Monday, August 17, 2009

H1N1 update: Conflicting reports on use of other vaccines...

Pneumonia vaccine may help limit swine flu deaths
H1N1 virus

The H1N1 virus seen under a microscope (Centers for Disease Control and Prevention / April 28, 2009)

In view of the growing sense of hopelessness and frustration among many, as we grapple with the growing menace of the H1N1 pandemic, there has been differing reports and suggestions that perhaps we can do more, by adopting measures which are unproven, although perhaps appearing rather sensible.

Pneumococal Vaccine for more people?

In an article in the LA Times by Thomas H. Maugh, on 4 August, 2009, it was reported that some scientists have advocated that perhaps the pneumococcal vaccine may be another weapon to use earlier to help reduce the severity and lethality of the H1N1 complications,

"there may yet be something that can be done to reduce hospitalizations and deaths associated with the virus, commonly known as swine flu", to quote certain public health authorities.

"Most of the serious consequences linked to the virus are the result of pneumonia, and an underused vaccine called Pneumovax can prevent, or at least limit, such complications in many patients.

The vaccine, made by Merck & Co., stimulates the body's ability to neutralize the bacteria responsible for many cases of pneumonia, and it has the potential to prevent an estimated one-third of pneumonia deaths linked to swine flu."

"We would certainly like to see the vaccine used more extensively," said Dr. William Schaffner, chairman of the preventive medicine department at Vanderbilt University School of Medicine and president-elect of the National Foundation for Infectious Diseases. Schaffner was a member of the Centers for Disease Control and Prevention advisory committee on vaccines that in early June strongly affirmed current recommendations for who should receive the vaccine.

Further, the vaccine provides protection against pneumonia for up to 10 years, meaning one vaccination provides at least some safeguard not just this year but for future flu seasons as well.

The CDC has issued an Interim guidance for use of 23-valent pneumococcal
polysaccharide vaccine during novel influenza A (H1N1) outbreak

However, not everyone shares the enthusiasm for this penumococcal vaccination initiative:

Some physicians are more skeptical about the pneumococcal vaccine's potential to limit flu deaths. "I think that the pneumococcal vaccine is a very important vaccine that should be taken by all for whom it is appropriate," said Dr. Aaron Glatt, president and chief executive of New Island Hospital in Bethpage, N.Y., and a spokesman for the Infectious Diseases Society of America. "Whether it could play a role in preventing complications from swine flu . . . I don't think that is known."

Not sure how many of H1N1 flu patients would develop bacterial pneumonia...
The problem is that there are many causes of pneumonia, an inflammation of the lungs that interferes with breathing and can be fatal. The influenza virus itself can cause pneumonia, as can many others. Or the lungs can be invaded by a bacterium such as Streptococcus pneumoniae or Staphylococcus aureus when the patient is weakened by a viral infection.

Pneumovax protects against 23 strains of
S. pneumoniae. It is not yet clear what proportion of swine-flu-related pneumonia is caused by S. pneumoniae and thus could be prevented or ameliorated by immunization.

But preliminary results presented to the CDC vaccine committee in June by Dr. Matthew R. Moore, a CDC medical epidemiologist, indicated that about 40% of swine-flu-related pneumonia had an unknown cause -- and that about 30% were caused by
S. pneumoniae. This suggests that at least a third of flu-related pneumonia deaths could be prevented by vaccination.

How many would need to be additionally vaccinated? Is it worth it?

At least 70 million Americans are in groups that the CDC recommends receive the vaccine, according to Moore. That includes about 22 million people ages 2 to 64 with chronic underlying conditions, such as diabetes and heart disease; about 3.5 million with asthma; about 30 million smokers; and all people over the age of 65, about 15 million.

About two-thirds of the elderly have been vaccinated, Moore said, but fewer than a third of the other groups have.
The committee has not recommended the vaccine for pregnant women, who are about six times as likely to die from complications of swine flu as the population at large.

The vaccine is relatively inexpensive. Merck charges $33 for the necessary one dose, and physicians who administer it typically charge the patient $50 to $75, which is covered by Medicare and private insurance.
The side effects "are mostly local, including swelling and tenderness," Horovitz said.

"Significant side effects are rare unless you are dealing with someone who has a problem with vaccines in general."


Local Scenario, not many with secondary infections to date...

Yet the reality may be less clear, at least for us here in Malaysia.

In our conversations with Dr Christopher Lee, chief of infectious disease at the Sungei Buloh Hospital, there appears to be few patients who develop secondary bacterial pneumonia, although in view of the very severe complications, cultures for bacteria had been performed (with few positive results) and even prophylactic antibiotics had been prescribed.

Still all these difficult cases are now being re-examined and scrutinised to see if some sense could be made to tease out why some patients do so badly, so rapidly...

NEJM Reports on Mexican H1N1 Experience
Recent reports from the Mexican Experience, reported in the New England Journal of Medicine, has also painted a predominantly viral pneumonitis, with few secondary bacterial infections as the cause of death or complications.

Example of Chest X-ray & Pathology of Lung Tissue


  • No patients had received oseltamivir before admission;
  • 14 received it in hospital, at a dose of 75 mg twice a day for a minimum of 5 days;
  • 11 began receiving it at admission (a mean of 8 days after the onset of symptoms) and
  • 3 between 2 and 10 days after admission.
  • Four patients who survived did not receive oseltamivir.
  • After admission, 17 patients received ceftriaxone and 10 received clarithromycin. (thus, antibiotics were given)
  • Additional antibiotics were prescribed in several patients, on the basis of their clinical course: three were given levofloxacin; seven, vancomycin; five, cefepime; five, imipenem; and two, dicloxacillin.

Clinical Course during Hospital Stay

  • Respiratory distress requiring intubation and mechanical ventilation developed in 10 patients within the first 24 hours after admission.
  • Two additional patients required mechanical ventilation during stay in the hospital
  • Mechanical ventilation needed for 7 to 30 days in patients who survived and from 4 to 17 days in patients who died.
  • Norepinephrine infusion was begun in 9 of 18 patients (50%) during the period of hospitalization, and 5 patients received corticosteroids (hydrocortisone at a dose of 300 mg per day or methylprednisolone at a dose of 60 mg per day). (this refers to hemodynamic or blood pressure support, and anti-stress hormone treatment)
  • Of the 6 patients in whom renal failure developed, five died.
  • 7 patients had multiorgan system failure.
  • No patients had disseminated intravascular coagulation or neurologic complications.
  • Four patients had ventilator-associated pneumonia, each case with a different cause: Acinetobacter baumannii, Achromobacter xylosoxidans, methicillin-resistant Staphylococcus aureus, or Escherichia coli.
  • Of 18 patients, 7 died, and 11 recovered and were discharged from the hospital.
  • Patients died within 10 to 23 days (mean, 14) after the onset of illness and between 4 and 18 days (mean, 9 days) after admission.
  • Pathological evaluation of the lung showed diffuse alveolar damage, thick hyaline membranes, and prominent fibroblast proliferation.

  • Mortality among the patients requiring mechanical ventilation was 58%,
  • four patients had nosocomial pneumonia,
  • in most patients, lung damage was most likely due to the primary effect of infection with influenza virus.
  • Possible mechanisms of damage include direct injury to the respiratory epithelium with a secondary cytokine storm.
  • We do not currently know whether our patients, especially those who died, had viremia, as was reported in association with H5N1 infection, a very aggressive variety of influenza.
  • Coinfection with other respiratory viruses could also explain the increased pathogenicity among our patients;
  • however, no other common respiratory viruses were found in our patients.
  • Only three of the patients had received influenza vaccine in fall 2009, since most patients were within the age groups for which vaccine was not recommended in Mexico.
  • It is currently unknown whether seasonal vaccination offered any protection against Swine-Origin Influenza Virus infection, however.

Note that no pneumococcus infection was detected in these group of patients from Mexico.

A few had what is commonly known as hospital acquired (nosocomial) infections due to long-standing use of mechanical ventilation or assisted respiration. Thus the verdict is still out...

More than half of those who required breathing support (mechanical ventilation) died

Once kidney or other multi-organ failure takes place the prognosis (outcome) is quite poor.

It is uncertain if seasonal flu vaccination helps to ameliorate the pandemic H1N1 flu severity, although few (only 3) patients with complications had such prior vaccination.

It suggests however, that the H1N1 virus is the main cause of severe penumonia in these patients who did very badly or who died...


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