Secondary Bacterial Co-infections cause 29% Deaths in H1N1 Flu in USA

Secondary Bacterial Co-infections cause 29% Deaths in H1N1 Flu in USA

WASHINGTON, Oct 1 — Many people who have died of H1N1 swine flu in the United States have also had bacterial infections, health officials reported yesterday.


A study of 77 patients who died of the new pandemic H1N1 virus showed 29 per cent of them had so called bacterial co-infections, the US Centres for Disease Control and Prevention reported.

About half of these had Streptococcus pneumonia, which can be prevented with a vaccine, the CDC said. It said doctors may be missing these infections in people severely ill with flu.

The CDC has already reported that H1N1, declared a pandemic in June, has become more active as weather cools and schools reopened after summer breaks. Cases are reported in all 50 states and it is still circulating globally.

H1N1 is not any more deadly than seasonal influenza so far but it attacks a younger age group than seasonal flu does and because virtually the entire population lacks immunity, it can infect far more people at once than seasonal flu usually does.

“The findings in this report indicate that, as during previous influenza pandemics, bacterial pneumonia is contributing to deaths associated with pandemic H1N1,” the team of experts at the CDC and state health departments reported.

“Our influenza season is off to a fast start and unfortunately there will be more cases of bacterial infections in people suffering from influenza,” CDC epidemiologist Dr. Matthew Moore, who helped organise the study, added in a statement.

The report noted in previous pandemics — in 1968, 1957 and 1918 — many of the patients who died were also infected with S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus and group A Streptococcus, which causes rheumatic fever and “strep throat”.

The CDC team noted that at first it did not appear that people who were seriously ill with swine flu or who died of it had secondary infections but doctors may have missed them.

“Routine clinical tests used to identify bacterial infections among patients with pneumonia do not detect many of these infections,” the CDC team reported.

Five of the patients who died, including a 9-year-old and an 11-year-old, had infections with the so-called superbug methicillin-resistant S. aureus or MRSA. None of the seven children who died had reported medical conditions that should put them at special risk of flu complications, although one was obese and one had Down syndrome.

The researchers cautioned that the patients whose cases were studied may not represent the nation as a whole. But like most of the victims of swine flu, they were young, with a median age of 31 and ranging from 2 months to 56 years.

Moore said people getting flu vaccinations should also ask about getting a pneumococcal vaccine.
Wyeth’s Prevnar is part of the routine series of immunisations that children should get, and Merck and Co. makes a vaccine against so-called pneumococcal bacteria that is available for adults, mostly those over 65. Merck also makes a Hib vaccine, although there is no vaccine to prevent group A streptococcal infections or MRSA. — Reuters

Flu experts gear up for pandemic of vaccine worry

Flu experts gear up for pandemic of vaccine worry

Health experts are already predicting a flood of problems that will follow the roll-out of the H1N1 vaccine. — Reuters pic

WASHINGTON, Sept 17 — One million heart attacks, 700,000 strokes and 900,000 miscarriages — US public health officials want Americans to know these will happen every single year with or without a swine flu vaccine campaign.


Yet this year, they know a significant number will be blamed on the H1N1 vaccine, which will roll out within weeks, and they are struggling to be ready.

They expect an avalanche of so-called adverse event reports, which are reports of death, illness or other health trauma that occur within two weeks after receiving treatment — in this case, the swine flu vaccine.

“We are going to be overwhelmed with potential events,” said Mike Osterholm, a public health expert at the University of Minnesota.

“Anything that happens to anybody in the period of seven to 14 days after vaccination will be reported.”

And not just to US officials. The World Health Organisation is trying to reassure a global audience that vaccines being made by 25 different companies, with various formulations, are all safe.

“If we have a safety signal in one country it could stop vaccination efforts in others,” WHO’s top flu expert Dr Keiji Fukuda told a meeting of infectious disease specialists organized by the US Institute of Medicine this week.

Flu experts themselves have little doubt the vaccine being made against H1N1 is safe. It is made using precisely the same technology as the annual seasonal flu vaccine, which is given to hundreds of millions of people every year.

But because H1N1 is new, vaccine makers have been testing it to learn what the right dose is.

SPIRIT OF ‘76
Memories linger of the 1976 swine flu debacle, when 43 million Americans were vaccinated against a virus that never spread, and newspapers filled with reports of a rare and crippling neurological disease called Guillain-Barre syndrome.

Guillain-Barre was never definitively linked with the vaccine, but many Americans have viewed immunisations with suspicion ever since.

“We have anticipated that there will be a need for enhanced surveillance for Guillain-Barre as well as other adverse events,” Dr Nancy Cox of the US Centres for Disease Control and Prevention told the meeting.

And there will be more to contend with than critical newspaper and television reports. The Internet did not exist in 1976. Nor did blogs, Facebook, Twitter or dozens of other ways for people to communicate globally and instantly.

“Information is the most globalized product of all,” Fukuda said. “The ability of blog sites to influence countries’ decision-makers and so on — coming to grips with how we deal with this is going to be a priority.”

To address this, CDC and the US Food and Drug Administration are gearing up for one of the biggest surveillance efforts ever. “We know how absolutely essential clear, transparent communications are to the public in order to have a successful vaccination campaign,” Cox said.

CDC’s weapons of choice — Facebook, Twitter, Internet RSS feeds, humorous “viral” videos posted on YouTube, iPhone apps such as the CDC News Reader. Children’s Hospital Boston has an app (short for application) called Outbreaks Near Me that allows people to track the pandemic locally. — Reuters

Singapore braces for second H1N1 wave

Singapore hospitals brace for new H1N1 wave

A recent Singapore press statement (The Straits Time, September 4, 2009) noted that hospitals in the tiny island republic, have been asked to brace for a possible second wave of Influenza A (H1N1), even as the number of cases decline recently.

So although some among our citizens and doctors have felt that this A(H1N1) flu is just another flu, 'hyped up' to be worse that it really is, such sentiments should be considered as outside conventional wisdom.

While we welcome contrarian viewpoints, we should still be prudent when it comes to public health initiatves and direction.


Infectious disease experts in Sinagpore estimated that the first wave had infected about 700,000 people there, which means that some four-fifths of the population have still not been exposed to the virus.

As of Aug 31, 1,181 people with H1N1 had been hospitalised, with 77 needing intensive care. To date, 17 have died: four had no pre-existing conditions.

Associate Professor Paul Ananth Tambyah, head of the National University Hospital’s infectious diseases division, said the numbers were in line with those from other countries and validated Singapore’s approach to have pandemic-preparedness clinics look after the vast majority of patients with flu.

The WHO predicts that two billion people will likely be infected worldwide by this new virus, with a “second wave” expected during winter in the northern hemisphere, the traditional flu season. But as the virus has not changed much so far, the outbreak is likely to be mild and not drawn out, said doctors.

The Singapore health ministry is taking no chances, and will have two million courses of the anti-viral drug Tamiflu by the end of this year, almost double the original stockpile. Another 200,000 courses of Relenza will be added to the current 550,000 in the national stockpile. Singapore has a contract with Australian drug maker CSL for a pandemic vaccine, enough for the population.

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

Pneumonia vaccine may help limit swine flu deaths

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."

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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










































Treatment

• 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

• 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.

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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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