| disease | Pediatric Influenza Common Cold |
| alias | Epidemic Influenza, Influenza |
Influenza, commonly known as the flu, is an acute respiratory infectious disease caused by the influenza virus. It is highly contagious and often occurs as local epidemics. When populations lack immunity to new variants of the influenza virus, it can lead to a global pandemic, characterized by sudden onset and rapid spread. The 1918–1919 pandemic was extremely widespread, resulting in 20 million deaths. The main clinical manifestations of influenza include sudden high fever, headache, body aches, fatigue, and respiratory inflammation such as cough and sore throat. Infants, young children, and the elderly are prone to complications like lung infections, making prevention and treatment efforts crucial.
bubble_chart Epidemiology
1. Source and Transmission Routes of Pestilence Patients are the primary source of pestilence, especially mild cases and asymptomatic carriers, as they are difficult to detect and have a wide range of activities. Healthy carriers shed the virus in small amounts and for a short duration, so they play a minor role in disease transmission. The virus can be excreted from the respiratory secretions of patients toward the end of the incubation period and spreads directly from person to person via droplets. The pestilence is most contagious within the first 3 days of illness, and most patients stop shedding the virus after fever subsides or after one week. Indirect transmission can also occur through droplets contaminating hands, utensils, clothing, etc. However, since the influenza virus survives in the air for no more than 30 minutes, such transmission opportunities are limited. Antigenic studies have confirmed that animal (pig, horse, bird) influenza viruses share the same origin as human influenza viruses. Therefore, animal influenza can transmit to humans, though it mostly serves as an initiating factor or contributes to long-distance transmission during the initial stage of an epidemic.
4. Season In temperate and cold temperate zones, influenza typically peaks in late winter and early spring, with more severe seasonal outbreaks in winter. In tropical and subtropical regions, outbreaks can occur in any season but are more common during the rainy season. Pandemics can also occur in summer, such as the July 1968 outbreak in Beijing and the summer 1981 outbreak in Shanghai.
5. Epidemiological Characteristics Influenza A infections can manifest as minor epidemics, localized outbreaks, explosive epidemics, or even global pandemics. Pandemics are mostly caused by the emergence of new subtypes due to antigenic mutations in the influenza virus. Historically, these occurred approximately every 10–15 years, while minor and localized epidemics result from quantitative antigenic changes, typically occurring every 2–3 years. Influenza B primarily causes localized outbreaks, occurring roughly every 4–7 years, whereas Influenza C often presents as sporadic cases. The most notable feature of influenza outbreaks is their sudden onset and rapid spread. Transmission generally follows railway or highway routes, moving from urban to rural areas and from densely populated communities to scattered households. Areas with high population density and crowded venues facilitate extremely fast transmission. Global pandemics can affect multiple continents within a short period. Since the 18th century, seven global pandemics have been documented. From the mid-19th to the mid-20th century, the trend of influenza virus mutations followed the sequence H2
N2 → H3N3 → H1N1. Since the 1980s, Influenza A3 (H3N2) and the new Influenza A1 (H1N1) have coexisted worldwide. In China, Influenza A1 predominates, with occasional cases of Influenza A3 and Influenza B. In contrast, South Africa and New Zealand primarily report Influenza A3. Since the late 1970s (third stage), no global pandemics have occurred, but localized outbreaks happen annually due to minor antigenic variations. For example, after the discovery of the A3 Hong Kong strain (H3N2) in 1968, it spread globally, causing a pandemic, followed by the emergence of variant strains in various regions. In the 1970s, outbreaks occurred in Southeast Asia and the Western Pacific. New strains were isolated in Sichuan and Shanghai in 1987, and a nationwide pandemic occurred in Japan in 1989–1990. After the new Influenza A1 (H1N1) was detected in northern China in 1977, new strains were isolated in the Soviet Union and Brazil in 1978, the UK in 1980, Chile in 1983, and Taiwan, China, in 1986. To date, Influenza A3 has been circulating for over 20 years, and Influenza A1 for over a decade. The emergence of new subtypes is now under close surveillance worldwide. In recent years, Influenza B and C have mostly presented as sporadic cases, such as Influenza B in Europe and Influenza C in the U.S. However, Influenza B can also cause epidemics, as seen in Japan in early 1990.
The mortality rate caused by influenza epidemics is closely related to the circumstances of each outbreak, region, economic culture, and social conditions. It generally ranges from 50 to 100 per 100,000 people, with higher rates among children and the elderly. Rural, remote, and impoverished areas have higher rates than urban and developed regions, with a case fatality rate of approximately 0.2%.
The influenza virus is a single-stranded RNA virus belonging to the Orthomyxoviridae family. It generally appears as irregular spherical particles with an envelope, measuring 80–120 nm in diameter. Newly isolated strains may exhibit elongated filamentous or polymorphic forms. The viral particle core consists of ribonucleic acid and nucleoprotein, along with small amounts of other proteins. The ribonucleic acid serves as the structural basis for viral replication, while the nucleoprotein acts as the soluble antigen (S antigen) of the virus. This antigen is stable and exhibits type-specificity, allowing the virus to be classified into types A, B, and C, which can serve as diagnostic markers but do not confer protective immunity. The viral envelope is composed of an inner membrane protein (MP) and a lipid outer membrane. The inner membrane protein also possesses stable, type-specific antigenicity but lacks protective effects. The viral envelope surface features two types of glycoprotein spikes, each with distinct surface antigenic properties (strain characteristics), which are used to classify viruses of the same type into subtypes or strains. The rod-shaped spikes are hemagglutinin (H), which facilitates viral attachment to receptors on susceptible cells and can induce agglutination of red blood cells in various animals. The dumbbell-shaped spikes are neuraminidase (N), which hydrolyzes the N-acetylneuraminic acid of cell surface glycoproteins, enabling the release of replicated viruses from the cell surface. Influenza A and B viruses possess both H and N antigens, while influenza C lacks the N antigen. These two surface antigens (H and N) are prone to variation. Minor quantitative changes (known as antigenic drift) result in new influenza virus strains, referred to as variants, which often lead to localized outbreaks, typically occurring every 2–3 years. When H and N undergo complete qualitative changes (known as antigenic shift), new subtypes emerge, often causing global pandemics, which generally occur every 10–40 years. For example, influenza A virus has undergone four major shifts in the past 50 years: the original A0 (H0N1, prevalent before 1946), the A1 (H1N1, prevalent after 1946), the Asian A2 (H2N2, prevalent after 1957), and the Hong Kong A3 (H3N2, prevalent after 1968). Since then, its surface antigens have continued to evolve, with localized outbreaks dominated by A3 and A1 subtypes after the 1980s, without major antigenic shifts. It is still believed that this continuous antigenic variation, from quantitative to qualitative changes, results from viral mutations (through recombination or zoonotic transmission) and selective pressure from population immunity. Serological surveys suggest a cyclical recurrence of these variations. For instance, the swine-origin virus (HswN1) outbreak in the U.S. in January 1976 and the A-type (H1N1) outbreak in northeastern China in May 1977 resembled historical strains from 1918–1928 and 1946–1957, respectively. Influenza B virus exhibits less pronounced antigenic variation than influenza A but can still cause outbreaks due to antigenic changes, occurring approximately every 4–7 years. Influenza C virus, in contrast, is relatively stable.Due to the frequent antigenic variations of influenza viruses and the complexity of virus strain nomenclature, the World Health Organization established in 1971 the following naming order:
Type, host name (if human, may be omitted), region, number, year of virus isolation, with antigenic components noted in parentheses, e.g., A/Hong Kong/1/68 (H2N2).
Influenza viruses are not heat- or acid-resistant (they lose pathogenicity at 56°C or pH 3) and are also sensitive to alcohol, phenol, bleaching powder, and ultraviolet radiation. 1% hydrochloric acid, lactic acid, or vinegar acid can be used as disinfectants. Under natural conditions, influenza B and C viruses only infect humans, while influenza A viruses can also infect pigs, horses, birds, etc. Among laboratory animals, only ferrets can be infected and develop respiratory inflammation. Influenza viruses are commonly cultured in chicken embryos, human embryonic kidney, bovine kidney, dogs' testis and penis, etc.
When the influenza virus comes into contact with sensitive respiratory epithelial cells, it quickly adheres to specific receptors on the cell surface via hemagglutinin on its outer layer. The viral envelope and cell membrane fuse, creating gaps in the outer cell layer. The seasonal virus sheds its outer membrane (uncoating) outside the cell, allowing the viral core genes to directly enter the cytoplasm through these gaps. With the involvement of viral RNA transcriptase and cellular RNA polymerase, viral replication and reproduction occur. Various viral components then migrate to the cell membrane for assembly. Once matured, they are enveloped by the protruding cell membrane, forming new infectious viral particles. After detaching from the cell surface, the virus can invade neighboring epithelial cells in the same manner, causing inflammation in the respiratory tract. In severe cases, the virus may invade other tissues and organs via the lymphatic and circulatory systems, although viremia is rare. Some researchers have reported isolating influenza viruses from tissues such as the brain, heart, and muscles. Clinical manifestations such as high fever, decreased white blood cell count, myocarditis, and encephalitis are mostly toxic effects.
bubble_chart Pathological Changes
Mild cases only present catarrhal changes in the upper respiratory tract, while severe cases are primarily characterized by hemorrhagic necrotic bronchitis and interstitial pneumonia. In the early stage, the respiratory mucosa shows mononuclear cell infiltration and edema; in the advanced stage, there is extensive epithelial cell necrosis and hemorrhagic exudate, with the basal layer cells remaining unaffected. The pulmonary interstitium also exhibits edema and cellular infiltration, and hyaline membranes may form within the alveoli. Inclusion bodies are found only in the cytoplasm and not in the nucleus. Pulmonary lesions can vary depending on secondary bacterial infections. In uncomplicated influenza, the basal layer epithelial cells begin to proliferate 5 days after the onset of illness, with undifferentiated epithelial cells reaching up to 7–8 layers. Cilia appear only after 15 days, along with mucus production. When secondary bacterial infection occurs, the basal layer cells are also damaged, delaying recovery.
bubble_chart Clinical Manifestations
1. Incubation period: Approximately several hours to 1–2 days.
2. Clinical symptoms: The clinical manifestations of influenza in children often vary by age. In older children, symptoms resemble those in adults, typically presenting as a common cold type with sudden onset, high fever, fear of cold, headache, back pain, limb soreness, fatigue, etc. Soon after, symptoms such as sore throat, dry cough, runny nose, conjunctival congestion, tearing, and localized lymphadenopathy may appear, with coarse rales sometimes heard in the lungs. Occasionally, gastrointestinal symptoms like abdominal pain, diarrhea, and abdominal distension and fullness are reported. In infants and young children, the clinical presentation is often similar to other respiratory viral infections and difficult to distinguish, involving inflammation of the upper respiratory tract, larynx, trachea, bronchi, bronchioles, and lungs, with more severe conditions. Japanese researchers reported that during influenza outbreaks, about one-fourth of children hospitalized for lower respiratory tract infections were confirmed to be caused by the influenza virus, a rate several times higher than those caused by respiratory syncytial virus or adenovirus during the same period. Affected children often experience sudden high fever accompanied by systemic toxic symptoms and clear nasal discharge, frequently with vomiting and diarrhea, and occasionally rashes or epistaxis. Body temperature fluctuates between 38–41°C, and febrile seizures may occur. Younger infants may develop severe laryngotracheobronchitis with thick mucus, even leading to respiratory obstruction. Neonatal cases often present with drowsiness, refusal to feed, and apnea, sometimes requiring mechanical ventilation. The clinical manifestations of influenza B are similar to those of influenza A but more commonly involve nasal and ocular symptoms, as well as myalgia caused by acute benign myositis, primarily in the lower limbs, especially the gastrocnemius muscle, while systemic toxic symptoms such as dizziness and fatigue are milder. Influenza C mostly presents as mild upper respiratory tract infection. Uncomplicated influenza fever typically lasts 3–4 days, with systemic toxic symptoms subsiding after fever resolution, but dry cough and physical weakness may persist for 1–2 weeks.
3. Blood picture: The total peripheral white blood cell count is mostly reduced, averaging around 4×109/L, with a significant decrease in neutrophils, a relative increase in lymphocytes, and sometimes an increase in monocytes. This distinctive blood pattern is often evident in the first few days of illness and may persist for 10–15 days. In cases complicated by pneumonia, the total white blood cell count may drop sharply to as low as 1–2×109/L. The erythrocyte sedimentation rate is generally normal, and cold agglutinin tests are mostly negative.
Since the manifestations of influenza are very similar to those of the common cold and upper respiratory tract infections, without very distinctive features, the initial cases are difficult to diagnose. Diagnosis should be made comprehensively based on epidemiological history, clinical symptoms, and etiological tests.
1. Epidemiological History: The most helpful diagnostic clue is local influenza outbreak information. During flu seasons, heightened suspicion should arise when similar symptoms appear in surrounding individuals.
2. Clinical Diagnosis: Sudden onset with fever, chills, headache, muscle pain in the limbs, fatigue, and gradually developing respiratory symptoms such as cough, sore throat, conjunctival congestion, and flushed cheeks. Catarrhal symptoms are less pronounced than in the common cold, and sore throat, pharyngeal redness, and tonsillar signs are less severe than in acute tonsillitis—these are clinical characteristics of influenza. A low or normal white blood cell count with notably reduced neutrophils may clinically suggest influenza. Infants and young children are even harder to distinguish from other upper respiratory viral infections based solely on clinical presentation, so early etiological diagnosis is essential.
3. Etiological Diagnosis:
(1) Virus Isolation: Collect nasopharyngeal washings, throat gargles, or throat swabs in preservation medium during the acute phase. Ideally, immediately inoculate these into the amniotic or allantoic cavity of chicken embryos or sensitive cell cultures like human embryonic kidney cells to isolate the influenza virus. If necessary, inoculate experimental animals for virus isolation. Specimens are best collected within 3–5 days of symptom onset; delayed collection reduces the positive rate.
(2) Hemagglutination and Hemagglutination Inhibition Tests: Influenza virus can agglutinate guinea pig red blood cells (or chicken and human "O" type red blood cells). Mix the patient's early nasopharyngeal washings (rinsed with saline) with guinea pig red blood cells; agglutination indicates a positive result, suggesting viral presence, though this test has low sensitivity. If specific anti-influenza serum is added beforehand for hemagglutination inhibition, a positive result confirms the presence of influenza virus and can further identify the strain.
(3) Fluorescent Antibody Staining of Nasal Mucosal Cells: Rotate a nasopharyngeal swab in the nasal cavity to collect exfoliated mucosal cells, smear onto a slide, dry, and stain with fluorescent antibody (anti-influenza virus-specific serum). Under fluorescence microscopy, multiple apple-green fluorescent cells indicate positivity. Non-specific fluorescent spots should be distinguished; positive results are definitive, but negative results do not fully exclude infection. This method is rapid (completed within 2 hours) and simple.
(4) Serum Antibody Detection: Methods include ① hemagglutination inhibition test, ② neutralization test, and ③ complement fixation test. A fourfold or greater increase in antibody titer during convalescence compared to the initial stage has diagnostic value, with a positive rate generally reaching 60–80%.
bubble_chart Treatment Measures
There is still no definitive and effective specific treatment for influenza, and the focus should be on general care and the prevention and treatment of complications. Sick children should rest in bed until their strength is restored, and isolation measures should be taken to prevent the {|###|}pestilence{|###|} of others and secondary bacterial infections. Emphasize general care, appropriate feeding, a light diet, and plenty of fluids. Symptoms such as high fever, {|###|}dysphoria{|###|}, restlessness, and {|###|}headache{|###|} should be treated symptomatically, using physical cooling methods or antipyretics such as acetylsalicylic acid, metamizole, and aminopyrine. Antibiotics should be administered early in the case of bacterial complications. Complications should be promptly managed according to the relevant sections.
1. Antiviral Drug Therapy Amantadine has been relatively confirmed to be effective against influenza A. It should be administered early, preferably within 24 hours of symptom onset, to shorten the course of the disease and alleviate symptoms. The {|###|}dose{|###|} is the same as the preventive dose, and side effects should be closely monitored. In recent years, a number of anti-influenza drugs have been screened domestically and internationally, such as rimantadine and spiroamantadine, which are more potent than amantadine. Moroxydine hydrochloride (ABOB, virugon, flumidin) is effective against 1 and 3 influenza. If taken within 24 hours of symptom onset, children can be given 3–4 mg/kg per dose, three times daily. Within 48 hours, {|###|}warm purgation{|###|} decreases, toxic symptoms lessen, and the marked effectiveness rate can reach 60%. Other drugs include inosine pranobex, ribavirin, and selenocystine. Recent domestic reports suggest that zinc gluconate lozenges have some efficacy in treating the {|###|}common cold{|###|}.
2. Immunomodulatory Therapy In recent years, the use of immunomodulators such as thymosin, human interferon, and interleukins has greatly advanced the treatment of viral infections. During influenza outbreaks, immunomodulators can be administered to the weak, young, elderly, and immunocompromised to enhance immune function and promote recovery.
3. {|###|}Chinese herbal medicine{|###|} Treatment Laboratory screening has identified dozens of {|###|}Chinese herbal medicines{|###|} that inhibit or inactivate the influenza virus, including Isatis Root, Arnebia, Eucalyptus Leaf, Shield-fern Rhizome, small centipeda herb, Virgate Wormwood, Lonicera, Coptis Rhizome, Skullcap Root, and Forsythia. These can be selected as appropriate.
The prognosis of this disease is closely related to the severity of the epidemic in the current year, the patient's age, immune status, and the presence of complications. A widespread and severe epidemic is associated with a higher fatality rate, with severe cases more common in the early stages of the outbreak. The elderly, young children, pregnant women, and those with weakened immune systems are prone to lower respiratory complications, such as secondary bacterial pneumonia, which can lead to severe illness, prolonged recovery, and life-threatening conditions. Therefore, these groups should be the primary focus of prevention and treatment efforts.
Establish a surveillance network for influenza outbreaks to closely monitor influenza epidemics, viral antigenic variations, and population immunity. This enables the early detection of cases and reporting of seasonal epidemic intelligence, predicting the occurrence and trends of outbreaks, and taking corresponding preventive measures as early as possible. By monitoring influenza virus antigenic variations across regions, incorporating the latest variant strains into vaccine preparation can enhance immunization efficacy and prevent the spread of new variants. Since 1947, the World Health Organization has established a global influenza surveillance network in countries worldwide, playing a crucial role in controlling influenza pandemics.
Patients should be isolated and disinfected. Sick children should rest at home, and if multiple cases occur in collective childcare facilities, on-site isolation and rest should be implemented to reduce transmission opportunities. The living quarters should be separate, with fresh air and ample sunlight. Respiratory secretions (pus, phlegm, etc.) should be disinfected with a 3% chloramine solution or a 10–20% bleach emulsion. Utensils should be boiled or soaked in 0.5% peracetic acid for 15–30 minutes. Clothing and bedding should be fumigated with ethylene oxide for 12–24 hours for disinfection. After the sick child leaves the room, furniture can be wiped with a 0.2–5% bleach solution, floors sprayed, ventilation improved, and ultraviolet light used for terminal disinfection. Indoors, lactic acid or ethylene oxide can also be used for sealed fumigation. Medical and caregiving staff should wear masks, change outer clothing and shoes, and frequently wash hands with river water and soap or soak hands in 0.5% peracetic acid.
During epidemics, widespread public education on preventing pestilence influenza should be conducted. Minimize taking children to crowded public places or hospitals with high patient concentrations. If necessary, suspend classes and childcare attendance, and encourage children to wear masks when going out. Open windows several times daily for ventilation.
1. Vaccination: Since its introduction, influenza vaccination has played a role in reducing incidence rates, though its effectiveness in controlling epidemics remains suboptimal. Currently, there are two types of influenza vaccines: inactivated vaccines and live attenuated vaccines. Inactivated vaccines are administered via subcutaneous injection to induce active immunity, but their preparation process is complex. They can be formulated as combined vaccines for types A and B, along with other viruses, and are expensive. They produce better serum antibody effects and can also enhance local antibodies. Older children receive two subcutaneous injections of the inactivated vaccine, 0.5–1 ml each, 6–8 months apart, with a booster every autumn. Antibody levels peak two weeks after vaccination, decline to one-third after 4–5 months, and typically disappear after a year, providing effective protection for 1/2–1 year. Side effects are minimal, making them particularly suitable for infants, the elderly, pregnant women, and those with chronic heart, lung, kidney diseases, or diabetes. Currently, there are concentrated purified vaccines, subunit vaccines, and adjuvant vaccines with even fewer side effects. Live attenuated vaccines use live influenza viruses attenuated through multiple passages in chicken embryo allantoic fluid or tissue culture. They are administered to the respiratory mucosal epithelium, where they replicate to induce active immunity. These vaccines are simpler to prepare, mostly containing monovalent type A virus, and are administered via nasal spray (0.25 ml per nostril) or aerosolized chlorine solution. Post-vaccination, both serum and local antibodies increase, with protection lasting 1/2–1 year. Domestic reports indicate a 50–70% reduction in incidence rates. Vaccines require refrigeration or dry formulation. Side effects may include fever and respiratory symptoms, generally mild, but more severe in those without baseline immunity. Thus, live attenuated vaccines are contraindicated for infants, the elderly, pregnant women, and those with chronic heart, kidney, lung, or nervous system diseases, diabetes, or immunodeficiency. Inactivated vaccines may be used if necessary.
2. Drug Prevention Currently, amantadine is relatively confirmed to have a preventive effect on influenza A but is ineffective against influenza B. This drug inhibits the uncoating process of influenza A virus, preventing it from entering host cells, thereby exerting its preventive effect. It is most effective when taken immediately after exposure to the virus. The dosage for children aged 1–9 is 4 mg/(kg·d), administered orally in two divided doses, with a maximum daily dose not exceeding 150 mg. For those aged 9 and above, the dosage is the same as for adults: 0.1 g twice daily. The protection rate can reach 50–70%. It may occasionally cause side effects such as excitement, insomnia, dizziness, or ataxia. Therefore, it is contraindicated for individuals with epilepsy, cardiovascular diseases, central nervous system disorders, as well as pregnant or lactating women. Methylamantadine and rimantadine are more potent than amantadine in combating influenza viruses. Additionally, ribavirin and exogenous human interferon have certain preventive effects. During epidemics, a 1:2000 solution of nitrofurazone or 10% eucalyptus leaf solution can be used for nasal drops or throat spray as a preventive measure. Traditional Chinese medicines such as Shield-fern Rhizome, Dyers Woad, Isatis Root, Arnebia, and Lonicera are also considered useful for prevention.
Usually, attention should be paid to physical exercise and nutrition to prevent rickets and malnutrition. In winter, the air in the living room should be fresh, the room temperature should be kept constant, and more outdoor activities in the sun should be carried out to enhance the body's ability to withstand cold.
Infection in infants and young children often affects the lower respiratory tract, with pneumonia being the most severe. Pneumonia can be caused by influenza viruses or secondary bacterial infections, primarily due to *Haemophilus influenzae*, *Staphylococcus aureus*, *Streptococcus pneumoniae*, or *Streptococcus* spp. The onset is abrupt, often presenting with high fever within 48 hours that persists; a minority may initially have moderate fever, which gradually rises over 2–3 days. Severe wheezing and cyanosis are common, and panting may persist even after fever subsides. Occasionally, straw-colored pleural effusion is observed. Vomiting and diarrhea are frequent, and in severe cases, coffee-ground-like vomitus or intestinal bleeding may occur, indicating critical illness. Early symptoms may include convulsions, unconsciousness, neck stiffness, etc. Cerebrospinal fluid pressure may increase, with normal cell counts and protein levels or slight elevation. Hemiplegia may occur during the course of the disease but usually recovers quickly. Early X-ray findings show punctate or flocculent irregular shadows on both sides of the hilum, which later coalesce into small patches or mass-like shadows. The duration of pneumonia ranges from as short as 1 week to over a month, with an average hospitalization of about 3 weeks. Temperature fluctuations are common, and lung signs resolve slowly.
Other complications may include rhinitis, tonsillitis, otitis media, laryngitis, tracheobronchitis, myocarditis, encephalitis, parotitis, etc. Influenza B may be complicated by Reye's syndrome. Rare complications include suppurative arthritis, peritonitis, neuritis, nephritis, and burning pain in the calves and heels.
