Monday, March 9, 2015

Influenza - Who needs Oseltamivir?

Everyday I come across several patients who walk into the ED asking for testing Influenza virus (flu) and getting a vaccine. So I thought we should review this one, recent guidelines from Ministry of Health and Family Welfare on Influenza discussing who needs to be tested/treated/admitted and vaccinated in addition to some basics.
History:
  • Swine flu is a respiratory disease caused by the influenza viruses that infect the respiratory tract of pigs, the virus can be transmitted to humans.
  • Swine flu viruses may mutate (change) so that they are easily transmissible among humans.
  • Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, H2N3,  H3N1, and H3N2.
  • Investigators decided the 2009 so-called “swine flu” strain, first seen in Mexico, should be termed novel H1N1 flu since it was mainly found infecting people and exhibits two main surface antigens, H1 (hemagglutinin type 1) and N1 (neuraminidase type1). The present flu virus in India is A(H1N1)2009 virus. This indicates that it is a Type A virus with H1 and N1 proteins in combination.
  • The World Health Organization declared the infection a global pandemic in August 2010

There are three types of seasonal influenza viruses: A, B and C.
  • Type A may infect multiple species- Humans, pigs, birds (seasonal flu/epidemics/ pandemics)
  • Type B only infects humans (seasonal flu/epidemics)
  • Type C may infect humans and pigs (mild respiratory symptoms)


Type A may have sub-types depending upon the combination of two proteins, namely Haemagglutinin (H) and Neuraminidase (N). These proteins may have different numbers:
H: 1 to 17 and N: 1 to 10
The combination of numbers determines the name of the virus. Thus, we have H1N1, H1N2, etc.
Disease transmission:
  • Inhalation or ingestion of droplets containing virus from people sneezing or coughing; it is not transmitted by eating cooked pork products.
  • People who work with poultry/swine are at increased risk of infection with this influenza virus.

Signs and Symptoms:
  • In humans the symptoms of “swine flu” H1N1 virus are similar to those of influenza and of influenza-like illness in general.
  • Symptoms include fever, cough, sore throat, body aches, headache, chills, fatigue and sometimes diarrhea and vomiting.
  • The most common cause of death is respiratory failure. 
  • Fatalities are more likely in young children and the elderly, or previously sick patients like on dialysis, DM, Immunocompromised etc.
Diagnosis: Investigation confirmation by the REAL TIME PCR of nasal and oral secretions. This test in Hyderabad is done by – IPM, Narayanaguda


Guidelines:



Categorization of patients based on risk: Cat A/Cat B/Cat C
Category A
Symptoms/ Signs: Mild fever + sore throat/ cough with/ without bodyache, headache, diarrhea and vomiting.
Treatment: Symptomatic
Oseltamivir: Not required
H1N1 testing: Not required
Monitoring: 24-48 hours by a doctor.
Prevention: Patients should stay at home and avoid mixing with public and high risk members of family.

Category B
This has two sub-categories:
i) In addition to signs and symptoms of Category A, high grade fever and sore throat is present.
May require home isolation and Oseltamivir
H1N1 testing: Not required
ii) In addition to signs and symptoms of Category Aone or more of the following high risk categories is present:
  •    Children with mild illness but with predisposing risk factors. 
  •    Pregnant women; 
  •    Persons aged 65 years or older;  
  •    Patients with lung diseases, heart disease, liver disease, kidney disease, blood disorders, diabetes, neurological disorders, cancer and HIV/AIDS; 
  •    Patients on long term cortisone therapy.
Treatment: Broad spectrum antibiotics as for Community Acquired Pneumonia
                     Oseltamivir
H1N1 testing: Not required
Prevention: All patients of category B (i) and (ii) should confine themselves at home and avoid mixing with general public; high risk members of their family

Category C
In addition to signs and symptoms of category A and category B, the patient has one or more of the following:
  •  Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discolouration of nails
  • Children with influenza like illness who had a severe disease as manifested by the red flag signs (Somnolence, high and persistent fever, inability to feed well, convulsions, shortness of breath, difficulty in breathing, etc)
  • Worsening of underlying chronic conditions.
Treatment: Immediate hospitalization and treatment
H1N1 testing: Required

OSELTAMIVIR (TAMIFLU)
MOA: Oseltamivir inhibits neuraminidase, it must be administered within 48 hours of symptom onset to provide optimal treatment for a selected subgroup of patients.
Dose: 75mg BD
Adverse events: nausea, vomiting, skin reactions and sporadic, transient neuropsychiatric events (self-injury or delirium)
Note: We are not going to discuss here whether tamiflu works or not but do remember Oseltamivir (Tamiflu) isn’t for everyone, and it doesn’t make a difference for most. It probably gives us 1-2 days of symptomatic relief at the cost of antiviral resistance. However, applying this drug to the right at-risk patients may help reduce severity of illness and will hopefully prevent deaths, where even a small therapeutic benefit might provide the right patients an added advantage.

General precautions:

  • Frequent Hand Washing
  • Covering mouth and nose with tissue paper when coughing/ sneezing
  • Avoiding crowded places and those with symptoms of influenza
  • Avoiding contact greetings- hugs/ embraces/ kisses/ hand shakes, etc.
  • Those with symptoms suggestive of influenza should visit a health care facility at the earliest for early diagnosis and treatment.
  • Patients should be provided with three-layered surgical mask in hospitals.


Vaccination
  • Not recommended for general public at present.
  • Recommended only for Health care workers working in close proximity to influenza patients:
  • Those working in the ED/ICU/Isolation wards of hospitals treating influenza cases 
  • Those identified for working in screening centres for categorization of patients


Even with appropriate matching with the circulating strains, efficacy of vaccine may be about 70% to 80%. So, vaccine should not give a false sense of security. Considering the risk perspective, the preventive modality of infection prevention and control practices should be strictly followed. The available vaccine takes about 2-3 weeks for development of immunity.


Further Reading:



  1. http://www.emlitofnote.com/2014/04/tamiflu-bell-tolls-for-thee.html
  2. http://www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf
  3. http://www.bmj.com/content/348/bmj.g2545
  4. http://www.ncbi.nlm.nih.gov/pubmed/25285542
  5. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
  6. http://mohfw.gov.in/index4.php?lang=1&level=0&linkid=372&lid=3066



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