Viral Diarrhea

Etiology

The most frequently studied human pathogens are rotavirus, enteric adenovirus, astrovirus, and the genera Norovirus and Sapovirus in the Caliciviridae family. Certain members of the Picornaviridae family, such as aichivirus, are believed to cause gastroenteritis, while the origins of other viral sources of diarrhea remain unidentified.[3][4][5] Norovirus, a member of the Caliciviridae family, is a small, nonenveloped, and single-stranded RNA virus that is the most common cause of acute viral gastroenteritis. This virus can lead to substantial outbreaks, often from contaminated water or food and through person-to-person transmission.

Other significant virus outbreaks may occur in schools, cruise ships, and other highly populated areas. Rotavirus, of the Reoviridae family, is a nonenveloped and double-stranded RNA virus. On the other hand, enteric adenovirus is a nonenveloped and double-stranded DNA virus, with types 40 and 41 primarily responsible for causing gastroenteritis, commonly observed in children younger than 2.[6]

Epidemiology

This disease peaks during the winter and spring seasons and easily transmits from one individual to another. Before the development of a vaccine, rotavirus was responsible for approximately 30% to 70% of hospital admissions in children with acute gastroenteritis. Around the world, rotavirus is responsible for causing approximately 800,000 cases of acute gastrointestinal illness in children. When adults contract rotavirus, their symptoms typically tend to be less severe than those experienced by infected children.

Norovirus is the predominant cause of community-acquired diarrhea, which gives rise to outbreaks of gastroenteritis and instances of foodborne disease both in the United States and worldwide. Current figures for Norovirus infection in the United States reveal that it contributes to approximately 800 deaths, 71,000 hospitalizations, 400,000 emergency department visits, 1.9 million outpatient visits, and 21 million morbidities yearly.[7][8] 

Adenoviruses are generally less infectious than rotaviruses and noroviruses, reducing medical impact. Two strains of adenovirus, serotypes 40 and 41, are frequently associated with gastroenteritis among children younger than 2, especially within daycare settings.

Every year, cases of diarrheal illness in the United States account for approximately 179 million outpatient visits, 500,000 hospitalizations, and over 5000 fatalities.[9]

Pathophysiology

In severe cases of rotavirus infection, analyses of duodenal biopsy specimens obtained from young children have revealed denuded villi and flattened epithelial surfaces, ultimately resulting in villus blunting and malabsorption. Furthermore, NSP4, an enterotoxin released by rotavirus, triggers intestinal secretion, ultimately resulting in the onset of diarrhea.[10]

Noroviruses are highly contagious, with a median infectious inoculum of 18 to 1000 viral particles. They can be transmitted through various means, including person-to-person contact, contaminated food, water, air, and fomites. Moreover, these viruses engage in error-prone replication, boasting 5 genogroups and a minimum of 30 genotypes—a combination that renders humans notably prone to recurrent infections.

Enteric adenoviruses primarily affect children younger than 4 and generally possess lower infectivity than rotaviruses and noroviruses. Adenovirus infection manifests an incubation period of 8 to 10 days and can persist for up to 2 weeks.[11]

Histopathology

Following rotavirus infection, histopathology of the small intestine reveals shortening and blunting of mucosal villi and mononuclear cell infiltration of the lamina propria in the jejunum and duodenum. Furthermore, rotavirus particles are detected within epithelial cells. Typically, within 4 to 8 weeks, biopsies tend to return to normal histological patterns.

Following Norovirus infection, histopathology of the jejunum reveals blunting of mucosal villi and infiltration of mononuclear and polymorphonuclear cells in the lamina propria. Typically, these alterations tend to resolve within 2 weeks. 

Adenoviruses can cause intranuclear inclusions, initially appearing in eosinophils and later in basophils. In some instances, these inclusions might be misinterpreted as cytomegalovirus inclusions.[12]

History and Physical

Symptoms linked to acute viral gastroenteritis typically manifest following an incubation period of 24 to 60 hours, with the expected duration ranging from 12 to 60 hours. Vomiting occurs frequently. The duration of diarrheal symptoms can differ among various viral pathogens.

In rotavirus infections, vomiting frequently marks the onset of the illness, followed by acute watery diarrhea. In addition, fever is present in approximately one-third of cases and may accompany these symptoms. The illness usually lasts between 5 and 7 days. Norovirus symptoms commonly include nausea, vomiting, and diarrhea. However, a smaller subset of children might experience only vomiting, whereas older adults may manifest solely diarrhea. The incubation period ranges from 12 to 48 hours, and symptoms typically persist for 1 to 3 days. Conversely, enteric adenovirus infection has an extended incubation period of 8 to 10 days, and the associated illnesses might endure for up to 2 weeks.

Patients often experience mild, diffuse abdominal pain upon palpation during a physical examination. Although voluntary guarding might be observable, the abdomen usually maintains a soft texture. Fever between 101 °F and 102 °F is observed in approximately half of all cases. Instances of moderate-to-severe dehydration are relatively infrequent.[9]

Evaluation

Patients should undergo further assessment to explore both infectious and noninfectious origins of their acute diarrhea. Diagnosing acute viral gastroenteritis primarily relies on clinical evaluation, rendering laboratory tests and stool studies unnecessary for diagnosis and treatment. Stool studies are usually negative results for leukocytes and blood. However, stool studies should be conducted in cases of persistent fever and dehydration or to detect the presence of blood or pus in the stool. If signs of dehydration are not present, it is not required to measure serum electrolytes. Assessing the complete blood count does not reliably assist in differentiating between viral and bacterial gastroenteritis. Reverse transcriptase–polymerase chain reaction (RT-PCR) of stool is the most frequently used laboratory test to diagnose viral gastroenteritis.

Rapid diagnostic tests are available for detecting rotavirus antigens and adenoviruses in fecal samples using monoclonal antibody-based enzyme immunoassay (EIA), latex agglutination, or nucleic acid amplification techniques (NAATs). The diagnosis of Norovirus has faced challenges due to its viral diversity. Consequently, Norovirus outbreaks have traditionally been identified using Kaplan criteria. These criteria comprise a brief incubation period of 1 to 2 days, a concise illness duration of 12 to 60 hours, and the presence of vomiting along with negative stool culture in more than 50% of affected persons. These criteria exhibit a sensitivity of 98% and a specificity of 68%. Noroviruses can be identified through the RT-PCR technique for genomic amplification or EIAs to detect antigens. Currently, no universal assay is approved by the U.S. Food and Drug Administration (FDA) to diagnose Norovirus infection.[13][14][15]

Treatment / Management

Viral diarrhea is an acute and self-limiting condition that usually does not require pharmacological therapy. This condition is usually addressed in an outpatient setting through supportive measures, primarily focusing on maintaining hydration in patients. Indications for hospitalization include severe dehydration, intractable or bilious vomiting, inability to tolerate or failure of oral fluids, renal or electrolyte abnormalities, neurologic dysfunction, and severe abdominal pain. Other indications for hospitalization include bloody diarrhea, patients aged 65 or older, weight loss, an immunocompromised state, uncertain home management circumstances and follow-up, pregnancy, or recent hospitalization or antibiotic use within the past 3 to 6 months, which prompts consideration of Clostridioides difficile infection.

The primary concerns in viral gastroenteritis are fluid and electrolyte imbalances. Sports drinks and broths can support adults with acute viral gastroenteritis without signs of volume depletion. Adults exhibiting mild-to-moderate volume depletion should receive treatment with oral rehydration solutions, which are preferable to sports drinks for maintaining proper electrolyte balance and hydration. Individuals experiencing severe hypovolemia or those unable to tolerate oral rehydration necessitate intravenous fluid repletion. Patients should be encouraged to consume food as their tolerance allows without imposing strict limitations. Recommendations may include choosing smaller meals and incorporating bland or low-residue food options in their diet.[16][17]

Antiemetics and antidiarrheal medications are occasionally used for intractable vomiting or diarrhea, although their routine usage is discouraged due to potential adverse effects. Similarly, the use of probiotics and prebiotics is generally not recommended.

Zinc supplementation has not been extensively studied in adult patients with acute diarrhea, so it is not recommended for individuals. However, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) recommend zinc administration for children with acute diarrhea, as diarrhea may lead to zinc deficiency, exacerbating symptom duration and severity.

Two commercially accessible rotavirus vaccines, a pentavalent and monovalent (RV1), exist, which are initially administered in multiple doses to children at 2 months of age.[18]

Differential Diagnosis

The differential diagnosis for acute viral gastroenteritis encompasses other infectious origins, including viral, bacterial, and parasitic infections, as well as noninfectious factors that contribute to acute diarrhea. When dealing with cases of diarrhea persisting for over 1 week, it is essential to gather a comprehensive patient history, including inquiries about recent travel, hiking, or engagement in oral or anal sexual activity. A positive historical account should lead to evaluation for protozoa such as Cryptosporidium and Giardia. In recent hospitalization or antibiotic use, it is essential to consider the possibility of C difficile infection.

Foodborne illnesses primarily caused by bacterial infections should be considered when symptoms emerge within a shorter incubation period, usually within 8 to 16 hours than is typically associated with viral infections. Noninfectious factors that might contribute to viral diarrhea and should be considered encompass conditions such as colorectal cancer, irritable bowel syndrome, inflammatory bowel disease, colitis, malabsorption, post-cholecystectomy diarrhea, and medications.

Prognosis

Acute viral gastroenteritis typically follows a temporary, self-limited course and has a favorable prognosis. Although hospitalization is not common, it is indicated in cases of severe dehydration, particularly among very young and older individuals. If the gastroenteritis symptoms do not improve, more frequent monitoring and possible hospitalization might be necessary.

Individuals with medical comorbidities are particularly susceptible to complications and more adverse outcomes, potentially requiring inpatient care if their symptoms fail to improve. Comorbid conditions include the following:

• Autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus
• Cancer
• Conditions requiring immunosuppressants, systemic corticosteroids, or diuretics 
• Hematopoietic cell transplant
• Immunodeficiency syndromes such as T-cell immunodeficiency or severe combined immunodeficiency
• Inflammatory bowel disease
• Metabolic diseases, including diabetes mellitus
• Renal impairment
• Solid organ transplant
• Structural heart disease

Complications

Although viral gastroenteritis can affect people of all age groups, it has a more severe impact on young children and older populations, resulting in higher morbidity and mortality rates in these groups. In developing countries, mortality is exceptionally high among children younger than 5. Complications arising from acute viral gastroenteritis caused by rotavirus might extend to respiratory or neurological issues, including seizures, encephalopathy, or even encephalitis. 

Individuals diagnosed with common variable immunodeficiency face an elevated risk of experiencing chronic and recurrent Norovirus infections. Certain patients exhibit persistent viral dissemination, whereas others suffer from severe enteropathy marked by recurrent diarrhea, malabsorption, inflammation, and villi atrophy.[19]