Comment
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Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417–28. Forns X, Lawitz E, Zeuzem S, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology 2014; 146: 1669–79. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatmentnaive patients: the COSMOS randomised study. Lancet 2014; published online July 26. http://dx.doi.org/10.1016/S0140-6736(14)61036-9. Jensen D, O’Leary J, Pockros P, et al. Safety and efficacy of sofosbuvir containing regimens for hepatitis C: A real world experience in a diverse longitudinal observational cohort. Hepatology 2014; 60: 219. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370: 1483–93.
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Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/ r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1604–14. Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2014; published online Nov 11. http://dx.doi. org/10.1016/S0140-6736(14)61795-5. Muir A, Poordad F, Lalezari J, et al. All oral fixed dose combination with daclatasvir asunaprevir and BMS 791325 plus or minus ribavirin for patients with chronic hepatitis C genotype 1 infection and compensated cirrhosis: Unity -2 phase 3 SVR12 results. Hepatology 2014; 60: LB–2. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2014. J Hepatol 2014; 61: 373–95.
HCV in people who inject drugs: a neglected epidemic Published Online December 3, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71054-0 See Articles page 36
4
Despite the serious health implications of hepatitis C virus (HCV), especially in the context of concurrent HIV infection, its prevention and management has not been a national health priority in India. With the advent of highly efficacious direct acting antiviral drugs for HCV that can be administered orally once daily,1 and activism around the reduction of treatment costs, HCV treatment might be added to the national health mission plan, which is especially important for people who inject drugs, the population most affected by HCV. Relevant epidemiological information is important to inform policy makers at this opportune moment. Sunil Solomon and colleagues2 report the results of a multisite community-based assessment in which 14481 people who inject drugs were recruited from 15 cities in 11 Indian states—five cities were from the north and northwestern part of the country, seven were from northeast India, and the other cities were from central, east, and western India; no cities from south India were included. Overall weighted anti-HCV antibody (HCVAb) prevalence in people who inject drugs in this assessment was 37%, with the lowest and highest prevalence being recorded from the northeast. The overall weighted prevalence of anti-HIV antibody (HIVAb) plus HCVAb in people who inject drugs in this study was 13%, with a geographical spread similar to that of HCVAb. This study makes an important and timely contribution to the area of HCV epidemiology. Several studies have documented HCV prevalence in people who inject drugs during the past two decades with substantial regional variation within India. For example, in Kolkata, an eastern Indian city, the
prevalence of HCVAb in people who inject drugs was 18% and in non-injection drug users was 14% during 1994–95, whereas HIV prevalence was 1%.3 In northeast India, a study done in injection heroin users in 1996 in Churachandpur, a district of Manipur bordering Burma, recorded an HCV prevalence of 98% and an HIV prevalence of 75%.4 An HCV prevalence of 62% and an HIV prevalence of 30% were reported from Chennai in 2008,5 and 49% and 29%, respectively, from Punjab in 2013.6 In all these studies, HCV prevalence was higher than HIV prevalence. A similar pattern of high HCV prevalence in people who inject drugs with very low HIV prevalence has been reported in Pakistan.7 This finding is biologically plausible because HCV is more infectious than HIV8 and can remain infectious, after drying at room temperature, for up to 6 weeks in blood spots, facilitating HCV transmission using needles or syringes and other paraphernalia.9 Furthermore, HCV prevalence reported in these studies is based on serological testing for HCVAbs, and a positive result can represent an acute, chronic, or resolved HCV infection. HCV RNA testing would, therefore, be necessary to arrive at reliable estimates of those with chronic infection needing treatment. Efforts are needed to make these tests more affordable and accessible. Solomon and colleagues report that only 5% of the HCV antibody positive people who inject drugs were aware of their serostatus.2 This finding, in view of the programmatic emphasis on HIV and neglect towards HCV, is not surprising. Low awareness about HCV in people who inject drugs was recorded in the capital city of Delhi and the northeastern city of Imphal in an www.thelancet.com/infection Vol 15 January 2015
Comment
earlier investigation done during 2006–07 in which 9% and 46% had heard of HCV, of whom 20% and 37%, respectively, underwent HCV testing.10 A 2010 systematic review of HIV prevention and care services for people who inject drugs estimated that although 78% of people who inject drugs were covered by HIV prevention and care services in India, the number of needles-syringes distributed per person who injects drugs per year was around 34 (22–58) and there were three oral substitution therapy recipients in 100 people who inject drugs;11 estimates for HIV positive people who inject drugs receiving antiretroviral therapy were not available. Moreover, the assessment from Punjab6 showed that people who inject drugs reporting irregular supply of syringes and needles from targeted intervention sites had almost twice the odds of being HCV seroreactive compared with their counterparts. All this evidence underscores the fact that access to prevention, care, and treatment remains a challenge for people who inject drugs. It will be a while before treatment for HCV infection becomes affordable and available through public health programmes. Prevention efforts should therefore consist of awareness about HCV (and hepatitis B), safe injection practices, including an emphasis on clean injection paraphernalia, oral substitution therapy, and sexual risk reduction in people who inject drugs. Global evidence is evolving such that quality coverage with comprehensive harmreduction interventions at a sufficient scale can reduce HCV incidence.12
Avina Sarna, *Samiran Panda Population Council, India Office,Dehli, India (AS); and National Institute of Cholera & Enteric Diseases (ICMR), Kolkata, West Bengal, India 700010 (SP) [email protected] 1 2
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The Lancet. Only just the beginning of the end of hepatitis C. Lancet 2014; 383: 281. Solomon SS, Mehta SH, Srikirishnan AK, et al. High burden of HCV disease and poor access to HCV services among people who inject drugs in India: A crosssectional study among 14,481 drug users across India. Lancet Infect Dis 2014; published online Dec 3. http://dx.doi.org/10.1016/S1473-3099(14)71054-0. Panda S, Chatterjee A, Sarkar S, et al. Injection drug use in Calcutta: a potential focus for an explosive HIV epidemic. Drug Alcohol Rev 1997; 16: 17–23. Eicher AD, Crofts N, Benjamin S, Deutschmann P, Rodger AJ. A certain fate: spread of HIV among young injecting drug users in Manipur, north-east India. AIDS Care 2000; 12: 497–504. Solomon SS, Srikrishnan AK, Mehta SH, et al. High prevalence of HIV, HIV/ hepatitis C virus coinfection, and risk behaviors among injection drug users in Chennai, India: a cause for concern. J Acquir Immune Defic Syndr 2008; 49: 327–32. Panda S, Roy T, Pahari S, et al. Alarming epidemics of human immunodeficiency virus and hepatitis C virus among injection drug users in the northwestern bordering state of Punjab, India: prevalence and correlates. Int J STD AIDS 2013; 25: 596–606. Platt L, Vickerman P, Collumbien M, et al. Prevalence of HIV, HCV and sexually transmitted infections among injecting drug users in Rawalpindi and Abbottabad, Pakistan: evidence for an emerging injection-related HIV epidemic. Sex Transm Infect 2009; 85 (suppl 2): ii17–22. Taylor LE, Swan T, Mayer KH. HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms. Clin Infect Dis 2012; 55 (suppl 1): S33–42. Paintsil E, Binka M, Patel A, Lindenbach BD, Heimer R. Hepatitis C virus maintains infectivity for weeks after drying on inanimate surfaces at room temperature: implications for risks of transmission. J Infect Dis 2014; 209: 1205–11. Sarna A, Tun W, Bhattacharya A, Lewis D, Singh YS, Apicella L. Assessment of unsafe injection practices and sexual behaviors among male injecting drug users in two urban cities of India using respondent driven sampling. Southeast Asian Journal of Tropical Medicine & Public Health 2012; 43: 652–67. Mathers BM, Degenhardt L, Ali H, et al. HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage. Lancet 2010; 375: 1014–28. Palmateer NE, Taylor A, Goldberg DJ, et al. Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions. PLoS One 2014; 9: e104515.
Sepsis in children: some good news, some confusing news In critically ill children in Australia and New Zealand, the incidence of invasive infections, sepsis, and septic shock has increased in the past decade while mortality has decreased. This simple message, reported in The Lancet Infectious Diseases by Luregn Schlapbach and colleagues,1 provides some reassurance that, despite the heavy burden of severe infections in children, clinical outcomes are improving. However, it also shows the complexity of understanding data in a subject as murky as sepsis. For instance, both in Schlapbach and colleagues’ study and in a similar report from the USA,2 most of the increase in incidence of severe infections was attributable to www.thelancet.com/infection Vol 15 January 2015
neonatal disease. Neonatal and paediatric sepsis are in many respects different diseases; therefore, conflating them into a single analysis makes interpretation challenging. Another example is the categorisation of patients into three supposedly non-overlapping groups: invasive infection, sepsis, and septic shock. Many readers will find it hard to understand how, for example, a patient with necrotising fasciitis who is sick enough to be in a paediatric intensive care unit would not be regarded as having sepsis. Such difficulties, which have long bedevilled studies of sepsis, do not detract from the importance of the overall conclusions of the study. But they do serve
Published Online December 1, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71044-8 See Articles page 46
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Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417–28. Forns X, Lawitz E, Zeuzem S, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology 2014; 146: 1669–79. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatmentnaive patients: the COSMOS randomised study. Lancet 2014; published online July 26. http://dx.doi.org/10.1016/S0140-6736(14)61036-9. Jensen D, O’Leary J, Pockros P, et al. Safety and efficacy of sofosbuvir containing regimens for hepatitis C: A real world experience in a diverse longitudinal observational cohort. Hepatology 2014; 60: 219. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370: 1483–93.
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Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/ r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1604–14. Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2014; published online Nov 11. http://dx.doi. org/10.1016/S0140-6736(14)61795-5. Muir A, Poordad F, Lalezari J, et al. All oral fixed dose combination with daclatasvir asunaprevir and BMS 791325 plus or minus ribavirin for patients with chronic hepatitis C genotype 1 infection and compensated cirrhosis: Unity -2 phase 3 SVR12 results. Hepatology 2014; 60: LB–2. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2014. J Hepatol 2014; 61: 373–95.
HCV in people who inject drugs: a neglected epidemic Published Online December 3, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71054-0 See Articles page 36
4
Despite the serious health implications of hepatitis C virus (HCV), especially in the context of concurrent HIV infection, its prevention and management has not been a national health priority in India. With the advent of highly efficacious direct acting antiviral drugs for HCV that can be administered orally once daily,1 and activism around the reduction of treatment costs, HCV treatment might be added to the national health mission plan, which is especially important for people who inject drugs, the population most affected by HCV. Relevant epidemiological information is important to inform policy makers at this opportune moment. Sunil Solomon and colleagues2 report the results of a multisite community-based assessment in which 14481 people who inject drugs were recruited from 15 cities in 11 Indian states—five cities were from the north and northwestern part of the country, seven were from northeast India, and the other cities were from central, east, and western India; no cities from south India were included. Overall weighted anti-HCV antibody (HCVAb) prevalence in people who inject drugs in this assessment was 37%, with the lowest and highest prevalence being recorded from the northeast. The overall weighted prevalence of anti-HIV antibody (HIVAb) plus HCVAb in people who inject drugs in this study was 13%, with a geographical spread similar to that of HCVAb. This study makes an important and timely contribution to the area of HCV epidemiology. Several studies have documented HCV prevalence in people who inject drugs during the past two decades with substantial regional variation within India. For example, in Kolkata, an eastern Indian city, the
prevalence of HCVAb in people who inject drugs was 18% and in non-injection drug users was 14% during 1994–95, whereas HIV prevalence was 1%.3 In northeast India, a study done in injection heroin users in 1996 in Churachandpur, a district of Manipur bordering Burma, recorded an HCV prevalence of 98% and an HIV prevalence of 75%.4 An HCV prevalence of 62% and an HIV prevalence of 30% were reported from Chennai in 2008,5 and 49% and 29%, respectively, from Punjab in 2013.6 In all these studies, HCV prevalence was higher than HIV prevalence. A similar pattern of high HCV prevalence in people who inject drugs with very low HIV prevalence has been reported in Pakistan.7 This finding is biologically plausible because HCV is more infectious than HIV8 and can remain infectious, after drying at room temperature, for up to 6 weeks in blood spots, facilitating HCV transmission using needles or syringes and other paraphernalia.9 Furthermore, HCV prevalence reported in these studies is based on serological testing for HCVAbs, and a positive result can represent an acute, chronic, or resolved HCV infection. HCV RNA testing would, therefore, be necessary to arrive at reliable estimates of those with chronic infection needing treatment. Efforts are needed to make these tests more affordable and accessible. Solomon and colleagues report that only 5% of the HCV antibody positive people who inject drugs were aware of their serostatus.2 This finding, in view of the programmatic emphasis on HIV and neglect towards HCV, is not surprising. Low awareness about HCV in people who inject drugs was recorded in the capital city of Delhi and the northeastern city of Imphal in an www.thelancet.com/infection Vol 15 January 2015
Comment
earlier investigation done during 2006–07 in which 9% and 46% had heard of HCV, of whom 20% and 37%, respectively, underwent HCV testing.10 A 2010 systematic review of HIV prevention and care services for people who inject drugs estimated that although 78% of people who inject drugs were covered by HIV prevention and care services in India, the number of needles-syringes distributed per person who injects drugs per year was around 34 (22–58) and there were three oral substitution therapy recipients in 100 people who inject drugs;11 estimates for HIV positive people who inject drugs receiving antiretroviral therapy were not available. Moreover, the assessment from Punjab6 showed that people who inject drugs reporting irregular supply of syringes and needles from targeted intervention sites had almost twice the odds of being HCV seroreactive compared with their counterparts. All this evidence underscores the fact that access to prevention, care, and treatment remains a challenge for people who inject drugs. It will be a while before treatment for HCV infection becomes affordable and available through public health programmes. Prevention efforts should therefore consist of awareness about HCV (and hepatitis B), safe injection practices, including an emphasis on clean injection paraphernalia, oral substitution therapy, and sexual risk reduction in people who inject drugs. Global evidence is evolving such that quality coverage with comprehensive harmreduction interventions at a sufficient scale can reduce HCV incidence.12
Avina Sarna, *Samiran Panda Population Council, India Office,Dehli, India (AS); and National Institute of Cholera & Enteric Diseases (ICMR), Kolkata, West Bengal, India 700010 (SP) [email protected] 1 2
3 4
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The Lancet. Only just the beginning of the end of hepatitis C. Lancet 2014; 383: 281. Solomon SS, Mehta SH, Srikirishnan AK, et al. High burden of HCV disease and poor access to HCV services among people who inject drugs in India: A crosssectional study among 14,481 drug users across India. Lancet Infect Dis 2014; published online Dec 3. http://dx.doi.org/10.1016/S1473-3099(14)71054-0. Panda S, Chatterjee A, Sarkar S, et al. Injection drug use in Calcutta: a potential focus for an explosive HIV epidemic. Drug Alcohol Rev 1997; 16: 17–23. Eicher AD, Crofts N, Benjamin S, Deutschmann P, Rodger AJ. A certain fate: spread of HIV among young injecting drug users in Manipur, north-east India. AIDS Care 2000; 12: 497–504. Solomon SS, Srikrishnan AK, Mehta SH, et al. High prevalence of HIV, HIV/ hepatitis C virus coinfection, and risk behaviors among injection drug users in Chennai, India: a cause for concern. J Acquir Immune Defic Syndr 2008; 49: 327–32. Panda S, Roy T, Pahari S, et al. Alarming epidemics of human immunodeficiency virus and hepatitis C virus among injection drug users in the northwestern bordering state of Punjab, India: prevalence and correlates. Int J STD AIDS 2013; 25: 596–606. Platt L, Vickerman P, Collumbien M, et al. Prevalence of HIV, HCV and sexually transmitted infections among injecting drug users in Rawalpindi and Abbottabad, Pakistan: evidence for an emerging injection-related HIV epidemic. Sex Transm Infect 2009; 85 (suppl 2): ii17–22. Taylor LE, Swan T, Mayer KH. HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms. Clin Infect Dis 2012; 55 (suppl 1): S33–42. Paintsil E, Binka M, Patel A, Lindenbach BD, Heimer R. Hepatitis C virus maintains infectivity for weeks after drying on inanimate surfaces at room temperature: implications for risks of transmission. J Infect Dis 2014; 209: 1205–11. Sarna A, Tun W, Bhattacharya A, Lewis D, Singh YS, Apicella L. Assessment of unsafe injection practices and sexual behaviors among male injecting drug users in two urban cities of India using respondent driven sampling. Southeast Asian Journal of Tropical Medicine & Public Health 2012; 43: 652–67. Mathers BM, Degenhardt L, Ali H, et al. HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage. Lancet 2010; 375: 1014–28. Palmateer NE, Taylor A, Goldberg DJ, et al. Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions. PLoS One 2014; 9: e104515.
Sepsis in children: some good news, some confusing news In critically ill children in Australia and New Zealand, the incidence of invasive infections, sepsis, and septic shock has increased in the past decade while mortality has decreased. This simple message, reported in The Lancet Infectious Diseases by Luregn Schlapbach and colleagues,1 provides some reassurance that, despite the heavy burden of severe infections in children, clinical outcomes are improving. However, it also shows the complexity of understanding data in a subject as murky as sepsis. For instance, both in Schlapbach and colleagues’ study and in a similar report from the USA,2 most of the increase in incidence of severe infections was attributable to www.thelancet.com/infection Vol 15 January 2015
neonatal disease. Neonatal and paediatric sepsis are in many respects different diseases; therefore, conflating them into a single analysis makes interpretation challenging. Another example is the categorisation of patients into three supposedly non-overlapping groups: invasive infection, sepsis, and septic shock. Many readers will find it hard to understand how, for example, a patient with necrotising fasciitis who is sick enough to be in a paediatric intensive care unit would not be regarded as having sepsis. Such difficulties, which have long bedevilled studies of sepsis, do not detract from the importance of the overall conclusions of the study. But they do serve
Published Online December 1, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71044-8 See Articles page 46
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