ABSTRACT
Pediatric influenza has certain peculiarities. Even a neonate is not immune to influenza. Yet, in first 6 months of life, it is infrequent to get it. In infants and young children, symptoms are atypical and include lethargy and poor feeding. The picture mimics other respiratory tract infections such as croup, bronchiolitis, bronchitis, or pneumonia.
On account of their immature immune system, children stand greater chance of getting infected by influenza viruses and have higher frequency and severity of complications. Children already suffering from chronic health conditions like asthma and diabetes are at even higher risk of getting the influenza and experiencing serious influenza-related complications.
That influenza vaccine is the best preventive means holds yet more eminently in children. No vaccine is available as yet for <6 months’ infants. It is the parents and other care-providers who should get vaccinated themselves and follow prevention tips to keep them healthy. Beyond 6 months, all children must get the influenza vaccine annually.
If the child is younger than 5 or has any chronic health conditions and experiences influenza-like symptoms, the family must contact a health care provider as soon as possible.
Teaching healthy habits, especially cough etiquettes, to children assists in its prophylaxis.
Treatment comprises supportive measures and specific antiviral drugs (which also have a role in prophylaxis). Zanamivir should not be given to children with underlying asthma. While antipyretic may be given to bring down high temperature, it is important to avoid using aspirin which may cause Reye's syndrome, a fatal hepatic encephalopathy.
INTRODUCTION
Influenza imposes a large burden on the health and well-being of children and families globally. According to conservative estimates, worldwide as many as 90–100 million children suffer from influenza every year despite the availability of an effective vaccine.1 No pediatric age is a bar, including neonates, though influenza is infrequent in neonates and in early infancy.2
4The key influenza symptoms in children include a high fever, chills and shakes, body aches, headaches and a dry hacking cough. Additionally, children often have nausea, vomiting and/or epigastric pain, distracting the attention from diagnosis of influenza. Sometimes, influenza is termed as “stomach flu”. In infancy, especially in neonates, presentation is often atypical with feeding difficulty, jitteriness, irritability and vomiting. High index of suspicion is, therefore, essential for detecting cases.3
PECULIARITIES
As in most other diseases, influenza in childhood has its own special features.1,4 Some peculiarities of pediatric influenza are listed in Box 1.1.
HIGH-RISK CHILDREN
Certain groups of children are at increased risk for complications of influenza. Box 1.2 lists children at great risk of serious influenza-related complications.5
Why are children at higher risk for the influenza? This is primarily because of the immature immune system. Children with chronic health conditions are at even higher risk of getting the influenza and experiencing complications. According to the CDC,5 treating children with the influenza can be costly. Severe complications are most common in children younger than 2 years. Children aged 6 months to 5 years are at risk of febrile seizures. Children with chronic health conditions such as asthma and diabetes have an extremely high risk of developing serious influenza-related complications.
Children 6 months and older should get the influenza vaccine.
Children younger than 6 months cannot get the influenza vaccine. Parents should get vaccinated themselves and follow prevention tips to keep them healthy.
Parents and care-providers of children younger than 5 years or with chronic health conditions should get the vaccine. If the child is younger than 5 or has any chronic health conditions and experiences influenza-like symptoms, the family must contact a health care provider as soon as possible (Fig. 1.1).
Influenza is caused by one of the three types of influenza viruses. Types A and B are responsible for the yearly epidemics. Type C virus causes sporadic mild or asymptomatic illness.
Type A virus, the predominant virus causing influenza, is further divided into different subtypes based on the chemical structure of the virus, i.e. surface proteins (hemagglutinin and neuraminidase).
Influenza is highly contagious, particularly, when children share close quarters in school classrooms and residential group facilities.
It spreads among children when a child either inhales infected droplets in the air (coughed up or sneezed by an infected person) or when the child comes in direct contact with an infected person's secretions.
A person can be contagious one day before onset of symptoms and 5–7 days after being sick.
This can happen, for example, when they share pencils at school or play computer games and share the remotes or share utensils such as spoons and forks. Hand-to-hand contact is also important in transmission and spread of influenza.
PATHOGENESIS
It is essentially the same as in adults. Following its entry into the child's airway, the virus attaches to sialic acid.1,8 Then, it residues on cells via hemagglutinin (HA). By endocytosis, it enters the vacuoles. In the vacuoles, with progressive acidification, it fuses with the endosomial membrane. There is also release of the viral RNA into the cytoplasm. Thereafter, RNA is transported to the nucleus and transcribed. RNA that is newly synthesized is returned to the cytoplasm where it gets translated into proteins which are transported to the cell membrane. Now the stage is set for budding of the virus through the cell membrane. Viral replication continues for 10–14 days.
Influenza virus invasion of the respiratory epithelium causes certain changes (Box 1.2) which renders it vulnerable to secondary bacterial infection either directly through the epithelium or through obstruction of the normal drainage by the Eustachian tube as happens in case of middle ear space.
At present, the exact immune mechanism involved in termination of primary infection and prevention against reinfection is poorly understood. The speculation is that it may correspond to the induction of cytokines that inhibit viral replication, e.g. interferon and tumor necrosis factor.1
A predominantly respiratory illness is the hallmark of influenza type A and B infections in older children.11,12 The symptoms are more severe than symptoms of a childhood common cold.
Symptoms start abruptly. Usually, the child feels the “worst” during the first two or three days of onset. The symptoms in children are listed in Box 1.3.
Notably, predominant manifestations may localize anywhere in the airway, producing an isolated upper respiratory tract illness—say, croup, bronchiolitis or pneumonia.13,14
Many of the symptoms of influenza are mediated through cytokine production by the respiratory tract epithelium. There is no systemic spread of the influenza virus.
Typically, influenza causes a febrile illness of 2–4 days with cough and evidence of small airway dysfunction persisting much longer, say few weeks.
High transmissibility of the influenza virus contributes to development of a similar illness by other family members or close contacts.
Finally, it needs to be re-emphasized that influenza being a less distinct illness in young children and infants, symptoms may well be localized to any region of the respiratory tract. Often, atypical presentation in the form of refusal of feed, irritability and jitteriness may fail to draw attention to the diagnosis of influenza.
Clinical
Clinical diagnosis of influenza in a child in the course of an outbreak can be made with reasonable certainty in the presence of fever without focus, malaise, cough, coryza, bodily pains, etc.
Adverse effects of influenza virus on respiratory epithelium.
- Loss of ciliary function
- Reduced mucus production
- Desquamation of the epithelial layer.
Routine
Nonspecific findings include a relative leukopenia and evidence of collapse or infiltrate in 1 in 10 children with influenza.
Specific
Rapid and reliable diagnostic tests for influenza are based on variations of PCR viral genome detection technology or of antigen capture like ELISA.
The confirmation of the diagnosis (made by rapid tests) can be made serologically with acute and convalescent sera drawn around the time of illness and tested by hemagglutination inhibition.
Isolation of the influenza virus from the nasopharynx by inoculation of the specimen into embryonated eggs or a limited number of cell lines that support the growth of influenza virus.
Hemadsorption that depends on the capacity of the HA to bind red cells confirms the presence of the virus in the culture.
PREVENTION
Annual influenza vaccination is the “gold-standard” and the best modality in influenza prophylaxis. All children aged 6 months and older need to receive the vaccine to prevent influenza. Vaccinating children with the influenza vaccine each year helps to protect them against influenza, especially, against severe influenza.
Healthy children over age 2 years who do not wheeze or do not have a history of asthma may have the option of getting the nasal spray vaccine (live attenuated vaccine). Children aged 6 months and older can receive the influenza shot (inactivate/killed vaccine).
Influenza vaccine is neither available nor recommended in infants <6 months. For them, the source of protection is immunity provided by the mother plus vaccinated family members and the care-providers.
Pregnant women and care-providers of children younger than 6 months or children with certain health conditions essentially need to be vaccinated. Vaccination to the mother is expected to elicit antibody that persists in the infant during the first 6 months when he is particularly prone to influenza. This explains why vaccine is not required by the baby in first 6 months. Neither is any such vaccine available.
However, a difficult situation crops up when mother has not received vaccine. Risk to the baby remains in such a case. It is, therefore, important that parents and other care-providers ensure taking the vaccine.
The seasonal influenza vaccine protects against three influenza viruses that the research indicates would be most common during the upcoming season. The 2014–2015 influenza vaccine protects against the three main viruses that are responsible for the most illness of the season. Precisely speaking, it is expected to protect against an influenza A (H1N1) virus, an influenza A (H3N2) virus and an influenza B virus.
The vaccination is especially important for children younger than 5 years of age and children of any age with a long-term health condition like asthma, 9diabetes and heart disease. These children are at higher risk of serious complications if they get the influenza.
Box 1.4 lists the contacts of children who are recommended for seasonal influenza vaccination by CDC.17
In addition, CDC recommends that all health care workers be vaccinated each year as a safeguard against spreading the infection to their patients.
Box 1.5 lists precaution for school children concerning influenza prevention.
Nonpharmaceutical Measures
In addition to vaccination, nonpharmaceutical measures, need to be enforced at quite a few levels (Boxes 1.6 to 1.8).
Chemoprophylaxis
During an influenza outbreak, indications for chemoprophylaxis include:
- High-risk cases (both vaccinated and unvaccinated)
- Healthcare providers of the index case
- Immunodeficient cases
- Children in whom vaccine is contraindicated.1
Approved antiviral agents for chemoprophylaxis are:
- Oseltamivir (Table 1.1)
- Zanamivir
- Amantadine.
In view of development of increasing resistance to amantidine, its use is no longer encouraged. Hence, we are left with only oseltamivir and zanamivir for a 10-day course for prophylaxis. A view is fast emerging that it is better to give the chemoprophylaxis for the whole period of exposure.
Chemoprophylaxis with zanamavir should be given only in children aged 5 years and beyond, provided that asthma is not coexisting. The dose of zanamivir is 10 mg daily for 10 days by inhalation. Two 5 mg inhalations (making a total of 10 mg) are needed daily.
Supportive Care
Influenza symptoms may last longer than 1 week. Caregivers can relieve and soothe children's aches and pains with basic supportive care. Acetaminophen may be administered for fever and relief of other symptomatology. In children having symptoms of influenza infection or colds, aspirin is not recommended because of an association with Reye's syndrome.
Use cough suppressants and expectorants to treat the cough. Steam inhalations may also be useful. If dehydration occurs, administration of oral or intravenous fluids is indicated.
There are useful home remedies and over-the-counter medications to treat flu symptoms in children. Keep in mind that antibiotics are ineffective against the influenza. Antibiotics are useful to treat bacterial infections. However, the flu is a viral infection and antibiotics will not help. Antiviral medicines are sometimes helpful for high-risk patients if they are started in the first two days of getting sick. They generally only shorten the duration of the flu of one to two days. However, the number one line of defense for flu is to get the flu vaccine. Some common home remedies for flu in children include:
- Getting plenty of rest
- Drinking plenty of liquids
- Using paracetamol, mefenamic acid or ibuprofen to lower fever and reduce aches (both are available in children's formulations).
Aspirin must not be employed in children or teenagers. Aspirin may increase risk of Reye's syndrome, a rare disorder that occurs almost exclusively in children and can cause severe liver and brain damage.
Over-the-counter (OTC) cough and cold medicines should not be given to children under 4–6 years of age in view of the serious adverse effects from them.
12In very young children with congestion, a nasal bulb should be used to remove mucus. Spraying three drops of saline into each nostril provides some relief.
Some children may be at increased risk for serious complications from flu. Especially those with chronic health conditions such as asthma or other lung disease, heart condition, or diabetes.
Indications for hospitalization are:
- The child has difficulty in breathing and does not improve even after nasal suctioning and cleaning.
- The skin color appears bluish or gray.
- The child appears sicker than in any previous episode of illness. The child may not be responding normally. For example, the child does not cry when expected or make good eye contact with the mother, or the child is listless or lethargic.
- The child is not drinking fluids well or is showing signs of dehydration. Common signs of dehydration include absence of tears with crying, decrease in amount of urine (dry diapers), irritability or decreased energy.
- A seizure occurs.
Antiviral Drugs
In general, antiviral drugs can be given if the child is at high risk of serious complications.
In some cases, antiviral drugs can also be used to prevent infection from influenza. These drugs block the replication of the flu virus, preventing its spread. In healthy children, antivirals such as oseltamivir (Tamiflu) and zanamivir (Relenza) may shorten the duration of flu and reduce the severity of flu symptoms (Table 1.2).
Special Considerations for Treatment of Avian Influenza
Hospitalization is required in patients with avian influenza if respiratory distress results in subsequent ventilatory support. Oseltamivir is the primary drug of choice. Longer therapy may be needed to treat highly pathogenic (HP) avian influenza than seasonal influenza.
The WHO recommendations for HP avian influenza A/H5N1 are as follows:
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13Patients with confirmed or suspected H5N1 infection should be treated with oseltamivir as soon as possible:
- Zanamivir might also be considered as an alternative if the patient is capable of using an inhaler.
- If neuraminidase inhibitors are available, amantadine and rimantadine should not be used as first-line therapies because of potential resistance.
- If neuraminidase inhibitors are not available, amantadine can be used as a first-line therapy, provided the virus is susceptible.
- If neuraminidase inhibitors are not available, ramantadine can be used if the virus is known to be susceptible because it has fewer side effects than amantadine.
- If neuraminidase inhibitors are available, and if the virus is susceptible, then a combination of neuraminidase inhibitors and M2 inhibitors can be used in confirmed cases of H5N1 infection.
- For prophylaxis in high-risk and moderate-risk exposures, give oseltamivir for 7–10 days from the day of exposure.
- Prophylaxis is not recommended for low-risk groups.
A combination of antiviral therapy (e.g., oseltamivir and adamantanes if susceptibility is expected) and antibiotics is recommended if pneumonia and rapid progression is noted. If septic shock is present, corticosteroids and vasopressors may play a role.
Acute respiratory distress syndrome (ARDS) should be managed according to guidelines.
If the patient is hospitalized, an isolation room is required, with airborne precautions or a negative-pressure room. A particulate mask, such as N95, and goggles are recommended.
Common complications of influenza in children include an ear infection, lower respiratory tract infection (LRTI) or laryngitis.
The following underlying/coexisting/pre-existing conditions, particularly, render a child to severe influenza:
- Cardiopulmonary disease
- Congenital heart disease
- Acquired valvular heart disease
- Asthma
- Bronchopulomonary dysplasia
- Cystic fibrosis
- Neuromuscular diseases involving accessory muscles of respiration
- Obesity
- Diabetes
- Immunodeficiency/immunosuppression
- Cancer chemotherapy
- Chronic exposure to cigarette smoking.
14Probability of a complication is significant if fever lasts more than three to four days or if the child complains of breathing difficulty, ear pain, congestion in the face or head, persistent cough, or seems to be getting worse. Young children under age 2 even healthy children—are more likely than older children to be hospitalized from the complications (Box 1.9).
PROGNOSIS/OUTCOME
Uncomplicated pediatric influenza shows excellent prognosis as far as recovery is concerned.1 However, full recovery may take a few weeks rather than just days.
SUMMARY AND CONCLUSION
Influenza is in infants and young children may present with atypical symptomatology, say lethargy, poor feeding, and poor circulation. In them, there is a greater chance of suffering from complications both in frequency and severity. Serious influenza-related complications occur more often in children already suffering from chronic health conditions like asthma, cardiovascular condition, diabetes, etc. Influenza vaccine (split) is the best preventive means in children. For infants <6 months, no vaccine is available as yet. Parents and other care-providers should get vaccinated themselves and follow prevention tips to keep them healthy. Beyond 6 months, all children must get the influenza vaccine. Healthy habits, especially cough etiquettes, assists in its prophylaxis. Whereas zanamivir should be avoided in children with underlying asthma, aspirin must never be used in children in the wake of risk of hepatic encephalopathy in the form of Reye syndrome.
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