influenza
INFLUENZA
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 Treatment

Principles of Therapy

  • Initial management of influenza in adults is based on clinical presentation and epidemiological data

Pharmacotherapy

Symptomatic Therapy

Fever and Myalgia

  • May be treated with analgesics (non-opioids) and antipyretics (eg Paracetamol)
  • Avoid salicylates in children ≤18 years of age because of the risk of Reye’s Syndrome

Cough and Colds

  • May be treated with cough and cold preparations (eg expectorants, mucolytics)

Antivirals for Seasonal Influenza

  • When used within 48 hours of symptom onset, antiviral agents may reduce the duration of symptoms
    • Should not be used if there is uncertainty about diagnosis or if bacterial infection cannot be ruled out
  • None of the following agents have been shown to be effective in preventing serious influenza-related complications
  • Data is limited concerning effectiveness of the antiviral agents for the treatment of patients at high-risk of serious complications of influenza

Baloxavir marboxil

  • The 1st approved influenza virus-specific enzyme polymerase acidic (PA) protein-targeting drug used for the treatment of acute uncomplicated seasonal influenza in patients ≥12 years old who exhibited symptoms for no more than 48 hours
  • Based on several studies, the therapeutic effect of a single dose of Baloxavir marboxil is comparable to that of the 5-day twice-daily treatment with Oseltamivir

M2 Inhibitors

  • Eg Amantadine or Rimantadine
  • Active against influenza A viruses, but not influenza B viruses
  • There continues to be high resistance to adamantanes among influenza A(H3N2) and influenza A(H1N1) pdm09 viruses
    • Thus, Amantadine and Rimantadine are not recommended for treatment and chemoprophylaxis of currently circulating influenza A viruses
  • Effects:
    • As treatment: When used within 48 hours of illness onset in otherwise healthy adults, can reduce duration of uncomplicated influenza
    • As chemoprophylaxis: Both drugs are 70-90% effective in preventing illness from influenza A infection
    • They prevent illness while allowing subclinical infection and the development of protective antibodies; therapy does not interfere with antibody response to vaccine
    • Incidence of CNS side effects is higher among persons taking Amantadine than those taking Rimantadine

Neuraminidase Inhibitors

  • Eg Oseltamivir, Peramivir, Zanamivir
  • Oral Oseltamivir and inhaled Zanamivir are used for the treatment and prophylaxis of infection with influenza A or B viruses
  • IV Peramivir is used for the treatment of influenza A and B viruses especially for those intolerant to oral medications
  • Combination treatment with neuraminidase inhibitors is not recommended
  • Effects:
    • As treatment: Can reduce duration of uncomplicated influenza A and B illness by approximately 1 day compared with placebo when used within 2 days of illness onset
    • Both drugs are effective, 82% Oseltamivir and 84% Zanamivir, in preventing febrile, lab-confirmed influenza illness in otherwise healthy individuals
    • As chemoprophylaxis: Experience in preventing spread of influenza within institutions is limited when compared to the M2 inhibitors

Antivirals for Avian Influenza

  • It is recommended that treatment with a neuraminidase inhibitor is started as early as possible in the clinical course
  • Data regarding the effectiveness of these antiviral medications against H5N1 infections is limited

Oseltamivir

  • Primary antiviral agent of choice for the treatment of influenza A(H5N1) and A(H7N9) virus infections
  • Cultivable virus generally disappears within 2-3 days after initiation of Oseltamivir among avian influenza survivors, although clinical progression has been reported
  • Standard duration of therapy is 5 days but may be extended to 10 days if with no clinical improvement

Other Neuraminidase Inhibitors 

  • Eg Peramivir, Zanamivir
  • Highly active in vitro and in animal models, including that due to Oseltamivir-resistant influenza A(H5N1) virus
  • Orally inhaled Zanamivir has low systemic absorption and may not be useful if extrapulmonary dissemination has occurred; IV Zanamivir may be considered for inpatients with suspected or confirmed resistance to Oseltamivir and Peramivir therapy
  • Early Amantadine treatment of patients with adamantane-susceptible influenza A(H5N1) virus infections in Hong Kong in 1997 may have been associated with clinical benefit
  • Zanamivir monotherapy is associated with rapid emergence of resistance
  • May be used as off-label treatment option in patients with confirmed or strongly suspected infection if Oseltamivir is unavailable especially if the virus is known or likely to be susceptible

M2 Inhibitors (Amantadine, Rimantadine)

  • Early Amantadine treatment of patients with adamantane-susceptible influenza A(H5N1) virus infections in Hong Kong in 1997 may have been associated with clinical benefit
  • Not recommended for patients with avian influenza A(H7N9) virus infection
  • Should only be considered in H5N1 influenza as a treatment option if with treatment failure after neuraminidase inhibitors

Combination Therapy

  • Combinations of Oseltamivir and M2 inhibitors have enhanced antiviral activity and reduced emergence of resistance
  • Demonstrated greater antiviral effects and increased survival compared to monotherapy in animal models
  • 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 the same 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 and pregnant women, Oseltamivir or Zanamivir should not be administered for chemoprophylaxis
    • Amantadine or Rimantadine should not be administered as chemoprophylaxis

Non-Pharmacological Therapy

  • Rest is recommended
    • Strenuous physical activities (eg running) should be avoided until complete recovery
  • Patients are advised not to go to work or school and to avoid crowded places to reduce transmission
  • Return to full activity gradually after illness has resolved, especially if it has been severe
  • Wear mask in public areas
  • Cover nose/mouth when coughing or sneezing
  • Frequent hand washing
  • Adequate fluid intake is necessary to prevent dehydration
  • Adequate nutrition will assist in recovery
  • Advise patient, if necessary, to stop smoking
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