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| SPECIAL ARTICLE |
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| Year : 2012 | Volume
: 56
| Issue : 1 | Page : 17-21 |
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Burden of rotavirus in India - Is rotavirus vaccine an answer to it?
Davendra K Taneja1, Akash Malik2
1 Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi, India
2 P.G.T, Department of Community Medicine, Maulana Azad Medical College, New Delhi, India
| Date of Web Publication | 6-Jun-2012 |
Correspondence Address:
Davendra K Taneja
Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi -110002
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0019-557X.96951
 Abstract | | |
Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries. Worldwide Rotavirus is responsible for 611,000 childhood deaths out of which more than 80% occur in low-income countries. The resistance of rotavirus to commonly used disinfectants and ineffectiveness of oral rehydration therapy due to severe vomiting indicates that if an effective vaccine is the preferred option. WHO has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. Currently two vaccines are available against rotavirus. Rotarix (GlaxoSmithKline) is a monovalent vaccine recommended to be orally administered in two doses at 6-12 weeks. Rota Teq (Merck) is a pentavalent vaccine recommended to be orally administered in three doses starting at 6-12 weeks of age. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. However, the efficacy of available rotavirus vaccines is less in low-income countries. Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. Indigenous vaccine, 116E (Bharat Biotech) based on human rotavirus of serotype G9P [11] is still under Phase 2 trials. Another multivalent vaccine is being developed by Shantha Biotechnics in India. The cost effectiveness of the three dose schedule of the available and the rsults of the field trials of the indigenous vaccines should be assessed before inclusion of rotavirus vaccine in the National Immunization Schedule. Keywords: Diarrhea, Rotavirus, Vaccine
How to cite this article:
Taneja DK, Malik A. Burden of rotavirus in India - Is rotavirus vaccine an answer to it?. Indian J Public Health 2012;56:17-21 |
How to cite this URL:
Taneja DK, Malik A. Burden of rotavirus in India - Is rotavirus vaccine an answer to it?. Indian J Public Health [serial online] 2012 [cited 2023 Mar 28];56:17-21. Available from: https://www.ijph.in/text.asp?2012/56/1/17/96951 |
World Health Organization's Strategic Advisory Group of Experts (SAGE) on immunization has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. [1]
While recommending rotavirus vaccine for the National Immunization Programme in India we have to consider a few laid down criteria for an informed decision making. These are:
- Disease burden (incidence/prevalence, absolute number of morbidity/mortality, epidemic/pandemic potential);
- Safety and efficacy of the vaccine under consideration;
- Affordability and financial sustainability of the vaccination programme, even if the initial introduction is supported by the external funding agency;
- Programme capacity to introduce a new antigen, including cold chain capacity;
- Availability of domestic or external vaccine production capacity;
- The cost effectiveness of the vaccination programme vis-à-vis alternatives other than vaccination.
These criteria and some other issues are discussed in relation to possibility of rotavirus vaccine introduction in the National Programme.
| Disease burden globally | |  |
Burden of Diarrhea : Diarrheal disease is one of the leading causes of illness and death in young children in the world, especially the developing countries. A review of articles from 89-2000 published in 2003 estimated that globally the incidence of diarrhea was 3.8 episodes per child per year for children < 11 months of age and 2.1 episodes per child per year for children 1-4 years of age, with an overall estimate of approximately 1.4 billion diarrhea episodes per year in children < 5 years of age. [2] These findings were further confirmed by WHO in its recent report estimating an average attack rate of 3.2 episodes of diarrhea per child per year globally. [3]
Diarrheal disease results in about 2 million deaths per year, ranking third among all causes of infectious disease deaths worldwide. [3],[4] Though global deaths from childhood diarrhea decreased during the past 2 decades, there has been an increase in the number of hospitalizations due to diarrhea. [4] The decrease in diarrhea deaths may largely be attributed to the oral rehydration therapy, which has been reported to prevent 3 million dehydration deaths in a year globally. [5]
Burden of Rotavirus Diarrhea: Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries.
Rotavirus shows proportionately increasing trend with time. It is estimated that rotavirus accounted for 21% hospitalized cases with diarrhea from 1986 to 1999, which increased to 39% of hospitalized cases with diarrhea in the period 2000-2004. [4] This proportionate increase in hospitalizations may explained by a number of factors. First, interventions to improve sanitation and hygiene are likely to have greater impact on diarrhea due to bacterial and parasitic agents as they are primarily transmitted through contaminated food or water, while rotavirus is spread from person to person. Second, use of oral rehydration therapy is difficult in cases of rotavirus diarrhea because of severe vomiting, while it has reduced hospitalizations and deaths due to bacterial and parasitic diarrhea. [6] Third, there is no specific treatment against rotavirus while effective therapy is available against bacterial and parasitic agents.
Rotavirus diarrhea causes about 611,000 childhood deaths (454,000-705,000). More than 80% of these deaths occur in low-income countries. [4]
| Disease burden in India | | |
Morbidity : Based on WHO estimate of 3.2 episodes of diarrhea per year per child (2008) [3] and 110.07 million children under 5 in India as per census 2001, it is estimated that there are 352.23 million episodes of diarrhea among under 5 each year. As 7-8% of community-based diarrhea episodes are due to rotavirus, [4],[7] 24.6-28.2 million episodes are expected to be caused by rotavirus.
Studies between 2001 and 2009 in India also showed an increasing trend of rotavirus isolation from 23.5 to 39.2% among hospitalized children with diarrhea. [2],[7],[8],[9] This is similar to global trends of decrease in hospitalizations due diarrhea caused by bacterial and parasitic agents, following better implementation of oral rehydration therapy, which perhaps has not reduced hospitalizations due to rotavirus diarrhea as these episodes are more severe and there is longer duration of vomiting. [8],[9]
Mortality: NICED in its report estimated that the total diarrheal deaths in India in 0-6 years of age is 1,58,2009. [10] This is lower than estimate of 2, 15, 000 deaths due to diarrhea among children under 5 worked out on the basis of total population of 1028.7 million, [11] crude death rate of 8 per 1000 population, [12] 19% of total deaths being in 0-4 years, and 13.8% deaths among under 5 being due to diarrhea. [13]
Considering the figure of estimated 2, 15, 000 deaths due to diarrhea and 39.2% cases to be due to rotavirus, it comes to >84000 deaths due to rotavirus diarrhea annually in India which is close to estimate of about 1 lakh deaths due to rotavirus diarrhea annually in India. [2]
Thus, the above assessment of the burden of rotavirus in India highlights the importance of rotavirus as an important public health problem of under 5 children in India.
Options for prevention and control: It will be best if measures like hygiene, sanitation, and safe water supply could control it. However, hygienic measures may not be effective in preventing its transmission. The virus survives for long periods on hard surfaces, in contaminated water, and on hands. It is relatively resistant to commonly used disinfectants though inactivated by chlorine. [14] Breast feeding although confers protection against severe rotavirus diarrhea during infancy, but it does not confer overall protection for children up to 2 years, thus it postpones rotavirus diarrhea rather than protect from it. [15]
The other options are either a vaccine to prevent disease or rehydration therapy to prevent deaths as there is no specific antiviral drug against rotavirus. Since, rotavirus diarrhea is relatively severe and with prolonged vomiting, oral rehydration therapy fails in a large number of cases necessitating hospitalization for parenteral therapy.
Thus, the present evidence indicates that if an effective vaccine is available it will be the preferred option.
| Serotype diversity and implications for rotavirus vaccine development | | |
Rotavirus structure : Rotavirus is characterized by its three-layer capsid, an outer and an inner capsid, and an internal shell that surrounds the 11-segment double-stranded RNA genome. The outer capsid is made of two proteins, VP4, also named "P protein," and VP7, also known as the "G protein," which define the "P" and "G" serotypes of the virus, respectively. Both are key neutralization determinants on the surface of the virion. [16]
Rotavirus Diversity: Globally, G1P[8], G2P[4], G3P[8], and G4P[8] constitute 72% of the prevalent serotypes. [17]
Worldwide emergence of G12 strain in 2005 and its increasing incidence subsequently parallels the emergence and subsequent spread of G9 strains that occurred almost a decade ago. It highlights the need for continued surveillance to respond to circulating virus and ensure that vaccines remain effective against emerging strains. [9]
In India, G2P[4] and G1P[8] are the commonest serotypes constituting 48.1% of the prevalent serotypes. There are also a number of unusual serotypes such as G9 P[8] (8.5%), G1P[6], G2 P[6], G2P[8], G9P[4], and G9P[6] which are not prevalent in other parts of the world. Mixed infections are also common. There are also intracountry differences between North, South, East, and West. [9]
| Approaches to Rotavirus vaccine development | | |
There are two approaches to development of rotavirus vaccines. First one is that the use of a monovalent vaccine may confer heterotypic protection as a result of cross-reactive antigens between serotypes. The other approach is based on serotype-specific immunity and it should contain most common HRV strains to achieve optimal protection.
The first clinically licensed rotavirus vaccine (1998) was Rotashield, a live oral tetravalent vaccine comprising of three rhesus human reassortant and one rhesus rotavirus strain. This vaccine was withdrawn soon after licensure due to occurrence of vaccine-associated intussusception. [18]
Currently, two live attenuated oral vaccines are available and others are at various stages of development.
Rotarix by GlaxoSmithKline is based on concept of heterotypic protection using monovalent serotype P1A[8]G1 HRV strain. It is recommended to be orally administered in two doses at 6-12 weeks, with an interval of 4 weeks between 1 st and 2 nd doses and series completion by 24 weeks of age. Rota Teq by Merck is based on the concept of serotype-specific immunity and is pentavalent bovine-human strain containing G1-G4 and P1A[8] antigens. It is recommended to be orally administered in three doses starting at 6-12 weeks of age, with the subsequent doses administration at 4-10 weeks interval, and the third dose administered before 32 weeks. [19],[20]
If we go by the concept of serotype-specific immunity, based on prevalent serotypes, Rota Teq is likely to protect only 48.1% cases diarrhea due of rotavirus in India. Rotarix vaccine may provide protection against strains that have different serotypes but have many cross-reactive antigens. Reports from Europe indicate cross-protection across genotypes with use of Rotarix. [21]
The trials done for both the current rotavirus vaccines world over have shown variable results in developed and developing nations, in terms of efficacy and seroconversion. A recent trial in India for two doses of Rotatrix has shown the seroconversion rate of 58.3%, which is low when compared to the trials in developed countries. [22] The same is true for other countries with intermediate to high Infant Mortality Rate (IMR) like South Africa and Malawi where the efficacy of Rotatrix against severe rotavirus gastroenteritis was 77% and 50%, respectively, unlike developed countries where efficacy ranged from 95.8% to 100%. [1]
Similarly, trials for Rotateq vaccines in Nicaragua, a country with intermediate IMR, showed an efficacy of 46% and 60% for any and very severe rotavirus cases, respectively. This is in contrast to a very high efficacy, ranging from 90 to 98% in developed countries with a low IMR. [1]
Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. [1]
Though efficacy of available rotavirus vaccines is less in low-income countries, in view of large number of deaths due to rotavirus in these countries WHO recommends that even a vaccine with approximately 60% efficacy may be given as it has the potential to save more than 1.5 million lives in Africa and Asia alone, between 2010 and 2025. [1]
| Indigenous development of rotavirus vaccines in India | | |
Indian vaccine manufacturers have started working on development of rotavirus vaccine following the technology transfer arrangement with National Institute of Health (NIH) of USA in the year 2005. Bharat Biotech International, Biological E. Ltd., Shantha Biotechnic, and Serum Institute of India have been granted licenses as part of the NIH initiative. Bharat Biotech's rotavirus vaccine 116E has entered phase 3 human studies in March 2009. [23]
116E is based on human rotavirus of serotype G9P [11] isolated from asymptomatic neonates in AIIMS nursery in mid-1980s. Because rotaviruses do not commonly infect infants in the first few months of life, this strain was unique in that it grew in the presence of transplacental antibodies from the mother. [24] Shantha Biotechnics is currently developing a multivalent vaccine against rotavirus in collaboration with the global nonprofit health organization PATH. [24]
Phase 2 randomized placebo control trial in India using three doses of oral rotavirus 116E vaccine given at 8, 12, and 16 weeks of age has demonstrated four-fold rise in titers in 89.7% of infants. [24] The results of field trial are awaited.
The decision about the efficacy of the vaccine will have to be based on protective efficacy rather than seroconversion as efficacy against severe rotavirus disease has exceeded seroconversion rate in some trials. [25],[26]
In conclusion, it can be stated that diarrhea due to rotavirus among children under 5 is an important public health problem in India. Since traditional measures like sanitation, safe water supply, and hygiene have little influence on its prevention, breast feeding provides protection only for a limited period during infancy and oral rehydration therapy is difficult in view of associated vomiting; an effective vaccine is the logical choice for prevention. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. Emergence of newer serotypes over period of time call for continued surveillance as periodically composition of the vaccine may require to be altered. Rotarix trial using two doses of vaccine in India and other developing countries has shown poor immunogenicity. Response to three doses of this vaccine can be evaluated. We have also to wait for results of field trials of indigenously developed vaccines. Cost consideration will also be important as the country requires about 100 million doses every year for a three-dose schedule. Till these issues are sorted, we will have to wait for recommendation of inclusion of rotavirus vaccine in the National Immunization Programme in India.
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