I. Three key words of seasonal enterovirus infection
(a) Infection: harmful colonization of macroorganisms by microorganisms. Micro-organisms are called pathogens and macro-organisms are called hosts.
Harmful, microorganisms cause damage to macroorganisms’ tissues and organs through various mechanisms, which can be summarized as direct damage caused by microorganism colonization and immune damage caused by macroorganisms’ rejection of microorganism colonization.
(i) Colonization, metabolism and reproduction of microorganisms on the body surface (skin surface, tissue interstitial and intracellular) or in vivo (mucosal surface, tissue interstitial and intracellular) of macroorganisms
(ii) Enterovirus: a concept that often gives rise to ambiguity. There are at least three understandings.
First, the genus Enterovirus of the family Small RNA Viridae, which uses the intestine as the first colonization site and multiple organs as the secondary colonization site. The genus Enterovirus has more than 100 serotypes. The first colonization site after the virus enters the human body is usually the intestine and respiratory tract, with the intestine being the main site; after the virus first multiplies in the first colonization site, it passes through the bloodstream and transfers to the second colonization site; the second colonization site is extensive, including the lung, heart, pancreas, nerves, muscles, skin, conjunctiva, etc., causing diseases in the corresponding areas.
Second, viruses of the non-small RNA virus family that use the intestine as the first colonization site and a single organ as the second colonization site. They are mainly hepatitis A and E viruses. The first colonization site after the virus enters the human body is the intestine; after the virus first multiplies at the first colonization site, it is transferred to the second colonization site, the liver, through the portal blood flow, causing hepatitis.
Third, viruses of the non-small RNA virus family that use the intestine as the colonization site and spread in the intestine. The virus enters the body with only one colonization site, the intestine, and causes only intestinal disease, i.e., enteritis.
The enteroviruses mentioned here are enteroviruses in a broad sense, covering the above three understandings, but mainly referring to the latter two.
(iii) Seasonality: Dissemination throughout the year and seasonal multiplicity.
Sporadic, the number of cases appearing each year is not significantly higher than the average number of cases appearing in the past three years, and there is no correlation between the onset of different patients.
Plurality, the number of cases appearing in a given season is significantly higher than in other seasons. Epidemic, antonym of epidemic. When an infection becomes epidemic, its seasonality may be broken.
II. Viral infections of the genus Enterovirus and the diseases they cause
The spectrum of diseases caused by viral infections of the genus Enterovirus of the family Small RNA Viruses is very broad, and the only diseases that have been characterized so far are polio and hand, foot and mouth disease, caused by poliovirus and coxsackievirus type A16 and enterovirus type 71, respectively.
(A) Poliomyelitis
It occurs mainly in winter and spring, and the main infected population is infants and children, and is usually endemic once every three years. It is now under control, with no more than 100 cases per year worldwide, all of which occur in Africa.
(B) Hand, foot and mouth disease
It occurs mainly at the turn of spring and summer, and the main infected population is also infants and young children, usually once every three years. The incubation period is 3 to 7 days. The characteristic manifestation is fever with flu-like and gastroenteritis manifestations, but gastroenteritis manifestations are relatively rare and last for 1 to 3 days; followed by oral and hand, foot and buttock skin herpes and ulcers, of which oral mucosal rash is often accompanied by salivation and pain, while hand, foot and buttock rashes are not painful, itchy and scarring; the duration of the disease is 5 to 10 days.
(C) Other enterovirus viral diseases
Including bronchopneumonia, myocarditis, pancreatitis and diabetes mellitus, meningoencephalitis, Guillain-Barre syndrome, conjunctivitis, herpes pharyngitis, epidemic chest pain, etc., can be caused by different serotypes of enterovirus infection, but their specific viral types have not been characterized. It often occurs in the summer and autumn and can affect both children and adults. The pathogenesis is also not characterized.
III. Non-enterovirus viral infections and liver diseases caused by them
The main types of hepatitis are hepatitis A and E. Hepatitis A and E viruses belong to the hepatophilic RNA virus family and hepatitis E virus family, respectively. Hepatitis A viruses are the most environmentally resistant, surviving for long periods of time in acidic, alkaline and cold environments, but are sensitive to ultraviolet light, while hepatitis E viruses are relatively less environmentally resistant, dying rapidly after leaving the weak alkaline environment of the intestine, but surviving for long periods of time by freezing.
Hepatitis A and E circulate throughout the year but are more prevalent at the turn of winter and spring, with epidemics occurring mostly in the tropical rainy season and subtropical/ temperate summer and fall, hence the name seasonal hepatitis. The basic mode of transmission of hepatitis A and E is fecal-oral transmission. Hepatitis A virus infects only humans and a limited number of primates; however, hepatitis E virus has a much broader host range, infecting not only humans and primates but also domestic animals, poultry and livestock, such as pigs, chickens and horses. Thus, hepatitis A can be transmitted by contact and by food, whereas sporadic hepatitis E is usually transmitted only by food.
The main populations affected by hepatitis A and E are adolescents and middle-aged and older adults, respectively, while hepatitis A is rare but hepatitis E is common in older adults. Hepatitis A virus infection results in almost lifelong immunity and secondary infection rarely occurs; the immune characteristics of hepatitis E virus infection are not known.
The incubation periods (time from exposure to the pathogen to the onset of first symptoms) for hepatitis A and E are 2 to 6 weeks and 3 to 8 weeks, respectively. The initial manifestations are fever, malaise and loss of appetite, and in severe cases, nausea and vomiting; the frequency of fever in hepatitis A and E is 80% and 40%, respectively; the temperature rarely exceeds 39°C and lasts for 1 to 2 days, a few for 3 to 5 days, and individually up to 1 week. The duration of malaise and decreased appetite is usually 5 to 7 days and 7 to 10 days, respectively. Some patients develop a deepening of urine color with a red-teal tint about 1 week after onset, along with yellowing of the skin and sclera. Those who appear and those who do not appear yellow staining of skin and sclera are called jaundiced and non-jaundiced hepatitis respectively; if malaise and loss of appetite progressively worsen for more than 3 weeks and yellow staining of skin and sclera progressively worsen for more than 2 weeks, the possibility of severe hepatitis should be considered. Further progression of severe hepatitis can result in critical hepatitis, which is the main type of disease leading to death of patients. The natural course of hepatitis A and E is 2 to 4 weeks and 4 to 8 weeks, respectively; the morbidity and mortality rates are 0.1% to 0.3% and 1% to 3%, respectively.
Once diagnosed with seasonal hepatitis, all require hospitalization. The purpose of hospitalization is three: first, the need for isolation, hepatitis A and E are legal infectious diseases, the infectious period is 3-6 weeks after the onset of the disease; second, the need for symptomatic and supportive treatment; third, the need to observe the disease, patients with a tendency to heavy hepatitis, early detection and early treatment can stop disease progression and reduce the risk of death.
Fourth, non-enterovirus genus infections and their resulting enteropathy
Mainly refers to enteritis caused by enteroadenovirus, norovirus, astrovirus, rotavirus.
(A) Rotavirus enteritis
Rotavirus belongs to the family of eutheroviridae. Rotavirus is relatively stable at room temperature and can survive on the surface of the environment for several days and in the feces for several weeks. pH adapts to a wide range (pH 3.5-10) and is not easily inactivated by gastric acid and bile. It is heat sensitive and can be inactivated at 55°C for 30 minutes.
Rotavirus enteritis has no obvious seasonal peak in tropical areas; in subtropical and temperate areas it is mostly prevalent in dry and cold seasons, with epidemics occurring mostly in November to April and peaks in November to December. Rotavirus has a wide variety of host animals, including pigs, horses, cattle, sheep, rats, monkeys, dogs, deer, etc., but the common mode of transmission is human-human transmission. The most common route of transmission is fecal-oral transmission.
Rotavirus enteritis occurs most often in children 4 to 24 months of age, and almost all children experience at least one rotavirus infection by age 5 years. Infection with rotavirus enteritis is the most common cause of diarrhea in infants and young children in developing countries and the leading cause of hospitalization for diarrhea in infants and young children in developed countries. Epidemics of rotavirus infection in adults are very rare. Rotavirus infection results in long-lasting immunity to the same serotype of virus, and the first rotavirus infection not only reduces the likelihood of reinfection, but also reduces the severity of reinfection.
The incubation period of rotavirus enteritis is usually 1 to 2 days. The symptomatic period usually lasts from 3 to 8 days. The spectrum of disease ranges from latent infection (no clinically significant manifestations) to severe dehydration. Approximately 50% of rotavirus infections have no significant discomfort. Overt infections (with significant clinical manifestations) are characterized by an acute onset of fever and vomiting followed by a jetty, watery diarrhea. The frequency of diarrhea is about 10 times a day. The severity of the overt infection was mild, moderate and severe in 62%, 35% and 3%, respectively; about 7% of the children required hospitalization.
(ii) Enteroadenoviral enteritis
Enteroadenovirus belongs to the family of adenoviruses. There are 51 serotypes of human adenovirus, among which serotypes 40 and 41 infections mainly cause adenoviral enteritis. Adenovirus is highly resistant to the environment. They have a wide range of tolerance to temperature and acidity. Adenovirus is highly resistant to ultraviolet light.
Adenovirus serotype 40 infections are not significantly seasonal, while serotype 41 infections tend to occur in late autumn. Adenoviruses have a variety of host animals, but there are few reports of animals as a source of infection. Fecal-oral transmission is the primary mode of transmission of adenoviral enteritis; although floating body transmission and waterborne transmission are important in other diseases caused by adenovirus infection, they play a very limited role in the transmission of adenoviral enteritis.
Approximately 90% of adenoviral enteritis occurs in infants and children. Enteroadenovirus and astrovirus infections are the second leading cause of diarrhea in infants and children, after rotavirus. Adenovirus infections result in durable immunity to the same serotype and secondary infections rarely occur.
The incubation period of enteric adenoviral enteritis is 3 to 10 days, and the duration of the disease is more than 1 week. Diarrhea is the most prominent symptom of adenoviral enteritis, mostly manifested as yellow water or watery diarrhea, vomiting is another prominent symptom of adenoviral enteritis. Adenoviral enteritis can be accompanied by fever and abdominal pain, the fever is mostly low to moderate, and the abdominal pain is mostly spasmodic. Adenoviral enteritis has a hospitalization rate of more than 50% and is an important cause of intussusception in children.
(iii) Astroviral enteritis
Astroviruses belong to the family of astroviridae. The resistance of astroviruses to their environment is not fully understood. It is known that stellate viruses are relatively stable at room temperature and can survive for days on the surface of the environment and weeks in the feces; they are acid-resistant (pH 3) and resistant to chlorinated disinfectants; they are heat-sensitive and remain active for 5 minutes at 60°C but can be inactivated for 10 minutes.
Stellate virus enteritis is prevalent in the tropics mainly during the rainy season; in subtropical and temperate regions mostly during the dry and cold season, with epidemics occurring mostly from November to May and peaking mostly in March to April. Stellate viruses have a variety of host animals, but there are few reports of animals as a source of infection. Fecal-oral transmission is the main mode of transmission of astrovirus enteritis, with contact transmission as a secondary mode of transmission, and water contamination and food contamination can occasionally cause epidemics of astrovirus enteritis.
Stellate virus enteritis occurs mainly in children under 5 years of age, but can also be seen in elderly people in nursing homes. Astrovirus and enteroadenovirus infections are the second leading cause of diarrhea in infants and children, after rotavirus. Astroviral infections can acquire protective immunity across adulthood and fade into old age.
The incubation period of astroviral enteritis is approximately 1 to 4 days, and the duration of diarrhea is 2 to 6 days. It is characterized clinically by mild watery diarrhea, equivalent to a mild form of rotavirus gastroenteritis, and may be accompanied by fever, loss of appetite, nausea, and abdominal pain.
Although astroviral enteritis rarely leads to dehydration or hospitalization, it is more severe in children with malnutrition, immunodeficiency, co-infections, and underlying intestinal disease.
(iv) Norovirus enteritis
Norovirus belongs to the adenovirus family. Norovirus heat and freezing resistance, 60 ℃ incubation 30min is still infectious, frozen for several years still remain active; Norovirus is sensitive to the treatment of sewage chlorine concentration of 10ppm, but to the treatment of drinking water chlorine concentration of 3.75 ~ 6.25ppm tolerance.
Norovirus enteritis is disseminated throughout the year with no significant seasonality, but there are insignificant winter or winter-spring peaks. Humans are the only known source of infection for norovirus gastroenteritis. Fecal-oral transmission is the primary mode of transmission, with aerosol transmission and contact transmission as secondary modes of transmission. Norovirus is the leading cause of diarrhea in school-age children and adults. Norovirus infection results in only short-term immunity to the same strain of virus but does not provide cross-protection against other strains; therefore, multiple infections may occur during a person’s lifetime.
The incubation period of norovirus enteritis is usually 12 to 48 hours. The first symptoms are abdominal cramps, nausea, vomiting or diarrhea, with abdominal cramps occurring in about 50% of cases and nausea, vomiting or diarrhea in about 65% to 75% of cases; about 25% to 35% of patients have chills, fever, headache and malaise. Primary patients mostly present with vomiting, which may be the only symptom; adults and sequelae patients mostly present with watery diarrhea. Pediatric patients tend to present with vomiting, and adult patients tend to present with diarrhea.
Although dehydration can occur in patients with severe vomiting and/or diarrhea, deaths are rare. Deaths are mainly seen in infants and children, frail or elderly patients who present with severe dehydration.