What happens if influenza is left untreated with oseltamivir (Tamiflu)?

Consequences of Untreated Influenza Without Oseltamivir (Tamiflu)

Without oseltamivir treatment, influenza infection can lead to prolonged symptoms, increased risk of complications including pneumonia, and potentially higher rates of hospitalization and death, especially in high-risk individuals.

Disease Progression Without Treatment

• Untreated influenza typically results in symptoms lasting 1-1.5 days longer compared to when treated with oseltamivir within 48 hours of symptom onset 1
• The severity of illness may be up to 38% greater in untreated cases compared to those receiving timely oseltamivir treatment 2
• Fever and viral shedding duration are both prolonged in untreated influenza cases 2, 3

Risk of Complications

• Untreated influenza increases the risk of secondary complications that may require antibacterial treatment 2
• The risk of developing pneumonia is approximately 50% higher in untreated patients compared to those receiving oseltamivir 1
• For hospitalized patients, untreated influenza is associated with:
  • Higher peak pulmonary disease severity 4
  • Increased risk of ICU admission (over 4 times higher odds compared to treated patients) 4
  • Greater likelihood of requiring kidney replacement therapy or vasopressor support 4
  • Higher in-hospital mortality (nearly 3 times higher odds of death) 4

Impact on Specific Populations

High-Risk Individuals

• The consequences of untreated influenza are more severe in high-risk populations, including:
  • Children younger than 2 years 1
  • Adults over 65 years 1
  • People with underlying medical conditions (asthma, cardiac disease, etc.) 1
  • Pregnant women 1

Children

• In children, untreated influenza may lead to:
  • Higher risk of otitis media (ear infections) 1
  • Increased risk of asthma exacerbations in children with asthma 1
  • Longer duration of fever and symptoms (approximately 29 hours longer in otherwise healthy children) 1

Timing Considerations

• The benefits of oseltamivir treatment decrease significantly when initiated more than 48 hours after symptom onset for uncomplicated influenza 1
• However, even delayed treatment (>48 hours) may provide some benefit in cases of severe, complicated, or progressive disease 1
• A retrospective study showed that patients receiving oseltamivir treatment >48 hours after symptom onset had a median hospital stay of 6 days versus 4 days for those treated within 48 hours 1

Important Caveats

• While oseltamivir reduces symptom duration and complication risk, a 2014 Cochrane review questioned its impact on reducing hospitalizations and death in uncomplicated cases 1, 5
• The FDA has described the overall performance of neuraminidase inhibitors like oseltamivir as "modest" 1
• The benefit-risk assessment should consider potential side effects of oseltamivir, including nausea (occurs in ~12-15% of patients) and vomiting (occurs in ~2.5-5% of patients) 6, 5

Clinical Decision Algorithm

1. If influenza is suspected and symptoms began <48 hours ago:

   • Treatment with oseltamivir should be initiated immediately for optimal benefit 1

2. If influenza is suspected and symptoms began >48 hours ago:

   • For patients with severe, complicated, or progressive disease: oseltamivir treatment is still recommended 1
   • For patients at high risk of complications: oseltamivir treatment is still recommended 1
   • For otherwise healthy patients with mild disease: benefits of treatment are minimal 1

3. For all patients with suspected influenza:

   • Do not delay treatment while waiting for definitive test results 1
   • Earlier treatment provides better clinical outcomes 1