- Email: [email protected]
Hepatitis virus and HIV interactions
Comment
likely will be sufficient alone to stop new HIV infections. PrEP might not be a perfect solution, but it is certainly an exceedingly good one. We must find ways to deliver PrEP to at-risk populations globally. Otherwise, as Voltaire is also quoted as saying, “Every man is guilty of all the good he did not do.” Susan Buchbinder San Francisco Department of Public Health, San Francisco, CA, USA [email protected] I have conducted PrEP studies funded by the National Institutes of Health. Gilead has provided drug for some of the PrEP trials in which I have been involved. 1
2
3
Baeten JM, Donnell D, Mugo NR, et al, for the Partners PrEP Study Team. Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial. Lancet Infect Dis 2014; published online Oct 7. http://dx.doi.org/10.1016/S1473-3099(14)70937-5. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367: 399–410. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363: 2587–99.
4
5 6
7
8
9
10
11
12
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367: 423–34. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012; 367: 411–22. Marrazzo J, Ramjee G, Nair G, et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE Study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections; Atlanta, GA, USA; March 3–6, 2013. 26LB (abtrs). Chan PA, Huang A, Kantor R. Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. J Int AIDS Soc 2012; 15: 17701. Cong ME, Mitchell J, Sweeney E, et al. Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. J Infect Dis 2013; 208: 463–67. Lehman DA, Baeten J, McCoy C, et al. PrEP exposure and the risk of lowfrequency drug resistance. 21st Conference on Retroviruses and Opportunistic Infections; Boston, MA, USA; March 3–6, 2014. van de Vijver DA, Nichols BE, Abbas UL, et al. Preexposure prophylaxis will have a limited impact on HIV-1 drug resistance in sub-Saharan Africa: a comparison of mathematical models. AIDS 2013; 27: 2943–51. Kessler J, Myers JE, Nucifora KA, et al. Evaluating the impact of prioritization of antiretroviral pre-exposure prophylaxis in New York City. AIDS 2014: published online Sept 10. Nichols BE, Boucher CA, van Dijk JH, et al. Cost-effectiveness of preexposure prophylaxis (PrEP) in preventing HIV-1 infections in rural Zambia: a modeling study. PLoS One 2013; 8: e59549.
Because of shared routes of transmission, 5–25% of the 34 million people with HIV worldwide are coinfected with either hepatitis B virus (HBV), hepatitis C virus (HCV), or both,1 with the highest number of co-infections in low-income countries. The negative effect of HIV infection on the progression of HBV and HCV infection is well established, with high rates of viral persistence, higher hepatitis viral load, and a more rapid progression to liver fibrosis and hepatocellular carcinoma in HIV-positive patients.2 In high-income countries, hepatic disease is the third highest cause of death in people with HIV after AIDS-related mortality and non-AIDS cancer deaths3, and hepatocellular carcinoma causes a quarter of liver-related deaths.2 Because of the increasing availability of antiretroviral therapy and the high burden of viral hepatitis, chronic hepatitis and its consequences are expected to become a leading burden of disease in resource-limited countries, although the true prevalence and clinical evolution of liver disease in low-income and middleincome countries are still largely unknown. In highly endemic regions such as Africa and Asia, the prevalence of HBV is estimated to be as much as 8% (10–15% in www.thelancet.com/infection Vol 14 November 2014
some countries), and HBV infection mostly occurs early in life through vertical or child-to-child transmission; the effect of hepatocellular carcinoma is likely to be even greater than estimated, particularly in Asia where HBV genotype C is highly prevalent.4 The clinical effect of viral hepatitis infection on the natural history of HIV infection is unclear. Some evidence suggests that viral hepatitis increases the risk of mother-to-child-transmission of HIV, accelerates HIVdisease progression, increases HIV viral setpoint, and blunts the response to antiretroviral therapy, resulting in a smaller and slower CD4 cell increase than reported in people without HBV or HCV. In The Lancet Infectious Diseases, Zhang and colleagues5 provide a unique overview of survival, virological response, and immunological response to antiretroviral therapy in a huge cohort of Chinese HIVpositive patients also infected with HBV, HCV, or both. To our knowledge, this cohort is the largest addressing this subject, and the most extensive study of triple infection reported so far. Although the prevalence of HBV co-infection in China reported by Zhang and colleagues (8·7%) is lower than that provided in
Imaginechina/Corbis
Hepatitis virus and HIV interactions
Published Online October 8, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70853-9 See Articles page 1065
1025
Comment
Country
Number of patients
Núñez and colleagues7
International
30 HIV, HBV, HCV seropositive
Viral interference HBsAg positivity is associated with lower HCV RNA levels
Arribas and colleagues8
Spain
19 HIV, HBV, HCV seropositive (five also with HDV); one HBV, HDV co-infected
HBsAg positivity is associated with HCV RNA undetectability; HDV seems to inhibit both HBV and HCV replication
Maida and colleagues9
International
67 HIV, HBV, HCV seropositive (16 of whom HDV seropositive)
HDV co-infection is associated with spontaneous HCV clearance
Sollima and colleagues10
Italy
21 HIV, HBV, HCV seropositive
Mutual interplay between HBV and HCV replication
Martín-Carbonero and colleagues11
Spain
22 HIV, HBV, HCV seropositive (four of whom HDV seropositive)
HBV and HDV replication are associated with HCV RNA undetectability
Ladep and colleagues12
Nigeria
453 HIV, HBV, HCV seropositive
HIV replication enhanced by viral hepatitis
HBV=hepatitis B virus. HCV=hepatitis C virus. HDV=hepatitis D virus.
Table: Principal studies of the interactions of multiple viral hepatitis infections and HIV
another study,6 it is consistent with that expected for a highly endemic country. Despite the expanded programme of immunisation started in China in 1992, vaccine coverage seems to be incomplete, particularly in patients older than 20 years, suggesting that prevention and screening strategies need to be improved. Triple infection is associated with a high risk of death and virological failure and low retention in treatment compared with infection with HIV only. Although viroimmunological response to antiretroviral therapy seems to be unaffected in patients with HCV–HIV coinfection, mortality was significantly higher in this group. HBV–HIV coinfection did not affect outcome, probably because of the extended use of lamivudine in the initial combination antiretroviral therapy regimen. However, tenofovir, presently recommended by international guidelines as first-line treatment of HBV infection (to avoid the high risk of resistance to firstgeneration drugs), had been started in only 18·6% of HBsAg positive patients. Despite an impressive number of patients studied (more than 33 000), Zhang and colleagues’ study has several limitations. First, the short follow-up period and the lack of any information for the causes of death might have hampered investigation of survival as well as the direct effect of viral hepatitis. Second, the absence of data for HBV and HCV viral replication might have led to overestimation of HCV chronic infections and underestimation of the effect of occult HBV infection, which has been related to faster HIV progression.6 Analysis of the large number of patients with HBV and HCV co-infection would have provided more definite data for viral interference with respect to the current evidence (table). Finally, hepatitis D virus (HDV) 1026
infection was not assessed. In Europe, about 15% of HIVpositive individuals with chronic hepatitis B also have HDV superinfection,13 and the presence of both viruses has been associated with more liver-related morbidity and mortality than in patients with HIV alone, or those with HIV and HBV or HCV.14 Despite the likelihood of unmeasured confounding associated with any observational study, the results of Zhang and colleagues improves knowledge of clinical aspects of multiple viral infections in HIV-positive populations and strengthens the recommendation to systematically test all HIV-positive patients for HBV, HCV, and HDV, to expand HBV vaccination, and the access to treatment for viral hepatitis. *Laura Milazzo, Spinello Antinori Department of Biomedical and Clinical Sciences L Sacco, University of Milan, Via GB Grassi 74, 20157, Milan, Italy (LM, SA) [email protected] We declare no competing interests. 1 2 3
4 5
6
7
8
Hoffmann CJ, Thio CL. Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. Lancet Infect Dis 2007; 7: 402–09. Joshi D, O’Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet 2011; 377: 1198–209. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384: 241–48. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142: 1264–73. Zhang F, Zhu H, Wu Y, et al. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010–12: a retrospective observational cohort study. Lancet Infect Dis 2014; published online Oct 8. http://dx.doi.org/10.1016/ S1473-3099(14)70946-6 Wang H, Li Y, Zhang C, et al. Immunological and virological responses to cART in HIV/HBV co-infected patients from a multicenter cohort. AIDS 2012; 26: 1755–63. Núñez M, Maida I, Babudieri S, et al. Hepatitis C viremia in HIV/HCVcoinfected patients: lower levels in presence of chronic hepatitis B. HIV Clin Trials 2005; 6: 103–06. Arribas JR, González-García JJ, Lorenzo A, et al. Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain. AIDS 2005; 19: 1361–65.
www.thelancet.com/infection Vol 14 November 2014
Comment
9
10
11
Maida I, Ríos MJ, Pérez-Saleme L, et al. Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era. AIDS Res Hum Retroviruses 2008; 24: 679–83. Sollima S, Caramma I, Menzaghi B, et al. Chronic coinfection with hepatitis B and hepatitis C viruses in an Italian population of HIV-infected patients. J Acquir Immune Defic Syndr 2007; 44: 606–07. Martín-Carbonero L, Barreiro P, Jiménez-Galán G, et al. Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral epatiti. J Viral Hepat 2007; 14: 392–95.
12
13 14
Ladep NG, Agaba PA, Agbaji O, et al. Rates and impact of hepatitis on human immunodeficiency virus infection in a large African cohort. World J Gastroenterol 2013; 19: 1602–10. Soriano V, Grint D, D’Arminio-Monforte A, et al. Hepatitis delta in HIV-infected individuals in Europe. AIDS 2011; 25: 1987–92. Fernández-Montero JV, Vispo E, Barreiro P, et al. Hepatitis Delta is a major determinant of liver decompensation events and death in HIV-infected patients. Clin Infect Dis 2014; 58: 1549–53.
Global burden of listeriosis: the tip of the iceberg Listeriosis is a rare but severe infection. Three main invasive forms are described: septicaemia, neurolisteriosis, and maternal–neonatal infection. Listeriosis can also present as febrile gastroenteritis. Its foodborne origin was evidenced in the early 1980s.1 Since then, listeriosis has been implicated in about 80 recognised outbreaks, which led, mainly in high-income countries, to the implementation of national and supranational surveillance systems.2 This implementation of surveillance systems had a key role in the dissection of risk factors and control of outbreaks. However, an estimation of the worldwide burden of listeriosis was still missing. In The Lancet Infectious Diseases, Charline Maertens de Noordhout and colleagues3 report the results of a meta-analysis that estimates for the first time the global number of listeriosis cases, related deaths, and disability-adjusted life years (DALYs).3 An important limitation of this study is that data were available for only 52% of the world population. No information could be retrieved for 3·2 billion people mostly living in Africa, Latin America, and Asia. The authors estimated that 23 150 cases related to listeriosis occurred worldwide in 2010, resulting in 5463 deaths and 172 823 DALYs. Perinatal infections accounted for 20·7% of the cases. As acknowledged by the authors, these mean estimations were based on information from heterogeneous data collection systems with uneven exhaustiveness levels. The absence of data in some regions required the use of a multilevel random-effects model that extrapolates missing national incidences either from other countries of the same WHO subregion or from other WHO subregions. Regions with higher estimated incidence were also those with larger CIs. Such extrapolations are necessary but intrinsically provide poor estimates of the real burden of the disease, in view of important local variations in food www.thelancet.com/infection Vol 14 November 2014
contamination levels, population characteristics, surveillance methods, or health-care systems organisation and proficiency. One would indeed wish to take into account all these variables, which might affect the estimation of incidence and related mortality at the country level. Food contamination is affected by environmental variables such as climate and bacterial biodiversity. Although Listeria monocytogenes isolates seem to be evenly distributed,4 the distribution of putative hypervirulent clones is unknown and could be heterogeneous. Additionally, food production and preparation, storage conditions (refrigeration selectively allows growth of L monocytogenes), food distribution (local or large-scale), and dietary habits (consumer lifestyle, type, and portion of food consumed) all modify individual exposure to L monocytogenes and vary greatly from one WHO subregion to another, and also within a geographical region, in accordance with local resources and cultural discrepancies. Public health policies and their implementation, as well as demographic variables are major factors that should ideally be included in the equation estimating the incidence of listeriosis. For example, maternal– neonatal listeriosis incidence is correlated with fertility rate, whereas non-maternal-neonatal listeriosis mostly affects elderly people and patients receiving immunosuppressive therapies, as well as patients with comorbidities such as diabetes or obesity, both increasingly reported worldwide, but with geographical disparities. Furthermore, the poor availability of diagnostic resources and concomitant occurrence of highly prevalent diseases with similar symptoms might both lead to listeriosis under-reporting. Neonatal mortality is associated to infection in 28% of cases5 and ranges from five in 100 000 people in Europe to 31 in 100 000 in Africa. In regions with higher neonatal
Published Online September 16, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70903-X See Articles page 1073
1027
likely will be sufficient alone to stop new HIV infections. PrEP might not be a perfect solution, but it is certainly an exceedingly good one. We must find ways to deliver PrEP to at-risk populations globally. Otherwise, as Voltaire is also quoted as saying, “Every man is guilty of all the good he did not do.” Susan Buchbinder San Francisco Department of Public Health, San Francisco, CA, USA [email protected] I have conducted PrEP studies funded by the National Institutes of Health. Gilead has provided drug for some of the PrEP trials in which I have been involved. 1
2
3
Baeten JM, Donnell D, Mugo NR, et al, for the Partners PrEP Study Team. Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial. Lancet Infect Dis 2014; published online Oct 7. http://dx.doi.org/10.1016/S1473-3099(14)70937-5. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367: 399–410. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363: 2587–99.
4
5 6
7
8
9
10
11
12
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367: 423–34. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012; 367: 411–22. Marrazzo J, Ramjee G, Nair G, et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE Study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections; Atlanta, GA, USA; March 3–6, 2013. 26LB (abtrs). Chan PA, Huang A, Kantor R. Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis. J Int AIDS Soc 2012; 15: 17701. Cong ME, Mitchell J, Sweeney E, et al. Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques. J Infect Dis 2013; 208: 463–67. Lehman DA, Baeten J, McCoy C, et al. PrEP exposure and the risk of lowfrequency drug resistance. 21st Conference on Retroviruses and Opportunistic Infections; Boston, MA, USA; March 3–6, 2014. van de Vijver DA, Nichols BE, Abbas UL, et al. Preexposure prophylaxis will have a limited impact on HIV-1 drug resistance in sub-Saharan Africa: a comparison of mathematical models. AIDS 2013; 27: 2943–51. Kessler J, Myers JE, Nucifora KA, et al. Evaluating the impact of prioritization of antiretroviral pre-exposure prophylaxis in New York City. AIDS 2014: published online Sept 10. Nichols BE, Boucher CA, van Dijk JH, et al. Cost-effectiveness of preexposure prophylaxis (PrEP) in preventing HIV-1 infections in rural Zambia: a modeling study. PLoS One 2013; 8: e59549.
Because of shared routes of transmission, 5–25% of the 34 million people with HIV worldwide are coinfected with either hepatitis B virus (HBV), hepatitis C virus (HCV), or both,1 with the highest number of co-infections in low-income countries. The negative effect of HIV infection on the progression of HBV and HCV infection is well established, with high rates of viral persistence, higher hepatitis viral load, and a more rapid progression to liver fibrosis and hepatocellular carcinoma in HIV-positive patients.2 In high-income countries, hepatic disease is the third highest cause of death in people with HIV after AIDS-related mortality and non-AIDS cancer deaths3, and hepatocellular carcinoma causes a quarter of liver-related deaths.2 Because of the increasing availability of antiretroviral therapy and the high burden of viral hepatitis, chronic hepatitis and its consequences are expected to become a leading burden of disease in resource-limited countries, although the true prevalence and clinical evolution of liver disease in low-income and middleincome countries are still largely unknown. In highly endemic regions such as Africa and Asia, the prevalence of HBV is estimated to be as much as 8% (10–15% in www.thelancet.com/infection Vol 14 November 2014
some countries), and HBV infection mostly occurs early in life through vertical or child-to-child transmission; the effect of hepatocellular carcinoma is likely to be even greater than estimated, particularly in Asia where HBV genotype C is highly prevalent.4 The clinical effect of viral hepatitis infection on the natural history of HIV infection is unclear. Some evidence suggests that viral hepatitis increases the risk of mother-to-child-transmission of HIV, accelerates HIVdisease progression, increases HIV viral setpoint, and blunts the response to antiretroviral therapy, resulting in a smaller and slower CD4 cell increase than reported in people without HBV or HCV. In The Lancet Infectious Diseases, Zhang and colleagues5 provide a unique overview of survival, virological response, and immunological response to antiretroviral therapy in a huge cohort of Chinese HIVpositive patients also infected with HBV, HCV, or both. To our knowledge, this cohort is the largest addressing this subject, and the most extensive study of triple infection reported so far. Although the prevalence of HBV co-infection in China reported by Zhang and colleagues (8·7%) is lower than that provided in
Imaginechina/Corbis
Hepatitis virus and HIV interactions
Published Online October 8, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70853-9 See Articles page 1065
1025
Comment
Country
Number of patients
Núñez and colleagues7
International
30 HIV, HBV, HCV seropositive
Viral interference HBsAg positivity is associated with lower HCV RNA levels
Arribas and colleagues8
Spain
19 HIV, HBV, HCV seropositive (five also with HDV); one HBV, HDV co-infected
HBsAg positivity is associated with HCV RNA undetectability; HDV seems to inhibit both HBV and HCV replication
Maida and colleagues9
International
67 HIV, HBV, HCV seropositive (16 of whom HDV seropositive)
HDV co-infection is associated with spontaneous HCV clearance
Sollima and colleagues10
Italy
21 HIV, HBV, HCV seropositive
Mutual interplay between HBV and HCV replication
Martín-Carbonero and colleagues11
Spain
22 HIV, HBV, HCV seropositive (four of whom HDV seropositive)
HBV and HDV replication are associated with HCV RNA undetectability
Ladep and colleagues12
Nigeria
453 HIV, HBV, HCV seropositive
HIV replication enhanced by viral hepatitis
HBV=hepatitis B virus. HCV=hepatitis C virus. HDV=hepatitis D virus.
Table: Principal studies of the interactions of multiple viral hepatitis infections and HIV
another study,6 it is consistent with that expected for a highly endemic country. Despite the expanded programme of immunisation started in China in 1992, vaccine coverage seems to be incomplete, particularly in patients older than 20 years, suggesting that prevention and screening strategies need to be improved. Triple infection is associated with a high risk of death and virological failure and low retention in treatment compared with infection with HIV only. Although viroimmunological response to antiretroviral therapy seems to be unaffected in patients with HCV–HIV coinfection, mortality was significantly higher in this group. HBV–HIV coinfection did not affect outcome, probably because of the extended use of lamivudine in the initial combination antiretroviral therapy regimen. However, tenofovir, presently recommended by international guidelines as first-line treatment of HBV infection (to avoid the high risk of resistance to firstgeneration drugs), had been started in only 18·6% of HBsAg positive patients. Despite an impressive number of patients studied (more than 33 000), Zhang and colleagues’ study has several limitations. First, the short follow-up period and the lack of any information for the causes of death might have hampered investigation of survival as well as the direct effect of viral hepatitis. Second, the absence of data for HBV and HCV viral replication might have led to overestimation of HCV chronic infections and underestimation of the effect of occult HBV infection, which has been related to faster HIV progression.6 Analysis of the large number of patients with HBV and HCV co-infection would have provided more definite data for viral interference with respect to the current evidence (table). Finally, hepatitis D virus (HDV) 1026
infection was not assessed. In Europe, about 15% of HIVpositive individuals with chronic hepatitis B also have HDV superinfection,13 and the presence of both viruses has been associated with more liver-related morbidity and mortality than in patients with HIV alone, or those with HIV and HBV or HCV.14 Despite the likelihood of unmeasured confounding associated with any observational study, the results of Zhang and colleagues improves knowledge of clinical aspects of multiple viral infections in HIV-positive populations and strengthens the recommendation to systematically test all HIV-positive patients for HBV, HCV, and HDV, to expand HBV vaccination, and the access to treatment for viral hepatitis. *Laura Milazzo, Spinello Antinori Department of Biomedical and Clinical Sciences L Sacco, University of Milan, Via GB Grassi 74, 20157, Milan, Italy (LM, SA) [email protected] We declare no competing interests. 1 2 3
4 5
6
7
8
Hoffmann CJ, Thio CL. Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. Lancet Infect Dis 2007; 7: 402–09. Joshi D, O’Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet 2011; 377: 1198–209. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384: 241–48. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142: 1264–73. Zhang F, Zhu H, Wu Y, et al. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010–12: a retrospective observational cohort study. Lancet Infect Dis 2014; published online Oct 8. http://dx.doi.org/10.1016/ S1473-3099(14)70946-6 Wang H, Li Y, Zhang C, et al. Immunological and virological responses to cART in HIV/HBV co-infected patients from a multicenter cohort. AIDS 2012; 26: 1755–63. Núñez M, Maida I, Babudieri S, et al. Hepatitis C viremia in HIV/HCVcoinfected patients: lower levels in presence of chronic hepatitis B. HIV Clin Trials 2005; 6: 103–06. Arribas JR, González-García JJ, Lorenzo A, et al. Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain. AIDS 2005; 19: 1361–65.
www.thelancet.com/infection Vol 14 November 2014
Comment
9
10
11
Maida I, Ríos MJ, Pérez-Saleme L, et al. Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era. AIDS Res Hum Retroviruses 2008; 24: 679–83. Sollima S, Caramma I, Menzaghi B, et al. Chronic coinfection with hepatitis B and hepatitis C viruses in an Italian population of HIV-infected patients. J Acquir Immune Defic Syndr 2007; 44: 606–07. Martín-Carbonero L, Barreiro P, Jiménez-Galán G, et al. Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral epatiti. J Viral Hepat 2007; 14: 392–95.
12
13 14
Ladep NG, Agaba PA, Agbaji O, et al. Rates and impact of hepatitis on human immunodeficiency virus infection in a large African cohort. World J Gastroenterol 2013; 19: 1602–10. Soriano V, Grint D, D’Arminio-Monforte A, et al. Hepatitis delta in HIV-infected individuals in Europe. AIDS 2011; 25: 1987–92. Fernández-Montero JV, Vispo E, Barreiro P, et al. Hepatitis Delta is a major determinant of liver decompensation events and death in HIV-infected patients. Clin Infect Dis 2014; 58: 1549–53.
Global burden of listeriosis: the tip of the iceberg Listeriosis is a rare but severe infection. Three main invasive forms are described: septicaemia, neurolisteriosis, and maternal–neonatal infection. Listeriosis can also present as febrile gastroenteritis. Its foodborne origin was evidenced in the early 1980s.1 Since then, listeriosis has been implicated in about 80 recognised outbreaks, which led, mainly in high-income countries, to the implementation of national and supranational surveillance systems.2 This implementation of surveillance systems had a key role in the dissection of risk factors and control of outbreaks. However, an estimation of the worldwide burden of listeriosis was still missing. In The Lancet Infectious Diseases, Charline Maertens de Noordhout and colleagues3 report the results of a meta-analysis that estimates for the first time the global number of listeriosis cases, related deaths, and disability-adjusted life years (DALYs).3 An important limitation of this study is that data were available for only 52% of the world population. No information could be retrieved for 3·2 billion people mostly living in Africa, Latin America, and Asia. The authors estimated that 23 150 cases related to listeriosis occurred worldwide in 2010, resulting in 5463 deaths and 172 823 DALYs. Perinatal infections accounted for 20·7% of the cases. As acknowledged by the authors, these mean estimations were based on information from heterogeneous data collection systems with uneven exhaustiveness levels. The absence of data in some regions required the use of a multilevel random-effects model that extrapolates missing national incidences either from other countries of the same WHO subregion or from other WHO subregions. Regions with higher estimated incidence were also those with larger CIs. Such extrapolations are necessary but intrinsically provide poor estimates of the real burden of the disease, in view of important local variations in food www.thelancet.com/infection Vol 14 November 2014
contamination levels, population characteristics, surveillance methods, or health-care systems organisation and proficiency. One would indeed wish to take into account all these variables, which might affect the estimation of incidence and related mortality at the country level. Food contamination is affected by environmental variables such as climate and bacterial biodiversity. Although Listeria monocytogenes isolates seem to be evenly distributed,4 the distribution of putative hypervirulent clones is unknown and could be heterogeneous. Additionally, food production and preparation, storage conditions (refrigeration selectively allows growth of L monocytogenes), food distribution (local or large-scale), and dietary habits (consumer lifestyle, type, and portion of food consumed) all modify individual exposure to L monocytogenes and vary greatly from one WHO subregion to another, and also within a geographical region, in accordance with local resources and cultural discrepancies. Public health policies and their implementation, as well as demographic variables are major factors that should ideally be included in the equation estimating the incidence of listeriosis. For example, maternal– neonatal listeriosis incidence is correlated with fertility rate, whereas non-maternal-neonatal listeriosis mostly affects elderly people and patients receiving immunosuppressive therapies, as well as patients with comorbidities such as diabetes or obesity, both increasingly reported worldwide, but with geographical disparities. Furthermore, the poor availability of diagnostic resources and concomitant occurrence of highly prevalent diseases with similar symptoms might both lead to listeriosis under-reporting. Neonatal mortality is associated to infection in 28% of cases5 and ranges from five in 100 000 people in Europe to 31 in 100 000 in Africa. In regions with higher neonatal
Published Online September 16, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70903-X See Articles page 1073
1027