Prevention of Rotavirus Diarrhea in India:

Is Vaccination the Only Strategy?

Guided by –

Dr. Y.D. BadgaiyanProf. and Head

Deptt of Community MedicineCIMS, Bilaspur (C.G.)

Diarrhea, is the third leading killer of children in India.

It is responsible for 13% of all deaths in children <5 years of age.

It kills an estimated 3,00,000 children in India each year.

Itroduction

Rotaviruses are the major agents causing endemic and epidemic of diarrhea in young children in both developed and developing countries.

In India, approximately 30% of hospitalized diarrhea cases are caused by rotaviruses.

In India, 1 of every 250 children die of rotavirus diarrhea each year.

Which is about 17 percent of the world’s estimated rotavirus deaths.

No specific treatment available but, vaccines are available for prevention of Rotavirus diarrhea.

WHO’s Strategic Advisory Group of Experts (SAGE) on immunization has recommended inclusion of rotavirus vaccine in the National Schedules in countries, where < 5 mortality due to diarrheal diseases is ≥ 10%.

Before inclusion of rotavirus vaccine in National Immunization Programme in India, we have to consider a few laid down criteria for an informed decision making.

Disease burden, safety and efficacy, affordability, programme capacity and cost- effectiveness of the vaccination programme are important issues.

The Rotavirus

Rotaviruses have a distinct wheel like appearance in electron microscopy,

thus have been named rota which in latin means wheel.

Virus is member of the family Reoviridae, and it has a genome of 11 segments of double-stranded RNA.

Rotavirus Structure

The rotaviruses are divided in seven groups A,B,C (human and animal viruses) and D,E,F,G (animal viruses).

Group A rotaviruses are the most frequently identified pathogens.

Rotavirus Particle

Clinical Profile of Rotavirus Diarhhea

Rotavirus diarrhea is most common in children of 6-24 months age group.

Rotavirus infections display seasonal pattern with peak incidence in winter (Oct-Feb).

Risk factors are overcrowding and malnutrition.

Rota viruses are transmitted by the feco-oral route through contaminated environment.

Respiratory route of transmission through aerosol is also suggested.

Low grade fever, vomiting, watery diarrhea, dehydration, and irritability.

Tachycardia and shock, resulting in ischemic injury to the kidneys and CNS are rare complications.

Clinical features

The incubation period of rotavirus diarrhoea varies from 1-7 days.

In newborns, the infection is usually asymptomatic, but 8-24 per cent of neonates may have minimal diarrhoea, and vomiting associated with fever.

In infants and young children, there is an abrupt onset of severe vomiting and diarrhea.

Vomiting usually precedes the onset of diarrhoea.

Stools are usually loose and watery, mucus may be present in 25 per cent of cases but blood is very rare.

Mild to moderate dehydration is seen in 80 per cent of cases and severe loss of fluids and electrolytes may be fatal if untreated.

Mild fever is seen in a large majority of cases.

The illness usually lasts 3-8 days, but virus shedding continues for about 10 days to 1 month.

In immunodeficient children, rotavirus can persist for months.

Older children and adults are infected but they generally suffer from subclinical infections and virus is infrequently detected in their stool samples.

Rotavirus is excreted in large numbers in the faeces (>106 particles/g faeces).

Direct EM examination of stool sample for rotavirus is specific test and has a sensitivity of 80-90 per cent.

Laboratory diagnosis

Other common tests are - - LA (Latex Agglutination) - ELISA and - PAGE (Poly- Acrylamide Gel

Electrophoresis).

Most widely used method is ELISA.

Reverse Transcriptase – polymerase chain reaction (RT-PCR) is confirmatory methods for detecting rotavirus in stool samples.

Epidemiology of Rotavirus in India

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.

Rotavirus diarrhea causes about 6,11,000 childhood deaths (454,000–705,000).

More than 80% of these deaths occur in low-income countries.

Based on WHO estimates, in India there is 3.2 episodes of diarrhea per child per year (2008).

and

110 million episodes of diarrhea in children under 5 year of age.

Burden of Rotavirus Diarrhea in India

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.

It is postulated that improvements in sanitation and use of antimicrobials have had a greater impact on prevention of bacterial and parasitic gastroenteritis (GE) , but not for the rotavirus diarrhea.

The prevalence of rotavirus in neonates is high in India, ranging from 22% to 73% .

Neonatal infections are commonly asymptomatic, with 69-95% not showing overt signs of GE.

Neonatal infections

Most rotavirus disease in India occurs in the first two years of life.

In hospital-based studies, 87% (ISV: 58- 95%) of all rotavirus cases in children under 5 yr occurred by 18 months of age.

Age distribution

Additionally, rotavirus Gastro-enteritis is uncommon in the youngest children.

Only 13% (ISV: 10-25%) of rotavirus cases in hospital studies were in children younger than 6 months old.

In young children, infection with rotavirus may be attenuated by the persistence of maternal antibodies and thus, severe disease is less common.

Most studies in India have found association between rotavirus infection and time of year.

Most have observed an increase in rotavirus-associated diarrhea during the winter months, October to February, throughout the country.

Seasonality

The observed proportion of rotavirus cases occurring in the cooler season has ranged from 59% to 72%.

The northern, more temperate regions may exhibit stronger seasonality.

Rotavirus isolates from India are genetically heterogeneous.

Such genetic diversity is characteristic of Asia as a whole.

It is suggested that rotavirus strains circulating in India are part of a larger Asian transmission pool.

Serotype diversity

No specific treatment exists for rotavirus gastroenteritis, and repeated infections are common in children.

Sanitation and hygiene improvements have had a tremendous impact on diarrheal diseases due to bacteria and parasites but less impact on rotavirus disease.

Treatment and Prevention

Reduced osmolality oral rehydration solution (ORS) effectively prevents and treats dehydration, and also reduces diarrheal output.

But the 2005 National Family Health Survey found that only 26% of children with diarrhea receive ORS.

Unlike many other diarrheal pathogens, the proportion of diarrhea caused by rotavirus does not vary widely between developed and developing countries.

To date, the only specific prevention strategy is immunization with rotavirus vaccines.

Rotavirus Vaccines

Currently, two rotavirus vaccines are available on the international market.

1. Rotarix

2. Rota Teq

ROTAVIRUS VACCINES

Rotarix (GlaxoSmithKline, Rixensart, Belgium) is a mono-valent rotavirus vaccine.

(RV1) created by attenuating a highly antigenic strain of human G1P rotavirus.

Rota Teq (Merck and Co., Whitehouse Station, USA) is a penta-valent vaccine.

(RV5) created by re-assorting G and P antigens from human rotavirus, G1, G2, G3, G4 and P with a bovine rotavirus strain.

These vaccines appear to be cross protective against non-vaccine strains, with similar efficacy against vaccine and non-vaccine strains.

In high and middle income countries, recent introductions of RV1 and RV5 have had remarkable impact on rotavirus disease despite limited uptake in the under 5 population.

Based on the experiences of other developing countries, a rotavirus vaccine introduced in India would be expected to exhibit lower efficacy against rotavirus GE than seen in high income countries,

but still prevent a significant proportion of all-cause GE mortality and hospitalizations.

Live oral vaccines have had an inconsistent performance in India and other developing countries.

For example, oral polio vaccine (OPV) is less immunogenic and requires more doses to protect children in India compared with children in the developed world.

Challenges to rotavirus vaccine performance in India

In developing countries, higher levels of maternal rotavirus antibodies are passively transferred to babies during gestation and persist in infancy.

Other reasons for poor vaccine performance could be a higher prevalence of distinct medical conditions such as tuberculosis, intestinal infections and malnutrition.

It is estimated that at current immunization levels, a national rotavirus vaccination program in India would prevent 27,000 to 44,000 deaths in children <5 years of age annually.

Rotavirus vaccine would prevent 1 case of severe gastroenteritis disease for every 11 children immunized, and prevent one death for every 470 children immunized.

Potential impact of rotavirus vaccines in India

The potential impact of rotavirus vaccines in India is partially hindered by a relatively low proportion of children who receive routine immunizations.

If full immunization with rotavirus vaccine were reached, an additional 14,000 rotavirus deaths each year could be prevented.

Improving the overall performance of the immunization system is critical to the success of any vaccine introduction.

Conclusions

Rotavirus diarrhea causes substantial mortality and morbidity in young children in India with the greatest burden among children <2 years of age.

Despite the tremendous diversity of rotavirus strains in India, rotavirus vaccines provide cross-protection and have been shown to be effective against both vaccine and non-vaccine strains.

Conclusions

At current coverage levels of routine childhood immunizations, the introduction of rotavirus vaccine in India could prevent up to only one third of rotavirus-related deaths.

Introduction of rotavirus vaccine into the national immunization program of India at an affordable price would be a cost effective way to reduce the tremendous morbidity and mortality due to rotavirus disease in Indian children.

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