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Gastroenteritis

Globally, diarrhoeal disease is responsible for around 1.87 million deaths in children under the age of 5 every year, accounting for 19% of total childhood deaths. Most of these deaths occur in developing countries. Even in industrialized countries, where deaths are less common, gastroenteritis is a major cause of morbidity especially in the very young. Acute gastroenteritis may be caused by a range of pathogens including bacteria, viruses and parasites. In recent years, improvements in hygiene, sanitation and water supply in developing countries has resulted in a drop in the proportion of cases due to bacterial causes. As a result the majority of diarrhoeal disease hospitalizations are due to viruses.

Clinical features

Infection occurs via the faecal-oral route. Viral gastro-enteritis has a short incubation period (about 24 hours). It presents with a sudden onset of vomiting and profuse watery (secretory) diarrhoea. The condition is self limiting and lasts for 2-3 days. Morbidity and mortality is due to dehydration and young infants are at greatest risk.

Pathogenesis

Viruses infect enterocytes of the upper small bowel, causing inflammation and transient blunting of the villi. In addition, some viruses (such as rotavirus) produce enterotoxins that promote fluid and electrolyte loss from enterocytes. Virus is cleared and symptoms resolve with the development of a local immune response. Specific secretory IgA antibodies confer immunity and prevent symptomatic re-infections with antigenically related viruses.

The four commonest viral causes of diarrhoea are:
Rotaviruses
Caliciviruses (Norovirus and Sapovirus)
Adenoviruses
Astroviruses

Virology of diarrhoeal viruses

 

Rotavirus

Norovirus

Adenovirus

Astrovirus

Family

Reoviridae

Caliciviridae

Adenoviridae

Astroviridae

Genome type

dsRNA

ssRNA

dsDNA

ssRNA

Genome organisation

Segmented

Linear

Linear

Linear

Enveloped

No

No

No

No

Morphology

Spherical with wheel-like surface structure

Small with star-like surface structure

Icosahedral

Small, with star-like surface structure

Rotavirus

Rotaviruses account for approximately 35% acute diarrhea in developing countries.

A simplified diagram of the location of rotavirus structural proteins, courtesy of Graham Colm on Wikipedia

Protective immunity is directed to 2 surface proteins: G (VP7) and P (VP4)
In nature there are numerous antigenically different G and P subtypes and humans can suffer repeated rotavirus infections.
Reassortment with different rotaviruses can occur (segmented genome).
Human disease is caused by rotaviruses that specifically infect humans, but there are rotaviruses that infect other animals as well. Animal rotaviruses can infect humans, but do not cause disease
Immunity following first infection is incomplete and humans can have repeated infections with rotaviruses of a different G or P subtype. Repeated infections tend to be less severe.

Disease severity is linked to the age of first rotavirus encounter. In the developing world, most children encounter rotavirus for the first time during the first year of life. Often in the first 3 months. Maternal antibody may ameliorate disease severity in the neonatal period, but protection is short lived.
Severe disease is usually only seen during first exposure. Infection is followed by partial immunity (immunity to severe disease) and is cross protective. i.e. protects from severe disease due to rotaviruses of another serotype.

Rotavirus vaccines:
Protection from re-infection/disease is antibody mediated (especially secretory IgA).
2 oral live attenuated rotavirus vaccines that protect against severe rotavirus disease are in current use:

Rotarix is a live attenuated monovalent vaccine derived from a human rotavirus. It has been serially passaged in cell culture and is of reduced virulence. It induces broadly cross reacting immunity to many rotavirus serotypes. Immune response to this is enough to reduce disease severity on second encounter with any other common rotavirus type. (Still can get disease, but not so bad!). This vaccine was introduced into the infant EPI programme in South Africa in August 2009. Infants receive 2 doses of vaccine at 10 and 14 weeks.
Rotateq is a pentavalent human and bovine rotavirus reassortant vaccine. It is a bovine rotavirus that has been reassorted to contain the genes that code for the 4 commonest G protein subtypes as well as the commonest P subtype seen in human rotaviruses. (Remember protective immunity is directed to the G and P proteins on the virus surface).

Caliciviruses (genus Norovirus)

Within the calicivirus family, noroviruses are a recognized cause of gastro-enteritis. They account for approximately 10% acute diarrhea in children under 5 years in developing countries. But they are also the commonest cause of food borne non bacterial gastro-enteritis outbreaks in people of all ages world wide. Noroviruses have been famously responsible for large food borne outbreaks (epidemics) in cruise ships and other gatherings.
Clinical features of infection are similar to other viral causes of gastro-enteritis.
Stool and vomitus are highly infectious. Transmission of infection is via feacal oral route, but also through aerosolized droplets. High attack rates are seen during outbreaks (in both children and adults). Immunity following infection is short lived and re-infections are common.

There are no vaccines available

Enteric Adenoviruses

Adenoviruses are responsible for a range of clinical conditions involving respiratory, gastrointestinal, ocular and urinary tracts. Two serotypes are responsible for causing acute gastro-enteritis, namely adenovirus 40 and 41 (group F adenoviruses).

Enteric adenoviruses 40 and 41 are responsible for around 6.5% acute diarrhea in children under 5 in developing countries. Their relative importance as a cause of gastro-enteritis varies in different parts of the world.

There is no vaccine.

Astroviruses

Account for about 3.5% of acute gastro-enteritis. There is no vaccine.

Laboratory diagnosis of viral gastro-enteritis:

Identifying the viral cause is not necessary for management of infants with acute gastro-enteritis. However, for epidemiological purposes it may be useful. A variety of rapid antigen detection tests are available for detecting gastro-enteritis viruses in stool samples.

Management

Supportive. The mainstay of treatment is rehydration. Most cases resolve spontaneously. Good infection control practices are essential to prevent spread in the hospital context. Many of these viruses are highly resistant to inactivation and can remain viable on environmental surfaces.

Prevention

Breast fed infants are at lower risk of viral gastro-enteritis (maternal IgA in breast milk provides protection and potentially contaminated feeds are avoided). For this reason exclusive breastfeeding for the fist six months is recommended by WHO.
Availability of clean water and improvements in sanitation and hygiene reduce the circulation of these viruses.
A live attenuated rotavirus vaccine has been introduced as part of the EPI programme in South Africa - see above.