Flu, Influenza, H1N1

Influenza,flu, H1N1

 Introduction

Influenza, commonly known as the “flu”, is an acute infection of the respiratory tract caused by influenza viruses. There are three types of seasonal influenza viruses – A, B and C. Influenza A viruses are further categorized into subtypes.

The 2009 pandemic influenza A(H1N1) virus (hereafter referred to as influenza A(H1N1)pdm09) which appeared for the first time in 2009 causing a global influenza pandemic, is now a seasonal influenza virus that co-circulates with other seasonal viruses (namely influenza A(H3N2) and influenza B viruses).

Influenza viruses are genetically dynamic and evolve in unpredictable ways. Influenza viruses are further classified into strains based upon antigenic properties.

Humoral immunity to influenza viruses is generally thought to be strain-specific and acquired through infection or vaccination.

Seasonal influenza epidemics can be caused by new virus strains that are antigenically distinct from previously circulating virus strains to which a population has immunity; this is known as antigenic drift.

Uncommonly, a completely new strain of influenza will emerge to which there is little or no existing immunity, this is known as antigenic shift and such novel strains can give rise to influenza pandemics such as 2009 pandemic influenza.

Categories of Influenza

Uncomplicated influenza: ILI (Influenza-like illness) may present with fever, cough, sore throat, coryza, headache, malaise, myalgia, arthralgia and sometimes gastrointestinal symptoms, but without any features of complicated influenza.

Complicated influenza: Influenza requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, tacchypnoea, lower chest wall indrawing and inability to feed), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.

Risk groups for severe/complicated influenza Disease:

• Pregnant women (including the post-partum period)
• HIV–infected individuals
• Individuals with tuberculosis
• Persons of any age with chronic diseases:
  • Pulmonary diseases (e.g. asthma, COPD) o Immunosuppression (e.g. persons on immunosuppressive medication, malignancy)
  • Cardiac diseases (e.g. congestive cardiac failure), except for hypertension
  • Metabolic disorders (e.g. diabetes)
  • Renal disease
  • Hepatic disease
  • Neurologic and neurodevelopmentalconditions
  • Haemoglobinopathies (e.g. sickle celldisease)
• Persons aged ≥65 years
• Persons ≤18 years receiving chronic aspirin therapy
• Persons who are morbidly obese (i.e. BMI ≥40)
• Young children (particularly <2 years of aged

Microbiology, Pathology and Pathogenesis

Human influenza viruses are single-strand RNA viruses that belong to the Orthomyxoviridae family, consisting of the genera influenza A, B, and C viruses. Only influenza A and B viruses cause epidemics in humans.

Based on their main antigenic determinants, the haemagglutinin (H or HA) and neuraminidase (N or NA) transmembrane glycoproteins, influenza A viruses are further subdivided into 18 H (H1–H18) and 11 N (N1–N11) subtypes, but only 3 hemagglutinin subtypes (H1, H2 and H3) and two neuraminidase subtypes (N1 and N2) have circulated stably in the human population and are responsible for annual epidemics.

HA and NA are critical for virulence, and are major targets for the neutralizing antibodies of acquired immunity to influenza.

The 2009 pandemic influenza A(H1N1) virus (hereafter referred to as influenza A(H1N1)pdm09) which appeared for the first time in 2009 causing a global influenza pandemic, is now a seasonal influenza virus that co-circulates with other seasonal viruses (namely influenza A(H3N2) and influenza B viruses).

Humoral immunity to influenza viruses is generally thought to be strain-specific and acquired through infection or vaccination.

Seasonal influenza epidemics can be caused by new virus strains that are antigenically distinct from previously circulating virus strains to which a population has immunity; this is known as antigenic drift.

Uncommonly, a completely new strain of influenza will emerge to which there is little or no pre- existing immunity, this is known as antigenic shift and such novel strains can give rise to influenza pandemics.

Transmission

Influenza viruses are spread from person-to-person.

They can be transmitted by exposure to infectious droplets expelled by coughing or sneezing that are then inhaled, or can contaminate hands or other surfaces.

The typical incubation period for influenza is 1-4 days (average 2 days). Most persons ill with influenza shed virus (i.e. may be infectious) from a few days before symptoms begin through 5-7 days after illness onset.

However, very young children can be infectious for >10 days after illness onset; adults with severe disease (e.g. viral pneumonia) may also shed virus for >10 days, and severely immunocompromised persons can shed virus for even longer.

Children have the highest rates of seasonal influenza infection and illness in this group can amplify viral transmission in the community.

Clinical Presentation and Risk Factors for Influenza

Infection with influenza viruses can give rise to a wide range of clinical presentations, ranging from asymptomatic infection to severe illness and death depending on the characteristics of both the virus and the infected person.

In the majority of people, influenza is an uncomplicated illness which is characterised by sudden onset of constitutional and respiratory symptoms such as fever, myalgia, cough, sore throat, rhinitis and headache.

Uncomplicated influenza illness resolves after 3-7 days although cough and malaise can persist for >2 weeks.

Influenza may be associated with more severe complications which include: influenza-associated pneumonia/ LRTI, secondary bacterial or viral infection (including pneumonia, sinusitis and otitis media), multi-organ failure, and exacerbations of underlying illnesses (e.g. pulmonary and cardiac illness).

Rare complications include encephalopathy, myocarditis, transverse myelitis, pericarditis and Reye syndrome.

For purposes of clinical management, influenza disease can be categorised as follows:

Uncomplicated influenza: ILI (Influenza-like illness) may present with fever, cough, sore throat, coryza, headache, malaise, myalgia, arthralgia and sometimes gastrointestinal symptoms, but without any features of complicated influenza.

Complicated/severe influenza: Influenza requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, tacchypnoea, lower chest wall indrawing and inability to feed), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.

Risk factors for complicated/severe influenza

Certain groups of patients are at higher risk of developing severe or complicated disease following influenza virus infection. However, influenza virus infection can result in severe/complicated illness in previously healthy individuals.

Similar to other studies showing increased risk of severe influenza- associated illness in certain individuals a recent study has found that younger and older age (< 5 years, in particular children < 1 year, and ≥65 years) and the presence of chronic underlying medical conditions, HIV infection and pregnancy were associated with increased risk of influenza associated-hospitalization.

In addition HIV-infected individuals with severe immunosuppression compared to those with mild immunosuppression had three times increased odds of influenza associated hospitalization.

Laboratory Diagnosis

Laboratory testing of uncomplicated illness (patients who fit the ILI case definition) is NOT routinely recommended, as it provides no advantage in the management of individual patients.

Testing can be considered for the following patients:

Patients who meet the criteria for complicated or severe influenza, where a laboratory diagnosis will assist in patient management.

Laboratory testing of uncomplicated illness (patients who fit the ILI case definition) is NOT routinely recommended, as it provides no advantage in the management of individual patients. Testing can be considered for the following patients:

Patients who meet the criteria for complicated or severe influenza, where a laboratory diagnosis will assist in patient management.

Clusters of cases where a diagnosis of the cause of the outbreak is needed (e.g. within institutions such as healthcare facilities, nursing homes). First 2-3 cases to be tested, thereafter testing not required.

In line with WHO recommendations, molecular diagnostics (real-time multiplex PCR for influenza A and B virus or Gene expert for influenza A and B virus) are currently the method of choice for influenza virus detection.

While specificity is high, the sensitivity of currently available rapid-point- of-care or immunofluorescence tests designed for direct detection of influenza A viruses is low (59%- 93%) and therefore they are not recommended for diagnostic purposes.

A negative Rapid Influenza Diagnostic Test (RIDT) result does NOT exclude influenza and should not preclude starting empiric antiviral treatment where sound indications exist.

Specimen Collection, Storage and Transportation

Combined nasopharyngeal and oropharyngeal swabs in universal transport medium (UTM) are the preferred specimen for testing.

Flocked swabs should be used to collect specimens as they provide a better yield on PCR. Dacron or rayon swabs may be used if flocked swabs are not available.

Cotton wool budded swabs are not recommended.

Once collected, these samples should be transported on ice to the testing laboratory.

The specimens must be refrigerated at 4°C if transport is expected to be delayed. If the specimen(s) cannot be shipped within 72 hours of collection, they should be kept frozen at -20°C. Avoid repeated freezing and thawing of specimens.

Clinical management and considerations for treatment of influenza

During the influenza season this increases to approximately 20-40% of all people hospitalised for pneumonia.

For this reason, influenza must be considered as an important potential cause of community acquired pneumonia (CAP) in all patients during the influenza season and consideration must be given to including oseltamivir as part of empiric treatment where indicated and available.

Note that because influenza vaccination is not 100% effective, a history of influenza vaccination does not exclude the possibility of influenza infection in patients with compatible clinical features.

Few patients with influenza require treatment and initiation of treatment should be based on clinical judgment taking into consideration the patient’s disease severity and progression, age, underlying medical conditions, likelihood of progressing to severe influenza, and time since onset of symptoms.

When indicated, antiviral treatment should be started as early as possible, ideally within 48 hours of symptom onset, and should not be delayed while awaiting laboratory confirmation.

However, antiviral treatment might still be beneficial in patients with severe, complicated or progressive illness, and in hospitalized patients when started more than 48 hours after illness onset.

Antiviral therapy is recommended as early as possible for any patient with confirmed or suspected influenza who has complicated or severe illness (including all hospitalised patients)
 is at higher risk for influenza complications.

Antiviral Medication Recommended for Treatment

Oral oseltamivir (Tamiflu) and inhaled zanamivir (Relenza) are chemically related antiviral medications that act as neuraminidase inhibitors and have activity against both influenza A and B.

These two medications are recommended for use during the 2017 influenza season. Adamantanes (amantadine and rimantadine) are not recommended for use due to high levels of resistance.

The standard adult dose and duration of oseltamivir treatment is 75mg twice daily orally for 5 days.

 

Considerations for treatment with Inhaled Zanamivir

Treatment with inhaled zanamivir is indicated in patients where oseltamivir-resistant influenza is demonstrated or strongly suspected.

Zanamivir is only recommended for use in persons aged ≥7 years.

Zanamivir contains lactose (powder for inhalation) and must NOT be administered by a
nebuliser.

It may also interfere with ventilator functioning in ventilated patients.

Other Interventions for Management

Antibiotic treatment: Antibiotics do not have a specific effect against the influenza virus but in cases of pneumonia, early empiric treatment for community acquired pneumonia is advised because of the high risk of secondary bacterial infection.

Since there is increased risk of secondary infection with S. pneumoniae, Staphylococcus aureus and Streptococcus pyogenes co-amoxiclav is a suitable empiric antibiotic.

Oxygen Therapy: Monitor Oxygen saturation and maintain SaO2 >90% (92-95% for pregnant women) with nasal cannulae or face mask. High flow oxygen may be required in severe cases.

Prevention of Influenza

Influenza vaccination is the most effective method for prevention and control of influenza infection available currently. In general, influenza vaccines are most effective among children ≥ 2 years and healthy adults.

A meta-analysis including data from years when there was a mismatch between vaccine and circulating strains estimated a pooled vaccine efficacy of 59% (95% CI: 51-67) in healthy adults.

Trivalent influenza vaccine has been shown to provide protection in HIV-infected adults without severe immunosuppression .

Data are unclear as to the effectiveness in HIV-infected children aged <5 years . In certain groups, including the elderly, immunocompromised individuals and infants, influenza vaccine is less effective; however, it may reduce the incidence of severe disease, e.g. bronchopneumonia, hospital admission and mortality.

Groups recommended for Influenza Vaccination

Because of limited resources and the fact that not all individuals who fall among the groups at risk for severe influenza disease respond well to influenza vaccination.

The recommendation for groups to be prioritised will be reviewed annually based on available data and resources.

The following are among the groups that are prioritised for the targeted public funded influenza vaccination campaign in 2017:

Pregnant women at all stages of pregnancy, including the postpartum period

• HIV-infected individuals
• Individuals (adults or children ≥ 6 months) who are at high risk for influenza and itscomplications because of underlying medical conditions and who are receiving regular medical care for conditions such as chronic pulmonary (including tuberculosis) and cardiac diseases, chronic renal diseases, diabetes mellitus and similar metabolic disorders, individuals who are immunosuppressed.

Persons aged >65 years

Other groups that would benefit from influenza vaccination but are not specifically targeted for vaccination by the National Department of health include:

Healthcare workers

Residents of old-age homes, chronic care and rehabilitation institutions

Persons aged 6 months - ≤18 years on long-term aspirin therapy and who therefore might be at risk for experiencing Reye syndrome after influenza virus infection

Individuals who are morbidly obese (body mass index ≥40 kg/m2)

Adults and children who are family contacts of individuals at high risk of severe influenza

Any persons wishing to minimise the risk of influenza acquisition, especially in workplace settings where large-scale absenteeism could cause significant economic losses.

Vaccine is recommended for healthcare workers to protect not only themselves against influenza, but more importantly their patients and vulnerable colleagues.

In order to improve vaccine coverage among the groups at risk for severe influenza disease, healthcare providers have a key role to play and they should recommend the vaccine and make it accessible for their patients e.g HIV clinics, antenatal clinics, Medical outpatient clinics and oncology clinics.

Dosage of influenza vaccine:

Recommended inactivated influenza vaccine (IIV)

 Adults                  -  0.5ml IMI single dose
 3 years - 8 years –   0.5ml IMI 1 or 2 doses*
 6 months-2 years-    0.25ml IMI 1 or 2 doses*
*2 doses should be administered ≥ 1 month apart during 1st year of vaccination, thereafter one dose

.

References:

World Health Organization. Seasonal influenza. In. WHO website 2016, Available from:http://www.who.int/mediacentre/factsheets/fs211/en/

World Health Organization. Recommended composition of influenza virus vaccines for use in the 2017