Brief overview of gastrointestinal viruses 

Specific viral pathogens cause various gastrointestinal (GI) diseases in both immunocompetent and immunocompromised individuals. The most common symptom among them is watery /bloody diarrhoea, whereas more severe cases can cause hepatitis, ulcerative diseases, motility disorders, and neoplastic diseases of the GI tract.

Infectious gastroenteritis, which involves inflammation from the stomach to the small intestine, is a major illness worldwide, especially in developing nations.¹

Some common viruses affecting the gastrointestinal system

Table 1: Summary of common GI viruses based on type, population, disease type, diagnosis and treatment. Fomites = contaminated objects and surfaces that can spread infection.

The structure of norovirus 

Human noroviruses (HNoVs) belong to the Caliciviridae family and are classified under the Norovirus genus. They are responsible for outbreaks of acute gastroenteritis and sporadic cases of the disease. HNoVs are small and round-shaped with a linear, positive-sense, single-stranded RNA genome.

The genome of HNoV is organised into three open reading frames (ORFs). 

• ORF1 encodes a polyprotein that is posttranslationally cleaved into seven nonstructural mature proteins (NS1–NS7). These seven nonstructural mature proteins play a role in viral replication
• ORF2 encodes the major capsid protein (VP1) that is involved in maintaining the virus structure, together with ORF3
• ORF3 encodes the minor capsid protein (VP2)²

HNoVs are currently classified into seven genogroups (G), three of which (GI, GII, and GIV) are involved in human outbreaks; more specifically, GI and GII are involved in the majority of clinical cases.²

Signs and symptoms

Norovirus, also known as the Norwalk virus, is a cause of acute gastroenteritis. It is transmitted mainly through the faecal-oral route. Individuals of almost all age groups can contract and become ill with norovirus. 

Symptomatic norovirus gastroenteritis typically develops within 12-48 hours and lasts 24-72 hours after consuming contaminated food, drinking contaminated water, or coming into contact with an infected individual. 

Symptoms include the following:

• Nausea and vomiting
• Watery diarrhoea (without blood)
• Abdominal cramps
• Headaches
• Myalgias and malaise

Vital signs in norovirus gastroenteritis include the following:

• Low-grade fever
• Tachycardia
• Possible hypotension with volume depletion³

Pathophysiology

Noroviruses are infectious viruses, capable of direct person-to-person transmission through contact, droplet sprays, or the faecal-oral route. The norovirus also survives in harsh environments and unfavourable conditions, even after exposure to chlorination or sanitisation for several weeks, and can withstand freezing and boiling temperatures of 60 degrees Celsius or less. It has an incubation duration of around one to two days, after which symptoms appear, and lasts for one to three pleasant days (or longer in immunocompromised persons). Infection with the virus may be followed by shedding, which may persist for up to three weeks.

The structure of noroviruses allows them to bind to polymorphic histoblood group antigens (HBGAs), which are thought to act as receptors or cofactors for norovirus infection. Different genocluster strains bind to various HBGAs. Blood Group I viruses show a strong preference for blood groups A and O, while Blood Group II viruses exhibit a high affinity to blood groups A and B. Some strains of the norovirus target a very small subset of the population; however, with the broad range of binding profiles seen in genogroup I and genogroup II viruses, almost every human is likely to be capable of contracting norovirus. Repeated episodes of the same sickness may occur throughout a lifetime due to the continuous availability of different norovirus strains and the absence of cross-strain immunity or long-lasting immunity.

If an infection occurs, damage is inflicted on the microvilli of the small intestine, resulting in blunted villi but intact mucosa and epithelium. Diarrhoea is caused by epithelial cell apoptosis, a break in tight junction proteins, D-xylose, fat malabsorption, and enzymatic dysfunction, while a delay in gastric emptying causes vomiting. There is no invasion of the colon by norovirus; hence, faecal leukocytes are generally absent and bloody stools are not common.³

Diagnosis and detection 

To diagnose Norovirus infection, the presence of the virus in stool specimens is ascertained through (immune) transmission electron microscopy (TEM), antigen ELISA, or polymerase chain reactions (PCR). Each method, TEM, ELISA, and PCR, works well for carrying out epidemiological inquiries into gastroenteritis outbreaks. When diagnosing a case in an individual patient, it is recommended that at least two of the methods be employed to enhance diagnostic accuracy.⁴

A stool culture must be performed to exclude the possibility of infectious agents, primarily bacterial organisms such as those belonging to the genera Yersinia, Shigella, Salmonella, and Campylobacter, among others.³

Management and treatment 

Oral or intravenous fluid replacement is the main factor for managing norovirus infection. Antiemetics and antidiarrheal agents are not included in standard treatment protocols for acute gastroenteritis in children. Nonetheless, in adults, rehydration may be complemented with the use of antiemetic, antimotility, and antisecretory agents. No antibiotic treatment is effective for norovirus infections.⁵

Rotavirus and its structure

Rotavirus consists of double-stranded RNA organised into 11 segments and is covered by a double-shelled capsid. It belongs to the family Reoviridae. Rotavirus is among the viruses that cause gastroenteritis. Rotavirus infections are self-limiting. In children, the losses due to watery stools might be excessive, and deaths due to dehydration are common, especially in third-world countries.⁶

Signs and symptoms 

More often, a history of exposure to other children with diarrhoea is reported.

Symptoms usually appear within two days of exposure and include the following:

• Loss of appetite
• Mild febrile temperature
• Painless, unbloody diarrhoea
• Regurgitation
• Colicky abdominal pain⁶

Pathophysiology

Rotaviruses multiply within fully developed enterocytes across the entire small intestine. This alters the small intestinal epithelium, resulting in increased water secretion and impaired nutrient absorption. Additionally, undigested sugars also draw more fluid into the small intestine, which contributes to the characteristic watery diarrhoea associated with rotavirus infection. Enhancement of intestinal motility due to rotavirus infection is another plausible mechanism linked with diarrhoea, the rationale of which remains ambiguous.⁶

Diagnosis and detection

Rotavirus has clinical features similar to those of other gastrointestinal infections caused by pathogens such as norovirus, enteric adenovirus, and astrovirus, as well as E. coli and Salmonella. In most cases, history and physical examination are adequate, where mild fever, vomiting, and watery diarrhoea raise the suspicion of rotavirus. Differing from other infections, however, rotavirus gastroenteritis can present with fever, acidotic diarrhoea (where acid builds up in the body), and low serum bicarbonate, but gross bloody diarrhoea usually points to another infectious agent.

Although seldom required, the laboratory examination is the sole means of confirming rotavirus infection. In cases of severe or ongoing illness, stool antigen tests (using ELISA or immunochromatography) and reverse transcription PCR may also be performed to confirm rotavirus infection and aid in genotyping for epidemiological purposes. Other detection methods include electron microscopy, electrophoresis, antigen tests, and virus culturing. Typically, confirmation is recommended only when it is likely to result in savings in hospitalisation costs or the avoidance of inappropriate interventions.⁶

Management and treatment

Oral rehydration therapy has been proven safe and effective in preventing and treating dehydration caused by a wide range of diarrhoeal illnesses, including rotavirus, particularly in infants and young children.

Improvements in hygiene and sanitation alone do not significantly reduce the incidence or impact of rotavirus disease. Before the vaccine was available, hospitalisations due to diarrhoea were similar, at approximately 40% in both high-income countries and low-income countries. As such, immunisation is the only focus that has positive outcomes in delivery.

The current principal vaccines include RV5 (RotaTeq, Merck, USA) and RV1 (Rotarix, GSK, Belgium). RV5 is a live pentavalent vaccine that combines reassorted rotaviruses containing five different human bovine reassortant rotaviruses having the G1, G2, G3, G4, and P1A VP4 or VP7 proteins [8]. In the USA, it is administered in three doses at 2, 4, and 6 months of age. RV1 is a live attenuated monovalent vaccine belonging to strain G1P[8] administered in two-week intervals of two doses, the first dose at 2 months and the second dose at 4 months. Similar schedules are generally followed in other parts of the world, although a different dosing regimen has also been tested.⁷

Summary

Norovirus and rotavirus are the major causes of acute gastroenteritis in children worldwide. They interact with their host by binding to histoblood group antigens (HBGAs) through various mechanisms. Diarrhoeal diseases contribute significantly to morbidity and mortality rates throughout the world, particularly among young children in developing countries. Among intestinal viruses, rotavirus and norovirus play the more significant roles in causing severe gastroenteritis in children. 

Before the introduction of rotavirus vaccines, rotavirus was responsible for 40% to over 60% of all paediatric admissions for acute gastroenteritis worldwide. Norovirus was identified as the causative agent in 3% to 31% of cases. In countries with successful rotavirus vaccination programs, norovirus has since become the leading cause of gastroenteritis in children.

Therefore, the assessment and control of both rotavirus and norovirus should be prioritised in intervention strategies aimed at improving the growth and health outcomes of young children.⁸