Facts on Rotavirus Enteritis

Dr Nazrul Neezam Paediatric Gastroenterologist Paediatric Institute, HKL

Introduction
First isolated in 1973 in Australia by Ruth Bishop at the Royal Children's Hospital in Melbourne EM identification from duodenal biopsies from children with diarrhea. "Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis," Lancet, 1:1281-3, 1973 Rota wheel Reoviridae family

Introduction
Cause more severe and acute diarrhea in children: 111 millions of cases require ambulatory care 25 millions of medical consultations 2 millions of hospitalized patients From 352,000 to 592,000 deaths of children.

Global Distribution of 527,000 Annual Rotavirus Deaths in Young Children

1 dot = 250 deaths

Parashar et al, JID, 2009

We do have Rotavirus deaths

10 cases of acute diarrheal deaths among 4689 admitted to an urban hospital over the period of 15 years
Lee et al. Deaths following acute diarrhoeal diseases among hospitalised infants in Kuala Lumpur Med J Malaysia 1999; 54:303-9

Based on an estimated 2.5 deaths/100,000 children, authors estimated that each year, there would be 34 children died of RV-A infection
Hsu et al. Estimates of the burden of rotavirus disease in Malaysia. J Infect Dis 2005; 192(Suppl 1):S80-6

Another nationwide study on the under-5 mortality in 2006, involving all government hospitals and rural health centers, showed that a total of 320 deaths were classified under certain infectious and parasitic diseases and 89 of these deaths were attributable to acute diarrheal disease
Wong SL, Hussain IMI. A study on under five deaths in Malaysia in the year 2006. Clinical Research Centre, Kuala Lumpur, 2008

We do have Rotavirus deaths

Wong SL, Hussain IMI. A study on under five deaths in Malaysia in the year 2006. Clinical Research Centre, Kuala Lumpur, 2008

We do have Rotavirus deaths

Important aetiology of severe diarrhea in less than 5 yrs

Developed Countries Developing Countries

Unknown

Rotavirus

Unknown

Rotavirus

Bacterial

Other Other Bacterial

A. Kapikian, Fields Virology 2003

Seasonality pattern
Patel et al. Global seasonality of Rotavirus disease. The Pediatric Inf Dis Journal 32(4) April 2013

In Malaysia..

AGE is the most common indication of hospital admission Rotavirus the most common identifiable enteropathogen, both in the community and in those who required hosp admission with estimated 8571 admissions yearly. High morbidity with rotavirus infection ie. about half of those admitted had moderate to severe dehydration

Hsu VP, Abdul Rahman H, Wong SL, et al. Estimates of the burden of rotavirus disease in Malaysia. J Infect Dis 2005;192(Suppl. 1):S806.

Hsu VP, Abdul Rahman H, Wong SL, et al. Estimates of the burden of rotavirus disease in Malaysia. J Infect Dis 2005;192(Suppl. 1):S806.

ctd
Significant financial burden with median direct cost of hosp admission to manage rotavirus AGE is estimated to be 211.91 USD Hence yearly cost of managing in patient rotavirus AGE is estimated to be 1.8 million USD Cost would be much higher if outpatient visits, non medical costs are included
Lee WS, Poo MI, Nagaraj S. Estimates of economic burden of providing inpatient care in childhood rotavirus gastroenteritis from Malaysia. J Paediatr Child Health 2007;43:818-25.

ctd

Lee WS, Poo MI, Nagaraj S. Estimates of economic burden of providing inpatient care in childhood rotavirus gastroenteritis from Malaysia. J Paediatr Child Health 2007;43:818-25

Transmission route
Fecal oral
Person to person, Foods, Food handlers, Fomites survives many days in the environment

Airway has been suggested due to - High rates of infection during first 3 yrs of life regardless of sanitary conditions - Failure to document fecal oral transmission in several outbreaks - Dramatic spread over large geographic areas during winter
UD Parashar. CDC Atlanta, USA

Clinical course of infection

Incubation period 1 3 days Sudden onset (6 days):
Vomiting disappear in 24-48 hours Fever Profuse watery diarrhea Dehydration Encephalopathy / Encephalitis reported

Contagiousness
8 days >30 days in immunocompromised

Management
General principles : - Identification of children at risk of complication - Prevention / correction of dehydration and electrolyte imbalance - Supplementary / adjuvant pharmacotherapy - Provision of adequate and appropriate nutrition

Oral rehydration

NO SIGNS OF DEHYDRATION

Home management if no excessive vomiting Continue usual feeding practice Normal diet ORS 10 mls/kg per purge
Needs replacement with 30-90 mls/kg of ORS within 2-3 hrs Followed by ORS 10 mls/kg per purge Small frequent feeds with reassessment Intravenous fluids if fails oral rehydration

SOME SIGNS OF DEHYDRATION

SEVERE DEHYDRATION

Intravenous fluids with or without fluid boluses depending on situation Oral rehydration to be encouraged

Oral rehydration
When oral rehydration fail: In about 5% of children the signs of dehydration do not improve during ORT, or they worsen after initial improvement. The usual causes are : Continuing rapid stool loss ( > 15-20ml/kg/hour ) Insufficient intake of ORS solution owing to fatigue or lethargy Frequent , severe vomiting Treatment : Give ORS solution by nasogastric tube Or IV fluids (amount to be given depend on the degree of dehydration)

Nutrition

Issues regarding nutrition When to refeed ? To dilute or not to dilute ? Specialized formula ? Use of zinc supplements ?

Nutrition

When to refeed ? - As tolerated, no specific withdrawal period. Should not be withdrawn longer than 4-6 hrs after rehydration. - Breast feeding and formula feeding to be continued.

Nutrition To dilute or not to dilute ? - No evidence to support dilution of formula during AGE episode. - During acute phase, diarrhea is as a result of combined secretory and osmotic hence slight reduction of stool output is expected. However, the duration of diarrhea remains the same. - Will affect the nutritional status whereby patients on diluted formula take longer time to regain their weight.
Brown et al. Use of non human milks in the dietary management of young children with acute diarhea : a meta analysis of clinical trials. Pediatrics 1994;93:17-27

Nutrition Soy formula ? Lactose free formula ? Extensively hydrolyzed formula ? Elemental formula ? - No specific indication to empirically start with these formulas during acute phase. - Soy or lactose free formulas can be considered if suspected to have secondary lactose intolerance. (soy not recommended for infants less than 6 mths old) - Extensively hydrolyzed formula (ailementum) / elemental formula (neocate / comidagen) are reserved for suspected secondary cows milk protein allergy.

Nutrition
Use of zinc supplements ? - In patients with pre existing malnutrition. Acrodermatitis enteropathica

Recommendation on the use of anti emetics and anti diarrheal agents as adjunctive treatment on childhood acute gastroenteritis Malaysian Guideline 2011

Prevention
Improved sanitation alone does not seem to reduce incidence worldwide Vaccination is single most effective preventive strategy WHO in 2009 has put up a recommendation to introduce rotavirus vaccine in all national immunization program but take up rate is low (only 28 countries) due to various factors The Philippines is the first SEA country that has introduced rotavirus vaccination into their national immunization program

Rotavirus vaccines

First licensed in August 1998 for infants less than 6 mths (ROTASHIELD) but withdrawn October 1999 due to excess number of recipient who developed intussuception during post-licensure surveillance Rotateq and Rotarix were reintroduced in 2006 following landmark clinical trials which demonstrated its safety and efficacy

BASIC FEATURES OF ROTATEQ ROTARIX VACCINES

RotaTeq Pharmaceutical company Origin Valency Merck & Co. Human/bovine reassortant Pentavalent

Rotarix GlaxoSmithKline Human attenuated Monovalent

Serotypes
Number of doses Number of children enrolled Study locations Efficacy against Any AGE Severe AGE

G1, G2, G3, G4, P[8]

Three 70 301 Five each of European and Latin American countries Taiwan and the United States 74% 98%

G1P[8]
Two 63 225 11 Latin American countries and Finland 87% 96%

Percentage of rotavirus tests with positive results from NREVSS laboratories, by week of year and region . JE Tate et al Trends in National Rotavirus Activity before and after introduction of Rotavirus Vaccine into the National Immunization Program in the US, 2000-2012. The Pediatric Infectious Disease Journal May 2013

Lee et al. Rotavirus genotypes in Malaysia and Universal rotavirus vaccination. Human Vaccines & Immunotherapeutics 8:10, 1-6; October 2012

The projected annual reduction in RVGE-related deaths was 27 to 32 deaths (from 34 deaths) for Rotateq and 28 to 32 deaths annually for Rotarix

So it is effective but why the take up rate is low ?? Main benefit of reducing mortality in low income countries Many suggest the lack of cost savings for morbidity primarily because the price of vaccines is high (middle income countries) Cost is also an issue in wealthy developed countries to justify the necessity for routine vaccination

Quite recently.

Thank You