Novel Influenza A (2009 H1N1)

BASICS

DESCRIPTION

Novel influenza ‚

2009 H1N1 virus, a novel influenza A virus originated from a reassortment of influenza viruses that circulated in North American and Eurasian pig herds
The 2009 H1N1 pandemic started in March 2009 in Mexico and then spread to many countries, including the United States.
The pandemic was declared over in August 2010 by the World Health Organization (WHO) (1).
Although the pandemic is over, 2009 H1N1 virus still exists and continues to cause disease.
According to CDC, 2009 H1N1 accounted for 219 (0.2%) of 52,518 seasonal influenza A cases between September 28, 2014 and May 23, 2015 (2).
Typically presents with influenza-like symptoms, but patients may also have diarrhea and vomiting.
Susceptible to neuraminidase inhibitors but resistant to adamantine antiviral agents
During the 2014 to 2015 U.S. influenza season, three cases of human infection with novel influenza A were reported: one with H3N2 variant and two with H1N1 variant.

EPIDEMIOLOGY

The CDC estimates that between 43 million and 89 million cases of 2009 H1N1 occurred between April 2009 and April 2010 in the United States, including ~274,000 hospitalizations and 12,470 deaths.
90% of the reported cases were accounted for by patients <64 years.
Predominant sex: male = female
Affected mostly young people
Older people protected by preexisting antibodies that cross-react with 2009 H1N1

ETIOLOGY AND PATHOPHYSIOLOGY

2009 H1N1 influenza was a quadruple reassortant strain with individual gene segments of the virus originating from humans, birds, North American pigs, and Eurasian pigs.
Reservoirs included infected human and pig populations.

RISK FACTORS

Spread primarily by respiratory secretions (similar to typical influenza)
Close contact (<6 feet) with confirmed case increases the risk for spread of respiratory droplets.
Risk factors for complications of or severe illness with 2009 H1N1 virus infection include:
- 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 (HIV/AIDS, transplantation, chemotherapy or corticosteroids, 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 to 2012, 2012 to 2013, and 2013 to 2014 seasonal influenza vaccines included 2009 H1N1 virus.
CDC recommends 2009 H1N1 vaccine for all individuals ≥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) and 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 to 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 (3):
- Fever
- Sore throat
- Cough
- Myalgias
- Nasal congestion
- Rhinorrhea
GI symptoms (more common than with seasonal influenza):
- Nausea
- Vomiting
- Diarrhea
Extrapulmonary complications include:
- 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 infection

DIAGNOSTIC TESTS & INTERPRETATION

Reverse transcription-polymerase chain reaction (RT-PCR; respiratory viral panel) is the test of choice (4,5)[A].
Rapid flu tests:
- The rapid antigen detection test and direct fluorescent antibody (DFA) have low sensitivities to detect 2009 H1N1 (17.8% and 46.7%, respectively).
Viral culture and polymerase chain reaction (PCR) test are highly sensitive (88.9% vs. 97.8%).

Initial Tests (lab, imaging)

Routine testing is 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 reduces mortality in patients admitted to hospital with pandemic influenza (2009 H1N1). Antiviral treatment is recommended as soon as possible (even if patient presents >48 hours after illness onset) for all patients requiring hospitalization or for those who have progressive, complicated illness. It is also recommended for 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 viral clearance.
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), zanamivir (Relenza), and peramivir (Rapivab).
Oseltamivir resistance is reported in <2% of strains tested globally, due to H275Y mutation. These strains remained susceptible to zanamivir.
During 2014 to 2015 U.S. influenza season, 64 2009 H1N1 isolates were tested for antiviral resistance. One isolate was found to be resistant to oseltamivir and one to peramivir. Among 58 2009 H1N1 isolates, no resistance was detected for zanamivir.

First Line

Oseltamivir (5)[A]:
- Adult dosage: 75 mg PO BID for 5 days
- Pediatric dosage (safety and efficacy not established for children <1 year):
  - ≤15 kg: 30 mg PO BID for 5 days; 16 to 23 kg: 45 mg PO BID for 5 days; 24 to 40 kg: 60 mg PO BID for 5 days; >40 kg: 75 mg PO BID for 5 days
- Infant dosage (<1 year old): 3 mg/kg PO BID for 5 days
- Consider longer treatment courses for patients who are hospitalized and remain severely ill after 5 days of treatment.
- Adverse effects:
  - Nausea and vomiting (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.
- Metabolized by liver
- Pregnancy Category C medication
- Chemoprophylaxis: indicated for ages 3 months and older
Zanamivir (not recommended for patients with respiratory conditions such as COPD or asthma or history of allergy to milk protein) (5)[A]:
- Adult dosage: 10 mg (two 5-mg inhalations) BID for 5 days
- Pediatric dosage: >7 years old: 10 mg (two 5-mg inhalations) BID for 5 days
- Limited quantities of IV zanamivir are available.
- Adverse effects:
  - May cause bronchospasm, especially in patients with preexisting respiratory illnesses
  - Common adverse symptoms include headache, nausea, dizziness, and cough.
  - Rare symptoms include neuropsychiatric symptoms, anaphylaxis, and severe skin reactions.
- Metabolized by liver
- Pregnancy Category C medication
- Chemoprophylaxis: indicated for ages 5 years and older
Peramivir (6)[A]:
- The FDA-approved peramivir in December 2014, for treatment of uncomplicated influenza in adults who have been ill for ≤2 days. Indicated for both influenza A and B. Few patients with influenza B were enrolled in clinical trials.
- Adult dosage: 600 mg IV single dose
- Not approved for use in children
- Adverse effects: Diarrhea is most common.
- Rare serious skin reactions and sporadic, transient neuropsychiatric events (self-injury or delirium; mainly reported among Japanese adolescents and adults)
- Pregnancy Category C medication
- Chemoprophylaxis: not applicable

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

11 World Health Organization. H1N1 in post-pandemic period. http://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_20100810/en/. Accessed August 10, 2010.22 Appiah ‚ GD, Blanton ‚ L, D 'Mello ‚ T, et al. Influenza activity " “United States, 2014-15 season and composition of the 2015-16 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2015;64(21):583 " “590.33 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 " “263.44 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 " “195.55 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 " “24.66 Kohno ‚ S, Kida ‚ H, Mizuguchi ‚ M, et al. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother. 2010;54(11):4568 " “4574.

ADDITIONAL READING

Dawood ‚ FS, Jain ‚ S, Finelli ‚ L, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360(25):2605 " “2615.
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.
Tooher ‚ R, Collins ‚ JE, Street ‚ JM, et al. Community knowledge, behaviours and attitudes about the 2009 H1N1 influenza pandemic: a systematic review. Influenza Other Respir Viruses. 2013;7(6):1316 " “1327.

CODES

ICD10

J10.1 Flu due to oth ident influenza virus w oth resp manifest ‚

ICD9

488.19 Influenza due to identified 2009 H1N1 influenza virus with other manifestations
488.12 Influenza due to identified 2009 H1N1 influenza virus with other respiratory manifestations
488.11 Influenza due to identified 2009 H1N1 influenza virus with pneumonia

SNOMED

influenza due to Influenza A virus subtype H1N1 (disorder)
Upper respiratory tract infection due to H1N1 influenza (disorder)
Pneumonia due to Influenza A virus subtype H1N1 (disorder)

CLINICAL PEARLS

2009 H1N1 pandemic lasted from March 2009 through August 2010.
Although the 2009 to 2010 pandemic is over, 2009 H1N1 virus still exists and continues to cause clinical disease. Most cases are self-limited and uncomplicated.
Up to 25% of patients with 2009 H1N1 disease report vomiting and diarrhea in addition to fever, headache, sore throat, and cough.
RT-PCR (respiratory viral panel) is the diagnostic test of choice.
2009 H1N1 is susceptible to neuraminidase inhibitors (oseltamivir, zanamivir and peramivir) but resistant to adamantine.
Peramivir is the most recent drug approved by FDA for treatment of uncomplicated influenza in adults.

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