Vaccine 32 (2014) 3367–3378

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Rotaviruses: Is their surveillance needed? Swapnil Jain, Jitendraa Vashistt, Harish Changotra ∗ Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan 1732 34, Himachal Pradesh, India

a r t i c l e

i n f o

Article history: Received 12 March 2014 Received in revised form 4 April 2014 Accepted 14 April 2014 Available online 30 April 2014 Keywords: Rotavirus Diarrhoea Diversity Surveillance Vaccination Genotypes

a b s t r a c t Rotaviruses, a major cause of gastroenteritis in children worldwide accounts for around 0.5 million deaths annually. Owing to their segmented genome and frequently evolving capability, these display a wide variation in their genotypes. In addition to commonly circulating genotypes (G1, G2, G3, G4, G9, P[4] and P[8]), a number of infrequent genotypes are being continuously reported to infect humans. These viral strains exhibit variation from one geographical setting to another in their distribution. Though the introduction of vaccines (RotaTeq and Rotarix) proved to be very effective in declining rotavirus associated morbidity and mortality, the number of infections remained same. Unusual genotypes significantly contribute to the rotavirus associated diarrhoeal burden, may reduce the efficacy of the vaccines in use and hence vaccinated individuals may not be benefited. Vaccine introduction may bring about a notable impact on the distribution and prevalence of these viruses due to selection pressure. Moreover, there is a sudden emergence of G2 and G3 in Brazil and United States, respectively, during the years 2006–2008 postvaccination introduction; G9 and G12 became predominant during the years 1986 through 1998 before the vaccine introduction and now are commonly prevalent strains; and disparity in the predominance of strains after introduction of vaccines and their natural fluctuations poses a vital question on the impact of vaccines on rotavirus strain circulation. This interplay between vaccines and rotavirus strains is yet to be explored, but it certainly enforces the need to continuously monitor these changes in strains prevalence in a particular region. Furthermore, these fluctuations should be considered while administration or development of a vaccine, if rotavirus associated mortality is ever to be controlled. © 2014 Elsevier Ltd. All rights reserved.

1. Introduction

1.1. Structure

Rotaviruses (RVs), an important cause of gastroenteritis in various animal species, cause approximately 0.5 million deaths (under the age group of five years) out of 0.8 million total diarrhoea associated child deaths annually [1,2]. Almost all children in the world get infected at least once before they reach the age of 5 and peak incidences occur below the age of 2 years. Furthermore, a recent Global Enteric Multicenter Study (GEMS) reported rotaviruses as the leading cause of diarrhoea in children which included cohort of over 20,000 children from Asia and Africa [2]. Underdeveloped and developing nations of the world are worst affected. Although the mortality rate due to diarrhoea has declined, there is no significant affect on rotavirus associated hospitalizations. In this review, we discuss various aspects of rotavirus focusing on its diversity which is a great challenge for the current vaccination programmes and hence imposing a need for continuous surveillance of this deadly virus.

Rotaviruses were first observed in 1973 by Bishop and colleagues as a 70 nm particles having a wheel like appearance. These belong to the family Reoviridae, have segmented genome (11 segments) of double stranded RNA with size of around 18,550 bp and length of RNA segments range from 667 to 3302 nucleotides. These RNA segments encode 6 structural (VP1, VP2, VP3, VP4, VP6, VP7) and 6 non-structural proteins (NSP1-NSP6). The viral genome is enclosed with a triple layered capsid (Fig. 1). The inner most layer is made up of VP1, VP2 and VP3; the intermediate layer is composed of VP6 protein; and VP4 and VP7 proteins assemble to form outermost shell of the virus. VP6 protein is the basis for classification of rotavirus in various groups (A–G) whereas VP4 and VP7 proteins contain epitopes against homotypic and heterotypic neutralizing antibodies.

∗ Corresponding author. Tel.: +91 1792239366. E-mail addresses: [email protected], [email protected] (H. Changotra). http://dx.doi.org/10.1016/j.vaccine.2014.04.037 0264-410X/© 2014 Elsevier Ltd. All rights reserved.

1.2. Pathogenesis Rotaviruses are transmitted via feaco-oral route and infect humans and animals by adhering to the epithelial lining of gastrointestinal tract. Various mechanisms [3] which contribute to pathophysiology of rotavirus diarrhoea are: (1) Viral entry causes

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and initial packaging of the viral genome. The newly formed progeny DLPs bud into endoplasmic reticulum with the help of NSP4 proteins present on the membrane of endoplasimc reticulum [10]. Here, the DLPs acquire their outermost layer and from fully developed TLPs. The mature triple layered virions leave the cell either by lysis or by trafficking pathway in the case of polarized cells. 2. Classification and strain diversity

Fig. 1. Schematic representation of Rotavirus structure. The major structural proteins i.e. VP1, VP2, VP3, VP4, VP6 and VP7 assemble to form a triple layered structure which encapsulates the segmented RNA genome within it.

destruction of mature enterocytes in the epithelial lining of intestinal villi leading to malabsorption by intestine. However, the latter is basically attributed to enterotoxin NSP4. (2) NSP4 protein mediates the release of Ca2+ from endoplasmic reticulum and results in increased intracellular Ca2+ concentration [4] that leads to disruption of the cytoskeletal network and cell lysis. (3) NSP4 alters biogenesis and integrity of the tight junctions of enterocytes which consequently results in paracellular flow of water and electrolytes. (4) Additionally, infection also dysregulates Na+ /K+ pump which is essential for retention of fluid and nutrients by the cells. This dysregulation is because of decreased expression of digestive enzymes following rotavirus infection. (5) Along with malabsorption factor, rotavirus infection also stimulates the secretion of electrolytes and fluid resulting in secretory diarrhoea. NSP4 is responsible for activation of enteric nervous system (ENS) which in turn results in increased secretion of electrolytes and water [5]. All these factors collectively contribute to loss of absorption capability of intestine and results in diarrhoea. 1.3. Replication The replication strategy used by rotaviruses is depicted in Fig. 2. Virus has double stranded segmented RNA genome. The segmented nature of genome along with gene reassortment allows large number of combinations resulting in the formation of new reassortment RVs with potential novel antigen combinations that leads to RV diversity generation. Typically, rotaviruses are transmitted by feaco-oral route and infect the enterocytes in the villus of intestine. Rotavirus enters into these cells as triple layered particle (TLP) either by direct penetration or by receptor mediated endocytosis. The virion particles bind to the sialic acid residues on enterocytes with the help of VP8 protein (formed by cleavage of VP4 into VP5 and VP8) [6]. The virion particles are transported in the cytoplasm with the help of early endosomes. The low calcium (Ca2+ ) level in the endosomes results in the uncoating of TLPs and release of the outer most layer of virions yeilding double layered particles (DLPs). Subsequently, DLPs penetrate the endosomal membrane to enter the cytoplasm [7], the place where whole life cycle of rotavirus occurs and this process is facilitated by VP5. In the cytoplasm, DLPs become transcriptionally active and synthesize RNA segments with the help of viral enzymes including RNA dependent RNA polymerase (RdRP). These newly formed positive (+) sense capped mRNA leave the DLP and undergo either translation or replication to synthesize viral proteins or double stranded RNA genome respectively [8]. The replication occurs in electron dense areas of cytoplasm which are located near nucleus and endoplasmic reticulum known as viroplasms which are mainly composed of two viral proteins, NSP2 and NSP5 [9]. The viroplasms are the viral factories and contain all the necessary components required for replication

International Committee on Taxonomy of Viruses (ICTV) divided rotaviruses in seven groups (A–G) on the basis of amino acid sequence of VP6 protein [11]. Out of the seven groups, only group A, B and C rotaviruses are known to infect humans, Group A being the major cause of rotavirus associated morbidity and mortality. Group D, E, F and G rotavirus have never been found to infect humans and are restricted to non-humans, especially aves. Further classification of rotaviruses is done with a G/P-genotyping system that is based on the analysis of (i) Glycoprotein VP7 (G type) and (ii) Protease-sensitive protein VP4 (P type) genes by reverse transcription-polymerase chain reaction (i.e., RT-PCR typing) or by cDNA sequencing [12]. Human rotaviruses constitute a diverse group. Until now, 27 G genotypes (G1–G27) and 35 P genotypes (P[1] – P[35]) have been detected [13]. Most commonly isolated G and P types are G1, G2, G3, G4, G9 and P[4], P[8] respectively. The genes encoding VP7 and VP4 proteins segregate independently and give rise to a large number of G-P combinations. Studies reveal the existence of more than 70 different G-P combinations. Out of these, G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8] are most commonly identified G-P combinations and accounts for around 74% of rotavirus infections globally [14]. Along with the common strains, a large number of surveillance studies have documented the existence of many rare and uncommon strains in humans. The application of advanced molecular techniques such as RT-PCR and sequencing analysis have resulted in exponential increase in the fraction of uncommon and newly detected strains. The evolution of rotavirus results from four mechanisms: point mutation, interspecies transmission of partial or whole virus, reassortment events during co infection of two different viruses in a common host and gene rearrangement that preferably targets non-structural protein (NSP) coding segment of the genome. These mechanisms work individually or in combination with each other resulting in the diverse group of rotaviruses. 2.1. Point mutation Point mutations (genetic drift) are one of the basis of rotavirus diversity. Rotavirus genome is prone to frequent point mutations and accounts for approximately one mutation per genome replication [15]. These mutations accumulate to generate genetic lineages [16] resulting in neutralizing antibody escape mutants. 2.2. Genetic reassortment Reassortment (antigenic shift) is well explored and established phenomenon resulting in continuous evolution of human rotavirus (HRV). It occurs during co infection of two or more strains in a single cell (Fig. 3A). Rotavirus genome is segmented and facilitates the occurrence of reassortment events. Group A rotaviruses that are responsible for most of the infections in humans belong to two major (Wa-like and DS-1-like) and one minor (AU-1) genotype constellations which are designated as I1-R1-C1-M1-A1-N1-T1-E1-H1, I2-R2-C2-M2-A2-N2-T2-E2-H2 and I3-R3-C3-M3-A3-N3-T3-E3-H3, respectively [17]. Here, each alphabet represents a protein encoding gene segment. The human Wa-like rotavirus strains share a common origin with porcine

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Fig. 2. Rotavirus replication cycle. Rotavirus particle enters the enterocytes with the help of cellular receptors or by direct endocytosis. DLPs are generated in the endosomes and become transcriptionally active to yield (+) sense RNA molecules in cytoplasm. The RNA molecules either undergoes translation to synthesize proteins required for asssembly of virion particle or replication to synthesize double stranded RNA genome. The replication and assembly of virus components occurs in viroplasm. This yields progeny DLPs which bud into endoplasmic reticulum to acquire their outer most layer. In the final step, the virus particles release from the cell either by lysis or by traficking pathways.

rotaviruses while human DS-1 like rotavirus strains have a common origin with bovine rotaviruses [18]. Multigenic reassortment within a genogroup (genotype constellation) is frequently observed, although reports of intergenogroup exchange of genes are less. The latter plays a significant role in evolution of HRV [19]. 2.3. Interspecies transmission Another mechanism responsible for diversity/evolution of rotaviruses is through transfer of animal virus or their gene segments in humans (Fig. 3B). Though transmission of whole virus of animal origin in humans is not a frequent event but still it has been reported as a cause of asymptomatic to severe diarrhoea in humans. The infection by unusual strains of bovine and porcine origin in humans mainly occurs in rural areas where humans are involved in rearing of cattles and are in close proximity to animals. The genomic analysis of some rotaviruses isolated from human stool revealed the identity of all the 11 segments with animal rotaviruses [20,21]. Transfer of gene segment from other species to human is a frequent event in comparison to the transmission of whole virus. During co-infection, the gene segments of animal rotaviruses reassort with human rotaviruses and result in human infecting reassortants having a part of genome from animals [22].

for the first time in 1980s when the rotaviruses isolated from stool samples of immunodeficient children were analyzed [24].

3. Geographical distribution of rotavirus Rotavirus is an important pathogen responsible for causing gastroenteritis worldwide. In 2011, Global Rotavirus Information and Surveillance Bulletin [25] depicted the distribution of rotavirus genotypes in various WHO regions of the world (Table 1). The genotype distribution varied widely among the different regions at a given time period. G1P[8] was the most prevalent genotype in the American (43%), European (33%) and Western Pacific (47%) Regions and hence the most frequently detected rotavirus genotype globally. However, prevalence of G4P[8] (23%) in European countries and G3P[8] (25%) in Western Pacific was noteworthy. In Eastern Mediterranean Region, G2P[4] (41%) was the most commonly identified genotype followed by a substantial proportion of uncommon strains (31%). The data from African and South-East Asian Regions revealed a different picture where uncommon rotavirus genotypes such as G2P[6], G3P[6], G12P[8], G12P[6] and G9P[6] were predominant. Their contribution to total rotavirus infections is very significant i.e. 35% in African region and 55% in South-East Asian Region. In other regions also, the uncommon genotypes share a significant proportion in rotavirus associated disease burden.

2.4. Genome rearrangement Genome rearrangements (deletions, duplications or insertions) also lead to diversity/evolution of rotaviruses. These rearrangements introduce mutations in the genes and subsequently mutate protein structures resulting in evolution of virus having novel characteristics. Gene rearrangement commonly occurs in segment 11 of the genome, which encodes two non-structural proteins, NSP5 and NSP6. However, segments 5–10 are also found to be involved in rearrangements [23]. Such rearranged gene segments were found

3.1. Unusual combinations and rare strains Reassortment and inter species transmission leads to evolution of novel genotypes in humans and thus contribute significantly to the diversity of rotavirus. This results in either generation of genotypes with unusual combinations or emergence of absolutely new genotypes (Tables 2 and 3). Following are the unusual combinations of G and P genotypes along with newly detected strains:

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Fig. 3. Mechanisms of rotavirus evolution (A) Reassortment in rotavirus. Co-infection of two different rotavirus strains (A and B) results in the generation/appearance of reassortants due to exchange of gene segments. The resulting reassortants acquire the gene segments from both the host. Reassortant 1 carries two gene segments from strain B and rest of the genome from strain A. Reassortant 2 harbours VP4 and VP7 encoding genes from strain B and thus bearing surface proteins identical to Strain B. (B) Interspecies transmission. Transmission of whole virus or gene segments from non-humans result in evolution and detection of novel rotavirus strains in humans. The novel strains detected in human may be a result of either direct transmission of an animal strain or it could be a reassortant virus which itself is evolved because of intergenogroup transmission between non-human species. Table 1 Distribution of rotavirus genotypes globally as reported by WHO [25]. WHO regions

African region (AFR) Region of Americas (AMR) Eastern Mediterranean Region (EMR) European Region (EUR) South-East Asian Region (SEAR) Western Pacific Region (WPR)

Distribution of rotavirus genotypes (%) G1P[8]

G2P[4]

G3P[8]

G4P[8]

G9P[8]

Uncommon

Mixed

Untypeable

14 43 7 33 7 47

10 36 41 13 8 10

3 2 – 12 – 25

3 – 8 23 – –

10 8 3 4 1 5

35 8 31 9 55 10

14 2 4 3 18 3

11 1 6 3 11 –

S. Jain et al. / Vaccine 32 (2014) 3367–3378 Table 2 Usual G-types with unusual combinations. G-Type

Commonly associated P-type

Unusual P-type association

G1

P[8]

G2

P[4]

G3

P[8]

G4 G9

P[8] P[8]

P[4] [27] P[6] [28] P[19] [26] P[6] [30] P[8] [31] P[2] [32] P[3] [33–35] P[4] [40] P[9] [36,38,39] P[10] [41,42] P[19] [44] P[25] [43] P[4], P[6] [45] P[4] [93] P[6] [69] P[19] [45,70]

Table 3 Unusual G genotypes of rotavirus. Genotype

Associated P-types

References

G5 G6 G8 G10 G11 G12

P[6], P[8] P[6], P[14], P[9] P[1], P[4], P[6], P[14],P[8] P[8], P[6], P[11], P[4] P[8], P[6], P[4], P[25] P[4], P[9], P[6], P[8]

[46–52] [53,54] [19,29,56,57,59,60] [45,72–75] [20,76–78] [17,79–83]

3.1.1. G1 G1 belongs to Wa-like genogroup and is usually associated with P[8]. Continuous reassortment and rearrangement of various genome fragments has lead to evolution of multiple unusual and rare HRV strains. For instance, G1P[19] strain reported in India was a result of human-porcine reassortment in which VP7/VP6 genes were of human origin and VP4/NSP4 genes resembled porcine species [26]. G1 genotype has also been identified in unusual association with other P-types such as P[4] and P[6] [27,28]. 3.1.2. G2 G2 infections are commonly associated with P[4]. Unusual combination of G2 with P[6] was firstly reported in Nigeria in 2001 [29]. Later, this strain was reported in an unusual outbreak in Philadelphia and accounted for 86% of G2 associated infections [30]. A rare association of G2 with P[8] was also reported in Denmark [31]. 3.1.3. G3 In 2011, a new G3 variant was reported where instead of commonly found P[8] genotype, P[2] was associated. This novel strain was a result of reassortment between simian like and group A rotavirus strains belonging to unknown animal and its subsequent human infection [32]. Multiple studies have shown the emergence of a novel HRV strain G3P[3] because of interspecies transmission and reassortment. In Thailand, the emergence of G3P[3] strain has been reported carrying simian-like VP7 and caprine-like VP4 genes [33]. Another example of interspecies transmission of rotavirus strains was documented recently in 2012; where rotavirus G3P[3] strain of canine origin was found to infect human [34]. A reassortment event responsible for generation of G3P[3] and G3P[9] strain was documented by multiple studies [35–37]. The existence of a novel strain G3P[9] was reported in 2011 and recently in 2013 which emerged as a result of reassortment between canine and feline rotavirus strains and subsequent transmission in humans [38,39]. Mutations in the gene segments of HRVs have also contributed towards their diversity. A G3 genotype was reported in Japan where multiple substitutions in amino acid sequences

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resulted in a new variant [40]. The same study also reported the occurrence of unusual combinations of G3P[4] and G2P[8]. An unusual genotype combination of G3 with P[10] was reported by Ghosh et al. (2012) where genes were derived from the Group A rotaviruses of human DS-1-like and AU-1-like strains of simian and caprine host species and presented an example of intergenogroup transmission [41]. A similar unusual G3P[10] was documented in Thailand where gene segments were found to have originated from distinct sources [42]. Genotype G3 has been also found to be associated with other VP4 proteins forming unusual combinations of G3P[25] and G3P[19] where the latter one represented strain diversity due to human-porcine reassortment [43,44]. 3.1.4. G4 G4 is a common G-type responsible for gastroenteritis, usually associated with P[8]. However, two novel combinations, G4P[4] and G4P[6] were also found to evolve in humans as a result of interspecies transmission and multiple reassortment [45]. 3.1.5. G5 G5 is rarely found to infect humans and therefore is responsible for a negligible fraction of rotavirus infection worldwide. This strain was identified in Brazil in 1994 and 1996 [46,47], in Argentina in 2001 [48], in Paraguay in 2002 [49] and in Cameroon in 2004 [50]. It has been reported in Asia for the first time in 2008 as G5P[6] and is supposed to be a result of human porcine reassortment [51]. Similar, human porcine reassortant having the genotype G5P[6] was identified in Bulgaria in 2012 [52]. 3.1.6. G6 Although uncommon, literature survey reveals the wide geographical distribution of G6 in humans around the globe. Many reports including the recent ones have documented the occurrence of G6 infection in association with various P genotypes such as P[6] and P[14] [53,54]. Molecular analysis of these reported strain depicted their evolution because of multigenic reassortment and subsequent transmission to humans. 3.1.7. G8 G8 is a commonly detected serotype in cattle [55]. However, zoonotic transmission of this strain has resulted in increased prevalence in humans especially in African and European regions of the globe [56,57]. Recent report has shown that G8 has crossed the geographical barrier to mark its occurrence in the United States as well [58]. This unusual strain was reported as an etiological agent of gastroenteritis in other parts of world including India and Korea [59,60]. 3.1.8. G9 After its first detection in 1987 [61], G9 disappeared for a long time and then detected again in mid-1990s to mark its clinical significance [62]. At present, G9 genotype has become the fifth most common genotype identified in humans [14]. A number of studies have documented G9 as the most predominant virus strain. In a recent study from Thailand, 91.6% of total rotavirus infections were associated with G9 [63]. Many other studies from different geographical regions also depicted G9 as a major contributing pathogen (Cuba 78.5%; Argentina, 61.5%; Italy, 53.3%; Spain, 87.7%) [64–67]. Genotype G9 with P[8] is generally responsible for majority of infections but other VP4 genotypes such as P[4], P[6], P[11] and P[19] are also reported with G9. Genomic analysis of these strains has revealed the role of interspecies transmission and reassortment events in the evolution of these strains [68–70].

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3.1.9. G10 G10 is a commonly prevalent G type among the cattle, though studies have reported its association with human gastrointestinal infections also [71]. Molecular characterization of G10 isolated from humans has shown significant similarity with the rotaviruses of animal origin indicating its zoonotic transmission [72]. Recent occurrence of G10 genotypes in human faeces has also been documented in Africa and India [73,74]. Commonly associated P types with G10 are P[8], P[4], P[11] and P[6] [45,72,74,75] 3.1.10. G11 G11 was found in human gastroenteritis cases for the first time in 2005 [76]. Later, some studies have shown the infrequent incidences of G11 infections [77,78]. G11 genotype identified in humans show a significant similarity with those of animal origin suggesting its zoonotic transmission [20]. 3.1.11. G12 Rotaviruses belonging to G12 genotype are one of the rapidly emerging agents of gastroenteritis worldwide. The first case of G12 infection in humans was reported among diarrhoeic children in the Philippines in 1987 [79]. Subsequently, in 1998 it was detected in Thailand. In the next year itself, it was detected in the United States followed by its heralded appearance in all the possible parts of the world [80,81]. Studies from different geographic locations indicate that human infecting G12 genotypes most commonly associate with P[6] and P[8] VP4 proteins [17]. However, inter species transmission from feline has resulted in origin of G12P[9] combination in some parts of globe [82,83]. The G12 rotavirus has remarkable diversity owing to its very frequent reassortment activity. 4. Vaccines and their impact on strain distribution Rotashield was the first rotavirus vaccine licensed in US in 1998. It was a quadrivalent human-rhesus reassortant which had shown a great efficacy (∼91%) against severe rotavirus associated diarrhoea. It was withdrawn from the market within a year of its introduction due to the risk of intussusceptions. Currently, two rotavirus vaccines; RotaTeq and Rotarix have been licensed in many countries of the world. RotaTeq is a live, attenuated, pentavalant vaccine containing five human-bovine reassortant rotavirus strains. It was developed by Merck and Company and licensed in US in 2006. The vaccine contain five commonly found antigens in human; G1, G2, G3, G4, P[8]. It is administered orally in 3 doses; the first dose at 6–12 weeks and two subsequent doses at 1–2 month intervals. Another vaccine, Rotarix is a live, attenuated vaccine developed by GlaxoSmithkline Biologicals having monovalent G1P[8] human rotavirus strain. It was licensed in 2008 and is orally administered in two doses. Both, these vaccines provide effective immunity against the emerging genotype G9 with no signs of intussusceptions in children. Selective vaccine pressure may have significant impact on the distribution of rotavirus strains. Post-vaccination surveillance studies from various countries including USA, Australia, Belgium and Brazil have reported the substantial increment in the prevalence of some genotypes (G2 and G3) in contrast to the pre-vaccination era (Table 4) [84–88]. Data from Unites States, where Rotateq was used for vaccination, depicted substantial increase in the prevalence of G3 genotype after the introduction of rotavirus vaccine; G3P[8] genotype percentage remained same (∼2.8) during the first year after its introduction and increased to 35.7 during the second year (Table 4A). Similarly, G9P[8] incidence decreased and then increased in the next 2 consecutive years post-vaccination. Percentage of G1P[8] in the pre-vaccination era from 1996–2005 to 2005–2006, respectively was 78.5 and 23.4 while it increased to

69.6 and came down to 29.6 during the next 2 consecutive years [8]. In Australia, where both Rotateq and Rotarix were used, G2 was detected as prominent genotype as a whole but in the regions where Rotarix was administered, showed a higher percentage of G3 strains (Table 4B). G9P[8] percentage decreased continuously during the years following vaccination while G1P[8] and G2[4] showed no continuous trend but showed fluctuations in their occurrence with increased prevalence during the first year post-vaccination. The laboratory based surveillance in Brazil reported an increase in G2 detection events and a significant decline in G9 genotypes after the introduction of Rotarix vaccine in 2006 (Table 4C) [89]. However, a noteworthy observation from the study is the decline in G2 genotype levels in 2009. During this year, G2 was reported in only 37.5% of cases in comparison to 49%, 66% and 85% in the preceding years. G3P[8] and G4[8] disappeared respectively during post-vaccination years 2007 and 2006 and emerged again during 2009 and 2008. G1P[8] genotype against which the vaccine was used, decreased in its prevalence continuously during the next three consecutive years and increased again to 20.4% in 4th year. One of the reasons could be that selective vaccine pressure leads to the emergence of vaccine resistant strains which are expressed during 2009. Based on the data available so far regarding circulating rotavirus genotypes, it is tempting to speculate that vaccine-induced selection pressure has significant impact on the distribution of rotaviruses in a particular region and also, acts as driving force in the emergence of new rotavirus strains which are less susceptible to vaccine. But there are reports documenting the similar fluctuations in genotypes prevalence and also, the re-emergence of disappeared genotypes during the pre-vaccination era suggesting the role of natural fluctuations/environmental factors in addition to vaccines. But before assigning it to after vaccine affects, continued surveillance data for extended years is needed to monitor strain changes after vaccination. In addition, some other studies showed the emergence and circulation of various uncommon strains in a significant proportion after the introduction of vaccination [58,90]. Furthermore, the regions where Rotarix was introduced have shown the increased prevalence of G3 and the RotaTeq states have shown the predominance of G2 strains [91,92].

5. Need for surveillance As discussed above, rotaviruses are continuously evolving viruses and exhibit great diversity because of frequent occurrence of events that include reassortment, interspecies transmissions, point mutations and gene rearrangements. This results in occurrence/emergence of strains with novel genotypes and unusual G/P combinations. Phylogenetic studies from various parts of the world have revealed the lineage relationship of the human rotavirus with those of other species such as equine, simian, avian etc. This transfer of animal RV entities into human RV strains affects the efficacy of the present vaccines and also remains a challenge for agencies involved in vaccine development. Moreover, the distribution of these strains in the different regions of the world varies significantly. This has been documented by Global Surveillance Network for Rotavirus, WHO which showed uneven distribution of rotavirus genotypes in the various regions of world (WHO, 2012). The predominance of common genotypes (G1, G2, G3, G4, G9, P[4], P[8]) was maintained universally but their contribution to total rotavirus infections varied significantly between the WHO regions. Notably, in the South East Asian region, the uncommon strains accounted for more than ∼55% of rotavirus associated diarrhoea. These factors emphasize the need for continuous

Table 4 Rotavirus genotypes (%) reported in pre-vaccination and post-vaccination era. Genotype

Pre-vaccination

Post-vaccination

1996–2005

2005–2006

2006–2007

2007–2008

78.5

23.4

69.6

29.6

9.2

15.6

7.9

12.8

1.7

2.8

2.6

35.7

0.8

0.0

0.3

0.0

3.6

7.0

1.3

14.5

6.2

51.2

18.3

7.4

(A) United States [84,87]

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Table 4 (Continued ) Genotype

Pre-vaccination

Post-vaccination

2004–2005

2005–2006

2006–2007

2007–2008

2008–2009a

2009–2010a

2010–2011a

48.2

40.2

36.7

52.0

22.5

49.3

26.0

0.9

1.3

4.6

19.8

50.3

21.1

51.0

36.6

14.7

23.3

11.0

4.2

6.6

11.0

0.7

22.6

0.0

0.0

0.5

0.2

6.0

6.7

15.1

31.1

12.2

1.1

1.2

1.0

0.9

0.7

0.4

0.5

1.6

2.6

2.0

6.0

5.3

3.9

4.5

19.8

19.0

3.0

(B) Australia [85]

S. Jain et al. / Vaccine 32 (2014) 3367–3378

Table 4 (Continued ) Genotype

Pre-vaccination

Post-vaccination

1982–2005

2006

2007

2008

2009

43.0

12.3

9.5

0.7

20.4

9.0

49.0

66.0

85.0

37.5

6.0

3.5

0.0

0.0

5.7

4.0

0.0

0.0

0.4

1.1

20.0

22.0

12.3

3.2

3.4

7.0

2.2

2.4

0.0

2.2

11.0

11.0

9.8

10.7

29.7

(C) Brazil [88,89]

S. Jain et al. / Vaccine 32 (2014) 3367–3378

*

a Rotavirus surveillance data from 2008 onwards deciphered G1, G2, G3, G4 and G9 in association with P[8], P[4], P[8], P[8], P[8] respectively. [NT] is an abbreviation for non-typeable.

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surveillance of rotavirus for the success of current vaccination programmes in a particular region and also form the basis of future vaccine development strategies. Furthermore, the data obtained from post-vaccination surveillance in various countries also enforce the need of continuous monitoring of rotavirus. The two rotavirus vaccines have shown great efficacy in prevention of rotavirus associated gastroenteritis. Although, it is too early to conclude that vaccines have a substantial effect on distribution of rotavirus genotypes, but there are fluctuations in the strains distribution of rotavirus before and after vaccination as well as in the different geographical regions. These uncommon and rare genotypes may demand new vaccination strategy to combat them. But, this strictly warrants the necessity of robust surveillance studies to better understand the correlation between vaccination and rotavirus strains diversity and monitor the prevalence of various strains in a particular region in order to be better prepared for disease epidemic. To conclude, rotaviruses are the most diverse group of viruses having a great impact on the human and animal health. Statistical figures suggest rotavirus associated diarrhoeal disease pose a considerable burden on the economy of any country around the globe. The worst affected parts are the poor and under developed nations of the world. However, as improved hygiene has no noteworthy effect on rotavirus infection, vaccination is the only alternative. Rotarix and RotaTeq have proved to be very useful in reducing the frequency of rotavirus infection but their cost is a big hurdle in introduction of these vaccines in poor countries. Recently, Bharat Biotech International Limited, an Indian biotech company has developed rotavirus vaccine under the trade name ‘Rotavac’. This vaccine is a serially passaged attenuated human-bovine reassortant rotavirus with G9 and P[11] antigens. The phase III trails have shown encouraging efficacy of the vaccine. Moreover, it is supposed to be much cheaper (∼20 times) in comparison with its preexisting competitors. This low cost of vaccine would prove helpful in accelerating the rate of immunization in low income setting and would also demand surveillance studies to continuously monitor the post-vaccination effects on the strains. Also, frequently evolving attribute of rotavirus, demands the need for continuous surveillance. The greater understanding of the circulating strains will provide a help in development of vaccines which could combat not only common strains but also the newly evolving uncommon and rare strains of the virus.

Acknowledgements SJ is thankful to Jaypee University of Information Technology, Solan, Himachal Pradesh, India and Indian Council of Medical Research, New Delhi, India for Junior and Senior Research Fellowships, respectively. Conflict of interest: The authors have no conflict of interest.

References [1] Rotavirus vaccines WHO position paper. Week Epidemiol Record 2013;88(January):49–64. [2] Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study – GEMS): a prospective, case–control study. Lancet 2013;382:209–22. [3] Ramig RF. Pathogenesis of intestinal and systemic rotavirus infection. J Virol 2004;78:10213–20. [4] Hyser JM, Collinson-Pautz MR, Utama B, Estes MK. Rotavirus disrupts calcium homeostasis by NSP4 viroporin activity. mBio 2010:1. [5] Ousingsawat J, Mirza M, Tian Y, Roussa E, Schreiber R, Cook DI, et al. Rotavirus toxin NSP4 induces diarrhea by activation of TMEM16A and inhibition of Na+ absorption. Pflugers Arch 2011;461:579–89. [6] Trask SD, McDonald SM, Patton JT. Structural insights into the coupling of virion assembly and rotavirus replication. Nat Rev Microbiol 2012;10:165–77.

[7] Ruiz MC, Abad MJ, Charpilienne A, Cohen J, Michelangeli F. Cell lines susceptible to infection are permeabilized by cleaved and solubilized outer layer proteins of rotavirus. J Gen Virol 1997;78(Pt 11):2883–93. [8] McDonald SM, Patton JT. Assortment and packaging of the segmented rotavirus genome. Trends Microbiol 2011;19:136–44. [9] Silvestri LS, Taraporewala ZF, Patton JT. Rotavirus replication: plus-sense templates for double-stranded RNA synthesis are made in viroplasms. J Virol 2004;78:7763–74. [10] Au KS, Mattion NM, Estes MK. A subviral particle binding domain on the rotavirus nonstructural glycoprotein NS28. Virology 1993;194:665–73. [11] Matthijnssens J, Otto PH, Ciarlet M, Desselberger U, Van Ranst M, Johne R. VP6sequence-based cutoff values as a criterion for rotavirus species demarcation. Arch Virol 2012;157:1177–82. [12] Gouvea V, Glass RI, Woods P, Taniguchi K, Clark HF, Forrester B, et al. Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens. J Clin Microbiol 1990;28:276–82. [13] Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Banyai K, Brister JR, et al. Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol 2011;156:1397–413. [14] Banyai K, Laszlo B, Duque J, Steele AD, Nelson EA, Gentsch JR, et al. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs. Vaccine 2012;30(Suppl. 1):A122–30. [15] Blackhall J, Fuentes A, Magnusson G. Genetic stability of a porcine rotavirus RNA segment during repeated plaque isolation. Virology 1996;225: 181–90. [16] Iturriza-Gomara M, Cubitt D, Steele D, Green J, Brown D, Kang G, et al. Characterisation of rotavirus G9 strains isolated in the UK between 1995 and 1998. J Med Virol 2000;61:510–7. [17] Matthijnssens J, Van Ranst M. Genotype constellation and evolution of group A rotaviruses infecting humans. Curr Opin Virol 2012;2:426–33. [18] Matthijnssens J, Ciarlet M, Heiman E, Arijs I, Delbeke T, McDonald SM, et al. Full genome-based classification of rotaviruses reveals a common origin between human Wa-Like and porcine rotavirus strains and human DS-1-like and bovine rotavirus strains. J Virol 2008;82:3204–19. [19] Nakagomi T, Doan YH, Dove W, Ngwira B, Iturriza-Gomara M, Nakagomi O, et al. G8 rotaviruses with conserved genotype constellations detected in Malawi over 10 years (1997–2007) display frequent gene reassortment among strains cocirculating in humans. J Gen Virol 2013;94:1273–95. [20] Matthijnssens J, Rahman M, Ciarlet M, Zeller M, Heylen E, Nakagomi T, et al. Reassortment of human rotavirus gene segments into G11 rotavirus strains. Emerg Infect Dis 2010;16:625–30. [21] Midgley SE, Hjulsager CK, Larsen LE, Falkenhorst G, Bottiger B. Suspected zoonotic transmission of rotavirus group A in Danish adults. Epidemiol Infect 2012;140:1013–7. [22] Maestri RP, Kaiano JH, Neri DL, Soares Lda S, Guerra Sde F, Oliveira Dde S, et al. Phylogenetic analysis of probable non-human genes of group A rotaviruses isolated from children with acute gastroenteritis in Belem, Brazil. J Med Virol 2012;84:1993–2002. [23] Schnepf N, Deback C, Dehee A, Gault E, Parez N, Garbarg-Chenon A. Rearrangements of rotavirus genomic segment 11 are generated during acute infection of immunocompetent children and do not occur at random. J Virol 2008;82:3689–96. [24] Hundley F, McIntyre M, Clark B, Beards G, Wood D, Chrystie I, et al. Heterogeneity of genome rearrangements in rotaviruses isolated from a chronically infected immunodeficient child. J Virol 1987;61:3365–72. [25] Global rotavirus information and surveillance bulletin. Reporting period: January through December 2010. World Health Organization; 2011. p. 4. [26] Chitambar SD, Arora R, Chhabra P. Molecular characterization of a rare G1P[19] rotavirus strain from India: evidence of reassortment between human and porcine rotavirus strains. J Med Microbiol 2009;58:1611–5. [27] Abdel-Haq NM, Thomas RA, Asmar BI, Zacharova V, Lyman WD. Increased prevalence of G1P[4] genotype among children with rotavirus-associated gastroenteritis in metropolitan Detroit. J Clin Microbiol 2003;41:2680–2. [28] Ghosh S, Urushibara N, Chawla-Sarkar M, Krishnan T, Kobayashi N. Whole genomic analyses of asymptomatic human G1P[6] G2P[6] and G3P[6] rotavirus strains reveal intergenogroup reassortment events and genome segments of artiodactyl origin. Infect Genet Evol 2013;16:165–73. [29] Adah MI, Wade A, Taniguchi K. Molecular epidemiology of rotaviruses in Nigeria: detection of unusual strains with G2P[6] and G8P[1] specificities. J Clin Microbiol 2001;39:3969–75. [30] Clark HF, Lawley D, DiStefano D, Maliga M, Kilby B, Kulnis G, et al. An unusual outbreak of rotavirus genotype G2P[6] during the 2005–2006 epidemic season in Philadelphia. Diagn Microbiol Infect Dis 2011;70:218–22. [31] Fischer TK, Eugen-Olsen J, Pedersen AG, Molbak K, Bottiger B, Rostgaard K, et al. Characterization of rotavirus strains in a Danish population: high frequency of mixed infections and diversity within the VP4 gene of P[8] strains. J Clin Microbiol 2005;43:1099–104. [32] Ghosh S, Gatheru Z, Nyangao J, Adachi N, Urushibara N, Kobayashi N. Full genomic analysis of a simian SA11-like G3P[2] rotavirus strain isolated from an asymptomatic infant: identification of novel VP1, VP6 and NSP4 genotypes. Infect Genet Evol 2011;11:57–63. [33] Khamrin P, Maneekarn N, Peerakome S, Yagyu F, Okitsu S, Ushijima H. Molecular characterization of a rare G3P[3] human rotavirus reassortant strain reveals evidence for multiple human–animal interspecies transmissions. J Med Virol 2006;78:986–94.

S. Jain et al. / Vaccine 32 (2014) 3367–3378 [34] Luchs A, Cilli A, Morillo SG, Carmona Rde C, Timenetsky Mdo C. Rare G3P[3] rotavirus strain detected in Brazil: possible human–canine interspecies transmission. J Clin Virol 2012;54:89–92. [35] Grant L, Esona M, Gentsch J, Watt J, Reid R, Weatherholtz R, et al. Detection of G3P[3] and G3P[9] rotavirus strains in American Indian children with evidence of gene reassortment between human and animal rotaviruses. J Med Virol 2011;83:1288–99. [36] Khamrin P, Maneekarn N, Peerakome S, Tonusin S, Phan TG, Okitsu S, et al. Molecular characterization of rare G3P[9] rotavirus strains isolated from children hospitalized with acute gastroenteritis. J Med Virol 2007;79:843–51. [37] Khananurak K, Vutithanachot V, Simakachorn N, Theamboonlers A, Chongsrisawat V, Poovorawan Y. Prevalence and phylogenetic analysis of rotavirus genotypes in Thailand between 2007 and 2009. Infect Genet Evol 2010;10:537–45. [38] Ch’ng LS, Lee WS, Kirkwood CD. Rare rotavirus strains in children with severe diarrhea, Malaysia. Emerg Infect Dis 2011;17:948–50. [39] Wang YH, Pang BB, Zhou X, Ghosh S, Tang WF, Peng JS, et al. Complex evolutionary patterns of two rare human G3P[9] rotavirus strains possessing a feline/canine-like H6 genotype on an AU-1-like genotype constellation. Infect Genet Evol 2013;16:103–12. [40] Phan TG, Trinh QD, Khamrin P, Kaneshi K, Ueda Y, Nakaya S, et al. Emergence of new variant rotavirus G3 among infants and children with acute gastroenteritis in Japan during 2003–2004. Clin Lab 2007;53:41–8. [41] Mukherjee A, Mullick S, Kobayashi N, Chawla-Sarkar M. The first identification of rare human group A rotavirus strain G3P[10] with severe infantile diarrhea in eastern India. Infect Genet Evol 2012;12:1933–7. [42] Khamrin P, Maneekarn N, Peerakome S, Malasao R, Thongprachum A, ChanIt W, et al. Molecular characterization of VP4, VP6, VP7, NSP4, and NSP5/6 genes identifies an unusual G3P[10] human rotavirus strain. J Med Virol 2009;81:176–82. [43] Theamboonlers A, Bhattarakosol P, Chongsrisawat V, Sungkapalee T, Wutthirattanakowit N, Poovorawan Y. Molecular characterization of group A human rotaviruses in Bangkok and Buriram, Thailand during 2004-2006 reveals the predominance of G1P[8] G9P[8] and a rare G3P[19] strain. Virus Genes 2008;36:289–98. [44] Wu FT, Banyai K, Huang JC, Wu HS, Chang FY, Hsiung CA, et al. Human infection with novel G3P[25] rotavirus strain in Taiwan. Clin Microbiol Infect 2011;17:1570–3. [45] Mukherjee A, Ghosh S, Bagchi P, Dutta D, Chattopadhyay S, Kobayashi N, et al. Full genomic analyses of human rotavirus G4P[4], G4P[6] G9P[19] and G10P[6] strains from North-eastern India: evidence for interspecies transmission and complex reassortment events. Clin Microbiol Infect 2011;17:1343–6. [46] Gouvea V, de Castro L, Timenetsky MC, Greenberg H, Santos N. Rotavirus serotype G5 associated with diarrhea in Brazilian children. J Clin Microbiol 1994;32:1408–9. [47] Leite JP, Alfieri AA, Woods PA, Glass RI, Gentsch JR. Rotavirus G and P types circulating in Brazil: characterization by RT-PCR, probe hybridization, and sequence analysis. Arch Virol 1996;141:2365–74. [48] Bok K, Castagnaro N, Borsa A, Nates S, Espul C, Fay O, et al. Surveillance for rotavirus in Argentina. J Med Virol 2001;65:190–8. [49] Coluchi N, Munford V, Manzur J, Vazquez C, Escobar M, Weber E, et al. Detection, subgroup specificity, and genotype diversity of rotavirus strains in children with acute diarrhea in Paraguay. J Clin Microbiol 2002;40:1709–14. [50] Esona MD, Armah GE, Geyer A, Steele AD. Detection of an unusual human rotavirus strain with G5P[8] specificity in a Cameroonian child with diarrhea. J Clin Microbiol 2004;42:441–4. [51] Li DD, Duan ZJ, Zhang Q, Liu N, Xie ZP, Jiang B, et al. Molecular characterization of unusual human G5P[6] rotaviruses identified in China. J Clin Virol 2008;42:141–8. [52] Mladenova Z, Papp H, Lengyel G, Kisfali P, Steyer A, Steyer AF, et al. Detection of rare reassortant G5P[6] rotavirus Bulgaria. Infect Genet Evol 2012;12:1676–84. [53] Nordgren J, Nitiema LW, Sharma S, Ouermi D, Traore AS, Simpore J, et al. Emergence of unusual G6P[6] rotaviruses in children, Burkina Faso, 2009–2010. Emerg Infect Dis 2012;18:589–97. [54] Mullick S, Mukherjee A, Ghosh S, Pazhani GP, Sur D, Manna B, et al. Genomic analysis of human rotavirus strains G6P[14] and G11P[25] isolated from Kolkata in 2009 reveals interspecies transmission and complex reassortment events. Infect Genet Evol 2013;14:15–21. [55] Browning GF, Snodgrass DR, Nakagomi O, Kaga E, Sarasini A, Gerna G. Human and bovine serotype G8 rotaviruses may be derived by reassortment. Arch Virol 1992;125:121–8. [56] Todd S, Page NA, Duncan Steele A, Peenze I, Cunliffe NA. Rotavirus strain types circulating in Africa: review of studies published during 1997–2006. J Infect Dis 2010;202(Suppl):S34–42. [57] Iturriza-Gomara M, Dallman T, Banyai K, Bottiger B, Buesa J, Diedrich S, et al. Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network. Epidemiol Infect 2011;139:895–909. [58] Weinberg GA, Payne DC, Teel EN, Mijatovic-Rustempasic S, Bowen MD, Wikswo M, et al. First reports of human rotavirus G8P[4] gastroenteritis in the United States. J Clin Microbiol 2012;50:1118–21. [59] Mukherjee A, Mullick S, Deb AK, Panda S, Chawla-Sarkar M. First report of human rotavirus G8P[4] gastroenteritis in India: evidence of ruminants-tohuman zoonotic transmission. J Med Virol 2013;85:537–45. [60] Le VP, Kim JY, Cho SL, Nam SW, Lim I, Lee HJ, et al. Detection of unusual rotavirus genotypes G8P[8] and G12P[6] in South Korea. J Med Virol 2008;80:175–82.

3377

[61] Clark HF, Hoshino Y, Bell LM, Groff J, Hess G, Bachman P, et al. Rotavirus isolate WI61 representing a presumptive new human serotype. J Clin Microbiol 1987;25:1757–62. [62] Arista S, Vizzi E, Migliore MC, Di Rosa E, Cascio A. High incidence of G9P181 rotavirus infections in Italian children during the winter season 1999–2000. Eur J Epidemiol 2003;18:711–4. [63] Khamrin P, Peerakome S, Wongsawasdi L, Tonusin S, Sornchai P, Maneerat V, et al. Emergence of human G9 rotavirus with an exceptionally high frequency in children admitted to hospital with diarrhea in Chiang Mai, Thailand. J Med Virol 2006;78:273–80. [64] Ribas Mde L, Nagashima S, Calzado A, Acosta G, Tejero Y, Cordero Y, et al. Emergence of G9 as a predominant genotype of human rotaviruses in Cuba. J Med Virol 2011;83:738–44. [65] Esteban LE, Rota RP, Gentsch JR, Jiang B, Esona M, Glass RI, et al. Molecular epidemiology of group A rotavirus in Buenos Aires, Argentina 2004–2007: reemergence of G2P[4] and emergence of G9P[8] strains. J Med Virol 2010;82:1083–93. [66] Martella V, Terio V, Del Gaudio G, Gentile M, Fiorente P, Barbuti S, et al. Detection of the emerging rotavirus G9 serotype at high frequency in Italy. J Clin Microbiol 2003;41:3960–3. [67] Diez-Domingo J, Baldo JM, Patrzalek M, Pazdiora P, Forster J, Cantarutti L, et al. Primary care-based surveillance to estimate the burden of rotavirus gastroenteritis among children aged less than 5 years in six European countries. Eur J Pediatr 2011;170:213–22. [68] Mukherjee A, Dutta D, Ghosh S, Bagchi P, Chattopadhyay S, Nagashima S, et al. Full genomic analysis of a human group A rotavirus G9P[6] strain from Eastern India provides evidence for porcine-to-human interspecies transmission. Arch Virol 2009;154:733–46. [69] Zeller M, Heylen E, De Coster S, Van Ranst M, Matthijnssens J. Full genome characterization of a porcine-like human G9P[6] rotavirus strain isolated from an infant in Belgium. Infect Genet Evol 2012;12:1492–500. [70] Ghosh S, Urushibara N, Taniguchi K, Kobayashi N. Whole genomic analysis reveals the porcine origin of human G9P[19] rotavirus strains Mc323 and Mc345. Infect Genet Evol 2012;12:471–7. [71] Armah GE, Hoshino Y, Santos N, Binka F, Damanka S, Adjei R, et al. The global spread of rotavirus G10 strains: detection in Ghanaian children hospitalized with diarrhea. J Infect Dis 2010;202(Suppl):S231–8. [72] Ramani S, Iturriza-Gomara M, Jana AK, Kuruvilla KA, Gray JJ, Brown DW, et al. Whole genome characterization of reassortant G10P[11] strain (N155) from a neonate with symptomatic rotavirus infection: identification of genes of human and animal rotavirus origin. J Clin Virol 2009;45:237–44. [73] Esona MD, Banyai K, Foytich K, Freeman M, Mijatovic-Rustempasic S, Hull J, et al. Genomic characterization of human rotavirus G10 strains from the African Rotavirus Network: relationship to animal rotaviruses. Infect Genet Evol 2011;11:237–41. [74] Mukherjee A, Nayak MK, Roy T, Ghosh S, Naik TN, Kobayashi N, et al. Detection of human G10 rotavirus strains with similarity to bovine and bovine-like equine strains from untypable samples. Infect Genet Evol 2012;12:467–70. [75] Matsushima Y, Nakajima E, Nguyen TA, Shimizu H, Kano A, Ishimaru Y, et al. Genome sequence of an unusual human G10P[8] rotavirus detected in Vietnam. J Virol 2012;86:10236–7. [76] Rahman M, Matthijnssens J, Nahar S, Podder G, Sack DA, Azim T, et al. Characterization of a novel P[25],G11 human group a rotavirus. J Clin Microbiol 2005;43:3208–12. [77] Shim JO, Baek IH, Le VP, Ko EM, Seok WS, Uh Y, et al. Molecular characterization of rotavirus diarrhea among children in South Korea: detection of an unusual G11 strain. Arch Virol 2011;156:887–92. [78] Hong SK, Lee SG, Lee SA, Kang JH, Lee JH, Kim JH, et al. Characterization of a G11,P[4] strain of human rotavirus isolated in South Korea. J Clin Microbiol 2007;45:3759–61. [79] Taniguchi K, Urasawa T, Kobayashi N, Gorziglia M, Urasawa S. Nucleotide sequence of VP4 and VP7 genes of human rotaviruses with subgroup I specificity and long RNA pattern: implication for new G serotype specificity. J Virol 1990;64:5640–4. [80] Rahman M, Matthijnssens J, Yang X, Delbeke T, Arijs I, Taniguchi K, et al. Evolutionary history and global spread of the emerging g12 human rotaviruses. J Virol 2007;81:2382–90. [81] Kokkinos PA, Ziros PG, Monini M, Lampropoulou P, Karampini A, Papachatzi E, et al. Rare types of rotaviruses isolated from children with acute gastroenteritis in Patras, Greece. Intervirology 2013;56:237–41. [82] Castello AA, Nakagomi T, Nakagomi O, Jiang B, Kang JO, Glass RI, et al. Characterization of genotype P[9]G12 rotavirus strains from Argentina: high similarity with Japanese and Korean G12 strains. J Med Virol 2009;81:371–81. [83] Pongsuwanna Y, Guntapong R, Chiwakul M, Tacharoenmuang R, Onvimala N, Wakuda M, et al. Detection of a human rotavirus with G12 and P[9] specificity in Thailand. J Clin Microbiol 2002;40:1390–4. [84] Hull JJ, Teel EN, Kerin TK, Freeman MM, Esona MD, Gentsch JR, et al. United States rotavirus strain surveillance from 2005 to 2008: genotype prevalence before and after vaccine introduction. Pediatr Infect Dis J 2011;30: S42–7. [85] Australian Rotavirus Surveillance Program annual report, 2005/2006, 2006/2007, 2007/2008, 2008/2009, 2009/2010, 2010/2011. Communicable diseases intelligence quarterly report. 2006-2011. [86] Zeller M, Rahman M, Heylen E, De Coster S, De Vos S, Arijs I, et al. Rotavirus incidence and genotype distribution before and after national rotavirus vaccine introduction in Belgium. Vaccine 2010;28:7507–13.

3378

S. Jain et al. / Vaccine 32 (2014) 3367–3378

[87] Gentsch JR, Hull JJ, Teel EN, Kerin TK, Freeman MM, Esona MD, et al. G and P types of circulating rotavirus strains in the United States during 1996–2005: nine years of prevaccine data. J Infect Dis 2009;1:S99–105. [88] Leite JP, Carvalho-Costa FA, Linhares AC. Group A rotavirus genotypes and the ongoing Brazilian experience: a review. Mem Inst Oswaldo Cruz 2008;103:745–53. [89] Carvalho-Costa FA, Volotao Ede M, de Assis RM, Fialho AM, de Andrade Jda S, Rocha LN, et al. Laboratory-based rotavirus surveillance during the introduction of a vaccination program Brazil, 2005–2009. Pediatr Infect Dis J 2011:30. [90] Weinberg GA, Teel EN, Mijatovic-Rustempasic S, Payne DC, Roy S, Foytich K, et al. Detection of novel rotavirus strain by vaccine postlicensure surveillance. Emerg Infect Dis 2013;19:1321–3.

[91] Kirkwood CD, Boniface K, Barnes GL, Bishop RF. Distribution of rotavirus genotypes after introduction of rotavirus vaccines Rotarix(R) and RotaTeq(R), into the National Immunization Program of Australia. Pediatr Infect Dis J 2011;30:S48–53. [92] Gurgel RQ, Cuevas LE, Vieira SC, Barros VC, Fontes PB, Salustino EF, et al. Predominance of rotavirus P[4]G2 in a vaccinated population Brazil. Emerg Infect Dis 2007;13:1571–3. [93] Quaye O, McDonald S, Esona MD, Lyde FC, Mijatovic-Rustempasic S, Roy S, et al. Rotavirus G9P[4] in 3 countries in Latin America, 2009–2010. Emerg Infect Dis 2013;19:1332–3.