The latest consensus on the diagnosis and treatment of influenza in children, experts comprehensively interpret CTS2021

*For medical professionals only, the flu season is here, have the kids been vaccinated? Influenza is one of the major public health problems facing human beings.
Children are a high-risk group of influenza and a high-risk group of severe cases
.

Recently, the 22nd National Academic Conference of Respiratory Medicine was held in Xiamen, Fujian Province
.

At the meeting, Professor Xu Baoping, Department of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University, interpreted the "Expert Consensus on Diagnosis and Treatment of Influenza in Children (2020)" (hereinafter referred to as the New Consensus, Figure 1)
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The new consensus is revised and updated on the basis of the 2015 version of the consensus, let's learn together! Figure 1 The cover of the two editions of the consensus.
In winter and spring, children should beware of influenza.
Influenza viruses belong to the family Orthomyxoviridae, with enveloped viruses.
They are divided into four types: A (A) B (B) C (C) D (D), and the first three types are all Can infect humans
.

The target cells are mainly respiratory epithelial cells
.

Influenza has a seasonal high incidence in winter and spring every year in temperate regions.
In tropical regions, especially Asia, the seasonality of influenza is highly diverse
.

The annual periodicity of influenza A increases with increasing latitude, and the spatial patterns are diverse; influenza B has a high incidence in a single winter in most areas of China
.

In general, the prevalence of influenza B in China is lower than that of influenza
A.

Infants, the elderly, and people with chronic illnesses are at high risk for influenza, with a higher risk of severe illness and death following influenza
.

Influenza-induced childhood deaths are more common in children with underlying medical conditions
.

The burden of influenza disease in children is relatively large.
The annual influenza epidemic rate in children is 20% to 39%, and the annual infection rate in high epidemic seasons can even reach about 50%
.

The death cases of confirmed influenza critical illnesses admitted to the Department of Critical Care Medicine of Beijing Children's Hospital from November 2017 to April 2018 were collected and analyzed, and it was found that children under 5 years old were a high-risk group of severe influenza, and those younger than 2 years old were more likely to suffer from severe flu.
The main causes of death are acute respiratory distress syndrome (ARDS) and influenza epidemic encephalopathy (IAE)
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Studies have confirmed that the diagnosis of severe influenza cases and the delay in antiviral treatment may be the relevant factors leading to death, and relevant examinations and treatment should be improved as soon as possible for children with influenza symptoms
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Influenza patients and latent infections are the main sources of influenza infection, which are mainly transmitted through droplets of their respiratory secretions, and can also be transmitted through direct or indirect contact with mucous membranes such as the mouth, nose, and eyes
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The common incubation period is 1 to 4 days (average 2 days), and it is infectious from the end of the incubation period to the acute stage of onset
.

Generally, infected persons can excrete the virus 24-48 hours before the onset of clinical symptoms, and the amount of excretion increases significantly 0.
5-1 day after infection, reaching a peak within 24 hours after the onset of symptoms
.

Adults and older children generally continue to detoxify for 3-8 days (average 5 days), while younger children take longer to detoxify.
In infants and young children, long-term detoxification is common (1-3 weeks)
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Children play an important role in the prevalence and spread of influenza, and the infection and morbidity rates are typically highest in children during the influenza season, often passing the influenza virus to family members or being a source of infection into schools and communities
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The clinical manifestations of influenza in children are generally healthy children infected with influenza virus may manifest as mild influenza, and the onset is usually sudden, the main symptom is fever, the body temperature can reach 39~40 ° C, there may be chills, chills, headache, and muscle aches all over the body.
, extreme fatigue, loss of appetite and other systemic symptoms, often cough, sore throat, runny nose or nasal congestion
.

Nausea, vomiting, and diarrhea occur in a small number of patients.
Children have more gastrointestinal symptoms than adults, and are common in influenza
B.

The clinical symptoms of influenza in infants and young children are often atypical
.

Influenza in neonates is rare, but if they suffer from influenza, they are prone to pneumonia, and often have symptoms of sepsis, such as lethargy, milk refusal, and apnea
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The symptoms of most uncomplicated children with influenza are relieved within 3 to 7 days, but the recovery of cough and physical strength usually takes 1 to 2 weeks
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Severely ill children develop rapidly, most of them develop pneumonia in 5-7 days, body temperature often persists above 39°C, breathing difficulties, and intractable hypoxemia, which can rapidly progress to ARDS, IAE, sepsis, and septic shock , heart failure, cardiac arrest, renal failure, and even multiple organ dysfunction
.

The main causes of death were respiratory complications and IAE
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Complications of influenza in children mainly include pneumonia, liver damage, kidney damage, central nervous system damage, myocardial damage and muscle damage
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Concomitant severe pneumonia, ARDS, and encephalitis/encephalopathy (eg, IAE/acute necrotizing encephalopathy (ANE)) are the main causes of death
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Imaging findings showed multifocal brain damage, including bilateral thalamus, periventricular white matter, internal capsule, putamen, upper brainstem tegmentum, and cerebellar medulla
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The mortality rate is as high as 30% to 75%, 20% of the survivors have severe neurological sequelae, and less than 10% of the patients can fully recover
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Similar diseases (infectious, metabolic, intermediate-high, autoimmune) must be excluded
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At present, early diagnosis and treatment have reduced the mortality rate of influenza in children and improved the prognosis
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Common tests for diagnosis and differential diagnosis of influenza in children include routine laboratory tests such as etiological testing and blood routine
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Generally, the total number of white blood cells is normal or decreased, and the lymphocyte count and proportion are increased
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C-reactive protein (CRP) can be normal or slightly elevated
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When combined with bacterial infection, the total number of white blood cells and neutrophils increased
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Its diagnostic methods include antigen detection, nucleic acid detection, and cell culture
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The diagnosis of influenza in children is mainly based on influenza-like symptoms: fever, body temperature ≥38°C; accompanied by cough and/or sore throat
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During the influenza epidemic season, the clinical manifestations of the above-mentioned influenza appear, there is epidemiological evidence, and other diseases that cause influenza-like symptoms are excluded, and the diagnosis can be confirmed
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Those who have the above clinical manifestations of influenza and have one or more of the following positive etiological test results can also be diagnosed: positive for influenza virus nucleic acid; positive for influenza antigen; positive for influenza virus isolation and culture; Specific immunoglobulin G (IgG) antibody levels were 4-fold or more elevated
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One of the following conditions is a severe case: dyspnea and/or increased respiratory rate: children over 5 years old > 30 times/min, 1-5 years old > 40 times/min, 2-12 months old > 50 times/min , Neonatal ~2 months old > 60 times/min; mental changes: unresponsiveness, lethargy, irritability, convulsions, etc.
; severe vomiting, diarrhea, dehydration; oliguria or renal failure; ; Other clinical conditions requiring hospitalization
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One of the following conditions is a critical case: respiratory failure; ANE; septic shock; multiple organ insufficiency; other serious clinical conditions requiring monitoring and treatment
.

Influenza needs to be differentially diagnosed with the common cold, see Table 1: Table 1 Differential diagnosis also needs to be differentiated from the new coronavirus infection.
The new coronavirus infection has the following characteristics: fever, fatigue, dry cough; It can be accompanied by gastrointestinal symptoms such as vomiting and diarrhea ; It can be manifested as upper respiratory tract infection, mild pneumonia, severe pneumonia, etc.
; small infants and neonates have atypical symptoms after infection; epidemiological history and etiological examination can be identified
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"Prevention" is better than "cure" for children's influenza.
"The biggest principle of childhood influenza treatment is the word "early"
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Clinically, the treatment plan for children with influenza is determined by evaluating the general status of the children, the severity of the disease, the onset of symptoms, and the local influenza epidemic
.

Early initiation of anti-influenza drug therapy within 48 hours of onset provides better clinical response
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But treatment 48 hours after the onset of flu-like symptoms is also beneficial
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Rational use of symptomatic drugs, to avoid blind or inappropriate use of antibiotics
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The current mainstay of treatment for influenza in children is neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir, and peramivir
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Oseltamivir: treatment in children of all ages and prophylaxis in children older than 3 months
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The benefits of treating term and preterm infants outweigh the risks
.

The best administration time is within 48 hours after the onset of flu symptoms, and the administration is effective after 96 hours after the onset of symptoms, and it is safe for children to use oseltamivir
.

Zanamivir: It is a dry powder and not an aerosol, so it should not be used through a nebulizer, ventilator, or other device used for nebulization therapy
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Zanamivir is not recommended for patients with chronic respiratory diseases such as asthma or COPD because of an increased risk of bronchospasm
.

Peramivir: Approved in September 2017 for the treatment of acute uncomplicated influenza in children 2 years of age and older
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Under normal circumstances, children can take peramivir 10mg/kg, once a day, a single intravenous infusion over 30 minutes, or according to the condition, it can be repeated daily for no more than 5 days, and the upper limit of a single dose is 600mg
.

Oral oseltamivir remains the antiviral drug of choice for the treatment of influenza
.

Zanamivir for inhalation is an acceptable alternative to prescription for patients without chronic respiratory disease
.

Peramivir is an option for children who cannot receive oral or enteral oseltamivir or who cannot receive inhaled zanamivir
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It should be noted that the dose of NAI should not be increased arbitrarily during treatment
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A study in Indonesia, Singapore, Thailand, and Vietnam in patients with severe influenza over the age of 1 year showed no additional benefit from double-dose NAI
.

The adverse reactions of NAI drugs are shown in Table 2
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Table 2 Other therapeutic drugs for NAI adverse reactions have not yet been listed in China, such as the hemagglutinin inhibitor Arbidol, which was launched in Russia in 1993, the RNA polymerase inhibitor favipiravir, which was approved in Japan in 2014, and the Baloxavir listed in the United States,
etc.

In response to the concern of drug resistance, 99% of the H1N1 virus strains currently tested are sensitive to oseltamivir and peramivir, and all tested influenza virus strains are sensitive to zanamivir
.

In children who do not respond to oseltamivir treatment or who have previously been ineffective in preventing influenza with oseltamivir, zanamivir or peramivir replacement therapy may be considered
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It should be noted that in severely immunocompromised children receiving prolonged antiviral therapy due to viral reactivation, the resistance profile may change
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The National Influenza Center of China is also continuously monitoring the domestic influenza epidemic
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As of November 28, 2021, monitoring data show that the positive rate of influenza testing in the northern and southern provinces has shown a significant upward trend recently, which is higher than the same period last year
.

Among the currently monitored influenza viruses, the B (Victoria) line is absolutely dominant
.

82 influenza B outbreaks were reported this week
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From April 5, 2021 to November 28, 2021 (based on the date of the experiment), 739 strains (36%) of the B (Victoria) line were similar strains of B/Washington/02/2019
.

Since April 5, 2021, drug resistance surveillance has shown that all influenza B strains are susceptible to NAI
.

In children with clinically or laboratory-confirmed influenza, if the following symptoms occur, further investigations should be performed concurrently with antiviral therapy for empiric treatment of the complicated bacterial infection, and the combined use of antibiotics should be considered: Early symptoms of severe influenza; early antiviral therapy for clinical improvement After that, the condition deteriorated again; after 3-5 days of antiviral treatment, there was no improvement
.

The principle of treatment for severe cases of influenza is to actively treat the primary disease, prevent complications, and provide effective organ function support, such as respiratory support, circulatory support, and kidney support
.

Influenza prevention in children is greater than treatment, and the means include: Vaccines: the first line of defense against influenza, children over 6 months of age can have a protective effect after being vaccinated according to the recommended procedures, and the protective effect of influenza vaccine on older children may be better than that of younger children; Influenza virus drugs: an important supplement to vaccine prevention, suitable for high-risk groups, people who need short-term immune protection, people who cannot use vaccine prevention, and when influenza virus has antigenic drift
.

For children aged 6 months to 8 years, who have never received influenza vaccine, two doses (interval ≥ 4 weeks) are required for the first vaccination
.

One dose is recommended for children who have received one or more doses of the flu vaccine in the previous season
.

Children over 8 years old need only 1 dose
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Non-drug interventions mainly include: maintaining good personal hygiene habits: washing hands frequently; during influenza epidemic season, try to avoid crowded places and avoid contact with patients with respiratory infections; maintain good respiratory hygiene habits, cough or sneeze, use tissue Cover your mouth and nose, wash your hands after coughing or sneezing, and try to avoid touching your eyes, nose or mouth; when family members have flu patients, try to avoid mutual contact; avoid cross-infection; schools, kindergartens and other collective units When influenza-like illness occurs, patients should rest at home to reduce the spread of the disease
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The protection of hospitalized children must achieve 4 points: effectively implement the isolation of respiratory diseases.
Disinfection work
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Influenza children must be treated separately from other ordinary children
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If conditions permit, they should be placed in a negative pressure ward
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If unconditional, live in a single room or be admitted to the same ward, and the distance between the beds is not less than 1.
2m
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Isolation rooms need to be affixed with isolation signs
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Children should wear medical surgical masks when their conditions permit, and their activities should be limited in the isolation ward
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Respiratory infectious diseases are not accompanied in principle
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Strictly implement the visiting management system, strengthen the management of hospitalized children visiting personnel, and limit the visiting time and number of people
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Persons with fever or respiratory symptoms are not allowed to visit the ward
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Summary: Children are susceptible to influenza and a high-risk group of severe cases, and the burden of influenza disease in children is heavy; the main symptoms are high fever, which may include chills, chills, headache, general muscle aches, extreme fatigue, loss of appetite and other systemic symptoms.
Cough, sore throat, runny nose or nasal congestion, and a small number of patients have nausea, vomiting, and diarrhea; children have many complications from influenza, and the main causes of death in severe influenza are respiratory complications and IAE; early treatment, the main treatment drug is NAI; prevention methods include Vaccines, drugs, non-drugs
.