para>Age <5 or >65 years
Pregnancy
Morbid obesity
Chronic medical conditions (diabetes, chronic cardiovascular conditions, cirrhosis, end-stage renal disease [ESRD] on hemodialysis [HD])
Chronic lung disorders (chronic obstructive pulmonary disease [COPD], asthma, cystic fibrosis)
Immunosuppression (associated with HIV infection, organ transplantation, receipt of chemotherapy or corticosteroids, or malnutrition)
Immunoglobulin (Ig) G2 subclass deficiency
Sickle cell disease
Native Americans/Alaska Natives
Persons aged <19 years on long-term aspirin therapy
Residents of nursing homes and other chronic care facilities
General Prevention
- 2009 H1N1 vaccination, monovalent or trivalent: The 2011 " 2012, 2012 " 2013, and 2013-2014 seasonal influenza vaccines included 2009 H1N1 virus.
- CDC recommends 2009 H1N1 vaccine for all person ≥6 months.
- No safety concerns were identified with 2009 H1N1 vaccine among pregnant women, infants, and children.
- Observe hand hygiene and appropriate cough etiquette.
- Health care personnel must observe droplet precautions (surgical mask or N95 mask and protective goggles) in addition to contact precautions for patients presenting with symptoms of an influenza-like illness (fever with cough or sore throat).
- When leaving exam or hospital rooms, symptomatic patients should be outfitted with a surgical mask to contain their respiratory secretions.
Diagnosis
History
- Incubation period: 1.5 " 3 days; may be up to 7 days
- Close contact with a suspected or confirmed case
- Clinical spectrum ranges from afebrile upper respiratory illness to fulminant viral pneumonia.
- Symptoms similar to regular seasonal influenza; most patients present with the following (3):
Fever
Sore throat
Cough
Myalgias
Nasal congestion
Rhinorrhea
- GI symptoms (more common than with seasonal influenza):
- Extrapulmonary complications include the following:
Hepatitis
Myocarditis
Rhabdomyolysis
Renal failure
Systemic or pulmonary vascular thrombosis
Reactive hemophagocytosis
In children, acute necrotizing encephalopathy or encephalopathy
Differential Diagnosis
- Seasonal influenza
- Respiratory viral infections from agents such as coronavirus, rhinovirus, and adenovirus
- Croup
- Pneumonia (typical and atypical)
- Infectious mononucleosis
- Pharyngitis (viral or streptococcal)
- HIV syndrome
Diagnostic Tests & Interpretation
- Rapid flu tests:
- Viral culture and polymerase chain reaction (PCR) test are highly sensitive (88.9% vs. 97.8%).
- Reverse transcription-polymerase chain reaction (RT-PCR; respiratory viral panel) is the test of choice (4,5)[A].
Initial Tests (lab, imaging)
- Routine testing often not necessary depending on patient 's clinical presentation. If laboratory testing is ordered, consider CBC with differential, complete metabolic panel, and blood cultures.
- Chest x-ray (CXR): Among those hospitalized for 2009 H1N1 infection, 50% had infiltrates on CXR.
Test Interpretation
Most consistent histopathologic findings are varying degrees of diffuse alveolar damage with hyaline membranes and septal edema, tracheitis, and necrotizing bronchiolitis.
Treatment
- Most infections are self-limited and uncomplicated.
- Treatment for seasonal influenza with neuraminidase inhibitors is most effective when administered within 48 hours of symptom onset.
- Neuraminidase inhibitor treatment has been shown to reduce mortality in patients admitted to hospital with pandemic influenza (2009 H1N1) virus infection (6)[A]. Antiviral treatment is therefore recommended as soon as possible (even if patient presents >48 hours after illness onset) for all requiring hospitalization or to those who have progressive, complicated illness; and persons with suspected or confirmed 2009 H1N1 infection regardless of previous health or vaccination status.
- Hospitalized patients of all ages, organ transplant recipients, and pregnant women with 2009 H1N1 who were treated with oseltamivir had faster resolution of symptoms and a more rapid clearance of viral shedding.
- Delayed oseltamivir therapy in severe cases of 2009 H1N1 has been associated with worse outcomes.
- High-risk patients with confirmed or suspected 2009 H1N1 should also be treated with antiviral agents, preferably within 48 hours of symptom onset.
- Consider antiviral treatment for high-risk patients with persistent symptoms who have a positive 2009 H1N1 test result even if specimen was obtained >48 hours after symptom onset.
Medication
- 2009 H1N1 is susceptible to the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza).
- Oseltamivir resistance is reported in <2% of strains tested globally, due to H275Y mutation. These strains remained susceptible to zanamivir.
- Genetic sequencing indicates increasing patterns of resistance to adamantine.
First Line
- Oseltamivir (5)[A]:
Adult dosage: 75 mg PO BID 5 days
Pediatric dosage (safety and efficacy not established for children <1 year):
Infant dosage (<1 year old): 3 mg/kg PO BID 5 days
Longer treatment courses can be considered for patients who are hospitalized and remain severely ill after 5 days of treatment.
Adverse effects:
Most common symptoms include nausea and vomiting, occurring in 9 " 10% of patients.
Neuropsychiatric events (e.g., hallucinations, delirium, and abnormal behavior) are rare symptoms.
Other rare symptoms include anaphylaxis and severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
Other considerations: metabolized by liver
Pregnancy class C medication
- Zanamivir (not recommended for patients with respiratory conditions such as COPD or asthma) (5)[A]:
Adult dosage: 10 mg (two 5-mg inhalations) BID 5 days
Pediatric dosage: >7 years old: 10 mg (two 5-mg inhalations) BID 5 days
Limited quantities of IV zanamivir were made available.
Adverse effects:
Most notably may cause bronchospasm, especially in patients with preexisting respiratory illnesses
Common adverse symptoms include headache, nausea, dizziness, and cough.
Rare symptoms are similar to those of oseltamivir, including neuropsychiatric symptoms, anaphylaxis, and severe skin reactions.
Other considerations: metabolized by liver
Pregnancy class C medication
- Peramivir:
FDA issued emergency use authorization (EUA) for peramivir, an investigational neuraminidase inhibitor for treatment of severely ill cases of confirmed or suspected cases of 2009 H1N1.
Administered IV
EUA for peramivir expired in June 2010
Additional Therapies
- Broad-spectrum antibiotics as needed for treatment of bacterial coinfections
- In patients with 2009 H1N1 with acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation may be necessary.
Complications
- ARDS
- Rapidly progressive pneumonia
- Respiratory failure
- Bacterial superinfection
- Encephalitis/encephalopathy
- Seizures
References
1.World Health Organization. In focus: H1N1 now in the post-pandemic period. www.who.int/csr/disease/swineflu/en/index.html. Accessed August 10, 2010.2.Flannery B, Thaker SN, Clippard J, Centers for Disease Control and Prevention (CDC). Interim estimates of 2013-14 seasonal influenza vaccine effectiveness " United States, February 2014. MMWR Morb Mortal Wkly Rep. 2014;63(7):137 " 142. [View Abstract]3.Cheng VC, To KK, Tse H, et al. Two years after pandemic influenza A/2009/H1N1: what have we learned? Clin Microbiol Rev. 2012;25(2):223 " 263. [View Abstract]4.Ginocchio CC, Zhang F, Manji R, et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol. 2009;45(3):191 " 195. [View Abstract]5.Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza " recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(1):1 " 24. [View Abstract]6.Muthuri SG, Venkatesan S, Myles PR, PRIDE Consortium Investigators. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014;2(5):395 " 404. [View Abstract]
Additional Reading
- Marshall HS, Collins J, Sullivan T, et al. Parental and societal support for adolescent immunization through school based immunization programs. Vaccine. 2013;31(30):3059 " 3064. [View Abstract]
- Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360(25):2605 " 2615. [View Abstract]
- Tooher R, Collins JE, Street JM, et al. Community knowledge, behaviours and attitudes about the 2009 H1N1 influenza pandemic: a systematic review. Influenza Other Respi Viruses. 2013;7(6):1316 " 1327. [View Abstract]
Codes
ICD10
- J09.X2 Flu due to ident novel influenza A virus w oth resp manifest
- J10.1 Flu due to oth ident influenza virus w oth resp manifest
ICD09
- 488.02 Influenza due to identified avian influenza virus with other respiratory manifestations
- 488.12 Influenza due to identified 2009 H1N1 influenza virus with other respiratory manifestations
- 488.82 Influenza due to identified novel influenza A virus with other respiratory manifestations
SNOMED
- 442438000 influenza due to Influenza A virus (disorder)
- 442696006 influenza due to Influenza A virus subtype H1N1 (disorder)
- 427873006 influenza due to influenza virus type A, avian, H5N1 strain (disorder)
- 450715004 Influenza due to Influenza A virus subtype H7 (disorder)
Clinical Pearls
- 2009 H1N1 pandemic started in March 2009 and was declared over in August 2010.
- Although the 2009 " 2010 pandemic is over, 2009 H1N1 virus still exists and is responsible for a majority of seasonal influenza cases during 2013 " 2014 in the United States. Most cases are self-limited and uncomplicated.
- Up to 25% of patients with 2009 H1N1 report vomiting and diarrhea in addition to fever, headache, sore throat, and cough.
- RT-PCR (respiratory viral panel) is the viral test of choice.
- 2009 H1N1 is susceptible to neuraminidase inhibitors (oseltamivir and zanamivir) but resistant to adamantine.