of Norovirus Gastroenteritis in Lebanon Nada M Melhem PhD American University of Beirut Faculty of Health Sciences Center for Infectious Diseases Research Faculty of Medicine December 7 2015 ID: 541954
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Slide1
Clinical, Epidemiologic and Genotypic Characteristics of Norovirus Gastroenteritis in Lebanon
Nada M. Melhem, PhDAmerican University of BeirutFaculty of Health SciencesCenter for Infectious Diseases ResearchFaculty of Medicine December 7, 2015
Melhem
, 2015Slide2
Introduction
Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide (Lamata et al., 2013). Data from the Centers for Disease Control and prevention (CDC) suggest that NoV is the leading cause of acute gastroenteritis across all age groups seeking medical care in emergency departments, outpatient clinics and the
community (Hall et al., 2011).
NoV
-gastroenteritis accounts for 10-15
% of
severe cases in children less than 5 years old (Patel et al., 2009).9-15 % of mild-to-moderate diarrhea are due to NoV among individuals of all ages (Patel et al., 2008).
Melhem
, 2015Slide3
NoV: Transmission, Pathogenesis and Management
Primary mode of transmission is through the fecal-oral route.The incubation period is 24-48 hours. The symptoms include: vomiting, diarrhea, nausea, abdominal cramps, malaise and low grade fever.The illness resolves in 12-72 hours.Treatment involves reversal of dehydration and electrolyte deficiency.
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, 2015Slide4
Genome Organization & Capsid Structure
Melhem, 2015Slide5
Melhem, 2015
Classification of Noroviruses and Viral Diversity (Vinjé et al. 2015) Slide6
Aim of the StudyTo our knowledge, there are no studies in Lebanon on
NoV and its association with gastroenteritis.The aim our study is to determine the prevalence of Norovirus gastroenteritis as well as the genotypic characterization of the virus among hospitalized children less than 5 years old. Melhem, 2015Slide7
Methods
Study Period: January 2011 to June 2013Age group: ≤5 years old Sample size: 739 stool samples from hospitalized children presenting with diarrhea
Collection sites and number of samples:
American
University of Beirut Medical
Center
(Capital Beirut): n=81 Hariri Governmental Hospital (Capital Beirut): n=47 Makassed Hospital (Capital Beirut): n=89 Nini Hospital (North Lebanon): n=316
Hammoud
Hospital
(South
Lebanon): n=116
Nabatiyeh
Hospital (South Lebanon
): n=90
Melhem
, 2015Slide8
Methods
QIAamp Viral RNA Mini Kit (Qiagen, Germany) was used for viral RNA extraction.For reverse transcription polymerase chain reaction (RT-PCR) QIAGEN OneStep RT-PCR Kit was used, using
genogroup-specific primers.
PCR products were analyzed by gel
electrophoresis and nucleotide
sequencing of
NoV positive samples was performed.Multiple sequence alignments were carried out using CLUSTALL or BioEdit.Phylogenetic trees were constructed using the MEGA 6 software.Melhem, 2015Slide9
Table 1. Demographic Characteristics of Study Participants
Melhem, 2015Slide10
Table 2. Clinical Characteristics of NoV
-associated GastroenteritisMelhem, 2015Slide11
Incidence of Norovirus by Region
RegionPositivesTotal Number of SamplesIncidence
South
28
206
13.59%
North3531611.08%Beirut
20
217
9.22%
Total
83
739
11.23%
13.59
11.08
9.22
Melhem
, 2015Slide12
Figure 1. Norovirus and Seasonal Distribution
Melhem, 2015Slide13
LBM073/2011 GII
LBH065/2011 GII
LBM123/2011 GII
LBM122/2011 GII
LBM104/2011 GII
LBN159/2011 GII
LBH048/2011 GII
LBH075/2011 GII
LBH062/2011 GII
LBH077/2011 GII
LBN120/2011 GII
LBN111/2011 GII
LBH009/2011 GII
LBN047/2011 GII
LBN086/2011 GII
LBH089/2011 GII
LBH049/2011 GII
LBN131/2011 GII
JB-15/KOR/2008 GII.4 Apeldoorn 2008
LBR034/2011 GII
LBN095/2011 GII
LBN142/2011 GII
LBN185/2011 GII
LBM097/2011 GII
LBH066/2011 GII
LBN154/2011 GII
LBM109/2011 GII
Orange/NSW001P/2008/AUS GII.4 New Orleans 2009
Farmington Hills/2002/USA GII.4 2002
Guangzhou/NVgz01/CHN GII.4 Asia 2003
Hunter504D/04O/AU GII.4 Hunter 2004
Kenepuru
/NZ327/2006/NZL GII.4 2006a
Osaka1/2007/JP GII.4 Osaka 2007
Yerseke38/2006/NL GII.4
Shellharbour-NSW696T/2006/AUS GII.4 2006b
LBA147/2012 GII
Sydney/NSW0514/2012/AUS GII.4 Sydney 2012
LBA163/2013 GII
LBN516/2013 GII
LBNG112/2012 GII
LBR040/2011 GII
LBN365/2012 GII
LBN330/2012 GII
LBN323/2012 GII
2012/FRA GII.4 variant Sydney
LBA113/2012 GII
LBN384/2012 GII
LBN478/2012 GII
LBN382/2012 GII
LBN393/2012 GII
LBN328/2012 GII
LBH208/2012 GII
LBNG175/2013 GII
LBN458/2012 GII
LBH054/2011 GII
LBH068/2011 GII
LBH185/2012 GII
LBH203/2012 GII
LBN259/2011 GII
LBR081/2012 GII
LBN339/2012 GII
LBN374/2012 GII
LBA126/2012 GII
LBH186/2012 GII
Sutherland/NSW505G/2007/AUS GII.4 Cairo 2007
Maizuru8915/2008/JPN GII.6
LBA057/2011 GII
LBN360/2012 GII
CBNU1/2006/KOR GII.3
LBNG107/2012 GII
LBA125/2012 GII
LBNG098/2012 GII
NSW743L/2008/AUS GII.7
HCMC-VNM30241/2009/VNM GII.9
LBN480/2012 GII
LBN052/2011 GII
LBH046/2011 GII
LBR082/2012 GII
LBM093/2011 GII
Maizuru8915/2008/JPN GII.6
LBA038/2011 GII
LBH028/2011 GII
LBNG147/2012 GII
Ascension208/2010/USA GII.1
LBM101/2011 GII
HS207/2010/USA GII.12
Vaals87/2005/NL GII.2
LBN329/2012 GII
LBN358/2012 GII
LBM102/2011 GII
10N4555/2010/NP GII.13
LBH091/2011 GII
Salisbury150/2011/USA GII.21
LBH221/2012 GII
LBNG129/2012 GII
LBN387/2012 GII
LBN373/2012 GII
LBN366/2012 GII
LBH098/ GI
LBH112/2011 GI
LBN187/2011 GI
LBN040/2011 GI
141/2009/BFA GI.3
JKPG 881/SWE/2007 GI.3
2008890321/2008/US GI.8
1643/2008/US GI.4
LBN343/2012 GI
Leuven/2003/BEL GI.2
CS-841/2001/USA GI
StromstadP7-587/2007/Sweden GI.1
74
70
88
92
88
92
98
97
91
97
96
70
75
75
94
99
99
99
93
99
98
100
97
0.2
GII.4
68
%
(
52/76)
GII.9
GII.3
GII.6
GII.13
GII.1
GII.2
GII.21
GI.3
80% (4/5)
GI.4
Melhem
, 2015
Figure 2. Phylogenetic Analysis of
NoV
VP1 Capsid Gene
GII.3 (5/76, 6.6%)
GII.9 (1/76, 1.3%)
GII.6 (7/76, 9.2%)
GII.13 (3/76, 3.95)
GII.1 (1/76, 1.3%)
GII.2 (1/76, 1.3%)
GII.21 (5/76, 6.6%) Slide14
LBM073/2011 GII
LBH065/2011 GII
LBM123/2011 GII
LBM122/2011 GII
LBM104/2011 GII
LBN159/2011 GII
LBH048/2011 GII
LBH075/2011 GII
LBH062/2011 GII
LBH077/2011 GII
LBN120/2011 GII
LBN111/2011 GII
LBH009/2011 GII
LBN047/2011 GII
LBN086/2011 GII
LBH089/2011 GII
LBH049/2011 GII
LBN131/2011 GII
JB-15/KOR/2008 GII.4 Apeldoorn 2008
LBR034/2011 GII
LBN095/2011 GII
LBN142/2011 GII
LBN185/2011 GII
LBM097/2011 GII
LBH066/2011 GII
LBN154/2011 GII
LBM109/2011 GII
Orange/NSW001P/2008/AUS GII.4 New Orleans 2009
Farmington Hills/2002/USA GII.4 2002
Guangzhou/NVgz01/CHN GII.4 Asia 2003
Hunter504D/04O/AU GII.4 Hunter 2004
Kenepuru/NZ327/2006/NZL GII.4 2006a
Osaka1/2007/JP GII.4 Osaka 2007
Yerseke38/2006/NL GII.4
Shellharbour-NSW696T/2006/AUS GII.4 2006b
LBA147/2012 GII
Sydney/NSW0514/2012/AUS GII.4 Sydney 2012
LBA163/2013 GII
LBN516/2013 GII
LBNG112/2012 GII
LBR040/2011 GII
LBN365/2012 GII
LBN330/2012 GII
LBN323/2012 GII
2012/FRA GII.4 variant Sydney
LBA113/2012 GII
LBN384/2012 GII
LBN478/2012 GII
LBN382/2012 GII
LBN393/2012 GII
LBN328/2012 GII
LBH208/2012 GII
LBNG175/2013 GII
LBN458/2012 GII
LBH054/2011 GII
LBH068/2011 GII
LBH185/2012 GII
LBH203/2012 GII
LBN259/2011 GII
LBR081/2012 GII
LBN339/2012 GII
LBN374/2012 GII
LBA126/2012 GII
LBH186/2012 GII
0.005
Melhem, 2015
Figure 3. Phylogenetic Analysis of
NoV
VP1: GII.4Slide15
Conclusions: NoV in Lebanon
This is the first study assessing NoV infections in Lebanon. Our results are compatible with globally reported ones where GII.4 contributes to the majority of viral gastroenteritis outbreaks ( Bull
and White, 2011;
Guo
et al., 2009;
Siebenga
et al., 2007).We report JB-15/KOR/2008 GII.4 Apeldoorn 2008-like variant strain circulating in 2011 among children less than 5 years.Between 2012 and 2013, the Apeldoorn variant was replaced by a variant sharing homology with Sydney/ NSW0514/2012/AUS GII.4 Sydney 2012 and the Sydney 2012/FRA GII.4.Melhem, 2015Slide16
Conclusions: NoV
in LebanonNoV GII.6 incidence was the second predominant cause of gastroenteritis among hospitalized children in Lebanon, similar to what has been reported in several countries including Brazil, Japan, South Africa and Finland (Ferreira et al., 2012).NoV GII.3 ranked third along with NoV
GII.21 among our study participants; after GII.4 and GII.6, while it ranked second in other countries.
Reports
show that
NoV
cases peak during the cold months in parts of Europe and North America with sporadic cases detected all year round as well as outbreaks during the summer time (Mounts et al., 2000; Rohayem, 2009; Thongprachum et al., 2015; Verhoef et al., 2008; Ahmed et al. 2013) .Our data support a peak incidence in July; the seasonal pattern of NoV in Lebanon should be further investigated.
Melhem
, 2015Slide17
NoV in
the Middle East and North Africa (MENA) Region In the MENA region, NoV was detected in stool samples of 6-30% of hospitalized children under 5 years.Only few studies further reported on the geno
-subgroups.
3
reported GII.3 being more
prevalent
(Romani et al., 2012; Leshem et al., 2015; Muhsen et al., 2013; Kaplan et al., 2011). Clear lack of data on the genetic relatedness and subtyping in the MENA . Melhem, 2015Slide18
Conclusions
Variants of the NoV GII.4 lineage have been associated with 62 to 80% of NoV outbreaks worldwide (Donaldson et al., 2010; Siebenga et al., 2009).
NoV
remains an understudied causative agent of acute
gastroenteritis and not included in the Global Burden of Diseases (GBD)
among the infectious agents causing gastroenteritis and
diarrhea.Thus there’s a lack of clinical diagnosis and reporting of NoV as an important cause of disease and further studies are needed to support intervention strategies.Melhem, 2015Slide19
Acknowledgments
Faculty of Health SciencesKhalil KreidiehRana CharideNour Rahal
Center for Infectious Diseases Research, Faculty of Medicine
Ghassan
Dbaibo
and team (Amjad Haidar)Hassan ZaraketMelhem, 2015