Burden of Rotavirus Diarrhea in underfive Indian Children: A Systematic Review
Sriparna Basu, Associate Professor, Department
of Pediatrics, Institute of Medical Sciences,
Banaras Hindu University, Varanasi
Ashok Kumar, Professor, Department of
Pediatrics, Institute of Medical Sciences, Banaras
Hindu University, Varanasi
Address correspondence:
Ashok Kumar, Professor & Head, Department of
Pediatrics, Institute of Medical Sciences, Banaras
Hindu University, Varanasi
E-mail: ashokkumar_bhu@hotmail.com
Introduction
• Rotavirus is the most common cause of severe diarrhea in infants and
young children worldwide. Globally it is responsible for 611,000
childhood deaths [1], and another 2 million hospitalizations [2] every
year.
• More than 80% deaths occur in low-income countries [1], and India
records the highest mortality [3].
• Rotavirus diarrhea accounts for 2,000,000 outpatient visits, 457,000 884,000 hospitalizations, and 122,000-153,000 deaths in under-5
children in India annually.
• There is huge economic impact of rotavirus diarrhea.
• It is estimated that India spends approximately Rs 1.8–3.2 billion (US$
37.4 to 66.8 million) in direct medical costs annually and Rs 107–176
million (US$ 2.2–3.7 million) in direct non-medical costs for the
treatment of rotavirus diarrhea in children <5 years of age, with a total
burden of Rs 2.0–3.4 billion (US$ 41–72 million) [4].
Epidemiology
• Rotaviruses are double stranded RNA viruses
comprising a genus within the family Reoviridae.
• The primary mode of transmission is via the fecaloral 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 six
to 24 months of age [5,6].
Rotavirus detection and strain
characterization
• 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) [18].
• ELISA is the method of choice for routine screening.
• The sensitivity of routine tests are high since the amount of virus
excreted by a child with rotavirus diarrhea (~1010 viruses/g of stool)
far exceeds the level of detection (~107 viruses/g of stool) [19].
• For genotyping, newer methods like multiplex RT-PCR based
genotyping, hybridization assays and nucleotide sequencing have
greatly improved data on circulating rotavirus strains.
Molecular epidemiology
• The mature virus particles are triple layered, with an approximate
diameter of 70 nm and icosahedral symmetry.
• The rotavirus genome consists of 11 segments of double-stranded
RNA, which code for 6 structural viral proteins, VP1, VP2, VP3, VP4,
VP6 and VP7 and 6 non-structural proteins, NSP1-NSP6 [20], where
gene segment 11 encodes both NSP5 and 6.
• Genome is encompassed by an inner core consisting of VP2, VP1 and
VP3 proteins. Intermediate layer or inner capsid is made of VP6
determining group and subgroup specificities.
• The outer capsid layer is composed of two proteins, VP7 and VP4
eliciting neutralizing antibody responses.
• Rotaviruses are classified into seven different groups (A-G) which is
based on the antigenic specificity of the VP6 capsid proteins, as well as
on the pattern of electrophoretic mobility of the 11 RNA segments of
the viral genome.
Molecular epidemiology
• Groups A, B and C are known to infect humans. Severe, lifethreatening disease in children worldwide is caused predominantly by
group A rotaviruses.
• Within group A, four different subgroups (SG); SGI, SGII, SGI and II,
and nonI/nonII, have been distinguished on the basis of VP6 diversity,
among which possibly SGI or SGII are the only humans strains [21].
• Further typing schemes to describe rotavirus strains are based on the
proteins of the outer capsid eliciting neutralizing antibodies, VP7 (G
serotypes) and VP4 (P serotypes).
• G and P serotypes are defined on the basis of their reactivity to specific
monoclonal antibodies.
• Variability in the genes encoding the two outer capsid proteins VP7
and VP4 form the basis of the current strain typing of group A
rotaviruses into G and P genotypes.
• All known G serotypes correspond with genotypes; though, more P
genotypes than serotypes have been identified.
Molecular epidemiology
• Current practice is to identify a rotavirus strain by a G genotype,
indicated by a number, followed by its P type.
• To distinguish strains identified by P genotyping from those identified
by P serotyping, the dual serotype/genotype nomenclature is used.
• P genotypes are expressed as P followed by a number in square
brackets whereas P serotypes are designated as P with serotype
number, followed by corresponding genotype in square brackets (e.g.,
the same strain could be represented as G9P[6], when both G and P
genotypes are used, or G9P2A[6] when G genotype is followed by P
serotype/genotype classification).
• Till date, at least 15 G genotypes and 25 P genotypes have been
identified [22].
Nosocomial diarrhea
• The Centers of Disease Control and Prevention defines
nosocomial diarrhea as an acute onset of diarrhea in
hospitalized patient, characterized by liquid stool for more
than 12 hr with or without vomiting and/or fever or the
occurrence of symptoms like nausea, vomiting, abdominal
pain in conjunction with objective evidence of enteric
infection obtained by stool culture, antigen or antibody
assay of feces or blood, routine microscopic examination
of stool or toxin assay.
• A period of at least 3 days of hospitalization prior to the
onset of diarrhea is necessary to term it as nosocomial
diarrhea [23].
Objective
• The high burden of rotavirus disease in India requires that
there is an urgent need to summarize and critically evaluate
all available information related to the prevalence of
rotavirus diarrhea in India.
• Comprehensive national estimates of the burden of
diarrheal diseases caused by rotavirus in India are still
lacking.
• The objective of this systematic review is to estimate the
burden of rotavirus diarrhea in the community and in
hospital in children <5 years of age in India.
Methods
Study Design
• We reviewed the epidemiology of rotavirus
diarrhea in under-5 Indian children. The
standard methodology for conducting a
narrative systematic review was used [12].
• Our primary research question was
‘epidemiology of rotavirus diarrhea in
under-5 children of India’.
Secondary research questions
(1) Epidemiology of rotavirus diarrhea in under-5 hospitalized children
from different parts of India
(2) Epidemiology of rotavirus diarrhea in under-5 children in community
from different parts of India
(3) Demographic profile of rotavirus diarrhea in under-5 Indian children
(4) Identification of molecular epidemiology of rotavirus diarrhea in
under-5 children from different parts of India
(5) Incidence of rotavirus infection as a cause of nosocomial diarrhea in
under-5 Indian children, and
(6) Mortality from rotavirus diarrhea in under-5 Indian children
• The primary databases searched were Medline through
PubMed (www.pubmed.com) and IndMed
(http://indmed.nic.in/).
• Other sources including World Health Organization
(WHO) reports available online (www.who.int), documents
of the UNICEF available online (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) available online were also accessed.
• We also searched the related articles and the reference lists
of included publications to identify additional studies.
Inclusion and Exclusion Criteria
• We included all types of publications available in scientific
public domain and reporting on rotavirus infection in India
by direct data collection through clinical examination,
and/or laboratory testing.
• No particular time frame was set.
• We limited our search in humans, and articles published in
English language.
Participants
• Children: 1 month to 5 years.
Searching the Literature
• For searching the PubMed, 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’.
Searching the Literature
• 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.
• An additional search was made for the secondary research
questions by combining keywords/MeSH terms for the
secondary research question using the search string “(*)
AND (rotavirus, infections) AND India”, where the
asterisk represents the MeSH term/keywords for the
secondary research question.
Searching the Literature
• To search the 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
excluding the titles which were obviously not
relevant; the remaining articles were studied
further.
Searching the Literature
• 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 were 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
2012 and updated on 15th November 2012.) using
‘rotavirus’ yielded 3905 articles.
• While searching, filters activated were: Humans, English,
Infant: 1-23 months, Preschool Child: 2-5 years. Search
with ‘rotavirus diarrhea’ yielded 2123 articles and search
with ‘rotavirus gastroenteritis’ yielded 1871 articles.
• Details of search strings and yield of articles have been
summarized in Table I.
• All included studies were observational with GRADE
quality of evidence ‘moderate’.
TABLE I: Results of Literature Search
Q.
No
.
Research
question
Search engine
Total
1
Epidemiology
of rotavirus
diarrhea in
under-5
hospitalized
children from
different parts of
India
Epidemiology
of rotavirus
diarrhea in
under-5 children
in community
from different
parts of India
Demographic
profile of
rotavirus
diarrhea in
under-5 Indian
children
Molecular
epidemiology of
rotavirus
diarrhea in
under-five
children of India
(epidemiology* OR burden OR
morbidity OR mortality or
incidence OR prevalence OR
profile OR hospital) AND
(rotavirus OR rotavirus diarrhea
OR rotavirus gastroenteritis OR
rotavirus disease) AND india
(epidemiology* OR burden OR
morbidity OR mortality or
incidence OR prevalence OR
profile OR community) AND
(rotavirus OR rotavirus diarrhea
OR rotavirus gastroenteritis OR
rotavirus disease) AND india
(epidemiology* OR demography
OR profile OR hospital OR
community) AND (rotavirus OR
rotavirus diarrhea OR rotavirus
gastroenteritis OR rotavirus
disease) AND india
(classification* OR genetics OR
phylogeny OR virology OR
genotype OR classification OR
genetic variation OR molecular
epidemiology) AND (rotavirus
OR rotavirus diarrhea OR
rotavirus gastroenteritis OR
rotavirus disease) AND india
(epidemiology* OR burden OR
morbidity OR mortality or
incidence OR prevalence OR
profile OR hospital OR
nosocomial) AND (rotavirus OR
rotavirus diarrhea OR rotavirus
gastroenteritis OR rotavirus
disease) AND india
(epidemiology* OR burden OR
morbidity OR morbidity OR
mortality or incidence OR
prevalence OR profile OR
hospital OR community OR case
fatality) AND (rotavirus OR
rotavirus diarrhea OR rotavirus
gastroenteritis OR rotavirus
disease) AND india
2
3
4
5
Incidence of
rotavirus
infection as a
cause of
nosocomial
diarrhea
6
Mortality from
rotavirus
infection in
under-5 children
from different
parts of India
After
abstract
screeni
ng
84
After
readin
g full
text
45
From
cross
referen
ce
4
Additio
nal
search
167
After
title
screeni
ng
93
0
Finall
y
includ
ed
49
152
82
27
15
0
0
15
138
95
46
35
0
0
35
134
97
51
43
2
1
46
122
18
9
5
0
0
5
168
38
22
14
0
1
15
Burden of Rotavirus diarrhea in hospitalized
children from different parts of India
• A total of 49 studies [24-72], carried out using samples
obtained from under-5 Indian children hospitalized with
rotavirus diarrhea were included (Table II, Fig. 1A, Fig.
1B).
• The studies were conducted in various geographic
locations. Eighteen studies were carried in Northern India,
7 in Western India, 8 in Eastern India and 11 in Southern
India.
• Six studies involved multiple geographical locations.
• 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.
Burden of Rotavirus diarrhea in hospitalized
children from different parts of India
• A total of 34397 stool samples were tested, of which 7448
(21.7%) tested positive.
• Rates of rotavirus positivity ranged from 4.6% in Kolkata,
Ghosh, et al.[51] to 89.8% in Manipur, Sengupta, et
al.[54].
• Largest number of samples came from Northern India
(9430), followed by Southern India (8840), multicentric
studies (7428), Western India (5927) and Eastern India
(2782).
• Region-wise, highest positivity was recoded from Eastern
India (31.7%), followed by Western India (20.8%),
Northern India (17.4%) and Southern India (17.2%).
• Studies conducted in multiple locations recorded an
incidence of 21.4%, replicating the overall incidence of
rotavirus diarrhea in hospitalized children in India.
• Details of studies have been summarized in Web Table I.
TABLE II: Rotavirus Positivity in Children Hospitalized with Diarrhea from
Different Parts of India
S.
No.
Reference
Place of
study
1
Broor, et al.[24]
Chandigarh
2
Singh, et al.[25]
Chandigarh
3
Ram, et al.[26]
Chandigarh
4
Delhi
8
Samantaray, et
al.[27]
Aggarwal, et al
[28]
Chakravarthi, et
al.[29]
Chakravarti, et
al.[30]
Broor, et al.[31]
9
Patwari, et al.[32]
Delhi
10
Husain, et al.[33]
Delhi
11
Chatterjee, et
al.[18]
Chakravarti, et
al.[34]
Bahl, et al.[35]
Delhi
Delhi
16
Chakravarti, et
al.[36]
Chakravarti, et
al.[37]
Sharma, et al.[38]
17
Nag, et al.[39]
Lucknow
18
Mishra, et al.[40]
Lucknow
5
6
7
12
13
14
15
Total
Delhi
Delhi
Delhi
Delhi
Delhi
Delhi
Delhi
North India
Study
period
(year)
Age
group
(years)
Detection
method
Stool samples
collected from
children
admitted with
diarrhea (n)
Positive,
n (%)
Northern
19821983
1982 1985
19841987
19801981
1985
India
<5
ELISA
242
44 (18.2)
<5
ELISA
694
111 (15.9)
<3
ELISA
1024
<5
ELISA
99
120
(11.72)
32(32.3)
<5
ELISA
256
19(7.4)
1987
1989
1987
1988
1988
1990
1989
1990
1990
1991
1990
-
<5
ELISA
978
176 (18.0)
-
<5
ELISA
288
44 (15.3)
-
<5
ELISA
990
104 (10.5)
-
<3
400
23 (6.0)
-
<5
Immunod
ot
ELISA/P
AGE
ELISA
450
60 (13.3)
157
71 (45.0)
ELISA/P
AGE
ELISA
1172
158 (13.5)
584
137 (23.5)
ELISA/P
AGE
ELISA
560
100 (17.8)
862
318(36.9)
ELISA
172
32 (19.0)
ELISA/P
AGE
ELISA
90
14(15.6)
412
79(19.2)
9430
1642(17.4)
1998 2000
2000 2001
1998 2000
2005 2007
Not
mentioned
20032004
2004 2008
<5
<5
<5
<3
<2
Not
mentio
ned
<2
<3
TABLE II: Rotavirus Positivity in Children Hospitalized with
Diarrhea from Different Parts of India contd…
S.
Reference
No.
Place of
study
19
Desai, et al.[41]
Mumbai
20
Kelkar, et al.[42]
Pune
21
Kelkar, et al.[43]
Pune
22
Kelkar, et al.[44]
Pune
23
Kelkar, et al.[45]
Pune
24
Borade, et al.[46]
Pune
25
Kelkar, et al.[47]
Thane
Total
Study
period
(year)
Age
group
(years)
Western India
1984 –
Not
1986
mentio
ned
1990 –
Not
1993
mentio
ned
1992 –
<5
1996
1990<5
1997
1993<5
1996
2009<5
2010 (?)
2000<5
2001
Detection
method
Stool samples
collected from
children
admitted with
diarrhea (n)
Positive,
n (%)
LA /EM /
ELISA
273
63 (21.0)
ELISA
722
188 (26.0)
ELISA
945
266 (28.2)
ELISA
3064
432 (14.1)
ELISA
628
177 (28.3)
ELISA
246
88 (35.8)
ELISA
39
27 (69.2)
5917
1241
(20.8)
TABLE II: Rotavirus Positivity in Children Hospitalized with
Diarrhea from Different Parts of India contd…
S.
Reference
No.
Place of
study
26
Phukan, et al.[48]
Dibrugarh
27
Saha, et al.[49]
Kolkata
28
Sen, et al.[50]
Kolkata
29
Ghosh, et al.[51]
Kolkata
30
Samajdar, et
al.[52]
Samajdar, et
al.[53]
Sengupta, et
al.[54]
Kolkata and
Berhampur
Kolkata
Mukherjee, et
al.[55]
Manipur
31
32
33
Total
Manipur
Study
period
(year)
Age
group
(years)
Eastern India
1999 <5
2000
1979<12
1981
1979Not
1981
mentio
ned
1986<6
1988
month
s
2003<4
2005
2005 <4
2006
1979
Not
mentio
ned
2005 <5
2008
Detection
method
Stool samples
collected from
children
admitted with
diarrhea (n)
Positive,
n (%)
ELISA
202
47 (23.3)
ELISA
245
55 (22.4)
ELISA
356
27 (7.6)
ELISA
218
10 (4.6)
ELISA
545
198 (36.3)
ELISA
668
249 (37.3)
ELISA
59
53 (89.8)
ELISA
489
244 (49.9)
2782
883 (31.7)
TABLE II: Rotavirus Positivity in Children Hospitalized with
Diarrhea from Different Parts of India contd…
S.
No.
Reference
Place of
study
34
Aijaz, et al.[56]
Bangalore
Aijaz, et al.[56]
Mysore
Chennai
37
Ananthan, et
al.[57]
Saravanan, et
al.[58]
Anand, et al.[59]
37
Shetty, et al.[60]
Karnataka
38
Ballal, et al.[61]
Karnataka
39
40
Anand, et al.[62]
Kang, et al.[63]
Tirupati
Vellore
41
Banerjee, et
al.[64]
Sowmyanarayana
n, et al.[65]
Paniker, et al.[66]
Vellore
35
36
42
43
Total
Chennai
Hyderabad
Vellore
Calicut
Study
period
(year)
Age
group
(years)
Southern India
1988 Not
1994
mentio
ned
1993 Not
1994
mentio
ned
1997 0 - 2,
1999
>2
1995 <3
1999
1998 <2
1999
Not
<5
mentioned
1995<5
2000
1991
<2
1995 <5
1998
2002 <5
2004
2005<5
2008
1976<5
1978
Detection
method
Stool samples
collected from
children
admitted with
diarrhea (n)
Positive,
n (%)
PAGE
694
150 (21.6)
PAGE
447
50 (11.2)
ELISA
245
51 (20.8)
ELISA/P
AGE
PAGE
745
168 (22.6)
352
57 (16.2)
LA
106
19 (18)
LA
780
40 (19.9)
ELISA
ELISA /
LA
ELISA/
LA
EIA/PCR
170
602
40 (23.5)
126 (20.9)
343
94 (27.1)
1001
354 (35.4)
EM
3355
368 (70.7)
8840
1517
(17.2)
TABLE II: Rotavirus Positivity in Children Hospitalized with
Diarrhea from Different Parts of India contd…
S. Reference
No.
Place of
study
44
Ramachandran, et Multiple 1
al.[67]
45
Jain, et al.[68]
Multiple 2
46
Kang, et al.[69]
Multiple 3
47
Das, et al.[70]
Multiple 4a
48
49
Das, et al.[71]
Kang, et al.[72]
Multiple 5
Multiple 6
Study
period
(year)
Age
Detection
group method
(years)
Multiple locations
1993
6 mo
to <5
yr
1996 <5
1998
1998 <5
1999
1998 <4
2000
2001
<4/allb
2005 <5
2007
Stool samples
collected from
children
admitted with
diarrhea (n)
Positive,
n (%)
ELISA
458
63 (13.7)
ELISA
1502
313 (20.8)
LA /EM /
ELISA
PAGE
365
82 (22.5)
406
141 (34.7)
PAGE
RT-PCR
454
4243
161 (35.4)
1405
(39.2)
2165
(21.4)
7448
(21.7)
Total
7428
All India total
34397
TABLE II: Rotavirus Positivity in Children Hospitalized
with Diarrhea from Different Parts of India contd…
• 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
Figure 1A: Overall Rotavirus
positivity in Indian children
hospitalized with diarrhea
Figure 1B: Region-wise breakup of
Rotavirus positivity in children
hospitalized with diarrhea
12000
40000
1642(17.4%)
1517(17.2%)
35000
10000
Rotavirus positive
Total stool samples
2165(21.4)
30000
No. of stool samples
No. of stool samples
8000
25000
20000
34397
15000
1241(20.8%)
6000
9430
8840
883(31.7%)
4000
7428
5917
10000
2000
5000
2782
7448 (21.7%)
0
0
Total stool samples
Rotavirus positive
Northern
India
Southern
India
Western
India
Eastern India
Multiple
locations
Burden of Rotavirus diarrhea in the
community from different parts of India
• A total of 15 studies, carried out using samples obtained
from under-5 Indian children in community with rotavirus
diarrhea were included (Table III, Fig. 2A, 2B).
• Nine studies were carried in Northern India, 2 in Western
India, 1 in Eastern India and 3 in Southern India.
• A total of 7566 stool samples were tested in children with
diarrhea and 2810 controls, 1504 (19.9%) were tested
positive in children with diarrhea and 117 (4.2%) in
controls.
• Rates of rotavirus positivity in diarrhea ranged from 33.7%
in Manipur [83], to 4% in Delhi, [74].
• In controls, stool positivity ranged from 0 in Vellore [84]
to 12.3% in North India [76].
• Details of studies have been summarized in Web Table II.
TABLE III: Burden of Rotavirus Diarrhea in the
Community from Different Parts of India
S.
No
.
Reference
1
Samantara
y, et al
[27]
Bhan, et
al [73]
Raj, et al
[74]
Bhan, et
al [75]
2
3
4
5
6
7
8
9
Total
Place of
study
Delhi
Delhi
Delhi
Delhi
Commu
nity
Semi
urban
Semi
urban
Semi
urban
Urban/r
ural
Panigrahi,
et al [76]
Malik, et
al [77]
Yachha,
et al [78]
North
India
Aligarh
Nath, et al
[79]
Nath, et al
[80]
Varanasi
Urban/r
ural
Semi
urban
Urban/p
eriurban/ru
ral
Urban
Varanasi
Urban
Chandigar
h
Study
Age Detection
period
(yr) method
(yr)
Northern India
1980<5
ELISA
1981
Diarrhea
Sample
size (n)
Positive
n (%)
Yes
No
212
82
45 (21.2)
2 (2.4)
19851986
19851986
1985
Yes
No
Yes
No
42 (20.6)
2 (2.0)
14 (4.0)
14 (6.6)
Yes
No
Yes
No
Yes
No
Yes
204
98
346
211
Urban
330
319
Rural
340
315
1050
350
216
216
218
Yes
No
Yes
376
299
607
56 (16.5)
9 (2.9)
44 (29.3)
43 (12.3)
40(18.5)
1(0.05)
25 (11.5)
rural-14
periurban-7
urban -4
67 (17.7)
12 (4)
100 (16.4)
Yes
No
3899
1890
483 (12.4)
87 (4.6)
<5
ELISA
<3
ELISA
<5
ELISA
Yes
No
1982 1983
19821983
1988 1991
<5
ELISA
<5
ELISA
<5
ELISA
1988 1989
1988 1989
<5
LA
<5
LA
50 (15.2)
6 (1.9)
TABLE III: Burden of Rotavirus Diarrhea in the
Community from Different Parts of India contd..
S.
No
.
Reference
Place of
study
Commu
nity
10
Desai, et
al [81]
Kelkar, et
al [82]
Mumbai
Urban
11
Pune
Study
Age Detection
period
(yr) method
(yr)
Western India
1984<5
EM/LA/E
1986
LISA
1993 <5
ELISA
1996
Total
12
Krishnan,
et al [83]
Manipur
Urban
Semi
urban
Eastern India
1989<5
ELISA
1992
Total
13
14
15
Maiya, et
al [84]
Mathew,
et al [85]
Vellore*
Urban
Vellore
Banerjee,
et al [64]
Vellore
Urban,
periurba
n,
rural
Urban
Total
All India total
Southern India
1974<2
EM
1975
1983<3
EM
1985
2002 2004
<5
ELISA
Diarrhea
Sample
size (n)
Positive
n (%)
Yes
No
Yes
273
273
489
63 (23)
3 (1.1)
76 (15.5)
Yes
No
762
273
139 (18.2)
3 (0.01)
Yes
No
787
457
265 (33.7)
22 (4.8)
Yes
No
787
457
265 (33.7)
22 (4.8)
Yes
No
Yes
No
50
30
916
587
13 (26)
0 (0)
95 (10.4)
5 (0.9)
Yes
1152
82 (7.1)
Yes
No
Yes
No
2118
617
7566
2810
190 (9)
5 (0.01)
1504 (19.9)
117 (4.2)
Figure 2A: Overall Rotavirus
positivity in Indian children from
community
10000
9000
1504 (19.9%)
Rotavirus positive
No. of stool samples
8000
Total stool samples
7000
6000
5000
4000
7566
117(4.2%)
3000
2000
2810
1000
0
With diarrhea
Without diarrhea
Figure 2B: Region-wise breakup of
Rotavirus positivity in children
with and without diarrhea from
community
Demographic profile of rotavirus diarrhea
• Demographic profile of rotavirus diarrhea has been
summarized in Table IV and Web Table III.
• A total of 35 studies could be identified which described
demographic profile of rotavirus diarrhea in children.
• Details of all the studies have been discussed in Web
Table III, 27 have been summarized in Table IV .
• Most cases of rotavirus diarrhea were found to occur in the
first two years of life, most commonly affected age group
was 7-12 months both in hospital and community settings.
• Most of the authors have observed an increase in
rotavirus-associated diarrhea during the winter months.
TABLE IV: Demographic Profile of Rotavirus Diarrhea
S.
No.
Reference
Place of study
Peak age incidence (%)
Gender affected
Peak season
1
Broor, et al.[24]
Chandigarh
7-12 mo
Not mentioned
Not mentioned
2
Ram, et al.[26]
Chandigarh
10-12 mo
M:F=3:1
November
3
Yachha, et al [78]
Chandigarh
6-11 mo
Not mentioned
November-February
4
Samantaray, et al.[27]
Delhi
0-6 mo
M:F=26:19
October - June
5
Bhan, et al [73]
Delhi
0-6 mo
Not mentioned
Not mentioned
6
Raj, et al [74]
Delhi
13-24 mo
Not mentioned
October – December
7
Patwari, et al.[32]
Delhi
7-12 mo
M:F=256:144
February-April
8
Panigrahi, et al [76]
North India
37-60 mo
Not mentioned
April-June
9
Malik, et al [77]
Aligarh
<1 yr
M=F
January-March
10
Nag, et al.[39]
Lucknow
6-12 mo
M:F=2.5:1
Not mentioned
11
Nath, et al [79]
Varanasi
<2 yr
F>M
November - February
12
Kelkar, et al.[43]
Pune
6-12 mo (64.7)
M>F
Winter
13
Borade, et al.[46]
Pune
11-20 mo
M=F
December - January
14
Kelkar, et al.[47]
Thane
6-12 mo
M>F
Not mentioned
15
Saha, et al.[49]
Kolkata
6-12 mo
M=F
January
TABLE IV: Demographic Profile of Rotavirus Diarrhea contd...
S.
No.
Reference
Place of study
Peak age incidence
(%)
Gender affected
Peak season
16
Sen, et al.[50]
Kolkata
<2 yr (25)
Not mentioned
Not mentioned
17
Sengupta, et
al.[54]
Manipur
Not mentioned
M:F=1.9:1
November
18
Ananthan, et
al.[57]
Chennai
7-12 mo (28.7)
Not mentioned
Not mentioned
19
Saravanan, et
al.[58]
Chennai
7-12 mo (62.5)
M:F=93:75
Sept-Feb
20
Shetty, et al.[60]
Karnataka
<2 yr-59(56)
Not mentioned
Winter (Dec-Feb)
21
Ballal, et al.[61]
Karnataka
7-12 (65)
Not mentioned
Not mentioned
22
Anand, et al.[62]
Tirupati
7-12 mo
M>F
Not mentioned
23
Kang, et al.[63]
Vellore
Mean age 19.5 mo
Not mentioned
Not mentioned
24
Banerjee, et al
[64]
Vellore
Not mentioned
Not mentioned
December-January
25
Sowmyanarayana
n, et al.[65]
Vellore
6-12 mo
M:F=75:51
January-February
26
Paniker, et al.[66]
Calicut
6-23 mo
M=F
November - January
27
Kang, et al.[72]
Multiple
locations
Mean age
12.9±9.0mo
M>F
Not mentioned
Rotavirus serotypes detected from various
parts of India
• A total of 46 studies could be identified which dealt with
serotyping of rotavirus, of which G and P typing were
done in 40 studies.
• Details of studies have been summarized in Table V, VI,
VII, Figure 3 - 12 and Web Table IV.
• Maximum number of studies was reported from southern
India (12), 8 from western India, 7 from eastern India and
6 studies were reported from northern India.
• Seven studies involved multiple locations.
Rotavirus G serotypes detected from
various parts of India
• Overall, G1 was the most common serotype isolated in
Indian studies (32%), followed by G2 (24%) and Guntypable (15%).
• On regional distribution, in northern India, G1 was the
most common serotype isolated (32%), followed by G2
(20%), G-untypable (13%) and G9(11%).
• In western India, G2 was predominant (28%), closely
followed by G-untypable (25%) and G1 (23%).
• In eastern India, G1 was detected in 40%, followed by G2
(30%).
• In southern India, G1 was predominant (31%), followed by
G2 (23%) and G-untypable (21%).
Figure 3
All India G serotypes
G1
15%
7%
32%
G2
G3
3%
G4
G9
8%
G12
6%
5%
24%
G-Mixed
G-UT
Figure 4-7: G serotyping
Western India
Northern India
G1
G1
13%
32%
8%
23%
25%
G2
G3
G4
G4
G9
8%
G12
11%
G9
8%
G12
G-mixed
2%
20%
6%
G2
G3
G UT
0%
28%
8%
G-mixed
G UT
1%
7%
Southern India
Eastern India
8%
G1
3%
G2
8%
40%
6%
G3
G4
G9
5%
G12
0%
30%
G1
21%
G-mixed
G UT
31%
G3
5%
G4
G9
1%
8%
G2
G12
5%
6%
23%
G-mixed
G UT
Rotavirus P serotypes detected from
various parts of India
• In P serotyping, P[4] was most prevalent (23%) all over
India, followed by P[6] (20%) and P Untypable/others
(13%).
• In northern India, P[6] was most common (22%), followed
by P[4] (19%).
• Prevalence of P[4] was 43% in western India and 32% in
eastern India.
• In southern India, untypable P type was documented in
40%, followed by P[8] (39%).
• P[4] was documented in 17%.
Figure 8
All India P serotypes
13%
23%
P[4]
11%
P[6]
P[8]
P[Mixed]
20%
33%
P UT/others
Figure 9-12: P serotyping
Northern India
Western India
0%
12%
19%
0%
P[4]
P[4]
11%
P[6]
22%
43%
45%
P[8]
P[8]
P mixed
P mixed
P UT/Other
P UT/Other
36%
12%
Southern India
Eastern India
19%
0%
17%
32%
P[4]
2%
40%
8%
P[4]
P[6]
P[6]
P[8]
P[8]
P mixed
P mixed
41%
P[6]
P UT/Other
2%
39%
P UT/Other
Nosocomial Rotavirus Infections
• Five studies were identified which dealt with nosocomial rotavirus
infection.
• Two studies were done in Kolkata [111-112], one in Delhi [110], two
in Vellore [113,114].
• A total of 3810 children hospitalized for illnesses other than diarrhea
were included.
• Among them 466 (12.2%) developed nosocomial diarrhea. Rotavirus
was identified as the etiological agent in 75 (16.1%) of them.
• Details of the studies have been discussed in Table VIII, Figure 13
and Web Table V.
Figure 13: Nosocomial Rotavirus Infections
4500
4000
3810
Number of stool samples
3500
3000
2500
2000
1500
1000
466
(12.2%)
500
75
(16.1%)
0
No. of children
admitted
Nosocomial
diarrhea
Rotavirus positive
Five studies were included in nosocomial rotavirus infection. One study was
done in Delhi [110], two studies in Kolkata [111-112] and two in Vellore
[113,114].
Rotavirus mortality
• Indian Rotavirus Strain Surveillance Network (IRSSN)
data, which covered pediatric admissions to 10 hospitals in
7 cities of India from December 2005 to November 2007,
showed that stool samples from 1405 (39%) of 3580
children hospitalized with diarrhea were positive for
rotavirus [72].
• The Million Death Study, a nationally representative
sample of 6.3 million people in 1.1 million households
within the Sample Registration System, recorded
approximately 334 000 diarrheal deaths in India during
2005, i.e., 1 in 82 Indian children died from diarrhea
before the age of 5 years [128].
• As per the IRSSN data, rotavirus was estimated to cause
approximately 34% (113,000; 99% confidence interval, CI:
86,000–155,000) of all diarrheal deaths in under-5
children.
Rotavirus mortality
• As per the IRSSN data, rotavirus was estimated to cause
approximately 34% (113,000; 99% confidence interval, CI:
86,000–155,000) of all diarrheal deaths in under-5
children.
• Taken together, there was an estimated mortality rate of
4.14 (99% CI: 3.14–5.68) deaths per 1000 live births
during 2005 suggesting that approximately 1 in 242
children will die from rotavirus infection before reaching
their fifth birthday.
• Rotavirus-associated mortality rate varied by gender, age
and region during 2005 [129].
• The rate among girls (4.89 deaths per 1000 live births;
99% CI: 3.75–6.79) was 42% higher than among boys
(3.45 deaths per 1000 live births; 99% CI: 2.58–4.66).
Rotavirus mortality
• Region-wise, most rotavirus-associated deaths during 2005
occurred in the central India and eastern India (56,400 vs.
28,900, respectively).
• State-wise mortality rate per 1000 live births due to
rotavirus infection among Indian under-5 children during
2005 is shown in Fig. 14.
• The mortality rate from rotavirus associated gastroenteritis
among under-5 children ranged from a low of 1.64 deaths
per 1000 live births in western India to as high as 5.49
deaths per 1000 live births in central India.
• Overall mortality rate was 4.1 per 1000 live births.
Rotavirus mortality
• Highest mortality rate was observed in Bihar (6.3)
followed by Uttar Pradesh (6.2).
• Lowest rate was recorded by Maharashtra (1.1).
• In absolute figures, more than half (64,400) of deaths were
estimated to occur in three states, Uttar Pradesh recording
the highest number (35,700), followed by Bihar (17,800)
and Madhya Pradesh (10,900) [127].
• The age distribution of deaths from rotavirus infection was
similar for boys across the country, but age of death was
lower in girls in the northern and southern India compared
to other regions.
U
t
M tar Bih
ad P a
hy ra r
a de
P sh
ra
d
H esh
ar
ya
n
O a
ri
Ja ssa
rk
A Ra han
nd j
hr ast d
a ha
P
C ra n
hh de
a t sh
tis
K ga
ar rh
na
ta
k
P a
un
j
G ab
Ta uja
m r
W il at
e s Na
t d
M Be u
ah ng
a a
O ra l
th sh
er tr
st a
at
es
Mortality rate from rotavirus infection/1000 live births
Figure 14: State-wise estimated mortality rate due to rotavirus
infection among Indian under-5 children during 2005
7
6.3 6.2
6
5.4
5
3
2
4.9 4.8
4.2
4
4
3.4
3.3
2.8 2.8 2.8
2.5
2.1
1.7
1.1
1
0
Discussion
• Limitations
• Lack of data from many geographical locations,
particularly central India, where the burden of diarrheal
disease is particularly heavy.
• There are many gaps in our understanding of the
epidemiology of rotavirus diarrhea in under-5 children
particularly at the community level.
• Most of the studies were confined to few places in each
region except southern India and sample size differed
widely in individual studies. Another shortcoming is use of
different methodologies employed for virus detection.
• The limitation is particularly applicable to the period prior
to 1994 when molecular methods for serotyping were not
available.
• Lastly, we did not perform any formal quality assessment
of the individual studies beyond selection criteria
requirements.
Discussion
• The burden of rotavirus diarrhea is high in India (GRADE
quality of evidence moderate)
• Incidence of rotavirus positive diarrhea is higher in
hospitalized children than in the community settings.
• 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.
• Mortality from rotavirus is still very high in India.
• There are large regional differences in the pattern of
circulating rotavirus strains.
• Overall, G1 was the most common serotype isolated in
Indian studies (32%), followed by G2 (24%) and Guntypable (15%).
Discussion
• Beyond the common G1, G2, G3 and G4, more unusual
strains like G9 and G12 are appearing as causative agents.
• Mixed infections, along with human-animal reassortments,
unusual G-types (G6 and G8) and strains (G3P[11] and
G9P[10]) had been described which highlights the wide
genetic and antigenic diversity of strains circulating in
different regions.
• Even group B and group C rotavirus have been
incriminated to cause diarrhea.
• Such variation necessitates continuous surveillance.
• In view of continuing high morbidity and mortality from
rotavirus diarrhea and enormous economic consequences
thereof, there is a strong case for immunization against
rotavirus infection.
• It is also crucial to assess and consider the strain variability
in the design of a new candidate vaccines and its clinical
evaluation in regions with high strain diversity.
Discussion
• Also after introduction of immunization, it is important to
have ongoing surveillance to measure the impact of largescale vaccination program on rotavirus diarrhea
hospitalization and mortality rates.
• As per latest WHO estimate, India as a country records
highest rotavirus deaths in under-5 children (22%).
• Unfortunately, very few studies dealt with mortality from
rotavirus diarrhea. Particularly, there is no study from
Bihar and very few studies in Uttar Pradesh, the states
which record highest mortality rate from rotavirus
diarrhea.
• More studies are needed at the community level to better
define the epidemiology of rotavirus diarrhea.
Conclusions
• Rotavirus diarrhea is a significant public health problem in
India (GRADE quality of evidence moderate).
• The incidence of rotavirus positive diarrhea is higher in
hospitalized children than in community, indicating
thereby that rotavirus accounts for more severe
dehydrating diarrhea in children.
• Most cases of rotavirus diarrhea in India are caused by G1,
G2, and G untypable strains with distinct regional
variations.
• Rotavirus is also an important cause of nosocomial
diarrhea in children.
• In view of continuing high morbidity and mortality from
rotavirus diarrhea and enormous economic consequences
thereof, there is a strong case for immunization against
rotavirus infection in India.
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