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review article

Indian Pediatr 2016;53: 607-617

Burden of Rotavirus Diarrhea in Under-five Indian Children

 

Ashok Kumar, Sriparna Basu, *Vipin Vashishtha and *†Panna Choudhury

From the Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India and *Indian Academy of Pediatrics, Kailash Darshan, Kennedy Bridge, Mumbai, India.†Deceased.

Correspondence to: Professor Ashok Kumar, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
Email: [email protected]
 

 


Need and purpose:
Rotavirus is the most common cause of severe diarrhea in infants and young children worldwide. The burden of rotavirus diarrhea in Indian children is not well established. The present study reviewed the epidemiology of rotavirus diarrhea in hospitalized children and in the community, molecular serotyping and under-five mortality caused by rotavirus diarrhea. Methods: Publications, reporting rotavirus diarrhea in Indian children, were retrieved through a systematic search of databases including Medline, PubMed, IndMed, websites of WHO, UNICEF, National Family Health Survey, Ministry of Health and Family Welfare, and Government of India. ‘Human’ studies in ‘English’ language were included. Age group selected was 0 month to 5 years. No restrictions were applied in terms of study design and time frame. Conclusions: Stool sample positivity varied from 4.6% in Kolkata to 89.8% in Manipur, among hospitalized children, and from 4% in Delhi to 33.7% in Manipur in community. Most cases of rotavirus diarrhea in India are caused by G1, G2, and G untypeable strains with distinct regional variations. Rotavirus was identified as an etiological agent in 5.2 to 80.5% cases of nosocomial diarrhea. Data are lacking for rotavirus mortality.

Keywords: Burden, Community, Epidemiology, Gastroenteritis, Incidence, Prevalence, Systematic review.


Rotavirus is the most common cause of severe diarrhea in infants and young children worldwide. It is estimated to be responsible for 611,000 annual childhood deaths globally [1], and another 2 million hospitalizations every year [2]. More than 80% of these deaths occur in low-income countries [1-3]. It is estimated that India spends approximately Rs. 2.0-3.4 billion (US$ 41-72 million) [4] annually for the treatment of rotavirus diarrhea in children <5 years of age.

Rotaviruses are double stranded RNA viruses within the family Reoviridae. The primary mode of transmission is via the fecal-oral route with symptoms typically developing after an incubation period of one to two days. Majority of children become infected with rotavirus within the first three years of life, with a peak incidence of rotavirus diarrhea between 6 to 24 months [5]. Previous infection offers protection from subsequent illnesses. However, re-infections are frequent but subsequent illnesses tend to be less severe [6].

Laboratory procedures for diagnosis of rotavirus include electron microscopy (EM), passive latex agglutination assays (LA), electropherotyping using polyacylamide gel electrophoresis (PAGE), enzyme-linked immunosorbent assays (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) [7]. ELISA is the method of choice for routine screening. For genotyping, newer methods like multiplex RT-PCR based genotyping, hybridization assays and nucleotide sequencing are used. Rotaviruses are classified into seven different groups (A-G), of which groups A, B and C are known to infect humans. Severe, life-threatening disease in children worldwide is caused predominantly by group A rotaviruses. Rotavirus strains are further subtyped based on the proteins of the outer capsid eliciting neutralizing antibodies, VP7 (G serotypes) and VP4 (P serotypes). Till date, at least 15 G genotypes and 25 P genotypes have been identified [8].

Considering the high burden of the disease, there is a need to summarize and critically evaluate all available information related to rotavirus diarrhea in India. The present review was done to estimate the burden of rotavirus diarrhea in under-five Indian children in the community and hospital settings.

Methods

The primary research question was ‘epidemiology of rotavirus diarrhea in under-five children of India’ which was further subcategorized into (i) epidemiology of rotavirus diarrhea in hospitalized children from different parts of India; (ii) epidemiology of rotavirus diarrhea in community from different parts of India; (iii) demographic profile of rotavirus diarrhea (iv) identification of molecular epidemiology of rotavirus diarrhea from different parts of India; (v) incidence of rotavirus infection as a cause of nosocomial diarrhea; and (vi) mortality from rotavirus diarrhea.

The primary databases searched were Medline through PubMed (www.pubmed.com) and IndMed (http://indmed.nic.in/). Other sources included online reports from the websites of World Health Organization (WHO) (www.who.int), documents of the UNICEF (www.unicef.org/india/), National Family Health Survey (http://www.nfhsindia.org/), and documents of the Ministry of Health and Family Welfare, Government of India (www.mohfw.nic.in). The related articles and the reference lists of included publications were also searched to identify additional studies.

All types of publications available in scientific public domain and reporting on rotavirus infection in India were included. No particular time frame was set. Our search was limited to ‘humans’, children (0 month to 5 years) and articles published in ‘English’ language. For searching PubMed, we followed a standard search methodology [9]. A search string was devised by converting each research question into problem, intervention, comparison, outcome (PICO) format. MeSH headings were looked for the research theme in question and added to the PubMed search builder. Salient keywords were included during search. A search for MeSH headings for ‘rotavirus’, revealed ‘rotavirus, infections’, which was relevant and yielded 31 subheadings from which we selected ‘rotavirus diarrhea’, ‘rotavirus gastroenteritis’, and ‘rotavirus disease’. For assessing the epidemiology of rotavirus diarrhea in India, we searched PubMed using the search string: "(epidemiology* OR burden OR morbidity OR mortality or incidence OR prevalence OR profile) AND (rotavirus OR rotavirus diarrhea OR rotavirus gastroenteritis OR rotavirus disease) AND India. For the subcategories, an additional search was made by combining keywords/MeSH terms using the search string "(*) AND (rotavirus, infections) AND India", where the asterisk represented the MeSH term/keywords for the subcategories. To search IndMed, the search string was kept simple using search keywords. The search date, search terms, search string and search output were recorded and saved. In the next step, we scrutinized all titles and excluded the titles which were not relevant; the remaining articles were studied further. The next step involved examination of the abstract or the introduction (where the abstract was not published) of the short-listed titles; the ones which were not found relevant were excluded and the remaining articles were processed further. In the next step examination of full-text articles was done. Related articles and cross-references in identified articles were also reviewed and similar steps were performed before short listing the cross-references.

Results

Initial search in PubMed (initially accessed on 19th August 2013 and updated on 1st March 2014) using ‘rotavirus’ yielded 4173 articles. While searching, filters activated were: Humans, English, Newborn: 0-1 month, Infant: 1-23 months, Preschool Child: 2-5 years. Search with ‘rotavirus diarrhea’ yielded 2241 articles and search with ‘rotavirus gastroenteritis’ yielded 2013 articles. Details of search strings and yield of articles have been summarized in Web Table I.

Burden of Rotavirus Diarrhea in Hospitalized Children

A total of 54 studies [8,10-62], carried out using samples obtained from under-five Indian children hospitalized with rotavirus diarrhea were included (Table I). There was large variability in sample size ranging from 39 [33] to 3064 [31]. Maximum number of studies (19) was carried in Northern India. The range of stool positivity for rotavirus was widely distributed, varying from 4.6% in Kolkata [38] to 89.8% in Manipur [35]. Most of the studies used ELISA/PAGE for the screening of rotavirus although latex agglutination assay, immunoblot and electron microscopy were also used in a limited number of studies.

TABLE I Rotavirus Positivity in Children Hospitalized with Diarrhea from Different Parts of India
Reference Place of study Study period Age group Detection Stool samples Positive, 
(year) (year) method collected n (%)
Northern India
Samantaray, et al.[10] Delhi 1980-1981 <5 ELISA 99 32 (32.3)
Broor, et al.[11] Chandigarh 1982-1983 <5 ELISA 242 44 (18.2)
Singh, et al.[12] Chandigarh 1982 - 1985 <5 ELISA 694 111 (15.9)
Ram, et al.[13] Chandigarh 1984-1987 <3 ELISA 1024 120 (11.72)
Aggarwal, et al [14] Delhi 1985 <5 ELISA 256 19(7.4)
Chakravarthi, et al.[15] Delhi 1987 - 1989 <5 ELISA 978 176 (18.0)
Chakravarti, et al.[16] Delhi 1987 - 1988 <5 ELISA 288 44 (15.3)
Broor, et al.[17] Delhi 1988 - 1990 <5 ELISA 990 104 (10.5)
Patwari, et al.[18] Delhi 1989 - 1990 <3 Immunodot 400 23 (6.0)
Chatterjee, et al.[8] Delhi 1990 <5 ELISA 157 71 (45.0)
Husain, et al.[19] Delhi 1990 - 1991 <5 ELISA/PAGE 450 60 (13.3)
Sharma, et al.[20] Northern India Not mentioned Not mentioned ELISA 172 32 (19.0)
Chakravarti, et al.[21] Delhi 1998 - 2000 <5 ELISA/PAGE 1172 158 (13.5)
Chakravarti, et al.[22] Delhi 1998 - 2000 <3 ELISA/PAGE 560 100 (17.8)
Bahl, et al.[23] Delhi 2000 - 2001 <5 ELISA 584 137 (23.5)
Nag, et al.[24] Lucknow 2003-2004 <2 ELISA/PAGE 90 14(15.6)
Chakravarti, et al.[25] Delhi 2005 - 2007 <2 ELISA 862 318(36.9)
Mishra, et al.[26] Lucknow 2004 - 2008 <3 ELISA 412 79 (19.2)
Gazal, et al. [27] Jammu & Kashmir Not mentioned <5 PAGE 210 88 (41.9)
Western India
Desai, et al.[28] Mumbai 1984 - 1986 Not mentioned LA /EM / ELISA 273 63 (21.0)
Kelkar, et al.[29] Pune   1990 - 1993 Not mentioned ELISA 722 188 (26.0)
Kelkar, et al.[30] Pune   1992 - 1996 <5 ELISA 945 266 (28.2)
Kelkar, et al.[31] Pune 1990-1997 <5 ELISA 3064 432 (14.1)
Kelkar, et al.[32] Pune 1993-1996 <5 ELISA 628 177 (28.3)
Kelkar, et al.[33] Thane 2000-2001 <5 ELISA 39 27 (69.2)
Borade, et al.[34] Pune 2009-2010 (?) <5 ELISA 246 88 (35.8)
Eastern India
Sengupta, et al.[35] Manipur 1979 Not mentioned ELISA 59 53 (89.8)
Saha, et al.[36] Kolkata 1979-1981 <12 ELISA 245 55 (22.4)
Sen, et al.[37] Kolkata 1979-1981 Not mentioned ELISA 356 27 (7.6)
Ghosh, et al.[38] Kolkata 1986-1988 <6 months ELISA 218 10 (4.6)
Phukan, et al.[39] Dibrugarh   1999 - 2000 <5 ELISA 202 47 (23.3)
Samajdar, et al.[40] Kolkata & Berhampur 2003-2005 <4 ELISA 545 198 (36.3)
Samajdar, et al.[41] Kolkata 2005 - 2006 <4 ELISA 668 249 (37.3)
Nair, et al.[42] Kolkata 2007-2009 <5 Not mentioned 648 312 (48.1)
Mukherjee, et al.[43] Manipur 2005 - 2008 <5 ELISA 489 244 (49.9)
Southern India
Paniker, et al.[44] Calicut 1976-1978 <5 EM 3355 368 (70.7)
Mathew, et al.[45] Kerala Not mentioned <5 ELISA 1827 648 (35.9)
Aijaz, et al.[46] Bangalore   1988 - 1994 Not mentioned PAGE 694 150 (21.6)
Aijaz, et al.[46] Mysore   1993 - 1994 Not mentioned PAGE 447 50 (11.2)
Ananthan, et al.[47] Chennai   1997 - 1999 0 - 2, >2 ELISA 245 51 (20.8)
Saravanan, et al.[48] Chennai   1995 - 1999 <3 ELISA/PAGE 745 168 (22.6)
Anand, et al.[49] Hyderabad 1998 - 1999 <2 PAGE 352 57 (16.2)
Shetty, et al.[50] Karnataka Not mentioned <5 LA 106 19 (18)
Ballal, et al.[51] Karnataka 1995-2000 <5 LA 780 40 (19.9)
Anand, et al.[52] Tirupati   1991 <2 ELISA 170 40 (23.5)
Kang, et al.[53] Vellore   1995 - 1998 <5 ELISA / LA 602 126 (20.9)
Banerjee, et al.[54] Vellore   2002 - 2004 <5 ELISA/ LA 343 94 (27.1)
Sowmyanarayanan, et al.[55] Vellore 2005-2008 <5 EIA/PCR 1001 354 (35.4)
Multiple locations            
Ramachandran, et al.[56] Multiple 1 1993 6 mo to <5 yr ELISA 458 63 (13.7)
Jain, et al.[57] Multiple 2 1996 - 1998 <5 ELISA 1502 313 (20.8)
Kang, et al.[58] Multiple 3 1998 - 1999 <5 LA /EM / ELISA 365 82 (22.5)
Das, et al.[59] Multiple 4a 1998 - 2000 <4 PAGE 406 141 (34.7)
Das, et al.[60] Multiple 5 2001 <4/allb PAGE 454 161 (35.4)
Kang, et al.[61] Multiple 6 2005 - 2007 <5 RT-PCR 4243 1405 (39.2)
Kang, et al.[62] Multiple 7 2005 - 2009 <5 RT-PCR 7285 2899 (40)
LA, latex agglutination; EM, electron microscopy; PAGE, polyacrylamide gel electrophoresis; ELISA, enzyme linked immunosorbent assay; Multiple 1: Shimla, Lucknow, Bhopal, Nagpur, Davengere; Multiple 2: Shimla, Lucknow, Bhopal, Nagpur, Davengere, Delhi, Hyderabad; Multiple 3: Vellore, Mysore, Jalandhar, Yamunagar; Multiple 4: Kolkata, Imphal, aData on disease burden from Kolkata only; Multiple 5: Kolkata, Dibrugarh, Bhuvaneshwar, Chandigarh; b<4/all: Samples collected from two groups: children <4 yr, patients of all age groups.

Kelkar, et al.[33] investigated an epidemic of diarrhea in Jawhar, a tribal area of Thane district, Maharashtra. Within a period of approximately 2 months, 490 cases of acute diarrhea were reported among children under-five years of age, with a case fatality rate of 0.40%. Twenty-seven out of 39 (69.2%) rectal swabs/fecal specimens obtained from hospitalized children up to 2 years of age were positive by ELISA for rotavirus.

Burden of Rotavirus Diarrhea in the Community

A total of 16 studies [3,10,54,63-75], carried out using samples obtained from under-five Indian children in community with rotavirus diarrhea were included (Table II). Stool sample positivity varied from 4% in Delhi [64] to 33.7% in Manipur [73].

TABLE II Burden of Rotavirus Diarrhea in the Community from Different Parts of India
Reference Place of study Community Study period Age (y) Detection Diarrhea Sample Positive, n (%)
    method   size (n)  
Northern India
Samantaray, et al [10]  Delhi Semi urban 1980-1981 <5 ELISA Yes 212 45 (21.2)
No 82 2 (2.4)
Panigrahi, et al [66] Northern India Urban/rural 1982 - 1983 <5 ELISA Yes 105 44 (29.3)
No 350 43 (12.3)
Malik, et al [67] Aligarh Semi urban 1982-1983 <5 ELISA Yes 216 40 (18.5)
No 216 1 (0.05)
Bhan, et al [63] Delhi Semi urban 1985-1986 <5 ELISA Yes 204 42 (20.6)
No 98 2 (2.0)
Raj, et al [64] Delhi Semi urban 1985-1986 <3 ELISA Yes 346 14 (4.0)
No 211 14 (6.6)
Bhan, et al [65] Delhi Urban/rural 1985 <5 ELISA Urban 6 (1.9)
Yes 330 50 (15.2)
No 319 6 (1.9)
Rural  
Yes  340 56 (16.5)
No 315 9 (2.9)
Yachha, et al [68] Chandigarh Urban/ 1988 - 1991 <5 ELISA Yes 218 25 (11.5) rural-14
peri-urban/   periurban-7;
  rural   urban -4
Nath, et al [69] Varanasi Urban 1988 - 1989 <5 LA Yes 376 67 (17.7)
No 299 12 (4)
Nath, et al [70] Varanasi Urban 1988 - 1989 <5 LA Yes 607 100 (16.4)
Western India                
Desai, et al [71] Mumbai Urban 1984-1986 <5 EM/LA Yes 273 63 (23)
/ELISA No 273 3 (1.1)
Kelkar, et al [72] Pune 1993 - 1996 <5 ELISA Yes 489 76 (15.5)
Eastern India
Krishnan, et al [73] Manipur Urban/Semi 1989-1992 <5 ELISA Yes 787 265 (33.7)
urban No 457 22 (4.8)
Southern India
Maiya, et al [74] Vellore* Urban 1974-1975 <2 EM Yes 50 13 (26)
No 30 0 (0)
Mathew, et al [75] Vellore Urban, 1983-1985 <3 EM Yes 916 95 (10.4)
periurban, rural No 587 5 (0.9)
Banerjee, et al [54] Vellore Urban 2002 - 2004 <5 ELISA Yes 1152 82 (7.1)
Gladstone, et al.[3] Vellore Urban 2002 - 2004 <5 ELISA/PCR Yes 1103 535 (48.5)
*Both hospital and community; NK, not known; EM, electron microscopy; LA, latex agglutination; ELISA, enzyme linked immunosorbent assay.

Demographic profile of Rotavirus Diarrhea

Demographic profile of rotavirus diarrhea has been summarized in Table III. A total of 27 studies [10,11,13,18,24,31,33-37,44,47,48,50-55,61,64-70] could be identified which described signs and symptoms of rotavirus diarrhea both in hospitalized children and in children from the community. Rotavirus infection is most common below 2 years of age, 7-12 months being the most commonly affected age group. Maximum infection occurs in winter months, from October-February.

TABLE III  Demographic Profile of Rotavirus Diarrhea 
Reference Study location Place of study Peak age incidence (%) Gender affected Peak season
Samantaray, et al.[10] Delhi Hospital 0-6 mo M:F=26:19 October - June
Broor, et al.[11] Chandigarh Hospital 7-12 mo Not mentioned Not mentioned
Ram, et al.[13] Chandigarh Hospital 10-12 mo M:F=3:1 November
Patwari, et al.[18] Delhi Hospital 7-12 mo M:F=256:144 February-April
Yachha, et al. [68] Chandigarh Community 6-11 mo Not mentioned November-February
Panigrahi, et al. [66] North India Community 37-60 mo Not mentioned April-June
Malik, et al. [67] Aligarh Community <1 yr M=F January-March
Bhan, et al .[65] Delhi Community 0-6 mo Not mentioned Not mentioned
Raj, et al. [64] Delhi Community 13-24 mo Not mentioned October - December
Nag, et al.[24] Lucknow Hospital 6-12 mo M:F=2.5:1 Not mentioned
Nath, et al .[69] Varanasi Community <2 yr F>M November - February
Kelkar, et al.[31] Pune  Hospital 6-12 mo (64.7) M>F Winter
Borade, et al.[34] Pune Hospital 11-20 mo M=F December - January
Kelkar, et al.[33] Thane Hospital 6-12 mo M>F Not mentioned
Saha, et al.[36] Kolkata Hospital 6-12 mo M=F January
Sen, et al.[37] Kolkata Hospital <2 yr (25) Not mentioned Not mentioned
Sengupta, et al.[35] Manipur Hospital Not mentioned M:F=1.9:1 November
Ananthan, et al.[47] Chennai Hospital 7-12 mo (28.7) Not mentioned Not mentioned
Saravanan, et al.[48] Chennai Hospital 7-12 mo (62.5) M:F=93:75 Sept-Feb
Shetty, et al.[50] Karnataka Hospital <2 yr-59(56) Not mentioned Winter (Dec-Feb)
Ballal, et al.[51] Karnataka Hospital 7-12 (65) Not mentioned Not mentioned
Anand, et al.[52] Tirupati   Hospital 7-12 mo M>F Not mentioned
Kang, et al.[53] Vellore Hospital Mean age 19.5 mo Not mentioned Not mentioned
Banerjee, et al. [54] Vellore Hospital Not mentioned Not mentioned December-January
Sowmyanarayanan, et al.[55] Vellore Hospital 6-12 mo M:F=75:51 January-February
Paniker, et al.[44] Calicut Hospital 6-23 mo M=F November -January
Kang, et al.[61] Multiple locations Hospital Mean age 12.9±9.0mo M>F Not mentioned

Rotavirus Serotypes

A total of 50 studies [3,19,22,23,25-30,32,40,41,44-48,76-95] could be identified which dealt with serotyping of rotavirus, of which G and P typing were done in 44 studies. Details of studies have been summarized in Web Tables II, III and IV.

Overall, G1 was the most common serotype isolated in Indian studies, followed by G2 and G-untypeable. On regional distribution, in Northern India, G1 was the most common serotype isolated, followed by G2, G-untypeable and G9. In Western India, G2 was predominant, closely followed by G-untypeable and G1. In Eastern India, G1 was commonest followed by G2. In Southern India, G1 was predominant, followed by G2 and G-untypeable. In P serotyping, P[4] was most prevalent all over India, followed by P[6] and P Untypeable/others. In Northern India, P[6] was most common, followed by P[4].

In the study of Kelkar, et al. [95], about 10% of stool specimen showed multireactivity in enzyme immunoassay with monoclonal antibodies specific for serotypes G1-4, 6, 8, and 10. The isolates were more close to G6 RF strain, which is a bovine rotavirus and is the first report of isolation of bovine serotype, G6 from India. Tran, et al. [96] provided evidence for the formation of the G3P[4] strain through genetic reassortment in which a G2P[4] strain with a typical DS-1 genogroup background acquired the VP7 gene from a co-circulating G3 human rotavirus strain.

Nosocomial Rotavirus Infections

Five studies were identified which dealt with nosocomial rotavirus infection, one in Delhi [97], two studies in Kolkata [98,99], and two in Vellore [100,101]. Details of the studies have been discussed in Table IV. Stool positivity for Rotavirus varied from 5.2% in Vellore [101] to 80.5% in Kolkata [98].

TABLE IV  Nosocomial Rotavirus Infections
Reference Placeof study Study period Age group No. of hospitalized Nosocomial Rotavirus positive,
(year) (years) children (n) diarrhea (n) n (%)
Uppal, et al. [97] Delhi Not mentioned Children 75 30 5 (16.7)
Dutta, et al. [98] Kolkata 1985 - 1986 <12 189 36 29 (80.5)
Dutta, et al. [99] Kolkata 1987 <5 3138 320 15 (8.4)
Desikan, et al.[100] Vellore 1990 - 1991 <3 194 39 13 (6.7)
Kamalaratnam, et al.[101] Vellore 1990 - 1991 <3 214 41 13 (5.2)

Rotavirus Diarrhea in Neonates

In hospitalized neonates, the prevalence of neonatal infection varies from 22-73% in India [102-106], though the infection remains asymptomatic in 69-95% [102,105-107]. Viral excretion begins as early as 2 days of age, peaking around 3-6 days and resolves by 2 weeks. The chance of acquiring an infection is inversely proportional to the length of hospital stay [102,105,107]. In two reports, neonatal infections are found to confer protection against future rotavirus diarrhea. Bhan, et al. [105] reported 46% fewer episodes of rotavirus diarrhea and 22% fewer episodes of all-cause diarrhea in the first year of life following neonatal rotavirus infections, whereas Vethanayagam, et al. [104] documented 37% less chance of infection after neonatal rotavirus diarrhea. However, a larger study from Vellore [106] did not find any association between neonatal infection and subsequent rotavirus diarrhea.

Strains responsible for neonatal infections included G9P[11], G10P[11], and G12P[6] in most studies [102-104,108,109]. Some of these strains were found to have genetic homology with non-human rotavirus, suggesting a role of human and animal reassortant viruses in neonatal infections [40,102,104,108].

Rotavirus Mortality

As per current global estimate, worldwide, each year, rotavirus related diarrhea results in 453 000 deaths (95% CI 420 000,494 000) in children younger than 5 years, accounting for 37% of diarrhea-related deaths and 5% of all deaths in this age group. The greatest proportion of these deaths is estimated to be contributed by India (98621, 22%) [110]. Child Health Epidemiology Reference Group of WHO and UNICEF documented an overall decline in the mortality of under-five children by only 14%, from 527,000 in 2004 to 453,000 in 2008 [111,112].

Discussion

In this review, we have examined the epidemiology of rotavirus diarrhea in under-five children of India both in hospitalized children and in children from the community. Overall, stool positivity for rotavirus was higher in hospitalized children than in community. Highest percentage of stool positivity was reported from North-Eastern India, both in hospital and community setting. This shows greater geographical burden of rotavirus diarrhea in this part of India.

In the present review, the average incidence of stool positivity for rotavirus in hospitalized children with diarrhea is found to be higher than previous ones. Earlier, Jain, et al [89] reviewed the epidemiology of rotavirus in India from 30 studies conducted between 1976 and 1997 from a total patient population of 12,164 children. Rotavirus was detected in 15-23% of patients hospitalized for severe diarrhea. In a later report, the proportion of diarrhea hospitalizations attributable to rotavirus appeared to have increased between 2000 and 2004, from 22% (range 17%-28%) to 39% (range 29%-45%) [113]. In the review of Ramani, et al. [114], a total of 29 studies carried out using samples obtained from 22 Indian cities in hospitalized children with diarrhea. A total of 15,476 samples were tested. Rates of rotavirus positivity ranged from 6-45%. The possible reasons could be either true increase in the incidence of rotavirus diarrhea compared to other etiological agents or an increase in the awareness of parents seeking early hospitalization. It can also be secondary to better diagnostic facilities in health care set ups. The authors explained this phenomenon by a relatively slower rate of decrease in hospitalizations for rotavirus compared with other causes of severe childhood diarrhea.

Two studies from Delhi reported 0-6 months as the most common age group [13,63]. On the other hand, Panigrahi, et al. [66], from Northern India reported a higher age group of 37-60 months. Some studies in India have found no association between rotavirus infection and time of year [8,18], though most have observed an increase in rotavirus-associated diarrhea during the winter months, October to February. Jain, et al. [89] found that rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between the ages of 1 to 2 years (20%), and children <7 months of age (13%).

G1 was the most commonly isolated serotype in Indian studies, followed by G2 and G-untypeable. On regional distribution, in northern India, G1 was the most common serotype isolated, followed by G2, G-untypeable and G9. In Western India, G2 was predominant, closely followed by G-untypeable and G1. In Eastern India, G1 was detected most commonly, followed by G2. In Southern India, G1 was predominant, followed by G2 and G-untypeable. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains [23].

In P serotyping, P[6] was most common in northern India, followed by P[4]. In western and eastern India, prevalence of P[4] was higher than other P serotypes. In southern India, untypeable P type was most commonly documented, closely followed by P[8]. P[4] was documented in lesser number of children. Several studies have also reported different G-P combinations [19,21,26,40,78]. Presence of nontypeable strains also posed a significant diagnostic challenge [29]. Emergence of G9 and G12 as important strains of rotavirus has been reported by several authors [40,43,57,59].

Very few studies examined the impact of rotavirus diarrhea in under-five mortality in India. Most of the data of rotavirus mortality are not direct; only estimated figures have been projected. World Health Organization estimates that globally 453000 (420 000 - 494 000) child deaths occurred during 2008 due to rotavirus infection [115].

The major limitation of this review was that we did not evaluate the quality of included studies, and a fomal meta-analysis was not carried out. Moreover, studies had marked heterogencity in terms of selection of patients/samples, method of diagnosis for rotavirus positivity, and molecular characterization. Moreover, some other studies may have been published since the last date of search of this review.

In conclusion, rotavirus diarrhea is a significant health problem in under-five children of India both in hospital and community setting. The prevalence of infection is not uniform, varying widely from region-to-region and state-to-state. Most of the studies are confined to few places, and sample size differed widely in individual studies. Different methodologies are employed for virus detection in different studies. Moreover, there is lack of data from many geographical locations, especially Central India, where the burden of diarrheal disease is particularly heavy.

Contributors: AK, SB: conceptualized the review and formulated the search methodology; AK, SB: jointly searched the literature; SB: drafted the initial manuscript; AK, SB, VMV, PC: helped in preparation of draft, gave critical inputs and approved the final manuscript; AK: will act as the guarantor of the review.

Funding: Indian Academy of Pediatrics; Competing interests: None stated.

References

1. Taneja DK, Malik A. Burden of rotavirus in India—Is rotavirus vaccine an answer to it? Indian J Public Health. 2012;56:17-21.

2. Simpson E, Wittet S, Bonilla J, Gamazina K, Cooley L, Winkler JL. Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries. BMC Public Health. 2007;7:281.

3. Gladstone BP, Ramani S, Mukhopadhya I, Muliyil J, Sarkar R, Rehman AM, et al. Protective effect of natural rotavirus infection in an Indian birth cohort. N Engl J Med. 2011;365:337-46.

4. Tate JE, Chitambar S, Esposito DH, Sarkar R, Gladstone B, Ramani S, et al. Disease and economic burden of rotavirus diarrhoea in India. Vaccine. 2009;27:F18-24.

5. Linhares AC, Velázquez FR, Pérez-Schael I, Sáez-Llorens X, Abate H, Espinoza F, et al. Human Rotavirus Vaccine Study Group. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet. 2008;371:1181-9.

6. Velazquez FR, Matson DO, Calva JJ, Guerrero ML, Morrow AL, Campbell SC, et al. Rotavirus infection in infants as protection against subsequent infections. N Engl J Med. 1996;335:1022-8.

7. Chatterjee B, Husain M, Kavita, Seth P, Broor S. Diversity of rotavirus strains infecting pediatric patients in New Delhi, India. J Trop Pediatr. 1996;42:207-10.

8. Greenberg HB, Flores J, Kalica AR, Wyatt RG, Jones R. Gene coding assignments for growth restriction, neutralization and subgroup specificities of the W and DS-1 strains of human rotavirus. J Gen Virol. 1983;64:313-20.

9. Haidich AB. Meta-analysis in medical research. Hippokratia. 2010;14:29-37.

10. Samantaray JC, Mohapatra LN, Bhan MK, Arora NK, Deb M, Ghai OP, et al. Study of rotavirus diarrhea in a north Indian community. Indian Pediatr. 1982;19:761-5.

11. Broor S, Singh V, Venkateshwarlu, Gautam S, Mehta S, Mehta SK. Rotavirus diarrhoea in children in Chandigarh, India J Diarrhoeal Dis Res. 1985;3:158-61.

12. Singh V, Broor S, Mehta S, Mehta SK. Molecular epidemiology of human rotavirus infections in Chandigarh (India). Indian J Med Res. 1990;91:9-14.

13. Ram S, Khurana S, Khurana SB, Sharma S, Vadehra DV, Broor S. Bioecological factors and rotavirus diarrhoea. Indian J Med Res. 1990;91:167-70.

14. Aggarwal P, Singh M, Guha DK. Prevalence of bacterial pathogens and rotavirus in hospitalised children with acute diarrhoea in Delhi, India. J Diarrhoeal Dis Res. 1988; 6:37-8.

15. Chakravarthi A, Broor S, Natarajan R. Epidemiological and clinical characteristics of acute diarrhea in children due to human rotavirus. J Trop Pediatr. 1992;38:192-3.

16. Chakravarti A, Kumar S, Mittal SK, Broor S. Clinical and epidemiological features of acute gastroenteritis caused by human rotavirus subgroups. J Diarrhoeal Dis Res. 1992;10:21-4.

17. Broor S, Husain M, Chatterjee B, Chakraborty A, Seth P. Temporal variation in the distribution of rotavirus electropherotypes in Delhi, India. J Diarrhoeal Dis Res. 1993;11:14-8.

18. Patwari AK, Srinivasan A, Diwan N, Aneja S, Anand VK, Peshin S. Rotavirus as an aetiological organism in acute watery diarrhoea in Delhi children: Reappraisal of clinical and epidemiological characteristics. J Trop Pediatr. 1994;40:214-8.

19. Husain M, Seth P, Dar L, Broor S. Classification of rotavirus into G and P types with specimens from children with acute diarrhea in New Delhi, India. J Clin Microbiol. 1996;34:1592-4.

20. Sharma P, Sehgal R, Ganguly NK, Vaidyanathan U, Walia BNS. Serogroups of rotavirus in north India. J Trop Pediatr. 1994;40:58-9.

21. Chakravarti A, Rawat D, Chakravarti A. Molecular epidemiology of rotavirus in Delhi. Indian J Pathol Microbiol. 2004;47:90-3.

22. Chakravarti A, Kumaria R, Chakravarti A. Prevalence of genotypes G1-G4 of human rotavirus in a hospital setting in New Delhi. Indian J Gastroenterol. 2005;24:127-8.

23. Bahl R, Ray P, Subodh S, Shambharkar P, Saxena M, Parashar U, et al. Delhi Rotavirus Study Group. Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of the infecting rotavirus strains. J Infect Dis. 2005;192:S114-9.

24. Nag VL, Khare V, Awasthi S, Agrawal SK. Clinical profile and prevalence of rotavirus infection in children presented with acute diarrhea at tertiary care referral hospital at northern part of India. J Commun Dis. 2009;41:183-8.

25. Chakravarti A, Chauhan MS, Sharma A, Verma V. Distribution of human rotavirus G and P genotypes in a hospital setting from Northern India. Southeast Asian J Trop Med Public Health. 2010;41:1145-52.

26. Mishra V, Awasthi S, Nag VL, Tandon R. Genomic diversity of group A rotavirus strains in patients aged 1-36 months admitted for acute watery diarrhoea in northern India: A hospital-based study. Clin Microbiol Infect. 2010;16:45-50.

27. Gazal S, Taku A, Bhat MA, Badroo G. Group A rotavirus and bacterial agents associated with diarrhoea-induced hospitalisations in children below 5 years of age in Jammu. Indian J Med Microbiol. 2014;32:57-59.

28. Desai HS, Banker DD. Rotavirus infection among children in Bombay. Indian J Med Sci. 1993;47:27-33.

29. Kelkar SD. Prevalence of human group A rotavirus serotypes in Pune, India (1990-1993). Indian J Med Res. 1997;106:508-12.

30. Kelkar SD, Purohit SG, Simha KV. Prevalence of rotavirus diarrhoea among hospitalized children in Pune, India. Indian J Med Res. 1999;109:131-5.

31. Kelkar SD, Ayachit VL. Circulation of group A rotavirus subgroups and serotypes in Pune, India, 1990-1997. J Health Popul Nutr. 2000;18:163-70.

32. Kelkar SD, Purohit SG, Boralkar AN, Verma SP. Prevalence of rotavirus diarrhea among outpatients and hospitalized patients: a comparison. Southeast Asian J Trop Med Public Health. 2001;32:494-9.

33. Kelkar SD, Ray PG, Shinde DN. An epidemic of rotavirus diarrhoea in Jawhar Taluk, Thane district, Maharashtra, India, December 2000-January 2001. Epidemiol Infect. 2004;132:337-41.

34. Borade A, Bais AS, Bapat V, Dhongade R. Characteristics of rotavirus gastroenteritis in hospitalized children in Pune. Indian J Med Sci. 2010;64:210-8.

35. Sengupta PG, Sen D, Saha MR, Niyogi S, Deb BC, Pal SC, et al. An epidemic of rotavirus diarrhoea in Manipur, India.Trans R Soc Trop Med Hyg. 1981;75:521-3.

36. Saha MR, Sen D, Datta P, Datta D, Pal SC. Role of rotavirus as the cause of acute paediatric diarrhoea in Calcutta. Trans R Soc Trop Med Hyg. 1984;78:818-20.

37. Sen D, Saha MR, Niyogi SK, Nair GB, De SP, Datta P, et al. Aetiological studies on hospital in-patients with acute diarrhoea in Calcutta. Trans R Soc Trop Med Hyg. 1983;77:212-4.

38. Ghosh AR, Nair GB, Dutta P, Pal SC, Sen D. Acute diarrhoeal diseases in infants aged below six months in hospital in Calcutta, India: an aetiological study. Trans R Soc Trop Med Hyg. 1991;85:796-8.

39. Phukan AC, Patgiri DK, Mahanta J. Rotavirus associated acute diarrhoea in hospitalized children in Dibrugarh, northeast India. Indian J Pathol Microbiol. 2003;46:274-8.

40. Samajdar S, Varghese V, Barman P, Ghosh S, Mitra U, Dutta P, et al. Changing pattern of human group A rotaviruses: emergence of G12 as an important pathogen among children in eastern India. J Clin Virol. 2006;36: 183-8.

41. Samajdar S, Ghosh S, Chawla-Sarkar M, Mitra U, Dutta P, Kobayashi N, et al. Increase in prevalence of human group A rotavirus G9 strains as an important VP7 genotype among children in eastern India. J Clin Virol. 2008;43: 334-9.

42. Nair GB, Ramamurthy T, Bhattacharya MK, Krishnan T, Ganguly S, Saha DR, et al. Emerging trends in the etiology of enteric pathogens as evidenced from an active surveillance of hospitalized diarrhoeal patients in Kolkata, India. Gut Pathog. 2010;2:4.

43. Mukherjee A, Chattopadhyay S, Bagchi P, Dutta D, Singh NB, Arora R, et al. Surveillance and molecular characterization of rotavirus strains circulating in Manipur, north-eastern India: increasing prevalence of emerging G12 strains. Infect Genet Evol. 2010;10:311-20.

44. Paniker CK, Mathew S, Mathan M. Rotavirus and acute diarrhoeal disease in children in a southern Indian coastal town.Bull World Health Organ. 1982;60:123-7.

45. Mathew MA, Paulose A, Chitralekha S, Nair MK, Kang G, Kilgore P. Prevalence of RotavirusDiarrhea among Hospitalized Under-five Children. Indian Pediatr. 2014;51:27-31.

46. Aijaz S, Gowda K, Jagannath HV, Reddy RR, Maiya PP, Ward RL, et al. Epidemiology of symptomatic human rotaviruses in Bangalore and Mysore, India, from 1988 to 1994 as determined by electropherotype, subgroup and serotype analysis. Arch Virol. 1996;141:715-26.

47. Ananthan S, Saravanan P. Genomic diversity of group A rotavirus RNA from children with acute diarrhoea in Chennai, south India. Indian J Med Res. 2000;111: 50-6.

48. Saravanan P, Ananthan S, Ananthasubramanium M. Rotavirus infection among infants and young children in Chennai, South India. Indian J Med Microbiol. 2004;22:212-21.

49. Anand T, Raju TA, Rao MV, Rao LV, Sharma G. Symptomatic human rotavirus subgroups, serotypes and electropherotypes in Hyderabad, India. Indian J Med Res. 2000;112:1-4.

50. Shetty M, Brown TA, Kotian M, Shivananda PG. Viral diarrhoea in a rural coastal region of Karnataka India. J Trop Pediatr. 1995;41:301-3.

51. Ballal M, Shivananda PG. Rotavirus and enteric pathogens in infantile diarrhoea in Manipal, South India. Indian J Pediatr. 2002;69:393-6.

52. Anand T, Lakshmi N, Kumar AG. Rotavirus diarrhea among infants and children at Tirupati. Indian Pediatr. 1994;31:46-8.

53. Kang G, Green J, Gallimore CI, Brown DWG. Molecular epidemiology of rotaviral infection in South Indian children with acute diarrhoea from 1995-1996 to 1998-1999. J Med Virol. 2002;67:101-5.

54. Banerjee I, Ramani S, Primrose B, Moses P, Iturriza-Gomara M, Gray J, et al. Comparative study of rotavirus epidemiology in children from a community based birth cohort and a tertiary hospital in south India. J Clin Microbiol. 2006;44:2468-74.

55. Sowmyanarayanan TV, Ramani S, Sarkar R, Arumugam R, Warier JP, Moses PD, et al. Severity of rotavirus gastroenteritis in Indian children requiring hospitalization. Vaccine. 2012;30:A167-72.

56. Ramachandran M, Das BK, Vij A, Kumar R, Bhambal SS, Kesari N, et al. Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol. 1996;34:436-9.

57. Jain V, Das BK, Bhan MK, Glass RI, Gentsch JR. Indian Strain Surveillance Collaborating Laboratories. Great diversity of group A rotavirus strains and high prevalence of mixed rotavirus infections in India. J Clin Microbiol. 2001;39:3524-9.

58. Kang G, Raman T, Green J, Gallimore CI, Brown DW. Distribution of rotavirus G and P types in north and south Indian children with acute diarrhoea in 1998-99. Trans R Soc Trop Med Hyg. 2001;95:491-2.

59. Das S, Sen A, Uma G, Varghese V, Chaudhuri S, Bhattacharya SK, et al. Genomic diversity of group A rotavirus strains infecting humans in eastern India. J Clin Microbiol. 2002;40:146-9.

60. Das S, Varghese V, Chaudhuri S, Barman P, Kojima K, Dutta P, et al. Genetic variability of human rotavirus strains isolated from Eastern and Northern India. J Med Virol. 2004;72:156-61.

61. Kang G, Arora R, Chitambar SD, Deshpande J, Gupte MD, Kulkarni M, et al. Multicenter, hospital-based surveillance of rotavirus disease and strains among Indian children aged <5 years. J Infect Dis. 2009;200:S147-53.

62. Kang G, Desai R, Arora R, Chitamabar S, Naik TN, Krishnan T, et al. Diversity of circulating rotavirus strains in children hospitalized with diarrhea in India, 2005-2009. Vaccine. 2013;31:2879-83.

63. Bhan MK, Kumar R, Khoshoo V, Arora NK, Raj P, Stintzing G, et al. Etiologic role of enterotoxigenic Escherichia coli and rotavirus in acute diarrhoea in Delhi children. Indian J Med Res. 1987;85:604-7.

64. Raj P, Bhan MK, PrasadAK, Kumar R, Bhandari N, Jayashree S. Electrophoretic study of the genome of human rotavirus in rural Indian community. Indian J Med Res. 1989;89:65-8.

65. Bhan MK, Raj P, Bhandari N, Svensson L, Stintzing G, Prasad AK, et al. Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis. Pediatr Infect Dis J. 1988;7:320-3.

66. Panigrahi D, Agarwal KC, Kaur T, Ayyagari A, Walia BN. A study of rotavirus diarrhoea in children in a north Indian community. J Diarrhoeal Dis Res. 1985;3:20-3.

67. Malik A, Rattan A, Malik MA, Shukla I. Rotavirus diarrhoea of infancy and childhood in a North Indian town–epidemiological aspects. J Trop Pediatr. 1987;33:243-5.

68. Yachha SK, Singh V, Kanwar SS, Mehta S. Epidemiology, subgroups and serotypes of rotavirus diarrhea in north Indian communities. Indian Pediatr. 1994;31:27-33.

69. Nath G, Singh SP, Sanyal SC. Childhood diarrhoea due to rotavirus in a community. Indian J Med Res. 1992;95: 259-62.

70. Nath G, Shukla BN, Reddy DC, Sanyal SC. A community study on the aetiology of childhood diarrhoea with special reference to Campylobacter jejuni in a semiurban slum of Varanasi, India J Diarrhoeal Dis Res. 1993;11:165-8.

71. Desai HS, Banker DD. Rotavirus infection among children in Bombay. Indian J Med Sci. 1993;4:27-33.

72. Kelkar SD, Purohit SG, Boralkar AN, Verma SP. Prevalence of rotavirus diarrhea among outpatients and hospitalized patients: a comparison. Southeast Asian J Trop Med Public Health. 2001;32:494-9.

73. Krishnan T, Burke B, Shen S, Naik TN, Desselberger U. Molecular epidemiology of human rotaviruses in Manipur: genome analysis of rotaviruses of long electropherotype and subgroup I. Arch Virol. 1994;134:279-92.

74. Maiya PP, Pereira SM, Mathan M, Bhat P, Albert MJ, Baker SJ. Aetiology of acute gastroenteritis in infancy and early childhood in southern India. Arch Dis Child. 1977;52:482-5.

75. Mathew M, Mathan MM, Mani K, George R, Jebakumar K, Dharamsi R, et al. The relationship of microbial pathogens to acute infectious diarrhoea of childhood.J Trop Med Hyg. 1991;94:253-60.

76. Reesu R, Bhattacharya D, Chaaithanya IK, Muruganandam N, Bharadwaj AP, Singhania M, et al. Emergence of an unusual genotype of rotavirus in andaman and nicobar islands, India. Intervirology. 2013;56:134-9.

77. Chakravarti A, Kumaria R, Chakravarti A. Prevalence of genotypes G1-G4 of human rotavirus in a hospital setting in New Delhi. Indian J Gastroenterol. 2005;24:127-8.

78. Sharma S, Ray P, Gentsch JR, Glass RI, Kalra V, Bhan MK. Emergence of G12 rotavirus strains in Delhi, India, in 2000-2007. J Clin Microbiol. 2008;46:1343-8.

79. Zade JK, Chhabra P, Chitambar SD. Characterization of VP7 and VP4 genes of rotavirus strains: 1990-1994 and 2000-2002. Epidemiol Infect. 2009;137:936-42.

80. Awachat PS, Kelkar SD. Evidence of rotavirus AU32 like G9 strains from nontypeable fecal specimens of Indian children hospitalized during 1993-1994. J Med Virol. 2004;74:656-61.

81. Awachat PS, Kelkar SD. Unexpected detection of simian SA11-human reassortant strains of rotavirus G3P[8] genotype from diarrhea epidemic among tribal children of Western India. J Med Virol. 2005;77:128-35.

82. Chitambar SD, Lahon A, Tatte VS, Maniya NH, Tambe GU, Khatri KI, et al. Occurrence of group B rotavirus infections in the outbreaks of acute gastroenteritis from western India. Indian J Med Res. 2011;134:399-400.

83. Samajdar S, Varghese V, Barman P, Ghosh S, Mitra U, Dutta P, et al. Changing pattern of human group A rotaviruses: emergence of G12 as an important pathogen among children in eastern India. J Clin Virol. 2006; 36:183-8.

84. Khetawat D, Dutta P, Bhattacharya SK, Chakrabarti S. Distribution of rotavirus VP7 genotypes among children suffering from watery diarrhea in Kolkata, India. Virus Res. 2002;87:31-40.

85. Barman P, Ghosh S, Samajdar S, Mitra U, Dutta P, Bhattacharya SK, et al. RT-PCR based diagnosis revealed importance of human group B rotavirus infection in childhood diarrhoea. J Clin Virol. 2006;36:222-7.

86. 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.

87. Samajdar S, Ghosh S, Dutta D, Chawla-Sarkar M, Kobayashi N, Naik TN. Human group A rotavirus P[8] Hun9-like and rare OP354-like strains are circulating among diarrhoeic children in Eastern India. Arch Virol. 2008;153:1933-6.

88. Mukherjee A, Chattopadhyay S, Bagchi P, Dutta D, Singh NB, Arora R, et al. Surveillance and molecular characterization of rotavirus strains circulating in Manipur, north-eastern India: increasing prevalence of emerging G12 strains.Infect Genet Evol. 2010;10:311-20.

89. Jain V, Parashar UD, Glass RI, Bhan MK. Epidemiology of rotavirus in India. Indian J Pediatr. 2001;68:855-62.

90. Anand T, Raju TA, Rao MV, Rao LV, Sharma G. Symptomatic human rotavirus subgroups, serotypes and electropherotypes in Hyderabad, India. Indian J Med Res. 2000;112:1-4.

91. Ramani S, Banerjee I, Gladstone BP, Sarkar R, Selvapandian D, Le Fevre AM, et al. Geographic information systems and genotyping in identification of rotavirus G12 infections in residents of an urban slum with subsequent detection in hospitalized children: emergence of G12 genotype in South India. J Clin Microbiol. 2007;45:432-7.

92. Mukhopadhya I, Anbu D, Iturriza-Gomara M, Gray JJ, Brown DW, Kavanagh O, et al. Anti-VP6 IgG antibodies against group A and group C rotaviruses in South India. Epidemiol Infect. 2010;138:442-7.

93. Banerjee I, Ramani S, Primrose B, Iturriza-Gomara M, Gray JJ, Brown DW, et al. Modification of rotavirus multiplex RT-PCR for the detection of G12 strains based on characterization of emerging G12 rotavirus strains from South India. J Med Virol. 2007;79:1413-21.

94. Ramachandran M, Das BK, Vij A, Kumar R, Bhambal SS, Kesari N, et al. Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol.1996;34:436-9.

95. Kelkar SD, Dindokar AR, Dhale GS, Zade JK, Ranshing SS. Culture adaptation of serotype G6 human rotavirus strains from hospitalized diarrhea patients in India. J Med Virol. 2004;74:650-5.

96. Tran TN, Nakagomi T, Nakagomi O. Evidence for Genetic Reassortment between Human Rotaviruses by Full Genome Sequencing of G3P[4] and G2P[4] Strains Co-circulating in India. Trop Med Health. 2013;41:13-20.

97. Uppal B, Wadhwa V, Mittal SK. Nosocomial diarrhea. Indian J Pediatr. 2004;71:883-5.

98. Dutta P, Bhattacharya SK, Saha MR, Dutta D, Bhattacharya MK, Mitra AK. Nosocomial rotavirus diarrhea in two medical wards of a pediatric hospital in Calcutta. Indian Pediatr. 1992;29:701-6.

99. Dutta P, Mitra U, Rasaily R, Bhattacharya SK, De SP, Sen D, et al. Prospective study of nosocomial enteric infections in a pediatric hospital, Calcutta. Indian Pediatr. 1993;30:187-94.

100. Desikan P, Daniel JD, Kamalarathnam CN, Mathan MM. Molecular epidemiology of nosocomial rotavirus infection. J Diarrhoeal Dis Res. 1996;14:12-5.

101. Kamalaratnam CN, Kang G, Kirubakaran C, Rajan DP, Daniel DJ, Mathan MM, et al. A prospective study of nosocomial enteric pathogen acquisition in hospitalized children in South India. J Trop Pediatr. 2001;47:46-9.

102. Ramani S, Sowmyanarayanan TV, Gladstone BP, Bhowmick K, Asirvatham JR, Jana AK, et al. Rotavirus infection in the neonatal nurseries of a tertiary care hospital in India. Pediatr Infect Dis J. 2008;27:719-23.

103. Cicirello HG, Das BK, Gupta A, Bhan MK, Gentsch JR, Kumar R, et al. High prevalence of rotavirus infection among neonates born at hospitals in Delhi, India: predisposition of newborns for infection with unusual rotavirus. Pediatr Infect Dis J. 1994;13:720-4.

104. Vethanayagam RR, Ananda Babu M, Nagalaxmi KS, Maiya PP, Venkatesh HA, Purohit S, et al. Possible role of neonatal infection with the asymptomatic reassortant rotavirus (RV) strain I321 in the decrease in hospital admissions for RV diarrhea, Bangalore, India, 1988-1999. J Infect Dis. 2004;189:2282-9.

105. Bhan MK, Lew JF, Sazawal S, Das BK, Gentsch JR, Glass RI. Protection conferred by neonatal rotavirus infection against subsequent rotavirus diarrhea. J Infect Dis. 1993;168:282-7.

106. Banerjee I, Gladstone BP, Le Fevre AM, Ramani S, Iturriza-Gomara M, Gray JJ, et al. Neonatal infection with G10P[11] rotavirus did not confer protection against subsequent rotavirus infection in a community cohort in Vellore, South India. J Infect Dis. 2007;195:625-32.

107. Broor S, Ghosh D, Mathur P. Molecular epidemiology of rotaviruses in India. Indian J Med Res. 2003;118:59-67.

108. Iturriza Gomara M, Kang G, Mammen A, Jana AK, Abraham M, Desselberger U, et al. Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in Vellore, India. J Clin Microbiol. 2004;42:2541-7.

109. Ray P, Sharma S, Agarwal RK, Longmei K, Gentsch JR, Paul VK, et al. First detection of G12 rotaviruses in newborns with neonatal rotavirus infection at all India Institute of Medical Sciences, New Delhi, India. J Clin Microbiol. 2007;45:3824-7.

110. Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD; WHO-coordinated Global Rotavirus Surveillance Network. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: A systematic review and meta-analysis. Lancet Infect Dis. 2012;12:136-41.

111. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: A systematic analysis. Lancet. 2010;375: 1969-87.

112. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lancet. 2005; 365:1147-52.

113. Parashar UD, Gibson CJ, Bresee JS, Glass RI Rotavirus and severe childhood diarrhea. Emerg Infect Dis. 2006;12:304-6.

114. Ramani S, Kang G. Burden of disease and molecular epidemiology of group A rotavirus infections in India. Indian J Med Res. 2007;125:619-32.

115. Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ. 2003;81:197-204.

 

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