BJID 874 1–5

ARTICLE IN PRESS
braz j infect dis 2 0 1 9;x x x(x x):xxx–xxx

The Brazilian Journal of

INFECTIOUS DISEASES
www.elsevier.com/locate/bjid

1 Original article

2 Hepatitis E virus prevalence in Egyptian children

3 with transfusion-dependent thalassemia

4 Q1 Doaa Abdelmawla a , Dalia Moemen a,∗ , Ahmad Darwish b , Wafaa Mowafy a

5
a Mansoura University, Faculty of Medicine, Department of Medical Microbiology and Immunology, Mansoura, Egypt
6
b Mansoura University, Faculty of Medicine, Department of Pediatrics, Mansoura, Egypt
7

8 a r t i c l e i n f o a b s t r a c t
9

10 Article history: Hepatitis E virus (HEV) infection is one of the major public health problems in develop-
11 Received 22 October 2018 ing countries. HEV can cause chronic infections in immunocompromised individuals e.g.
12 Accepted 3 January 2019 thalassemic patients with increased risk of morbidity and mortality. In addition there is
13 Available online xxx possibility of HEV transmission through blood transfusion. Therefore, the present study
14 aimed to investigate the seroprevalence and risk factors of HEV infection in ␤-thalassemic
Q2 children.
15 Keywords:
16 Hepatitis E virus (HEV) Methods: This cross-sectional study was conducted on 140 Egyptian children suffering from
17 Prevalence ␤-thalassemia, attending the hematology outpatient clinic from April to October 2016.
18 Thalassemia Serum samples from patients were collected and anti-HEV antibodies (IgG and IgM) were
19 Transfusion measured by enzyme-linked immunosorbent assay (ELISA).
Results: The seroprevalence of HEV in ␤-thalassemic chidren was relatively high (27.15%).
Anti-HEV IgG prevalence was 24.29% while that of IgM was 2.86%. There was significant
association between HEV infection and age, residence, liver enzymes and amount of blood
transfusion per year.
Conclusions: Thalasemic patients are vulnerable to chronicity and increased risk of morbid-
ity and mortality from HEV infection. Frequent assessment of liver enzymes in thalassemic
patients to monitor subclinical HEV is recommended. Close monitoring and HEV screening
of blood donations should be taken in consideration. Public awareness about HEV endemic-
ity, modes of transmission, and risk hazards especially in high risk group should be done to
reduce the disease burden.
© 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is
an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).

Introduction
Q3
Hepatitis E virus infection is endemic in many develop- 20

ing countries while sporadic HEV infections have also been 21

reported in some developed countries.1 Although HEV infec- 22

∗
Corresponding author. tion is usually associated with acute self-limited hepatitis, 23

E-mail address: dr daliamoemen@yahoo.com (D. Moemen). fulminant hepatic failure with morbidity and mortality may 24

https://doi.org/10.1016/j.bjid.2019.01.007
1413-8670/© 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: D. Abdelmawla, D. Moemen, A. Darwish, et al.. Hepatitis E virus prevalence in Egyptian children with
transfusion-dependent thalassemia. Braz J Infect Dis. 2019. https://doi.org/10.1016/j.bjid.2019.01.007 BJID 874 1–5
 BJID 874 1–5
ARTICLE IN PRESS
2 b r a z j i n f e c t d i s . 2 0 1 9;x x x(x x):xxx–xxx

25 occur especially in immunocompromised hosts.2 High preva- other than thalassemia, patients with alpha-thalassemia, and 80

26 lence of HEV infection was reported in Africa, Central and patients with less than 10 blood transfusions were excluded 81

27 Southeast Asia, and Mexico.3 In France, the seroprevalence from the study. This study was approved by the Medical 82

28 of HEV (anti-HEV immunoglobulin G (IgG) and IgM) varied Research Ethics Committee, Mansoura University (IRB no. 83

29 from 21.9% to 71.3%, according to geographic distribution, MS/16/03/82). 84

30 with average 39.1%.4 People with low educational level may

31 be at a higher risk of exposure and infection than those with Data collected from patients 85

32 higher educational level. In Egypt, low educational level and

33 socioeconomic status resulted in lack of knowledge about Data collected from patients included age, sex, residence, 86

34 avoidable possible risk factors associated with HEV infection. amount of blood transfused per year, abdominal examination 87

35 Thus HEV was highly endemic in Egyptian rural communities of liver and spleen, serum ferritin, liver function tests (ALT and 88

36 with genotype 1 subtype 3 most circulating.5,6 There are four AST), and viral hepatitis markers (HBs Ag and HCV Abs). 89

37 documented routes of transmission of HEV including fecal-

38 oral route, vehicle-borne including water-borne and zoonotic Sample collection and processing 90
39 foodborne, bloodborne transmission through parenteral blood
40 transfusion, and perinatal via vertical transmission from Two milliliters of venous blood were obtained from each 91
41 mother-to-infant.7,8 Chronic HEV infection was acquired in selected patient and collected in a sterile tube, cen- 92
42 1.4% of patients following liver transplantion which subse- trifuged immediately for serum separation. Serum samples 93
43 quently resulted in persistent damage of the liver graft.9 were stored at −20 ◦ C. Presence of anti-HEV antibodies 94
44 Thalassemia is one of the most common genetic diseases (anti-HEV IgG indicating past infection and anti-HEV IgM 95
45 worldwide. It is a major public health problem, causing much indicating recent infection) in the patients’ sera were 96
46 morbidity, early mortality, and great financial and emotional measured by enzyme-linked immunosorbent assay; HEV- 97
47 burden for a family. Thalassemia is the most common form IGM Elisa (Immunospec, USA, BL147710) and HEV-IGG Elisa 98
48 of inherited anemia around the world.10 ␤-thalassemia fre- (Immunospec, USA, BL147709). 99
49 quencies are common in almost all Arab countries.11 In Egypt,
50 ␤-thalassemia is the most common type with a carrier rate Statistical analysis 100
51 ranging from 5.3% to ≥9%. It was estimated that 1000/1.5
52 million live births/year suffer from thalassemia disease in The collected data was coded, processed and analyzed 101
53 Egypt.12 Many thalassemia patients develop chronic liver dis- using SPSS (Statistical package for social science) version 102
54 ease (CLD) like chronic hepatitis C. HAV and HEV infections 23 for windows. Descriptive statistics were calculated as 103
55 show more severe clinical courses in the CLD patients.13 Some mean ± standard deviation (SD), median, interquartile range 104
56 authors documented HEV seropositivity among hemodialy- (IQR), and frequency (number-percent). Parametric Student’s 105
57 sis and thalassemia patients.14,15 It was reported that HEV t-test (unpaired) and non-parametric Mann Whitney test were 106
58 RNA detected in blood donations through studies by blood used as appropriate to compare means of continuous vari- 107
59 banks in several European countries.16 Therefore, some coun- ables of two different groups. Chi square test was used for 108
60 tries began HEV RNA screening of blood donations and others inter-group comparison of categorical data. p-Value less than 109
61 selectively applied blood screening for high risk patients.17 A 0.05 (5%) was considered statistically significant. Significant 110
62 previous study conducted on patients with acute viral hep- variables on univariate analysis were entered into a logistic 111
63 atitis in Egypt reported HEV infection in about 12–42% of all regression model to determine which of these factors were 112
64 cases.18 Another study carried out on blood samples collected independently associated with HEV infection. 113
65 from 134 jaundiced patients in Egypt, revealed that 51 (38.1%)
66 patients were positive for anti-HEV IgG.19 Also, study on chil-
67 dren with acute viral hepatitis in Assiut, Egypt, detected 30.9% Results
68 HEV infection in children.20 The present study aimed to detect
69 the seroprevalence of HEV infection in thalassemic children The seroprevalence of HEV antibodies in ␤-thalassemic 114

70 to assess the role of blood transfusion as a risk factor for HEV patients was 27.15% (38/140 patients); 34 (24.29%) patients 115

71 infection. were positive for anti-HEV IgG, and four (2.86%) patients were 116

positive for anti-HEV IgM. As shown in Table 1, there was sig- 117

nificant association between age and anti-HEV IgG and IgM 118

Patients and methods seropositivity (p = 0.004, and 0.044, respectively). HEV seropos- 119

itivity increased with age. There was significant association 120

72 Patients between rural residence and anti-HEV IgG (p < 0.001). Regard- 121

ing clinical data, there was significant association between 122

73 This cross-sectional study was conducted on 140 Egyptian liver enzymes and anti-HEV IgG. No patients in our study had 123

74 children suffering from ␤-thalassemia, attending the hema- HBV infection. Splenectomy was significantly associated with 124

75 tology outpatient clinic in Mansoura University Children’s HCV and HEV infection (Table 2). Table 3. In Univariate analy- 125

76 Hospital (MUCH) from April 2016 through October 2016. sis, there was significant association between Age, residence, 126

77 Patients included in this study were patients with beta- liver enzymes, and amount of blood transfusions per year were 127

78 thalassemia aged up to 18 years who frequently received significantly associated with HEV seropositivity on univariate 128

79 blood transfusion. However, patients with hemolytic anemia analysis. On multivariate analysis only rural residence and 129

Please cite this article in press as: D. Abdelmawla, D. Moemen, A. Darwish, et al.. Hepatitis E virus prevalence in Egyptian children with
transfusion-dependent thalassemia. Braz J Infect Dis. 2019. https://doi.org/10.1016/j.bjid.2019.01.007 BJID 874 1–5
 BJID 874 1–5
ARTICLE IN PRESS
b r a z j i n f e c t d i s . 2 0 1 9;x x x(x x):xxx–xxx 3

Table 1 – Demographic data associated with HEV seropositivity in thalassemic children.

Demographic data Anti-HEV IgG Anti-HEV IgM

Positive (n = 34) Negative (n = 106) p-Value Positive (n = 4) Negative (n = 136) p-Value

a
Age range (years) 2–6 5 (14.7%) 33 (31.1%) 0.004 0 (0.0%) 38 (27.9%) 0.044a
6–12 14 (41.2%) 55 (51.9%) 1 (25.0%) 68 (50.0%)
12–18 15 (44.1%) 18 (17.0%) 3 (75.0%) 30 (22.1%)
Sex Female 16 (47.1%) 49 (46.2%) 0.933 1 (25.0%) 64 (47.1%) 0.383
Male 18 (52.9%) 57 (53.8%) 3 (75.0%) 72 (52.9%)
Residence Rural 28 (82.4%) 51 (48.1%) <0.001b 3 (75.0%) 76 (55.9%) 0.447
Urban 6 (17.6%) 55 (51.9%) 1 (25.0%) 60 (44.1%)

n, number.
a
Significance <0.05.
b
High significance.

Table 2 – Clinical parameters associated with HEV seropositivity in thalessemic children.

Clinical data Anti-HEV IgG Anti-HEV IgM

Positive (n = 34) Negative (n = 106) p-Value Positive (n = 4) Negative (n = 136) p-Value

Splen-ectomy Yes 16 (47.1%) 42 (39.6%) 0.444 2 (50.0%) 56 (41.2%) 0.724

No 18 (52.9%) 64 (60.4%) 2 (50.0%) 80 (58.8%)
HCV Positive 11 (32.4%) 25 (23.6%) 0.309 1 (25.0%) 35 (25.7%) 0.974
Negative 23 (67.6%) 81 (76.4%) 3 (75.0%) 101 (74.3%)
HBV Positive 0 (0.0%) 0 (0.0%) – 0 (0.0%) 0 (0.0%) –
Negative 34 (100.0%) 106 (100.0%) 4 (100.0%) 136 (100.0%)
ALT Elevated 28 (82.4%) 47 (44.3%) <0.001b 4 (100.0%) 71 (52.2%) 0.059
Normal 6 (17.6%) 59 (55.7%) 0 (0.0%) 65 (47.8%)
AST Elevated 23 (67.6%) 39 (36.8%) 0.002a 3 (75.0%) 59 (43.4%) 0.210
Normal 11 (32.4%) 67 (63.2%) 1 (25.0%) 77 (56.6%)

ALT, alanine transaminase; AST, aspartate transaminase; n, number.

a
Significance <0.05.
b
High significance.

Table 3 – Univariate and multivariate analyses of factors associated with HEV seropositivity in thalassemic children.
Univariate analysis Multivariate analysis

p Value OR 95% C.I. p Value OR 95% C.I.

a
Age (years) 0.001 1.18 1.07–1.29
Male sex 0.807 1.098 0.52–2.32
Rural Residence 0.001a 4.98 2.01–12.35 0.003a 4.277 1.65–11.09
Splenectomy 0.385 1.39 0.66–2.96
Abnormal AST 0.001a 3.97 1.79–8.80
Abnormal ALT <0.001a 7.32 2.81–19.04 <0.001b 6.486 2.43–17.32
Amount of blood transfused (mL/year) 0.008a 1.00 1.00–1.00
Serum ferritin (␮g/L) 0.313 1.00 1.00–1.00

Q4 ALT, Alanine transaminase; AST, Aspartate transaminase; p, probability; OR, odd’s ratio; CI, confidence interval.

130 elevated ALT levels were independently associated with HEV IgM were 10% and 1.8%, respectively.23 Reasons such as dif- 138

131 seropositivity. ferences in socioeconomic, cultural, hygienic, and climatic 139

factors across geographical areas may explain the lower preva- 140

lence rates in developed countries compared to developing 141

Discussion countries.24 In our study, age was significantly associated with 142

HEV antibodies. The highest HEV prevalence rate found in the 143

132 The prevalence of HEV antibodies among thalassemic chil- age group 12–18 years indicated that the risk of HEV infection 144

133 dren in our study was 27.15%, 24.29% anti-HEV IgG positive increased with age. Previous studies carried out in Egypt25 and 145

134 and 2.86% anti-HEV IgM positive. Results of previous stud- in other geographic regions reported the same finding.26–28 146

135 ies showed seroprevalence of HEV antibodies of 2.4% in This could be explained by the fact that older children had 147

136 thalassemic patients in Scandinavia21 and 10.7% in Saudi likely received more transfused blood, in addition to have 148

137 Arabia.22 In Iran, the seroprevalence of HEV IgG and HEV been more exposed to contaminated junk food than younger 149

Please cite this article in press as: D. Abdelmawla, D. Moemen, A. Darwish, et al.. Hepatitis E virus prevalence in Egyptian children with
transfusion-dependent thalassemia. Braz J Infect Dis. 2019. https://doi.org/10.1016/j.bjid.2019.01.007 BJID 874 1–5
 BJID 874 1–5
ARTICLE IN PRESS
4 b r a z j i n f e c t d i s . 2 0 1 9;x x x(x x):xxx–xxx

150 children. In this study, the prevalence of HEV antibodies in should be taken into consideration. Frequent assessment of 206

151 rural areas (81.6%) was higher than in urban areas (18.4%), liver enzymes in ␤-thalassemic patients to monitor subclini- 207

152 respectively. In rural Egypt, more than 60% of children with cal HEV infections and other viral infections is recommended. 208

153 aged over 10 years had positive anti-HEV IgG.29 On the con- Public awareness about HEV endemicity, modes of transmis- 209

154 trary, another study conducted on HCV infected thalassemic sion, and risk hazards, especially in high-risk groups should 210

155 patients in Iran reported higher HEV seropositivity in tha- be done to reduce the disease burden. 211

156 lassemic patients from urban regions than those from rural
157 areas.6 Regarding liver enzymes, 84.2% of patients with HEV Funding
158 seropositivity showed elevated ALT levels, compared to 68.4%
159 of elevated AST levels. Liver enzymes were higher among
None declared. 212
160 those with non-HEV antibodies compared to those with HEV
161 antibodies. This may be due to presence of other causes of
162 hepatitis either viral causes, mostly HCV, or non-viral causes. Conflicts of interest
163 Although 100% and 75% of anti-HEV IgM positive patients had
164 elevated ALT and AST levels, respectively, there was no sig- The authors declare no conflicts of interest. 213

165 nificant association between liver enzymes and anti-HEV IgM 214

166 seropositivity, probably due to small number of anti-HEV IgM references

167 positive patients. Previous studies reported that subclinical 215

168 HEV infection might be the cause of elevated ALT.30 There-

169 fore, in cases of unexplained ALT and AST elevation, HEV 1. Romano’ L, Paladini S, Tagliacarne C, Canuti M, Bianchi S, 216

170 may be the reasonable cause. In two studies conducted in Zanetti AR. Hepatitis E in Italy: a long-term prospective study. 217

171 Japan on voluntary blood donors with elevated ALT levels, J Hepatol. 2011;54:34–40. 218
2. Arends JE, Ghisetti V, Irving W, et al. Hepatitis E: an emerging 219
172 anti-HEV IgG was positive in 3.7% and 7.1% of participants.31,32
infection in high income countries. J Clin Virol. 2014;59:81–8. 220
173 These findings suggest that patients with ongoing subclini-
3. Balayan MS. Epidemiology of hepatitis E virus infection. J Viral 221
174 cal HEV infection had the potential to transmit HEV through Hepatitis. 1997;4:155–65. 222
175 blood transfusion. Our study revealed that there was signifi- 4. Clemente Casares P, Ramos Romero C, Ramirez Gonzalez E, 223

176 cant association between the amount of blood transfused per Mas A. Hepatitis E virus in industrialized countries: the silent 224

177 year and HEV seropositivity (p = 0.008). On the other hand, threat. BioMed Res Int. 2016:9838041. 225

178 a previous study showed no significant association between 5. Amer AF, Zaki SA, Nagati AM, Darwish MA. Hepatitis E 226
antibodies in Egyptian adolescent females: their prevalence 227
179 the amount of blood transfused and anti-HEV seropositivity
and possible relevance. J Egypt Public Health Assoc. 228
180 in thalassemic patients.21 This difference may be due to geo- 1996;71:273–84. 229
181 graphic difference and use of assays with low sensitivity that 6. Elizee PK, Alavian SM, Miri SM, et al. The seroprevalence of 230
182 could underestimate HEV prevalence.33 Studies conducted in entrically transmitted viral hepatitis in HCV infected 231

183 blood banks of several European countries reported that about thalassemia and hemophilia patients in Iran. Jundishapur J 232

184 0.02–0.14% of blood donations were HEV RNA positive.16,34 This Microbiol. 2013;6:e9091. 233
7. Mushahwar IK. Hepatitis E virus: molecular virology clinical 234
185 finding supports the possibility of HEV transmission through
features, diagnosis, transmission, epidemiology, and 235
186 blood transfusion. Since recently in Ireland, blood donations
prevention. J Med Virol. 2008;80:646–58. 236
187 are routinely screened for HEV RNA. Also in 2017, the UK, 8. Lewis HC, Wichmann O, Duizer E. Transmission routes and 237
188 and Netherlands began HEV RNA screening in blood dona- risk factors for autochthonous hepatitis E virus infection in 238
189 tions. In France and Germany, screening selectively occurs Europe: a systematic review. Epidemiol Infect. 239

190 in high-risk patients, while blood authorities in Italy, Spain, 2010;138:145–66. 240

191 Portugal and Greece are assessing whether HEV screening 9. Feray C, Pawlotsky JM, Roque-Afonso AM, Samuel D, 241
Dhumeaux D. Should we screen blood products for hepatitis E 242
192 should be implemented or not.17 A previous study conducted
virus RNA? Lancet. 2014;383:218. 243
193 in Egypt showed that about 0.45% of blood donors have ongo-
10. Quek L, Thein SL. Molecular therapies in beta-thalassaemia. 244
194 ing subclinical HEV infection.35 It was reported that the risk of Br J Haematol. 2007;136:353–65. 245
195 transmission through blood transfusion is increased in high- 11. Hamamy HA, Al-Allawi NA. Epidemiological profile of 246

196 risk patients in developing regions than in other locations.23 common haemoglobinopathies in Arab countries. J Commun 247

197 HEV is endemic in Egypt and besides the possibility of HEV Genet. 2013;4:147–67. 248

198 transmission through blood, our study showed significant 12. El-Beshlawy A, Youssry I. Prevention of hemoglobinopathies 249
in Egypt. Hemoglobin. 2009;33 Suppl 1:S14–20. 250
199 association between amount of blood transfused and HEV
13. Cho HC, Paik SW, Kim YJ, et al. Seroprevalence of anti-HAV 251
200 seropositivity. Therefore, further studies should be carried among patients with chronic viral liver disease. World J 252
201 out to detect HEV infection in risk group patients and blood Gastroenterol. 2011;17:236–41. 253
202 donors. 14. Morteza P, AbdolReza S, Hamid N. Hepatitis E virus infection 254
in hemodialysis patients: a seroepidemiological survey in 255
Jahrom, Southern Iran. Hepatitis Mon. 2009;3(Summer):232–5. 256
15. Jahromi AS, Ahmadi-Vasmehjani A, Zabetian H, et al. 257
Conclusion
Sero-epidemiological study of hepatitis E virus among 258
Thalassemia as high risk patients: a cross-sectional survey in 259
203 In conclusion, the seroprevalence of HEV in ␤-thalassemic Jahrom, Southern Iran. Global J Health Sci. 2016;8:245–50. 260
204 patients was relatively high. Therefore, close monitoring of 16. Gallian P, Couchouron A, Dupont I, et al. Comparison of 261
205 these patients in addition to HEV screening of blood donations hepatitis E virus nucleic acid test screening platforms and 262

Please cite this article in press as: D. Abdelmawla, D. Moemen, A. Darwish, et al.. Hepatitis E virus prevalence in Egyptian children with
transfusion-dependent thalassemia. Braz J Infect Dis. 2019. https://doi.org/10.1016/j.bjid.2019.01.007 BJID 874 1–5
 BJID 874 1–5
ARTICLE IN PRESS
b r a z j i n f e c t d i s . 2 0 1 9;x x x(x x):xxx–xxx 5

263 RNA prevalence in French blood donors. Transfusion. of the seroprevalence of HEV in eastern China. Arch Virol. 298
264 2017;57:223–4. 2007;152:739–46. 299
265 17. Domanovic D, Tedder R, Blumel J, et al. Hepatitis E and blood 27. Taremi M, Mohammad Alizadeh AH, Ardalan A, Ansari S, Zali 300
266 donation safety in selected European countries: a shift to MR. Seroprevalence of hepatitis E in Nahavand Islamic 301
267 screening? Euro Surveill. 2017;22:30514. Republic of Iran: a population-based study. East Mediterr 302
268 18. Zakaria S, Fouad R, Shaker O, et al. Changing patterns of Health J. 2008;14:157–62. 303
269 acute viral hepatitis at a major urban referral center in Egypt. 28. Anderson DA 7th. Hepatitis E virus. In: Anderson DA 7th, 304
270 Clin Infect Dis. 2007;44:e30–6. editor. Mandell, Douglas, and Bennett’s principles and 305
271 19. El-Tras WF, Tayel AA, El-Kady NN. Seroprevalence of hepatitis practice of infectious diseases. Churchill Livingstone Elsevier; 306
272 E virus in humans and geographically matched food animals 2010. p. 2411–23. 307
273 in Egypt. Zoonoses Public Health. 2013;60:244–51. 29. Fix AD, Abdel-Hamid M, Purcell RH, et al. Prevalence of 308
274 20. Hasan G, Assiri A, Marzuuk N, et al. Incidence and antibodies to hepatitis E in two rural Egyptian communities. 309
275 characteristics of hepatitis E virus infection in children in Am J Trop Med Hyg. 2000;62:519–23. 310
276 Assiut Upper Egypt. J Int Med Res. 2016;44:1115–22. 30. Gao D, Peng G, Zhu J, Sun L, Zheng Y, Zhang J. Investigation of 311
277 21. Psichogiou M, Tzala E, Boletis J, et al. Hepatitis E virus sub-clinical infection of hepatitis E virus in blood donors. 312
278 infection in individuals at high risk of transmission of non-A, Chin J Hepatol. 2004;12:11–2. 313
279 non-B hepatitis and sexually transmitted diseases. Scand J 31. Fukuda S, Sunaga J, Saito N, et al. Prevalence of antibodies to 314
280 Infect Dis. 1996;28:443–5. hepatitis E virus among Japanese blood donors: identification 315
281 22. Al-Fawaz I, Al-Rasheed S, Al-Mugeiren M, Al-Salloum A, of three blood donors infected with a genotype 3 hepatitis E 316
282 Al-Sohaibani M, Ramia S. Hepatitis E virus infection in virus. J Med Virol. 2004;73:554–61. 317
283 patients from Saudi Arabia with sickle cell anaemia and 32. Gotanda Y, Iwata A, Ohnuma H, et al. Ongoing subclinical 318
284 beta-thalassemia major: possible transmission by blood infection of hepatitis E virus among blood donors with an 319
285 transfusion. J Viral Hepatitis. 1996;3:203–5. elevated alanine aminotransferase level in Japan. J Med Virol. 320
286 23. Sotoodeh Jahromi A, Ahmadi-Vasmehjani A, Zabetian H, et al. 2007;79:734–42. 321
287 Sero-epidemiological study of hepatitis E virus among 33. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, 322
288 thalassemia as high risk patients: a cross-sectional survey in Echevarria JM. Comparative sensitivity of commercial tests 323
289 Jahrom, Southern Iran. Glob J Health Sci. 2016;8:53885. for hepatitis E genotype 3 virus antibody detection. J Med 324
290 24. Junaid SA, Agina SE, Abubakar KA. Epidemiology and Virol. 2015;87:1934–9. 325
291 associated risk factors of hepatitis e virus infection in plateau 34. Hogema BM, Molier M, Sjerps M, et al. Incidence and duration 326
292 state Nigeria. Virology (Auckl). 2014;5:15–26. of hepatitis E virus infection in Dutch blood donors. 327
293 25. Stoszek SK, Engle RE, Abdel-Hamid M, et al. Hepatitis E Transfusion. 2016;56:722–8. 328
294 antibody seroconversion without disease in highly endemic 35. Ibrahim EH, Abdelwahab SF, Nady S, et al. Prevalence of 329
295 rural Egyptian communities. Trans R Soc Trop Med Hyg. anti-HEV IgM among blood donors in Egypt. Egypt J Immunol. 330
296 2006;100:89–94. 2011;18:47–58. 331
297 26. Dong C, Dai X, Shao JS, Hu K, Meng JH. Identification of
genetic diversity of hepatitis E virus (HEV) and determination

Please cite this article in press as: D. Abdelmawla, D. Moemen, A. Darwish, et al.. Hepatitis E virus prevalence in Egyptian children with
transfusion-dependent thalassemia. Braz J Infect Dis. 2019. https://doi.org/10.1016/j.bjid.2019.01.007 BJID 874 1–5