INFLUENZA

Influenza is a highly contagious viral illness of respiratory tract with seasonal outbreaks (seasonal influenza) and intermittent pandemics (pandemic influenza). Seasonal influenza is common in winter season and outbreaks tend to subside after 4-6 weeks with low morbidity and mortality.

Pandemic influenza refers to particularly contagious strains of virus that spread rapidly to create a worldwide pandemic. Latest global pandemic by novel influenza strain (H1N1) was originated in USA and initially affected pigs (Swine flu). India was affected soon after in 2009, though it has gradually weakened now with development of herd immunity.

Etiology: Influenza is a large RNA virus of family Orthomyxoviridae, with three major serotypes affecting humans—A, B, and C. While all pandemics have been caused only by serotype A, seasonal outbreaks are usually due to A and B serotypes. Type C virus is responsible for sporadic and mild upper respiratory tract infections.

Serotype A is further classified on the basis of two surface proteins—hemagglutinin (HA) and neura­minidase (NA) and strains are named on the basis of the combination of HA and NA proteins, e.g. H1N1, H2N2, H3N2, etc.

On-going global pandemic has been caused by H1N1 infection, though seasonal outbreaks due to H3N2 serotype B infections are common.

Epidemiology of influenzae virus is interesting, as prevalent serotypes during outbreaks are known to change every year, due to minor antigenic changes following point mutations, termed antigenic drift, seen in both A and B serotypes. Infrequently, subtypes changes dramatically due to reassortment of viral gene segments, resulting in emergence of novel subtypes by the process termed antigenic shift, seen only in serotype A.

Pathogenesis: Human influenza virus is usually transmitted as a droplet infection from the infected host and enters the host cells through specific cell-surface virus receptors, mostly located in upper respiratory tract.

Pathology involves direct tissue damage as well as immune-mediated inflammatory damage, due to release of pro-inflammatory cytokines, e.g. IL-6 and interferon. While direct viral damage is essentially confined to upper respiratory tract or airways, pneumonia, ARDS and systemic damage is usually caused the cytokine storm. Secondary bacterial pneumonia is common.

Clinical spectrum: Season influenza is more common in younger population, usually presenting as influenza like illness (ILI). Severe disease or mortality is rare except at extremes of age.

Influenza-like illness (ILI) usually begins as a non­specific respiratory viral illness after an incubation period of 1-3 days (maximum 7 days), with fever, sore throat, cough, nasal congestion, malaise headache, myalgia and loss of appetite. Nausea, vomiting and diarrhea may also develop. Most cases recover spontaneously within a week. Over 1/3^rd of infections are asymptomatic.

Complications are rare except in high-risk cases, e.g. young infants or those with cardio-respiratory disease, hemoglobinopathies and immunocompromised states; and include acute hemorrhagic pneumonia, myocarditis, myositis, toxic-shock syndrome and rarely, neurological complications including Guillain-Barre syndrome.

Diagnosis must be suspected on epidemiological and clinical considerations. Confirmation usually depends on RTPCR, though rapid diagnostic tests are available with poor sensitivity (10-80%) but higher specificity (95-100%). Specimen for laboratory diagnosis must be obtained by multiple swabs from nasopharynx, throat or trachea and must be transported in specific liquid media with reverse cold-chain.

Viral cultures are possible and serodiagnosis with fourfold rise in specific neutralizing antibodies may be used for epidemiological studies.

Management depends on categorization of cases according to the severity of illness and a risk-based approach for home isolation, testing, treatment and hospitalization has been recommended by Government of India 2015, updated 2022 (Table 10.43), some important steps in the management include:

a. Category A cases must be managed at home with isolation measures and supportive therapy including bed rest, adequate hydration and antipyretics, e.g.

*Risk factors: Underlying lung disease, heart disease, liver disease, kidney disease, blood disease, neurological disorders, cancer, diabetes, HIV/ AIDS, long-term steroid therapy

paracetamol. Aspirin should be avoided due to potential risk of Reye syndrome.

b. Category B cases can also be managed at home, like category A, but with antiviral therapy without viral testing, discussed below.

c. Category C cases should be hospitalized and managed in isolation with infection control measures, along with fluid and electrolyte therapy, parenteral nutrition, oxygen/ventilatory support, cardiovascular support and antibiotics for secondary infection.

Antiviral therapy with PO Oseltamivir for 5 days is indicated only in category B and C disease and should be started preferably with 48 hours of the onset of symptoms, as follows:

• Infancy age-wise: lt;3 months: (12 mg BD), 3-5 months: (20 mg BD); 6-11 months (25 mg BD)

• Post-infancy weight-wise: lt;15 kg (30 mg BD), 15-23 kg (45 mg BD), 24-40 kg (60 mg BD) and gt;40 kg (75 mg BD).

Alternative therapy with other neuraminidase inhibi­tors, e.g. zanamivir and peramivir, is not approved in children lt;5 years.

Prevention involves general measures to prevent spread of airborne infections and vaccination of high-risk cases. Chemoprophylaxis or presumptive treatment with Oseltamivir, in close household contacts has been used but generally not recommended in children.

IAP recommends influenza vaccine to all children from 6 months to 5 years of age and to high-risk children beyond this age including those with - chronic cardiac, pulmonary (excluding asthma), hematologic, renal (including nephrotic syndrome) and liver disease and diabetes mellitus, and immunodeficiency states. Currently available influenza vaccines are inactivated trivalent or Quadrivalent vaccines containing WHO recommended strains. All of them include H1N1 strain (Fig. 9.2.2). Two doses of vaccines are recommended in the first year (after 6 months of age), followed by single dose annually before the onset of season.

Some other influenza-like illnesses (ILI) are as follows: Rhinovirus infections: Although no age is immune, these infections are more common in young children and during winter or late summer season.

Clinical spectrum: Apart from common cold, the commo­nest manifestation (Ch 16.5.1), rhinoviral infections are associated with—(a) pneumonia in very young children,

(b) acute asthmatic exacerbations in schoolchildren, and

(c) chronic bronchitis in adults.

Treatment is symptomatic. Antiviral drugs do not seem to affect the course or severity of disease.

Parainfluenza viruses have four serotypes, of which seasonal outbreaks in summer/rainy season are usually due to type 1 and 2, while type 3 is endemic.

Clinical spectrum: Fever is typically uncommon in para­influenza infections, which may present with: (a) acute laryngotracheobronchitis or croup (commonest cause), (b) acute bronchiolitis or bronchitis, and (c) persistent pneumonia in an immunocompromised host.

Treatment is symptomatic and specific antiviral therapy with Ribavarin is indicated only in immuno­compromised children.

Adenovirus infections, usually due to three serotypes (1, 2, 5), are more prevalent in spring and winter season and many states have witnessed outbreaks of respiratory

*in immunocompromised host only.

adenoviral infections in 2022-23, often indistinguishable from influenza or COVID-19 infections.

Clinical spectrum of these infections is very wide (Table 10.44), the commonest being acute upper respi­ratory or conjunctival infections. Adenoviruses are most common cause of follicular conjunctivitis and epidemic keratoconjunctivitis.

Pharyngoconjunctival fever is a distinct presentation of adenoviral 3 infection, characterized by high fever, pharyngitis, conjunctivitis and cervical lymphadeno­pathy, lasting for 3-5 days.

Diagnosis, apart from viral studies, is supported by characteristic histology, i.e. dense lymphocytic infiltrates, destruction of bronchiolar epithelium, focal necrosis of mucosal glands, hyaline membrane formation and nuclear inclusion bodies.

Treatment is non-specific, although Ribavarin has been used on immunocompromised cases.

Prevention: A monovalent vaccine is available for US military recruits, but not for general use.

Respiratory syncytial virus (RSV) infections are most common in infancy, during winter season or as nosocomial outbreaks.

Clinical spectrum: RSV infections are commonest cause of: (a) acute bronchiolitis, apart from causing, (b) acute laryngotracheobronchitis (croup) and rarely, (c) pneumonia in high-risk infants, e.g. those with cyanotic heart disease, bronchopulmonary dysplasia or severe immunodeficiency.

Treatment is symptomatic, though Ribavarin aerosol therapy has been used with modest effect on RSV pneumonia in high-risk cases.

Prevention: No vaccine is currently available, but passive prophylaxis with 'Palivizumab'—a monoclonal antibody, or RSV-enriched IVIG is recommended in high-risk cases with chronic cardiopulmonary disease.

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