feasibility pilot. Br J Anaesth 2015; 114: 1000–01. Raja A, Tridane A, Gaffar A, Lindquist T, Pribadi K. Android and ODK based data collection framework to aid in epidemiological analysis. Online J Public Health Inform 2014; 5: 228.
Behavioural research to inform understanding of hepatitis C resistance Michael Mina and colleagues’ Review1 of the genetic and immunological determinants of hepatitis C virus (HCV) resistance among highly exposed but seronegative (HESN) individuals complements behavioural research with people who inject drugs (PWID). Epidemiological research has shown that some individuals remain uninfected despite reporting risk factors such as sharing of injecting equipment with people known to be HCV positive.2 This finding increased our interest in developing a qualitative research programme to more clearly understand how and why some PWID can avoid HCV infection. In our study of HCV-uninfected PWID from a well characterised cohort in Melbourne, Australia, we sought to identify factors affecting avoidance
www.thelancet.com/infection Vol 15 November 2015
Correspondence
of HCV infection in settings with high infection prevalence.3 We qualitatively interviewed 28 participants who had been injecting drugs for 5 years or more, and asked them to reflect on practices, tactics, and strategies that they believed to have protected them from infection. Results showed that individual injection practices remain important in restricting HCV transmission. Several strategies and tactics were implemented to avoid infection—eg, planning the purchase and use of drugs ahead of time, specific injection techniques to avoid blood exposure, injecting alone or injecting with others known to be HCV negative, and avoidance of drug withdrawal.4 However, participants also reported occasions of sharing injecting equipment. Narratives highlighted that sociospatial environments, and the social relations and practices implicit within networks of injectors, increase the likelihood of HCV transmission. Features of sociospatial environments identified as potentially protective included small, bounded networks (ie, home-based rather than street-based networks of injectors) and social processes and actions such as trust, serostatus negotiation, shared safer injecting norms, and collective confinement of injection (and equipment sharing) within the network. Because effective HCV vaccines are still in early stages of development and individuals are unlikely to know whether they have protective immunity, we should continue to focus on behavioural interventions to prevent HCV transmission. Our understanding of networks of injectors shows that these networks have a central role in both increasing and potentially blocking HCV transmission.5 Our findings support the conclusions of epidemiological research2 that sociospatial environments and network relations and practices, above and beyond individual injection practices, are key to
understanding transmission dynamics and possible prevention interventions for HCV. Further research with longterm HCV-negative PWID can inform the development of multicomponent prevention interventions that take into account individual practices and the sociospatial environments in which injection takes place. We declare no competing interests.
*Peter Higgs, Robyn Dwyer, Shelley Cogger, Margaret Hellard, Lisa Maher [email protected] National Drug Research Institute, Faculty of Health Sciences, Curtin University, Fitzroy, VIC 3065, Australia (PH, RD); Burnet Institute, Melbourne, VIC, Australia (SC, MH); and Kirby Institute, University of New South Wales Australia, Kensington, NSW, Australia (LM) 1
2
3
4 5
Mina MM, Luciani F, Cameron B, et al. Resistance to hepatitis C virus: potential genetic and immunological determinants. Lancet Infect Dis 2015; 15: 451–60. Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis 2011; 204: 74–83. Sacks-Davis R, Aitken CK, Higgs P, et al. High rates of hepatitis C virus reinfection and spontaneous clearance of reinfection in people who inject drugs: a prospective cohort study. PLoS One 2013; 8: e80216. Higgs P. WHACK 31—Emerging Trends Vol 2 (Melbourne), 2013: 12–14. Aitken C, Lewis J, Hocking J, Bowden S, Hellard M. Does information about IDU’s injecting networks predict exposure to the hepatitis C virus? Hepat Mon 2009; 9: 17–23.
Hepatitis C prevalence among people who inject drugs in Hungary Data have been published in Hungary,1 showing that between 2011 and 2014, prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) rose from 24% to 49% in the country, from 34% to 61% in the capital city Budapest, and from 10% to 33% outside Budapest (figure). Additionally, in March and May, 2014, two incident cases of HIV were detected among PWIDs. Since around 2010, the number of new psychoactive substances
www.thelancet.com/infection Vol 15 November 2015
(NPS; also known as designer drugs or legal highs) in Europe has almost exponentially increased. 2 NPS have overwhelmingly replaced traditional drugs, such as cannabis, amphetamines, and heroin, in Hungary. Injection of NPS is associated with a very high number of daily injecting episodes (on average six times a day) and a high prevalence of syringe sharing and reuse. Spread of NPS among PWID, therefore, created a strong demand for harm reduction, which was unmet by harm reduction services in Hungary. For example, owing to ongoing fierce political attacks and related scarcity of government funding, the two largest needle exchange programmes in Hungary were forced to close down in the second half of 2014, effectively halving the number of free syringes available for PWID. The HIV epidemics that occurred in 2011 in Romania and Greece among PWID were preceded by a shift from heroin and amphetamines to injectable NPS and a related increase in injecting frequency and syringe sharing 3—similar to the present situation in Hungary. The number of distributed syringes per PWID was about ten in Greece and about 50 in Romania during the years before the HIV outbreaks4—this number is 39 in Hungary now, which is far lower than the minimum of 100 recommended by WHO. Mathematical models describing the spread of HIV and HCV among PWID show that the probability of an HIV epidemic is low when HCV prevalence is under 35%, but above this threshold, the potential for an HIV outbreak substantially increases.5 Doubling of HCV prevalence among PWIDs in Hungary in the past few years to much above this threshold suggests that the probability of an HIV outbreak might now be very real—potentially ending an era of near-zero HIV prevalence among PWID in the country. We declare no competing interests.
1261