influenza
INFLUENZA
Treatment Guideline Chart
The clinical spectrum of influenza ranges from asymptomatic infection to primary viral pneumonia that may progress to death.
Patients presenting with influenza-like illness (ie temperature of 37.8ºC, cough and/or sore throat and absence of a known cause other than influenza) might be infected with different types of influenza virus (eg avian influenza [H5N1]) as well as other respiratory pathogens.
A high index of suspicion is needed to recognize influenza in hospitalized patients.
Pneumonia is the most common complication of influenza virus.

Influenza Management

Prevention

Follow local programs for control of priority diseases, if available

Timing of Seasonal Influenza Vaccination

  • Influenza vaccine is administered yearly to provide optimal protection against influenza virus infection
  • Vaccine should be administered before influenza activity in the community begins
  • Vaccination should commence throughout the flu season due to its varying duration
  • Vaccination campaigns may start earlier (July-August or as soon as vaccines are available) to ensure that there is sufficient time for the community to be vaccinated against influenza while adapting to the social distancing practices implemented in different countries to reduce the spread of SARS-CoV-2

Northern Hemisphere

  • Typically administer annual vaccinations to high-risk individuals and their close contacts by the end of October 
  • Vaccination given in December or later might be considered in most influenza seasons
  • Influenza activity typically occurs during October-May

Southern Hemisphere

  • Typically administer annual vaccinations to high-risk individuals and their close contacts between March-May
  • Influenza activity typically occurs during April-September

Tropical or Subtropical Regions

  • Lab-confirmed influenza can occur anytime throughout the year
    • Peaks of influenza activity can occur 1-2 times in a year
  • Epidemics often coincide with the rainy season
  • Public health programs where high-risk individuals and their close contacts are vaccinated should be performed at the same time each year if >1 peak of influenza activity occurs within a year
    • Latest available vaccine formulation should be used

Influenza Vaccines

The following recommendations apply to seasonal influenza only; vaccines against avian influenza are still being developed

  • Vaccines are the primary preventive measure against influenza
    • Decreases morbidity and mortality caused by influenza
    • Vital in reducing the impact of influenza-related respiratory illnesses in the population and resulting burdens on the healthcare system during the COVID-19 pandemic
  • Vaccines used should comply with current WHO recommendations
  • Influenza vaccine should be given annually for persons ≥6 months with no contraindication/s to any of its components
    • An age-appropriate formulation of inactivated influenza vaccine (IIVs), recombinant influenza vaccine (RIV) or live attenuated influenza vaccine (LAIV) should be given
  • Special populations that may be given influenza vaccine:
    • With history of egg allergy who only have hives after exposure
    • With history of egg allergy other than hives (ie angioedema, lightheadedness, recurrent emesis, respiratory distress and those who required Epinephrine or other emergency medical intervention)
    • Pregnant women and for those who want to become pregnant
  • Vaccinations should be done in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are readily available
  • Severe allergic reaction (eg anaphylaxis) is a contraindication for vaccination with any form of influenza vaccine
    • History of severe allergic reaction to any egg-based IIVs, RIV or LAIV is a precaution for the use of cell-based IIVs
    • History of severe allergic reaction to any egg-based IIVs, cell-based IIVs or LAIV is a precaution for the use of RIV4
  • Travelers who would want to reduce the risk for influenza may receive influenza vaccination at least 2 weeks prior to departure

Composition

  • For the 2023/2024 northern hemisphere flu season, the recommended egg-based trivalent vaccine should contain an A/Victoria/4897/2022 (H1N1)pdm09-like virus, an A/Darwin/9/2021 (H3N2)-like virus and a B/Austria/1359417/2021 (B/Victoria lineage)-like virus 
    • Quadrivalent vaccines will contain above three viruses, plus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus
  • For the 2023/2024 northern hemisphere flu season, the recommended cell culture- or recombinant-based trivalent vaccine should contain an A/Wisconsin/67/2022 (H1N1)pdm09-like virus, an A/Darwin/6/2021 (H3N2)-like virus and a B/Austria/1359417/2021 (B/Victoria lineage)-like virus 
    • Quadrivalent vaccines will contain above three viruses, plus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus
  • For the 2023 southern hemisphere flu season, the recommended egg-based trivalent vaccine should contain an A/Sydney/5/2021 (H1N1)pdm09-like virus, an A/Darwin/9/2021 (H3N2)-like virus, and a B/Austria/1359417/2021 (B/Victoria lineage)-like virus 
    • Quadrivalent vaccines will contain above three viruses, plus a B/Phuket/3073/2013 (B/Yamagata/16/88 lineage)-like virus
  • For the 2023 southern hemisphere flu season, the recommended cell- or recombinant-based trivalent vaccine should contain an A/Sydney/5/2021 (H1N1)pdm09-like virus, an A/Darwin/6/2021 (H3N2)-like virus, and a B/Austria/1359417/2021 (B/Victoria lineage)-like virus
    • Quadrivalent vaccines will contain above three viruses, plus a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus
  • LAIV4 is an option for patients ≥2-49 years of age without contraindications (eg anatomic and functional asplenia, cerebrospinal fluid leak, cochlear implants)

Trivalent Flu Vaccines

  • Contains two type A strains and one type B strain of influenza 
  • Standard-dose trivalent shots (IIV3) are manufactured using virus grown eggs and is recommended for 18-64 years
  • High-dose trivalent shot is approved for people ≥65 years of age
  • Trivalent shot with adjuvant is approved for people ≥65 years of age

Quadrivalent Flu Vaccines

  • Contains two type A strains and two type B strains of influenza 
  • Intradermal doses are approved for people 18-64 years of age
  • High-dose inactivated quadrivalent shots (HD-IIV4), quadrivalent recombinant vaccine (RIV4) and quadrivalent adjuvanted vaccine (aIIV4) are recommended for patients ≥65 years of age
    • The Standing Committee on Vaccination (STIKO) 2023 recommends HD-IIV4 to patients ≥60 years of age
    • Use of high-dose influenza vaccines over standard-dose influenza vaccines is recommended in patients ≥65years of age
  • Quadrivalent flu shot with virus grown in cell culture is recommended for children ≥4 years of age

 Coadministration with Other Vaccines

  • IIVs and RIV4 may be administered simultaneously or sequentially with other inactivated or live vaccines
  • LAIV4 may be administered simultaneously with other inactivated or live vaccines
    • For live vaccines given sequentially, an interval of at least 4 weeks is recommended
  • Current guidelines indicate that COVID-19 vaccines can be administered with influenza vaccines
    • IIVs and RIVs may be given at the same time as COVID-19 vaccines but should be administered on another site

Inactivated Influenza Vaccine (IIV)

  • Given IM and contains killed or inactivated viruses so it cannot cause influenza
  • Licensed for use among persons aged >6 months, including those who are healthy and those with chronic medical conditions
  • Effects: If the vaccine used contains the predominant circulating influenza strains, it can be 70-90% effective in preventing illness in healthy adults aged <65 years
    • Approximately 50-77% effective when the vaccine strains were antigenically dissimilar to the majority of circulating strains
  • Patients with concurrent medical conditions may have a reduced rate of severe respiratory illness and death (up to 50%)
    • Main benefit of vaccination in these patients is the prevention of severe consequences of infection rather than preventing uncomplicated illness
  • Vaccines that conform to international standards of purity and potency are usually free from systemic side effects

Live Attenuated Influenza Vaccine (LAIV)

  • Given intranasally and contains live attenuated viruses that may cause mild signs and symptoms
  • Licensed for use among nonpregnant persons aged 2-49 years including healthcare personnel and other close contacts of high-risk persons (except severely immunocompromised persons who require care in a protected environment)
    • May be used postpartum
  • Recommended for healthy children 2-8 years with no contraindications or precautions
  • Effects: Significantly reduces the incidence of severe febrile illnesses, number of sick days, frequency of physician visits and antibiotic use
    • A 55% reduction in culture-confirmed influenza among children who received LAIV compared with those who received IIV
    • A 52% greater efficacy than TIV in preventing influenza among children aged 6-71 months who had previously experienced recurrent respiratory tract infection
    • A 32% increased protection in preventing culture-confirmed influenza in children and adolescents aged 6-17 years with asthma
  • LAIV should not be used in the following populations:
    • Children and adolescents who are receiving Aspirin or Aspirin-containing products
    • Persons who have experienced severe allergic reactions to the vaccine or any of its components and previous dose of any influenza vaccine
    • Pregnant women
    • Immunosuppressed children and adults (includes suppression caused by medication and HIV)
    • Caregivers and close contacts of immunocompromised individuals who require a protected environment
    • Children 2-4 years with asthma or with wheezing episode
    • Persons who took influenza antiviral medications within the previous 48 hours

Recombinant Influenza Vaccine (RIV)

  • Approved influenza vaccine that is neither inactivated or weakened and recommended for patients aged ≥18 years
  • Does not contain any egg protein
  • Uses recombinant DNA technology and insect virus expression system to produce an egg protein-less vaccine against seasonal influenza

Recommendations for Influenza Vaccination and Coronavirus Disease 2019 (COVID-19)

  • Reducing the prevalence of influenza through vaccination may help the symptoms that are confused with those of COVID-19 
  • For patients with mild or asymptomatic COVID-19, vaccination should be deferred to avoid confusing COVID-19 illness symptoms with postvaccination reactions
  • For patients with moderate to severe COVID-19, vaccination should be deferred until fully recovered
  • For individuals who are unvaccinated or partially vaccinated against COVID-19 with COVID-19 infection or had close contact exposure with a COVID-19-positive individual, influenza vaccination should be delayed until quarantine or isolation period has been fulfilled
    • Symptomatic individuals should have fully recovered prior to going to a vaccination site
  • For patients already admitted in a healthcare facility:
    • Patients who have been fully vaccinated and with no known recent exposure to individuals with suspected or confirmed COVID-19 infection may proceed to receive influenza vaccine
    • Influenza vaccine may be given to patients in quarantine due to close contact exposure with a COVID-19-positive individual if another opportunity to be vaccinated is not likely; vaccination may be deferred until quarantine has been completed if possible symptoms of COVID-19 infection may cause diagnostic confusion
    • Vaccination should be delayed for symptomatic individuals with suspected or confirmed COVID-19 infection until criteria to discontinue isolation is fulfilled (at least 10 days after symptom onset and 24 hours afebrile without the use of fever-reducing medications) and COVID-19 symptoms are improving, and the person is no longer moderately to severely ill
    • Vaccination may be given to asymptomatic or presymptomatic individuals with suspected or confirmed COVID-19 infection, or those who have fully recovered and are now asymptomatic, even if criteria to discontinue isolation has not been fulfilled, especially if another opportunity to be vaccinated is not likely

Recommended Target Groups for Seasonal Influenza Vaccination

For individual protection, administration of seasonal influenza vaccination is recommended for the following persons at higher risk for complications secondary to severe influenza:

  • All persons aged ≥6 months without contraindications 
  • Children aged 6-59 months
  • Adults aged ≥50 years
  • Those who are immunocompromised, including those caused by human immunodeficiency virus (HIV) and medications
  • Individuals with chronic pulmonary (including asthma, chronic obstructive pulmonary disorder, cystic fibrosis), cardiovascular (congenital heart disease, congestive heart failure, coronary artery disease except isolated hypertension), renal, hepatic, hematologic (including sickle cell anemia) metabolic disorders (including diabetes mellitus)
  • Individuals who are morbidly obese (ie body mass index [BMI] ≥40 kg/m2)
  • Children and adolescents 6 months to 18 years of age currently receiving Aspirin- or salicylate-containing medications who will be at increased risk for Reye syndrome after a bout of flu
  • Women anticipating pregnancy and pregnant women during the flu season
    • The World Health Organization (WHO) considers the vaccine safe at any gestational age of pregnancy
  • Poultry workers, pig farmers and those in pig-slaughtering industry
  • Caregivers or other individuals who live with high-risk individuals
    • Healthy household members and caregivers of high-risk individuals
    • Healthcare workers
  • Residents of institutions for the physically and mentally disabled and other long-term care facilities
  • Others
    • Members of other groups are advised to consult their physician should they wish to obtain seasonal influenza vaccine

Prophylaxis

Seasonal Influenza 

  • Antivirals agents (eg Baloxavir marboxil, Oseltamivir, Zanamivir) may be used to prevent spread of influenza among unvaccinated high-risk household members and during an influenza outbreak in an institutionalized setting
  • May be used in persons who cannot be vaccinated due to contraindications to vaccine
    • Do not start until influenza epidemic has begun and stop only when epidemic is over
  • May be used in persons at high-risk for complications who have been vaccinated after an outbreak of influenza has begun
    • Give for 2 hourly starting from day of vaccination to give sufficient time for immunity to develop

Avian Influenza

  • Where neuraminidase inhibitors are available:
    • In high-risk exposure groups, including pregnant women, Oseltamivir should be administered as chemoprophylaxis continuing for 7-10 days after the last exposure; Zanamivir could be used in thesame way as an alternative
    • In moderate-risk exposure groups, including pregnant women, Oseltamivir might be administered as chemoprophylaxis continuing for 7-10 days after the last exposure; Zanamivir might be used in the same way
    • In low-risk exposure groups, Oseltamivir or Zanamivir should probably not be administered for chemoprophylaxis
    • Pregnant women in the low-risk group should not receive Oseltamivir or Zanamivir for chemoprophylaxis
    • Amantadine or Rimantadine should not be administered as chemoprophylaxis
  • Where neuraminidase inhibitors are not available:
    • In high- or moderate-risk exposure groups, Amantadine or Rimantadine might be administered for chemoprophylaxis if local surveillance data show that the virus is known or likely to be susceptible to these drugs
    • In low-risk exposure groups, Amantadine and Rimantadine should not be administered for chemoprophylaxis
    • In pregnant women, Amantadine and Rimantadine should not be administered for chemoprophylaxis
    • In the elderly, people with impaired renal function and individuals receiving neuropsychiatric medication or with neuropsychiatric or seizure disorders, Amantadine should not be administered for chemoprophylaxis

Infection Control/Isolation Procedures

Infection Control Measures for Outpatients

  • Frequent hand washing with soap and water
  • Cover nose and mouth when sneezing or coughing
  • Dispose of nasal and mouth discharge and used tissue papers properly
  • Use of surgical mask by the ill person; paper mask is not recommended
  • Travelers should get a flu vaccine before traveling to areas with ongoing influenza activity and should avoid outbreak areas
  • All members of the household should be educated on personal hygiene and infection control measures, eg hand washing, use of surgical mask
  • Avoid sharing of utensils, towels and bedding between patients and others
    • Clean all environmental surfaces soiled by body fluids with a household disinfectant according to manufacturer’s instruction, wear gloves during this activity
  • Adults: Restriction of social contacts (patient should not go to work, school or other public areas)
    • Continue infection control precautions until 21 days after resolution of fever and improved or absent respiratory symptoms
  • Children <12 years: Restriction of social contacts (patient should not go to school or other public areas)
    • Continue infection control precautions until 21 days after resolution of fever and improved or absent respiratory symptoms
  • Household members or other close contacts of diagnosed avian influenza patients who develop fever or respiratory symptoms should immediately contact local public health authority or WHO hotlines

Isolation Precautions for Hospitalized Patients

Isolation precautions should be implemented for all hospitalized patients with confirmed or suspected influenza A as follows:

  • Standard Precautions: Scrupulous hand hygiene before and after patient contact along with appropriate use of gloves/gowns when needed
  • Droplet Precautions: Wear a surgical mask if within 1 meter of the patient
  • Airborne Precautions: Controversial; warranted for selected patient care procedures
    • If available, place the patient in an airborne isolation room (ie monitored negative air pressure in relation to the surrounding areas with 6-12 air exchanges/hour)
    • When entering the room, use a high-efficiency mask, if available, or surgical mask

Restrictions

  • If a single room is not available, place patients separately in designated multibed rooms or wards
    • Beds should be placed 1 meter apart from other beds and preferably separated by a physical barrier (eg curtain or partition)
  • Limit the number of healthcare workers who have direct contact with the patient; these healthcare workers should not look after other patients
  • Restrict the number of visitors and provide them with the appropriate personal protective equipment (mask, gown, gloves and face shield or goggles) and instruct them in their use

Discharge

  • Hospitalized patients discharged after <14 days should implement the necessary isolation precautions as listed above for outpatients

Remarks

  • Clinicians should check with the local health authority on the requirements for disease notification and for the latest updates because recommendations will change as new information becomes available

Follow Up

Outpatients

  • As resources permit, the local health facility should follow up non-hospitalized patients by home visits and telephone contact
  • Follow-up should be done within 24-48 hours as most avian influenza patients develop pneumonia on day 4-5 after onset of symptoms
  • Patient should seek medical treatment if condition worsens
  • Adults: Social contact restriction and infection control procedures for 7 days after resolution of fever and symptoms
  • Children <12 years: Social contact restriction and infection control procedures for 21 days after resolution of symptoms and fever

Inpatients

  • Isolation precautions should be continued for 14 days after the onset of symptoms until an alternative diagnosis is established or until diagnostic test results indicate that patient is not infected with influenza A virus
  • Serial respiratory and blood specimens to check for possible bacterial infection
  • For patients discharged before 14 days, it is recommended that they be isolated in the home setting but should seek medical treatment urgently if condition worsens at home
Editor's Recommendations
Special Reports