Reply to Chen et al

Reply to Chen et al To the Editor—In response to an article by Manor et al [1], Chen et al recently reported on an outbreak of acute hepatitis A virus (HAV) in northern Taiwan that affected primarily men who have sex with men (MSM) who had human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) [2]. That outbreak started in mid-2015 and peaked with >1000 cases of acute HAV reported in 2016. By contrast, <100 cases of acute HAV were reported in all of Taiwan for the year 2014. The incidence of acute HAV fell rapidly after October 2016 when the Taiwan Centers for Disease Control implemented a free vaccination campaign targeting MSM with HIV infection or other STIs [3]. Acute outbreaks of HAV infection among MSM also occurred from mid 2016 to February 2017 in several European countries, including the Netherlands, Germany, and the United Kingdom [4–6]. Phylogenetic analysis has linked the outbreaks in Asia and Europe, with transmission presumably through oral–anal sexual contact [4]. No outbreak of acute HAV has been reported in the Bangkok metropolitan area since 2002, when a cluster of <100 cases occurred in the neighboring Nonthaburi province [7]. The low endemicity for HAV in Thailand has been attributed to improving hygiene, healthcare, and economic factors. The age at which 50% of the population tested anti-HAV immunoglobulin G (IgG) positive, a marker for past infection or immunization against HAV, rose from 6 years in 1976 to 42 years in 2014 [7]. MSM may be at higher risk for HAV infection due to sexual behavior that includes oral–anal contact. HIV-infected MSM are at higher risk for onward transmission of HAV because they have higher and more prolonged HAV viremia during acute infection [8]. In one cross-sectional study of MSM in Bangkok with a median age of 25 years, 27% were anti-HAV IgG positive, with HIV-infected MSM having a higher seroprevalence at 32% [9]. The SEARCH010/RV254 cohort has recruited participants with acute HIV infection (AHI) since 2009 [10]. A total of 478 individuals enrolled through June 2017. No cases of acute HAV (defined as anti-HAV immunoglobulin M positive with symptoms of acute hepatitis) were identified in the cohort until 2017, when 5 cases were identified between March and May. All were male, with a median age of 37 (range, 20–43) years. Clinical manifestations included abdominal pain (n = 5), fatigue (n = 5), jaundice (n = 3), fever (n = 3), and nausea/vomiting (n = 2). All cases reported male sexual partners within the preceding 3 months. None had traveled outside of Thailand. Four cases were on antiretroviral therapy with a median duration of 19.5 (range, 7–53) months, virally suppressed with HIV RNA <20 copies/mL and median CD4 count of 804 (range, 602–1008) cells/μL. The fifth case was diagnosed with acute HAV concurrently with AHI and had HIV RNA 7.2 log10 copies/mL and CD4 count 132 cells/μL. Median laboratory abnormalities included peak alanine aminotransferase 760 (range, 572–2611) IU/L, total bilirubin 5.7 (range, 3.4–7.8) mg/dL, and direct bilirubin 5.4 (range, 2.5–5.9) mg/dL. All cases were treated with supportive care only, with resolution of clinical manifestations and laboratory abnormalities within 12 weeks. HAV was sequenced from plasma and/or stool from 3 cases (GenBank accession MF784495–MF784497); phylogenetic analysis of a 378-bp sequence of VP1 showed 100% concurrence between the 3 Bangkok MSM cases and HAV from the recent Taiwan and Netherlands outbreaks (Figure 1). An additional female case aged 10 years in Bangkok not in the cohort and not known to have HIV (GenBank MF784494) was diagnosed in June 2017 with 99.7% similarity to the MSM cases on the 378-bp sequence and 99.9% similarity to the first identified MSM case (MF784495) on a longer 1122-bp sequence. Figure 1. View largeDownload slide Phylogenetic analysis of selected hepatitis A isolates among human immunodeficiency virus–infected men who have sex with men (MSM) in Bangkok, Thailand, 2017. Roman numerals indicate genotype; numbers at nodes are bootstrap values. Produced in MEGA version 6.0. ● = MSM case, Bangkok 2017. ▲ = non-MSM case, Bangkok 2017. █ = Thailand case outbreak prior to 2015. Figure 1. View largeDownload slide Phylogenetic analysis of selected hepatitis A isolates among human immunodeficiency virus–infected men who have sex with men (MSM) in Bangkok, Thailand, 2017. Roman numerals indicate genotype; numbers at nodes are bootstrap values. Produced in MEGA version 6.0. ● = MSM case, Bangkok 2017. ▲ = non-MSM case, Bangkok 2017. █ = Thailand case outbreak prior to 2015. This is the first outbreak of acute HAV infection reported in the Bangkok area for more than a decade. The concentration of the outbreak among MSM and the phylogenetic link to MSM cases in Taiwan and Europe indicates that transmission was via oral–anal sexual contact rather than through contamination of food or water. However, the phylogenetic similarity of HAV in a female child diagnosed after the MSM cases suggests potential onward transmission outside of the MSM population, most likely through the fecal–oral route. The same strain of HAV has been identified in MSM cases in at least 5 countries in Asia and Europe [4–6]. Globalization and rising international travel will only increase the opportunity for communicable diseases, including HAV, to spread among networked at-risk populations such as MSM, without regard to international borders. Within Thailand, increased efforts are needed to monitor for outbreaks of HAV and to promote vaccination, which has proven efficacy in both HIV-infected individuals and the HIV-uninfected population [11]. Notes Disclaimer. The views expressed are those of the authors and should not be construed to represent the positions of the participating institutions, the US Army, or the US Department of Defense. Financial support. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, and the US Department of Defense, the Thai National Science and Technology Development Agency Research Chair Grant (P-15-50004), and the Center of Excellence in Clinical Virology (GCE 59-00930-005) at Chulalongkorn University, and by contributions from the Thai Red Cross AIDS Research Center and the Chulalongkorn University Faculty of Medicine. Potential conflicts of interest. J. A. has received honoraria from ViiV Healthcare, Roche, and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Presented in part: 2018 Conference on Retroviruses and Opportunistic Infections, Boston, USA, 4–7 March 2018. Poster 626. References 1. Manor Y, Lewis M, Ram Det al.   Evidence for hepatitis A virus endemic circulation in Israel despite universal toddlers’ vaccination since 1999 and low clinical incidence in all age groups. J Infect Dis  2016; 215: 574– 80. 2. Chen GJ, Lin KY, Hung CC, Chang SC. Hepatitis a outbreak among men who have sex with men in a country of low endemicity of hepatitis A infection. J Infect Dis  2017; 215: 1339– 40. Google Scholar CrossRef Search ADS PubMed  3. Chen GJ, Lin KY, Sun HYet al.   Incidence of acute hepatitis A among HIV-positive patients during an outbreak among MSM in Taiwan: impact of HAV vaccination. Liver Int  2017: 1– 8. 4. Freidl GS, Sonder GJ, Bovee LPet al.   Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017. Euro Surveill  2017; 22: 30468. Google Scholar CrossRef Search ADS PubMed  5. Werber D, Michaelis K, Hausner Met al.   Ongoing outbreaks of hepatitis A among men who have sex with men (MSM), Berlin, November 2016 to January 2017—linked to other German cities and European countries. Euro Surveill  2017; 22: 30457. 6. Beebeejaun K, Degala S, Balogun Ket al.   Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017. Euro Surveill  2017; 22: 30454. Google Scholar CrossRef Search ADS   7. Sa-nguanmoo P, Posuwan N, Vichaiwattana Pet al.   Declining trend of hepatitis a seroepidemiology in association with improved public health and economic status of Thailand. PLoS One  2016; 11: e0151304. Google Scholar CrossRef Search ADS PubMed  8. Ida S, Tachikawa N, Nakajima Aet al.   Influence of human immunodeficiency virus type 1 infection on acute hepatitis A virus infection. Clin Infect Dis  2002; 34: 379– 85. Google Scholar CrossRef Search ADS PubMed  9. Linkins RW, Chonwattana W, Holtz THet al.   Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006–2008. J Med Virol  2013; 85: 1499– 505. Google Scholar CrossRef Search ADS PubMed  10. Ananworanich J, Chomont N, Fletcher JLet al.   Markers of HIV reservoir size and immune activation after treatment in acute HIV infection with and without raltegravir and maraviroc intensification. J Virus Erad  2015; 1: 116– 22. Google Scholar PubMed  11. Mena G, García-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: a review. Hum Vaccin Immunother  2015; 11: 2582– 98. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Infectious Diseases Oxford University Press

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© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
ISSN
0022-1899
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Abstract

To the Editor—In response to an article by Manor et al [1], Chen et al recently reported on an outbreak of acute hepatitis A virus (HAV) in northern Taiwan that affected primarily men who have sex with men (MSM) who had human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) [2]. That outbreak started in mid-2015 and peaked with >1000 cases of acute HAV reported in 2016. By contrast, <100 cases of acute HAV were reported in all of Taiwan for the year 2014. The incidence of acute HAV fell rapidly after October 2016 when the Taiwan Centers for Disease Control implemented a free vaccination campaign targeting MSM with HIV infection or other STIs [3]. Acute outbreaks of HAV infection among MSM also occurred from mid 2016 to February 2017 in several European countries, including the Netherlands, Germany, and the United Kingdom [4–6]. Phylogenetic analysis has linked the outbreaks in Asia and Europe, with transmission presumably through oral–anal sexual contact [4]. No outbreak of acute HAV has been reported in the Bangkok metropolitan area since 2002, when a cluster of <100 cases occurred in the neighboring Nonthaburi province [7]. The low endemicity for HAV in Thailand has been attributed to improving hygiene, healthcare, and economic factors. The age at which 50% of the population tested anti-HAV immunoglobulin G (IgG) positive, a marker for past infection or immunization against HAV, rose from 6 years in 1976 to 42 years in 2014 [7]. MSM may be at higher risk for HAV infection due to sexual behavior that includes oral–anal contact. HIV-infected MSM are at higher risk for onward transmission of HAV because they have higher and more prolonged HAV viremia during acute infection [8]. In one cross-sectional study of MSM in Bangkok with a median age of 25 years, 27% were anti-HAV IgG positive, with HIV-infected MSM having a higher seroprevalence at 32% [9]. The SEARCH010/RV254 cohort has recruited participants with acute HIV infection (AHI) since 2009 [10]. A total of 478 individuals enrolled through June 2017. No cases of acute HAV (defined as anti-HAV immunoglobulin M positive with symptoms of acute hepatitis) were identified in the cohort until 2017, when 5 cases were identified between March and May. All were male, with a median age of 37 (range, 20–43) years. Clinical manifestations included abdominal pain (n = 5), fatigue (n = 5), jaundice (n = 3), fever (n = 3), and nausea/vomiting (n = 2). All cases reported male sexual partners within the preceding 3 months. None had traveled outside of Thailand. Four cases were on antiretroviral therapy with a median duration of 19.5 (range, 7–53) months, virally suppressed with HIV RNA <20 copies/mL and median CD4 count of 804 (range, 602–1008) cells/μL. The fifth case was diagnosed with acute HAV concurrently with AHI and had HIV RNA 7.2 log10 copies/mL and CD4 count 132 cells/μL. Median laboratory abnormalities included peak alanine aminotransferase 760 (range, 572–2611) IU/L, total bilirubin 5.7 (range, 3.4–7.8) mg/dL, and direct bilirubin 5.4 (range, 2.5–5.9) mg/dL. All cases were treated with supportive care only, with resolution of clinical manifestations and laboratory abnormalities within 12 weeks. HAV was sequenced from plasma and/or stool from 3 cases (GenBank accession MF784495–MF784497); phylogenetic analysis of a 378-bp sequence of VP1 showed 100% concurrence between the 3 Bangkok MSM cases and HAV from the recent Taiwan and Netherlands outbreaks (Figure 1). An additional female case aged 10 years in Bangkok not in the cohort and not known to have HIV (GenBank MF784494) was diagnosed in June 2017 with 99.7% similarity to the MSM cases on the 378-bp sequence and 99.9% similarity to the first identified MSM case (MF784495) on a longer 1122-bp sequence. Figure 1. View largeDownload slide Phylogenetic analysis of selected hepatitis A isolates among human immunodeficiency virus–infected men who have sex with men (MSM) in Bangkok, Thailand, 2017. Roman numerals indicate genotype; numbers at nodes are bootstrap values. Produced in MEGA version 6.0. ● = MSM case, Bangkok 2017. ▲ = non-MSM case, Bangkok 2017. █ = Thailand case outbreak prior to 2015. Figure 1. View largeDownload slide Phylogenetic analysis of selected hepatitis A isolates among human immunodeficiency virus–infected men who have sex with men (MSM) in Bangkok, Thailand, 2017. Roman numerals indicate genotype; numbers at nodes are bootstrap values. Produced in MEGA version 6.0. ● = MSM case, Bangkok 2017. ▲ = non-MSM case, Bangkok 2017. █ = Thailand case outbreak prior to 2015. This is the first outbreak of acute HAV infection reported in the Bangkok area for more than a decade. The concentration of the outbreak among MSM and the phylogenetic link to MSM cases in Taiwan and Europe indicates that transmission was via oral–anal sexual contact rather than through contamination of food or water. However, the phylogenetic similarity of HAV in a female child diagnosed after the MSM cases suggests potential onward transmission outside of the MSM population, most likely through the fecal–oral route. The same strain of HAV has been identified in MSM cases in at least 5 countries in Asia and Europe [4–6]. Globalization and rising international travel will only increase the opportunity for communicable diseases, including HAV, to spread among networked at-risk populations such as MSM, without regard to international borders. Within Thailand, increased efforts are needed to monitor for outbreaks of HAV and to promote vaccination, which has proven efficacy in both HIV-infected individuals and the HIV-uninfected population [11]. Notes Disclaimer. The views expressed are those of the authors and should not be construed to represent the positions of the participating institutions, the US Army, or the US Department of Defense. Financial support. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, and the US Department of Defense, the Thai National Science and Technology Development Agency Research Chair Grant (P-15-50004), and the Center of Excellence in Clinical Virology (GCE 59-00930-005) at Chulalongkorn University, and by contributions from the Thai Red Cross AIDS Research Center and the Chulalongkorn University Faculty of Medicine. Potential conflicts of interest. J. A. has received honoraria from ViiV Healthcare, Roche, and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Presented in part: 2018 Conference on Retroviruses and Opportunistic Infections, Boston, USA, 4–7 March 2018. Poster 626. References 1. Manor Y, Lewis M, Ram Det al.   Evidence for hepatitis A virus endemic circulation in Israel despite universal toddlers’ vaccination since 1999 and low clinical incidence in all age groups. J Infect Dis  2016; 215: 574– 80. 2. Chen GJ, Lin KY, Hung CC, Chang SC. Hepatitis a outbreak among men who have sex with men in a country of low endemicity of hepatitis A infection. J Infect Dis  2017; 215: 1339– 40. Google Scholar CrossRef Search ADS PubMed  3. Chen GJ, Lin KY, Sun HYet al.   Incidence of acute hepatitis A among HIV-positive patients during an outbreak among MSM in Taiwan: impact of HAV vaccination. Liver Int  2017: 1– 8. 4. Freidl GS, Sonder GJ, Bovee LPet al.   Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017. Euro Surveill  2017; 22: 30468. Google Scholar CrossRef Search ADS PubMed  5. Werber D, Michaelis K, Hausner Met al.   Ongoing outbreaks of hepatitis A among men who have sex with men (MSM), Berlin, November 2016 to January 2017—linked to other German cities and European countries. Euro Surveill  2017; 22: 30457. 6. Beebeejaun K, Degala S, Balogun Ket al.   Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017. Euro Surveill  2017; 22: 30454. Google Scholar CrossRef Search ADS   7. Sa-nguanmoo P, Posuwan N, Vichaiwattana Pet al.   Declining trend of hepatitis a seroepidemiology in association with improved public health and economic status of Thailand. PLoS One  2016; 11: e0151304. Google Scholar CrossRef Search ADS PubMed  8. Ida S, Tachikawa N, Nakajima Aet al.   Influence of human immunodeficiency virus type 1 infection on acute hepatitis A virus infection. Clin Infect Dis  2002; 34: 379– 85. Google Scholar CrossRef Search ADS PubMed  9. Linkins RW, Chonwattana W, Holtz THet al.   Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006–2008. J Med Virol  2013; 85: 1499– 505. Google Scholar CrossRef Search ADS PubMed  10. Ananworanich J, Chomont N, Fletcher JLet al.   Markers of HIV reservoir size and immune activation after treatment in acute HIV infection with and without raltegravir and maraviroc intensification. J Virus Erad  2015; 1: 116– 22. Google Scholar PubMed  11. Mena G, García-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: a review. Hum Vaccin Immunother  2015; 11: 2582– 98. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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The Journal of Infectious DiseasesOxford University Press

Published: Apr 23, 2018

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