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[A SYSTEMATIC REVIEW ON HEPATITIS E VIRUS GLOBALLY]

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2014 [A SYSTEMATIC REVIEW ON HEPATITIS E VIRUS GLOBALLY] Table of contents 1. Background Methods... 3 i. Article Search... 3 ii. Article selection Results... 7 I. African region... 7 A.
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2014 [A SYSTEMATIC REVIEW ON HEPATITIS E VIRUS GLOBALLY] Table of contents 1. Background Methods... 3 i. Article Search... 3 ii. Article selection Results... 7 I. African region... 7 A. Seroprevalence of anti-hev antibodies... 8 B. Sporadic HEV cases... 8 C. HEV outbreaks... 8 D. Case fatality rate (CFR)... 9 II. Americas region... 9 A. Seroprevalence of anti-hev antibodies B. Sporadic HEV cases C. Case fatality rate (CFR) III. Eastern Mediterranean region A. Seroprevalence of anti-hev antibodies B. Sporadic HEV cases C. HEV outbreaks D. Case fatality rate (CFR) IV. South East Asia Region A. Seroprevalence of anti-hev antibodies B. Sporadic HEV cases... 17 C. HEV outbreaks D. Case fatality rate (CFR) V. Western Pacific Region A. Seroprevalence of anti-hev antibodies B. Sporadic HEV cases C. HEV outbreaks D. Case fatality rate (CFR) VI. European region A. Seroprevalence of anti-hev antibodies B. Sporadic HEV cases C. HEV outbreaks D. Case fatality rate (CFR) References... 31 A systematic review of Hepatitis E virus globally 1. Background The objective of this systematic review was to collect country specific data on the incidence, prevalence and severe outcomes related to Hepatitis E Virus (HEV) infections on a country-level basis. A systematic review has been conducted by the World Health Organization (WHO) in 2010 to retrieve country-specific data on Hepatitis E. The published systematic review included countryspecific data from The present systematic review complements the previous systematic review. Articles published between December 2009 and January 2014 have been included in this systematic review. Results presented in this summary are preliminary and analysis is still ongoing. 2. Methods i. Article Search The article search conducted following the exact article search methodology used in the previous WHO systematic review. Articles were searched from the PubMed, Scopus and Embase databases. The selected articles included original articles and reports published between December 2009 and January In order to address the potential bias in reporting and publication for large outbreaks, case series and case-reports were to be included. Pub Med In PubMed, the following search terms were used: ( Hepatitis E OR Hepatitis E virus OR HEV OR Hepatitis E antibody* OR (enterically transmitted non a non b hepatitis) OR ET- NANBH ) AND ( 2009/01/01 [PDAT]: 2014/01/14 [PDAT]) AND Country_name Embase The following search terms were used in Embase for each country: Steps Keyword search 1. Hepatitis E.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name] 2. hepatitis E/ or hepatitis E antibody/ or hepatitis E antigen/ or hepatitis non A non B/ or hepatitis E vaccine/ or hepatitis non A non B non C/ or Hepatitis E virus/ or Hepatitis virus non A non B/ 3. #1 OR #2 4. Limit 3 to yr= Scopus The following search was conducted in Scopus by country: HEV OR Hepatitis E OR Hepatitis E virus OR Hepatitis E antibodies OR ET-NANBH OR enterically transmitted non a non b hepatitis AND Name of the country ii. Article selection A total of 1279 articles were identified from PubMed, Scopus and Embase (see Figure 1). Articles were first screened at a title and abstract level and a total of 734 articles were excluded. An additional 214 articles were excluded when reviewed at a full text level. A total of 5 articles were unavailable and ordered and as a result not included in the results of this systematic review. Translation was required for a total of 25 articles and was not included in the results of this review. Review articles were not included in this report; this resulted in 86 articles being excluded. Data was extracted from a total of 301 articles and were included for analysis in this systematic review. Figure 1: Flow Diagram for article selection Eligible articles included original articles, studies reporting on outcomes of interest including HEV prevalence, incidence, mortality or HEV related outbreaks. Case reports, case-series, cohorts, cross-sectional and case-control studies were included in the systematic review. Review articles, animal studies, environmental studies, studies not reporting any HEV outcomes of interests listed above and articles reporting data solely on travellers were excluded. Additionally, studies not reporting numerators and denominators for HEV outcomes were excluded. Data was extracted from studies that met the inclusion criteria. Studies were grouped into three categories: seroprevalence, sporadic acute hepatitis and outbreaks. Studies reporting anti-hev IgG were considered seroprevalence studies unless clinical symptoms consistent with an HEV infection were reported. In the latter case, studies were classified under sporadic cases of HEV. Studies reporting anti-hev IgM or HEV RNA were classified as sporadic acute hepatitis studies. Prevalence was reported from seroprevalence studies and incidence was reported from acute sporadic hepatitis studies as well as outbreak studies. In outbreak studies, incidence was reported as attack rates. The extracted studies from the article search were separated into 6 geographical regions as defined by the World Health Organization: Africa, South-East Asia, Eastern Mediterranean, the Americas, Europe and Western Pacific. For each region, a summary of seroprevalence, sporadic acute hepatitis and outbreak studies was provided. 3. Results Results from this review are preliminary. Analysis from the article selection phase is ongoing. I. African region A total of 3 studies in the African region reported seroprevalence data. Seroprevalence ranged from 4.6 % to 10.7% in data retrieved from Yemen, Ghana, Burkina Faso and Zambia. The lowest prevalence was noted among blood donors. Sporadic cases of HEV were reported from Ghana, Angola and Mayotte. Two case reports were reported in the African region and genotype 3 was responsible for one of the cases. A study conducted in Ghana among pregnant women reported an incidence of 64.4% among pregnant women. Among the 5 outbreaks reported in this region, genotype was reported for one study and identified as genotype 1. Attack rates for outbreaks ranged from 33 to 72% in a variety of population including pregnant women, workers and displaced populations. In studies reporting age specific attack rates, older adults displayed a higher attack rates than younger age groups. Mortality was reported in two studies conducted on pregnant women and ranged from 14% to 66%. A. Seroprevalence of anti-hev antibodies Table 1 Seroprevalence anti-hev antibodies Country % Seroprevalence Sample demographics Sample size Diagnostic methods Genotype Reference Ghana 4.6 Blood donors 239 IgG NS Meldal, 2013 (1) Burkina Faso 16.2 Blood donors and pregnant women 191 IgG NS Traoré, 2012 (2) Zambia 24.7 Individuals living in urban settings 300 IgG NS Jacobs, 2013 (3) B. Sporadic HEV cases Table 2 Sporadic HEV cases Country % Incidence Sample demographics Sample size Diagnostic methods Genotype Reference Ghana 64.4 Pregnant women 157 IgM NS Adjei, 2009 (4) Angola 100 Fulminant HEV case 1 IgM NS Pires, 2012 (5) Mayotte 100 Adult male 1 IgM 3 Epelboin, 2011 (6) C. HEV outbreaks Table 3: HEV outbreaks Country Sample Clinical attack Diagnostic Attack rate by Attack rate by Genotype Source demographics rate methods age gender Central African Republic Pregnant women 33.3 IgM NS NS NS Goumba, 2010 (7) Central African Patients with 51.8 IgM NS NS NS Goumba, 2010 Republic jaundice (7) Central African Male workers 72.7 IgM NS NS NS Bouscaillou, Republic 2013 Uganda Uganda Acute hepatitis E cases Displaced persons 45.6 NS 1-15 years: 44.7%; years: 47.5% 67.9 IgM 1-15 years: 63.5%; years: 71.4%; years: 64.0%; (8) NS NS Howard, 2010 (9) NS 1 Teshale, 2010 (10) D. Case fatality rate (CFR) Country Sample demographics CFR in pregnant women (%) Central African Republic Genotype Stillbirth (%) Overall CFR (%) Reference Pregnant women Goumba, 2010 (7) Ghana Pregnant women Bonney, 2012 (11) II. Americas region Seroprevalence data was retrieved from a total of 8 studies conducted in the United States of America and Cuba and ranged from 3% to 31%. Sex specific seroprevalence was reported in only one study and did not vary greatly between males and females (9% vs. 11% respectively). Sporadic HEV cases have been reported in Brazil, the United States of America, Uruguay, Venezuela and Argentina. Incidence in this region ranged from 1.6% to 30% and increased with age. Five case reports due to HEV were reported in the region of the Americas and amongst studies with genotypes available, all cases were attributable to genotype 3. The cases reported in case report studies occurred in the United States and Uruguay. A total of three American studies reported mortality data. The case fatality rates ranged from 0.7 to 3.9%. Genotypes 1, 3, and 4 have been documented in this region. No outbreak was reported in the region of the Americas. A. Seroprevalence of anti-hev antibodies 1. Table 1 Seroprevalence anti-hev antibodies Country % Seroprevalence Sample demographics Sample size Diagnostic methods Genotype Reference United States of America 31.8 Healthy individuals 440 IgG NS Basu, 2012 (12) United States of America 16.9 Individuals seronegative for HAV or HBV 154 IgG NS Drobeniuc, 2013 (13) Cuba 10.0 Patients without a history of jaundice 469 IgG NS Villalba, 2010 (14) United States of America 18.8 Blood donors 1939 IgG NS Xu, 2013 (15) United States of America 3.1 Personnel with frequent workplace contact with 64 IgG NS Sarkar, 2012 (16) United States of America pigs 3.2 Blood donors 63 IgG NS Sarkar, 2012 (16) United States of America United States of America 14.5 Patients visiting clinical sites 0.59 Individuals who participated in the National Health and Nutrition Examination Survey 318 IgG NS Davern, 2009 (17) 8814 NS NS Ditah, 2013 (18) B. Sporadic HEV cases Table 2 Sporadic HEV cases Country % Incidence Sample demographics Sample size Diagnostic methods Genotype Reference Brazil 1.56% Patients with acute hepatitis 64 IgM 3 dos Santos, 2010 (19) United States of America 18.0 Drug-induced liver injury patients 318 IgM 3 Davern, 2011 (20) United States of America United States of America 27.1 Acute non-a, non-b, non-c hepatitis patients 42.1 Patients with acute liver failure 129 IgM 1, 3, 4 Drobeniuc, 2011 (21) 699 IgG NS Fontana, 2012 (22) Venezuela 29.8 Hepatitis A patients 74 IgM 1, 3 Garcia, 2012 (23) Uruguay 9.0 Sporadic HEV cases 100 IgM 3 Mirazo, 2011 (24) Argentina 6.1 Acute hepatitis patients 231 NS 3 Munne, 2011 (25) C. Case fatality rate (CFR) Country Sample demographics CFR in pregnant women Stillbirth Overall CFR Genotype Reference United States of America United States of America United States of America Individuals seronegative for HAV and HBV Acute non-a, non-b, non-c hepatitis patients Patients with acute liver failure NS NS 3.9 NS Drobeniuc, 2013 (13) NS NS 2.7 1, 3, 4 Drobeniuc, 2011 (21) NS NS 0.7 NS Fontana, 2012 (22) III. Eastern Mediterranean region Seroprevalence studies were retrieved from Iran, Yemen, Saudi Arabia and Egypt. Seroprevalence in this region ranged from 2% to 59% with Egypt reporting the highest seroprevalence in the Eastern Mediterranean region. Males and females displayed similar seroprevalence (approximately 3% to 50%). Age specific seroprevalence increased with age. Data on incidence was reported from the United Arab Emirates, Iraq, Egypt, Iran, Afghanistan and Tunisia. Incidence in this region ranged from less than 1% to 41%. In studies conducted on blood donors, detection of anti-hev IgM antibodies were reported to be as high 14%. In studies reporting incidence data, a higher incidence was observed in females compared to males. Three outbreaks were documented in Iraq, Sudan and Egypt. Overall attack rates ranged from 18 to 38%, however male specific attack rates were greater (84%). Mortality was reported in one study conducted in Egypt. Evidence of genotype 1 has been documented in this region. A. Seroprevalence of anti-hev antibodies Table 1 Seroprevalence anti-hev antibodies Country % Seroprevalence Sample demographics Sample size Diagnostic methods Genotype Reference Iran 14.2 Residents of the great Mashhad capital 1582 NS NS Ahmadi, 2013 (26) Iran 3.8 Residents of Isfahan province 816 NS NS Ataei, 2009 (27) Yemen 10.7 Patients attending primary health care 538 IgG NS Bawazir, 2010 (28) facilities Saudi Arabia 18.7 Blood donors 900 IgG NS Johargy, 2013 (29) Iran 3.7 Pregnant women 136 NS NS Khameneh, 2013 (30) Egypt 58.6 HCV and non-hcv positive pregnant women Iran 14.2 Local population during pilgrimage Iran 9.3 Randomly selected individuals by postal code 116 IgG NS Gad, 2011 (31) 1582 NS NS Ghezelddasht, 2013 (32) 551 NS NS Mohebbi, 2012 (33) Iran 7.8 NS 400 NS NS Raoofi, 2012 (34) Iran 8.5 School children 566 IgG NS Shamsizadeh, 2009 (35) Egypt 6.0 Asymptomatic HEV cases 235 NS NS Shata, 2012 (36) Egypt 46.7 Asymptomatic pregnant women 60 IgG NS Mousa, 2011 (37) Egypt 39.0 Healthy adolescent 95 NS NS Zaki, 2011 females Iran 2.3 Healthy children and young adults (38) 1080 IgG NS Saffar, 2009 (39) B. Sporadic HEV cases Table 2 Sporadic HEV cases Country % Incidence Sample demographics Sample size Diagnostic methods Genotype Reference United Arab Emirates 40 Acute hepatitis patients 165 NS NS Abro, 2009 (40) Iraq 1.6 Patients with suspected acute viral hepatitis 2692 IgM NS Al-Naaimi, 2012 (41) Egypt 0.9 Acute hepatitis patients 1950 IgM 1 Astagneau, 2012 (42) Iran 0.5 Residents of northern Iran 439 IgM NS Babamahmoodi, 2010 (43) Egypt 20.2 Patients with acute hepatitis 287 NS 1 Blackard, 2009 (44) Afghanistan 28.4 Residents of Kabul who visited a field hospital 102 IgM NS Carmoi, 2009 (45) Egypt 38.1 Patients with acute hepatitis 134 IgM NS El-Tras, 2013 (46) Iran 14.3 Blood donors 530 RNA NS Ehteram, 2013 (47) Tunisia 4.8 Blood donors and hepatitis patients 889 IgM NS Houcine, 2012 (48) Egypt 41.2 Pediatric patients with acute hepatitis 68 IgM NS Zaki, 2009 (49) Egypt 5.0 Acute on chronic liver patients 100 IgM NS Zaki, 2011 (50) Egypt 2.3 Patients with high ALT and AST 214 IgM NS Youssef, 2009 (51) Egypt 15.8 Patients with acute hepatitis 235 IgM NS Eldin, 2010 (52) Egypt 7.0 Asymptomatic healthy individuals 200 IgM NS Eldin, 2010 (52) Egypt 0.4 Blood donors 760 IgM NS Bouamra, 2014 (53) Country Iraq Egypt C. HEV outbreaks Sample demographics Patients with jaundice Symptomatic HEV cases Clinical attack rate Diagnostic methods Attack rate by age Attack rate by gender 38.1 IgM 1-15 years: 12.9; Male: 35.6; years: 39.5; Female: IgM NS Male: 84.0; Female: 67.8 Genotype Source NS Al-Nasrawi, 2010 (54) NS Shata, 2012 (36) D. Case fatality rate (CFR) Country Sample demographics CFR in pregnant women Stillbirth Overall CFR Genotype Reference Sudan Pregnant women in outbreak setting in nonpregnant women NS Rayis, 2013 (55) IV. South East Asia Region Seroprevalence studies were reported from India, Bangladesh and Thailand. Seroprevalence ranged from 11% to 34%. Incidence varied from 5% to 94%. A total of 11 outbreaks have been reported between 2009 and January 2014 in this region. Outbreaks attributable to genotype 1 were characterized by high attack rates (80% to 100%). The highest attack rate was reported in a study conducted on fulminant hepatic failure patients. Eight studies reported case fatality rates. Additionally, five case reports were reported in India and no fatal outcome was reported in the cases. Genotypes 1 and 4 were identified in the cases reported from India. Overall, genotypes 1 and 3 have been documented in this region. A. Seroprevalence of anti-hev antibodies Table 1 Seroprevalence anti-hev antibodies Country % Seroprevalence Sample demographics Sample size Diagnostic methods Genotype Reference India 13.7 Blood donors 262 IgG NS Bajpai, 2011 (56) India 33.7 Pregnant women 300 IgG NS Begum, 2009 (57) India 11.9 Children 109 NS NS Bhat, 2011 (58) Bangladesh 27.2 Control of HEV cases 184 IgG NS Labrique, 2013 (60) Thailand 15.7 Nursing students 281 NS NS Pilakasiri, 2009 (61) India 14.5 Healthy individuals 2279 IgG NS Vivek, 2010 (63) India 11.3 Medical students 160 IgG NS Jahan, 2009 (64) B. Sporadic HEV cases Table 2 Sporadic HEV cases Country % Incidence Sample demographics Sample size Diagnostic methods Genotype Reference Bangladesh 64.2 Patients with Fulminant Hepatic Failure (FHF) 67 IgM NS Alam, 2009 (65) India 35.3 Females with acute viral hepatitis or FHF patiens 167 IgM NS Begum, 2010 (66) India 35.0 Acute hepatitis patients 585 IgM NS Chandra, 2012 (67) India 38.7 Acute hepatitis patients 736 NS NS Chaudhry, 2009 (68) India 18.0 Acute viral hepatitis patients 267 IgM NS Jain, 2013 (69) India 38.7 Patients with viral hepatitis 685 IgM 1 Kumar, 2011 (70) India 41.4 Patients with FHF 70 IgM 1 Kumar, 2011 (70) India 58.3 Pregnant women 24 IgM 1 Kumar, 2011 (70) India 94.1 Jaundice patients 233 IgM NS Chauhan, 2010 (71) India 9.6 Clinical acute hepatitis patients with jaundice and liver disease 104 IgM 1 Deka, 2010 (72) India 78.6 Outpatient clinic patients 156 IgM NS Gupta, 2013 (73) India 25.5 NS 141 IgM NS Hazam, 2010 (74) India 9.4 Chronic liver disease patients 53 IgM 1 Kumar, 2011 (70) Bangladesh 17.0 Symptomatic hepatitis cases 279 IgM NS Labrique, 2013 (60) Bangladesh 47.2 Patients with acute hepatitis 267 IgM NS Mahtab, 2009 (75) Bangladesh 56.5 Patients with FHF 23 IgM NS Mahtab, 2009 (75) India 45.5 Acute viral hepatitis cases 224 IgM NS Nandi, 2009 (76) Bangladesh 25.0 Patients with acute sporadic hepatitis 36 IgM 1 Sugitani, 2009 (77) Bangladesh 33.3 Patients with fulminant hepatitis 12 IgM 1 Sugitani, 2009 (77) Bangladesh 21.4 Patients with chronic liver disease 14 IgM 1 Sugitani, 2009 (77) India 4.8 Male blood donors 460 IgM NS Bhatnagar, 2013 (78) Bangladesh 58.3 Viral hepatitis patients 60 NS NS Rashid, 2009 (79) India 8.9 Suspected cases of hepatitis 79 IgM NS Basavaraj, 2012 (80) India 16.8 Acute hepatitis patients 3945 IgM NS Malhotra, 2012 (81) Nepal 20.7 Pregnant women with acute hepatitis 29 NS NS Shrestha, 2009 (82) India 32.0 Acute viral hepatitis cases 1147 IgM NS Singh, 2012 (83) India 9.6 Acute sporadic HEV cases 94 RNA 1 Vivek, 2013 (84) Nepal 75.0 Pregnant women 124 NS NS Shrestha, 2011 (62) Bangladesh General population from a random representative sample 1134 NS NS Labrique, 2010 (59) Country India India C. HEV outbreaks Bangladesh Sample demographics Patients with jaundice and acute hepatitis Acute hepatitis cases Non-seasonal outbreak patients Clinical attack rate Diagnostic methods Attack rate by age Attack rate by gender Genotype Source 64.2 IgM NS NS NS Arora, 2013 (85) 61.4 IgM NS NS NS Ippagunta, 2011 (86) IgM NS Male: 88.5; 1 Harun-or- Female: 11.5 Rashid, 2013 (87) 84.1 IgM NS NS NS Hossain, 2009 (88) 82.5 IgM NS NS 1 Majumdar, 2013 (89) Bangladesh Women of reproductive age India Patients with suspected acute viral hepatitis India Jaundice patients 16.6 NS 1-15 years: 11.7; years: Male: 17.5; Female: 15.9 NS Martolia, 2009 (90) India Bangladesh India India India Patients with acute viral hepatitis Patients with acute viral hepatitis Cluster of acute hepatitis Icteric hepatitis cases Acute hepatitis cases IgM NS NS 1 Pujhari, 2010 (91) 39.2 IgM NS NS NS Sugitani, 2009 (77) 98.0 IgM NS NS NS Swain, 2010 (92) 80.0 IgM NS NS 1 Vivek, 2010 (93) 0.04 IgM 1-15 years: Male: 0.05; NS Sailaja, ; Female: 0.03 (94) years: 0.01 D. Case fatality rate (CFR) Country Sample demographics CFR in pregnant women Stillbirth Overall CFR Genotype Reference Bangladesh Patients with FHF NS NS 65.1 NS Alam, 2009 (65) Bangladesh Women of reproductive age NS NS 22.7 NS Hossain, 2009 (88) India Cluster of acute hepatitis NS NS 0.9 NS Swain, 2010 (92) Thailand Acute HEV cases NS NS Poovorawan, 2012 (95) India Acute hepatitis cases NS NS 0.2 NS Sailaja, 2009 (94) India Acute hepatitis cases 22.2 NS NS NS Chandra, 2012 (67) Nepal Pregnant women
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