Results tagged “infectious disease” from Pathophilia
Last week's report of a beta-lactam-resistant superbug in the United Kingdom,* which was likely imported from India, highlights the infectious risks associated with medical tourism, according to an accompanying editorial. The growing trend of traveling to get medical care in non-Western countries—particularly for procedures not covered by insurance (eg, gastric bypass)—is expected to grow in India at an annual rate of 30%, says a 2009 news report. By 2015, medical tourism in India will be a 95-billion-rupee or $2-billion industry (if I'm calculating correctly).
At least one Indian doctor is accusing the report's corresponding author, who happens to be from the UK, of fear mongering and racism (despite the fact that multiple nationalities are represented by the listed investigators).
* Specifically Klebsiella pneumoniae and E. coli containing New Delhi metallo-beta-lactamase 1.
Scanning electron micrograph of E. coli bacterium from CDC/Janice Haney Carr.
While the NYT may have a story in the charge that OSHA isn't in lockstep with biotech safety, throwing up ex-Pfizer scientist Becky McClain as an example is simply irresponsible. By all reports, McClain was diagnosed with hypokalemic periodic paralysis, a genetically determined illness—which she, nevertheless, dubiously claimed was caused by a lentivirus from a Pfizer laboratory. (For background on this story, go here.)
Tossing McClain's case into the OSHA-biosafety mix also does a disservice to those very few scientists who probably did acquire disease in the workplace, like...
- Ru-ching Hsia, a Department of Agriculture scientist who developed coma-inducing hemolytic uremic syndrome after becoming infected in 2003 with laboratory-derived E. coli O157:H7;
- Jeannette Adu-Bobie, who contracted meningococcal septicemia in 2005 while working in a New Zealand vaccine laboratory; and
- Malcolm Casadaban, a U of C researcher who died September 13, 2009, of infection caused by a weakened version of Yersinia pestis.
According to Wikipedia, "[t]he last known case of a scientist dying from a pathogen he was studying was Howard Taylor Ricketts, who died of typhus in 1910."*
* The Rickettsiaceae guy!
OSHA = Occupational Safety Health Administration (which reportedly denied McClain's claim).
King Tut was buried in his condo made of stone-a after succumbing to the severest form of malaria, malaria tropica, say preeminent medical archaeologists in this week's JAMA. The boy king also had a form of osteochondrosis—namely, avascular necrosis of the second and third metatarsal bones (in the foot). The bone disease, which probably caused limping, explains the afterlife canes placed in Tut's tomb.
The conclusions about Tut's medical problems were made on the basis of an unprecedented combination of anthropologic, genetic, and radiologic studies and free access to the mummified remains of Tut and those of other Egyptian royalty. The researchers propose that the immediate cause of Tut's death was likely a leg fracture (possibly from a fall), which precipitated a series of life-threatening events in the already medically compromised teenager.
Crashing the curiosity party, U Michigan's Howard Markel raises the sticky issue of ethics when conducting medical examinations on historical subjects in an accompanying JAMA editorial. "Are major historical figures entitled to the same privacy rules that private citizens enjoy even after death?" he asks. While Markel acknowledges, "All historians are guilty of enjoying reading the mail and personal materials of others," he advises,
[B]efore disturbing the dead with the penetrating wonders of 21st-century medical science, it is essential to follow the lead of these authors by pondering all the ethical implications of such inquiries to avoid opening a historical Pandora's box.
Steve Martin, who wrote that Tut "gave his life for tourism," would probably concur.
Photo of banner advertising the 2008 tour of Tut's tomb artifacts from http://www.atlantaga.gov/media/citynewsbytes_040808.aspx.
Pandemic influenza may "notably increase" the overall death rate for pregnant American women in 2009. The prediction is based on data from pregnant or postpartum women who died of infection with the 2009 H1N1 virus in California during a 4-month period. An assessment of flu-related hospitalizations and deaths in this population is available in the latest issue of the NEJM.
Investigators from the California Pandemic (H1N1) Working Group collected data from 239 pregnant, postpartum, or nonpregnant women of reproductive age who were hospitalized with or died of probable or confirmed* pandemic flu between April 23 and August 11, 2009. Most (~78%) acquired infection in June or July.
Underlying chronic conditions, specifically asthma, were observed in substantial percentages of all women and particularly nonpregnant women—confirming that pregnancy itself is a risk factor for severe infection with the 2009 H1N1 virus.
|
Patient Feature |
Pregnant |
Postpartum |
Not Pregnant |
P Value [b] |
|
Chronic illness, % |
34 |
25 |
60 |
<.001 |
|
Asthma, % |
16 |
0 |
28 |
.04 |
|
Nongestational diabetes, % |
2 |
0 |
15 |
.002 |
|
Immunosuppression, % [c] |
3 |
0 |
15 |
.006 |
|
Neurologic disorder, % |
1 |
12 |
10 |
.009 |
|
Hypertension, % |
5 |
12 |
17 |
.009 |
|
Gastrointestinal disease, % |
2 |
0 |
14 |
.006 |
a. Percentages based on pregnant women for whom data were available.
b. Pregnant women vs nonpregnant women.
c. Related to cancer or transplantation.
Notable among pregnant women was a rapid clinical deterioration that looked qualitatively different from typical seasonal influenza. About 25% of pregnant women who required mechanical ventilation were intubated at the time of hospitalization, and several deliveries were made in intensive care units. ICU admission and death were about 4 times more likely in pregnant women who received antiviral treatment after 48 hours of symptom onset. Delay of antiviral treatment appeared to be associated with false-negative rapid-antigen test results.
During the 4-month period, the mortality ratio for pandemic flu in pregnant women was estimated at 4.3. Previous mortality ratios for all-cause death among pregnant women in California (2005) and in the United States (2006) were 19.3 and 13.3, respectively.
The authors urge pregnant women to be vaccinated against pandemic flu on the basis of their findings and preliminary vaccine-trial results.
RT-PCT = reverse-transcriptase polymerase chain reaction.
* Probable disease was defined as a positive result by real-time RT-PCR for influenza A that could not be subtyped H1 or H3. Confirmed disease was defined as a positive result by real-time RT-PCR that was specific of 2009 H1N1 influenza.
Depiction of H1N1 virus from Wikipedia.
No. 1: Pandemic H1N1
You were expecting something else?
Coming out of left field (ie, Mexico)* in April, the novel 2009 H1N1 ("swine flu") virus caused an official global pandemic in June, according to the World Health Organization. Cases mounted rapidly, but fear of disease was mitigated by its relatively low mortality rate.** Drawing on their experience from the swine-flu epidemic of 1976, leading US neurologists first believed that a government-led vaccination campaign would be unlikely because of 1) low mortality and 2) the possibility of vaccine-associated Guillain-Barre syndrome (GBS). Boy, were they wrong.
In August, the CDC released its recommendations for the administration of developing H1N1 vaccines to 5 groups. The surprise: Instead of the historically targeted elderly, the CDC prioritized vaccination for children, young adults, and pregnant women because of their emerging risks of disease-related complications and death. Consequently vaccination was recommended for an estimated 159 million Americans as soon as vaccines became available, sometime in mid-October.
In May, the DHHS had contracted with 5 companies—CSL Biotherapies, GSK, MedImmune, Novartis, and sanofi-pasteur—to produce either injectable or nasally administered vaccines for pandemic H1N1 to the tune of $932 million. Government orders for another $883,977,920 and $438,143,025 were placed in July and September, respectively. The total amounted to about 9 bucks per vaccine, which was being produced by the traditional method of viral incubation in fertilized chicken eggs.
This tried-and-true method ultimately led to a delay in vaccine production for 2 primary reasons: the fastidious nature of the 2009 H1N1 virus (when compared with seasonal influenza viruses) and limited chicken eggs. Turns out the pandemic virus required 2 eggs to create a single vaccine dose, instead of the usual one. By October, the federally contracted companies had only cranked out about 10% of the promised 120 million vaccine doses for US residents. Time was a-wastin'.
In October, the CDC investigators estimated that about 3 million citizens had already experienced symptomatic pandemic flu between April and July, on the basis of a probabilistic model. Confirming previous assessments, the incidence of disease and disease-related hospitalizations were considerably higher in children and young adults. Pandemic flu, overall, had necessitated about 14,000 hospitalizations and had caused about 800 deaths in the United States.
The following month, the CDC estimated that up to 34 million Americans had been infected between April and mid-October. Respective hospitalizations and deaths now ranged from 63,000 to 153,000 and from 2500 to 6000. Another age breakdown revealed that disproportionate numbers of younger adults (and to a lesser extent, children) remained susceptible to pandemic flu generally and severe disease specifically. About 45% of Americans who had died from pandemic flu had been healthy.
And then disease began to wane. Earlier this month, only 25 states reported widespread activity. At the same time, data showed that the pandemic flu vaccines (the supplies of which were up) remained effective and were comparably safe. Specifically the risk of GBS appeared no higher than the typical background rate.
The latest recommendations: More than 30 "major health care provider organizations," including the American Medical Association, the American Academy of Pediatrics, and the American Red Cross, are encouraging all US residents to receive a pandemic flu vaccine in anticipation of another wave of infection. An "open letter" to the American people states,
The H1N1 flu vaccine is safe, effective, and the best way to protect yourself and your family from the H1N1 flu. Over 110 million doses...are now available, with more coming every day. Now is the time to protect yourself and those around you by getting vaccinated against the H1N1 flu.
Links to selected Pathophilia posts on pandemic flu (and a few on seasonal flu) are provided here in chronological order.
* Instead of the historically expected East Asia.
** Estimated in the United States at 0.007%-0.032%.
Depiction of H1N1 virus from Wikipedia.
The estimated mortality rate of pandemic influenza in England is 0.026% (case fatality rate, 26 per 100,000), according to a report in this week's BMJ. This rate is similar to the mid-level US mortality rate that has been estimated by CDC officials.
Approximately 540,000 people (range, 240,000-1,100,000) have sustained symptomatic infection with pandemic influenza in England between June 1 and November 8 of this year, with 138 deaths meeting the described H1N1 case definition. Death rates appear to be highest for individuals aged 65 years or older and lowest for school-aged children and young adults. (By using midlevel estimates from the CDC, the case fatality rate for US individuals aged 65 years or older is substantially lower, at 32 per 100,000.)
|
Age Group, y |
Case Fatality Rate* |
Mortality Rate, |
|
<1 |
30 (2-260) |
0.030 |
|
1-4 |
27 (3-120) |
0.027 |
|
5-14 |
11 (3-36) |
0.011 |
|
15-24 |
12 (3-40) |
0.012 |
|
25-44 |
30 (10-88) |
0.030 |
|
45-64 |
64 (21-200) |
0.064 |
|
≥65 |
980 (300-3200) |
0.980 |
|
All |
26 (11-66) |
0.026 |
|
Age Group, y |
US Case Fatality Rate* |
US Mortality Rate, |
|
0-17 |
7 |
0.007 |
|
18-64 |
28 |
0.028 |
|
≥65 |
32 |
0.032 |
|
All |
21 |
0.021 |
As in the United States, there was no or only mild preexisting illness in about one third of England's fatal cases of pandemic flu. Most (78%) of these patients were prescribed antiviral drugs, but three quarters did not receive them within 48 hours of illness onset.
Despite England's relatively low mortality rate, the authors conclude that it "is not a justification for public health inaction." On the contrary, they argue, their data support expansion of the vaccination program to lower-risk groups [blogger's note: which evidently should include England's elderly] and the timely use of antiviral treatment.
* Deaths per 100,000 cases of pandemic influenza.
Depiction of H1N1 virus from Wikipedia.
In the midst of the 2009 pandemic influenza epidemic, BMJ editor Fiona Godlee takes Roche to task for not supplying the necessary data to confirm or refute the benefits of oseltamivir (Tamiflu) in otherwise healthy people with influenza. In one of 2 BMJ editorials, Godlee chides Roche for not supplying unconditional access to raw data from a pooled analysis of 10 company-sponsored trials (Kaiser et al; PubMed link here) to Cochrane reviewers Jefferson et al. Consequently the reviewers were "obliged to disregard" the bulk of these data (8 of the 10 trials) and were unable to verify that oseltamivir prevents lower-respiratory-tract complications (eg, pneumonia) due to influenza.
In their previous 2006 Cochrane review, Jefferson et al had concluded that oseltamivir 150 mg daily prevents such complications on the basis of the Kaiser article. However, the authors were criticized through a public feedback mechanism for using the 10-trial analysis without having access to the raw data. Prompted by this criticism, Jefferson et al then conducted another review, published this week in the BMJ, in which they affirmed their critic's perspective:
Data on the effectiveness of oseltamivir against complications of influenza principally came from one study...This was a meta-analysis of 10 trials containing a mixture of published and unpublished data, two of which are reported in this update and the remainder inaccessible to proper scrutiny, so that we are now obliged to disregard them. The remaining data showed no benefit for oseltamivir against complications.
In her editorial, Godlee asks, "Where does this leave oseltamivir, on which governments around the world have spent billions of pounds?" She, moreover, emphasizes that the Cochrane review data apply only to healthy adults with influenza, but they "say nothing about [oseltamivir's] use in patients judged to be at high risk of complications—pregnant women, children under 5, and those with underlying medical conditions." Even the drug's ability to reduce influenza-related symptoms (which Jefferson et al reconfirmed) are doubted, because there are no head-to-head studies with oseltamivir and NSAIDs, for instance.
In another BMJ editorial (with Cochrane director Mike Clarke), Godlee concludes that the latest Cochrane review and a "linked investigation undertaken jointly by the BMJ and Channel 4 News cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted." In their investigation, Cochrane reviewers became concerned about the actual involvement of listed authors on the Kaiser analysis, the possibility of ghostwriting, the high rates of influenza in the trials, and the low rates of serious adverse events.
Initial responses from Roche employees, who first declined to provide the data and then offered selected files, were less than satisfactory to the reviewers. The latest response from the company: it is "committed to making the 'full study reports' available on a password protected site soon."
On the basis of this experience, Godlee and Clarke conclude that the current system for reporting drug research "isn't working" and offer a number of potential remedies—including government-mandated access to raw data that are used to license and market a drug (eg, something in the spirit of the FDA Amendments Act of 2007).
News sources are all over this story (eg, Bloomberg), and the BMJ offers full-text access to the following relevant articles, including a response from a Roche employee—who chastises Jefferson et al for enlisting the investigative help of a TV news station.**
- Godlee F. We want raw data, now.
- Godlee F, Clarke M. Why don't we have all the evidence on oseltamivir?
- Smith J, on behalf of Roche. Roche replies to the authors of the Cochrane Review on oseltamivir.
- Cohen D. Complications: tracking down the data on oseltamivir.
- Doshi P. Neuraminidase inhibitors--the story behind the Cochrane review.
- Freemantle N, Calvert M. What can we learn from observational studies of oseltamivir to treat influenza in healthy adults?
- Jefferson T, Jones M, Doshi P, Del Mar C. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis.
- Web extra (including the criticism that got the ball rolling).
* And I mean that in the nicest possible way.
** Roche's Smith writes, "It is unclear to us why Dr Jefferson would adopt this approach, particularly given that he was a paid ad hoc consultant to Roche working on flu and oseltamivir between 1997 and 1999. During that period he worked closely with Roche experts, many of whom are still in the company, and he would therefore not have had difficulty in contacting them directly to discuss his requirements."
Photo from Vermin Inc at Flickr.
Vaccines for pandemic influenza appear to be as safe as current seasonal influenza vaccines, reports the CDC. The Center's preliminary assessment of safety reports from the US Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) are available in the latest issue of the MMWR.
Data from VAERS*—which includes publicly volunteered information—reveal overall adverse-event (AE) rates of 82 per 1 million doses of pandemic flu vaccine (0.0082%) and 47 per 1 million doses of seasonal flu vaccine (0.0047%). Respective rates of serious AEs (eg, death, life-threatening illness, hospitalization, prolonged hospitalization, persistent or significant disability, congenital anomaly) are 4.4 and 2.9 per 1 million vaccine doses each. However, the percentage of serious AEs among all reports is slightly higher with seasonal flu vaccines (6.1% vs 5.4%). No substantial differences are noted between pandemic and seasonal flu vaccines in the types of serious AEs reported, and no AE differences between injectable and intranasal vaccines are apparent.
Among the 13 reported deaths of those who received the pandemic flu vaccine, 9 were associated with a "significant" underlying illness; 1 was the result of a motor vehicle accident; and 3 cases are under review by the CDC. There are 12 reports of Guillain-Barre syndrome (GBS), 4 of which currently meet diagnostic criteria, and 19 reports of possible anaphylaxis. (The background incidence of GBS is 1-2 per 100,000.)
In the VSD**—which includes data from more than 400,000 vaccinated individuals among 8 managed-care organizations—there are no reports of GBS and only 1 case of anaphylaxis. Increased rates of other neurologic or allergic conditions have not been detected.
Historically higher rates of GBS associated with the swine-flu vaccination in the mid-1970s may be related to contemporary methods of vaccine production, the CDC speculates. The Center reports that it continues to monitor vaccine-associated AE data and advises that the number of vaccines administered in the VSD population, in particular, may be too small as yet to detect an increased risk of vaccine-associated GBS.
As of December 3rd, more than 72 million doses of pandemic flu vaccine have been allocated in the United States.
N.B. The CDC states that it used a number of methods (eg, advertising in medical journals) to enhance the reporting of vaccine-associated AEs to VAERS this season.
* As of November 24, 2009.
** From October 1 to November 21, 2009.
Only 25 US states are reporting widespread activity of pandemic influenza, according to the latest update from the CDC. During the previous 3 consecutive weeks, widespread activity was reported in 46, 43, and 32 states. The CDC advises, nevertheless, that most indicators for flu activity remain higher than normal for this time of year.
As of December 3rd, more than 72 million doses of pandemic flu vaccine have been allocated (ie, ready for distribution) in the United States; more than 63 million have been shipped to ordering states or US territories. Approximately one half of the supplies have been allocated for 10 states.
|
State |
Doses Allocated as of 12/03/09 |
|
California |
8,296,500 |
|
Texas |
5,565,000 |
|
New York* |
4,536,300 |
|
Florida |
4,306,800 |
|
Pennsylvania |
2,544,500 |
|
Ohio |
2,672,100 |
|
Illinois |
2,422,300 |
|
North Carolina |
2,172,500 |
|
Michigan |
2,329,000 |
|
Georgia |
2,280,900 |
* Including New York City.
A "potentially significant" mutation of the 2009 H1N1 virus has been detected in 3 severe cases (including 2 fatalities) of pandemic flu in Norway; however, the mutated virus is nothing new, according to the World Health Organization. The spontaneous mutation—which does not confer resistance to the antiviral drugs oseltamivir (Tamiflu; Roche) or zanamivir (Relenza; GSK)—was detected as early as April and has been found sporadically in both severe and mild flu cases in other countries,* reports WHO.
The 2009 H1N1 mutation has not been described or labeled explicitly in news reports. But according to a quoted Norwegian health official, the mutation "makes it possible for the virus to fasten itself or infect deeper into the bronchioles, and therefore provide for a more serious progress of the disease." This description suggests that the mutation lies in the gene encoding the viral binding protein, hemagglutinin.
WHO maintains that the current pandemic flu vaccine does produce immunity against the mutated virus.
* Namely Brazil, China, Japan, the Ukraine, and the United States.
Depiction of H1N1 virus from Wikipedia.
Pandemic influenza activity has declined during the last week in the United States, according to today's CDC briefing from Anne Schuchat, MD, Director of the National Center for Immunization and Respiratory Diseases. A total of 43 states are now reporting "widespread" activity, Schuchat said, which is down from 46 states last week.
However, Schuchat advised, flu activity at this time is much greater than activity during the same time last year. She further cautioned that flu activity, particularly during this season, is unpredictable.
In addition, there have been a cumulative 171 laboratory-confirmed pediatric deaths due to pandemic flu; about two thirds of these fatalities were children with underlying conditions (eg, cerebral palsy, muscular dystrophy). But the CDC estimates a far greater number of pediatric deaths due to H1N1. The Center will provide new mortality estimates in the near future.
The supply and distribution of pandemic flu vaccine continues to increase. Schuchat reported that a cumulative number of 54.1 million doses have been made available, which is 11 million more doses than 1 week ago. And 93% of the available supplies have been ordered by states. A total of 94.5 million doses of seasonal flu vaccine, the distribution of which is managed by the private sector, have been disseminated.
Schuchat also provided 4 tips for holiday travel:
- Travel "well"—meaning, if possible, travel only when you're well.
- Wash your hands.
- Cover your coughs.
- Get vaccinated—particularly if you're in a targeted population.
Statements from the media included comments about "potentially significant" viral mutations discovered in 3 H1N1-related cases (2 fatalities and 1 seriously ill patient) in Norway. Schuchat responded that these mutated viruses, although possibly concerning, have been seen in mild cases as well.
Using a model to account for the underascertainment of cases, the CDC now estimates that 14-34 million Americans were infected with the pandemic influenza virus between April and October 17, 2009. The Center previously estimated the number of US cases between April and July 23rd of this year at 1.8-5.7 million.
A breakdown by age (years) shows that pandemic flu has preferentially affected younger adults and children. (The graph provides midlevel estimates of cases [horizontal bars] and estimated ranges [vertical bars].)
By using the CDC's midlevel estimates, the mortality rate of pandemic flu is 0.018%—which is consistent with the range of mortality rates provided by Harvard epidemiologist Marc Lipstich (0.007%-0.045%).
One of the latest apparent victims of pandemic flu is University of Ottawa chemistry professor Keith Fagnou, 38, an otherwise healthy father of 3 children. Fagnou died of suspected H1N1 disease on November 11, 3 days after being hospitalized.
HT: In the Pipeline.
Question: What kind of protection does the seasonal influenza vaccine provide against pandemic influenza?
Brief answer: None.
Longer answer: Recent surveillance data from 356 adults in 8 states indicate that the likelihood of contracting pandemic flu is unaffected by receiving a seasonal flu vaccine. Results of the data analysis are available in the latest issue of MMWR.
After adjusting for age and chronic medical conditions,* the CDC found that the overall effectiveness of the seasonal flu vaccines against contracting pandemic flu was -10%, with a wide 95% confidence interval (CI) straddling zero (-43%, +15%). Data were obtained during the period from May to June of this year.
These epidemiologic data complement known serologic (laboratory) data, which suggest that the trivalent seasonal flu vaccines are unlikely to provide meaningful cross-protection against pandemic flu. Likewise a recent Australian study showed that, in children or adults who received seasonal flu vaccines, cross-reactive antibodies against pandemic flu were not produced. The overall age-adjusted effectiveness of the seasonal flu vaccines against pandemic flu in this study was 3% (CI: -56%, +40%). An unpublished study of high schoolers in New York City also suggests no protective benefit of seasonal flu vaccines against pandemic flu.
However, these data are at odds with those from a recently published Mexican study, which reported a seasonal flu vaccine effectiveness rate of 73% against pandemic flu. But control patients in this study were more likely to have chronic medical conditions—making seasonal flu vaccine coverage more likely in this group. Unpublished data from Canada suggest that "medically attended" pandemic flu may actually be more likely in recipients of the seasonal flu vaccine.
The MMWR editors advise that studies with more rigorous designs and methods are currently under way to evaluate any immunity conferred by seasonal flu vaccines against pandemic flu.
* Which increase the risk of influenza-related complications (eg, heart disease, asthma, diabetes, cancer).
Forever brainstorming, Google is now helping Americans find a flu shot (either against seasonal or pandemic influenza) through the company's beloved Maps feature. The new tool (found here) is the product of a collaboration between Google and the US DHSS, the CDC (flu.gov), and the American Lung Assocation.
For example, here's where residents of the White House can possibly get a seasonal (blue) or pandemic (red) flu shot. (To the left of the map would be a list of the locations, ordered by proximity to the entered address and labeled "A" through whatever.)
Keep in mind that the Goggle tool is in its beta stages: locations for many flu shot clinics may be missing, the company advises, and locations currently listed may be out of stock. Nevertheless, it's a starting point for consumers.
For more information about the tool's development, go here.
HT: Mashable by way of attentionusa.com.
A GSK version of the pandemic H1N1 vaccine has now been approved by the FDA, says a company press release dated yesterday. The US DHHS has ordered 7.6 million doses of the vaccine to supplement the approximately 250 million doses of vaccine already obtained by the US government. GSK will produce multidose vials of the vaccine, which are expected to begin shipping in December.
The pandemic flu vaccines of 4 companies—CSL, MedImmune, Novartis, and sanofi pasteur—were approved by the FDA in mid-September. GSK's vaccine was delayed by a US government decision to omit immunity-boosting adjuvant (eg, aluminum salts) from all available pandemic flu vaccines, reports the LA Times. (GSK also announced yesterday that it will be donating 50 million doses of its adjuvant-containing pandemic flu vaccine to WHO for use in developing countries.)
As of November 4, more than 26 million doses of pandemic flu vaccine have been shipped throughout the United States and its territories, according to the CDC. The top 10 recipients have received about half of the supply.
|
California |
2,953,000 |
|
Texas |
2,092,700 |
|
New York and |
1,687,100 |
|
Florida |
1,495,700 |
|
Illinois |
1,096,600 |
|
Ohio |
983,500 |
|
Pennsylvania |
948,600 |
|
Michigan |
819,100 |
|
New Jersey |
795,700 |
|
Virginia |
781,800 |
|
Total |
13,653,800 |
According to the HHS, the latest US government spend on pandemic H1N1 vaccines is $2,255,120,945, or about $8.75 per vaccine dose.
|
Novartis |
$979,144,920 |
|
MedImmune |
$446,668,000 |
|
sanofi pasteur |
$395,908,025 |
|
GSK |
$253,400,000 |
|
CSL |
$180,000,000 |
|
Total |
$2,255,120,945 |
DHHS = Department of Health and Human Services.
N.B.--GSK also makes Relenza (zanamivir), an anti-influenza treatment.
The acute awareness of pandemic influenza (2009 H1N1) has led to an unprecedented demand for, and subsequent shortage of, vaccines for seasonal influenza. According to today's NYT, the shortage of seasonal flu vaccines is so severe that the NYC health department has asked doctors to refrain from vaccinating healthy adults younger than 65 years of age.
The number of doses of seasonal flu vaccine that were manufactured for this year, 114 million, is slightly higher than the number made last year, and about 90 million doses have been shipped so far, reports the NYT. But the shipped supply has nearly been consumed, with an estimated 85 million shots administered to date (which is about 24 million more than the number given out by this time last year). Manufacturers cannot make more seasonal flu vaccine, because they are committed to producing the pandemic flu vaccine.
Among the 5 FDA-approved vaccines for seasonal flu, a total of 248 lots have been released. (But how many packages or doses in a lot is unclear. The numbers may also vary, depending on the manufacturer or distributor. If lot numbers are uniform, then 1 lot represents about 46,000 doses [114 million divided by 248].)
|
Vaccine and Manufacturer |
No. Lots |
Package |
National Drug Code (NDC) |
|
Afluria; CSL Ltd |
52 |
10 single-dose |
33332-009-01 |
|
10-dose vial |
33332-109-10 | ||
|
Fluarix; GSK |
16 |
5 single-dose |
58160-876-46 |
|
Flulaval; ID Biomedical Corp of Quebec (distributed by GSK) |
19 |
10-dose vial |
19515-886-07 |
|
FluMist; MedImmune |
36 |
10 single-dose |
66019-107-01 |
|
Fluvirin; Novartis |
39 |
10 single-dose |
66521-112-02 |
|
10-dose vial |
66521-112-10 | ||
|
Fluzone; sanofi-pasteur |
86 |
10 single-dose |
49281-009-25 |
|
10 single-dose |
49281-009-50 | ||
|
Single-dose vial |
49281-009-50 | ||
|
10-dose vial |
49281-384-15 |
1 dose = 0.5 mL, unless otherwise indicated.
Except in the case of Flumist,* the seasonal flu vaccines contain the following inactivated viruses:
- A/South Dakota/6/2007 (H1N1) (an A/Brisbane/59/2007-like virus)
- A/Uruguay/716/2007 (H3N2) (an A/Brisbane/10/2007-like virus)
- B/Brisbane/60/2008
* Flumist contains the attenuated viruses.
N.B.--The NDC contains an initial 5-digit labeler code, which is assigned by the FDA, and a 3- or 4-digit product code, which is assigned by the drug firm.
Results of an Australian study—which were used by the Institute of Medicine and the CDC to recommend fitted N95 respirators to prevent influenza among healthcare workers—have been retracted. The retraction was made in a surprise announcement over the weekend, reported MedPage Today, at the annual meeting of the Infectious Diseases Society of America in Philadelphia.
A reanalysis of the Australian study was prompted by initial criticism of the study's design, which did not use randomly selected hospitals as a control group. Follow-up statistical adjustments, to compensate for "clustering" and "multiple testing," revealed nonsignificant differences between infection rates with N95 respirators and those with surgical face masks, reported the authors at the meeting. The reanalysis triggered a retraction of the original conclusions, which had favored the preferential use of N95 respirators. The new, nonsignificant findings are consistent with results of a recent Canadian study, which showed no added, protective benefit from N95 respirators among hospital nurses.
By advocating the more expensive N95 respirator, the originally reported Australian study had considerable cost implications. To provide a rough idea of the price differential between the 2 mask options: At labsafety.com, a 20-pack of 3M N95 respirator/surgical masks costs $24.90 ($1.25/mask), and a 50-pack of run-of-the-mill surgical masks will set you back $9.70 ($0.20/mask).
From 1.8 to 5.7 million Americans experienced symptomatic swine flu (2009 H1N1 pandemic influenza) between April and July 23rd of this year. This estimate is based on a "probabilistic multiplier model" that adjusts for the underascertainment of pandemic flu cases in the United States. The results of the model, which was created and applied by investigators at the CDC and the Harvard School of Public Health, are available in an expedited article in the journal Emerging and Infectious Diseases.
The probabilistic multiplier model was used to adjust for the underascertainment of pandemic flu cases at each of the following steps (as diagrammed in the provided figures): the pursuit of medical care; the collection of specimens from persons seeking medical care; the submission of specimens for confirmatory testing (ie, RT-PCR); the laboratory detection of the 2009 H1N1 virus; and the reporting of confirmed cases. The model was adjusted separately for hospitalized patients (B)—who, by definition, had already sought medical care.
- Every reported case of pandemic flu represents 79 total cases (90% probability range, 47-148).
- The estimated median number of symptomatic cases is 3.0 million.
- The estimated incidence of pandemic flu in persons ≥65 years of age is 107/100,000.
- The estimated incidence of pandemic flu in persons 5-24 years of age is 2196/100,000.
- Every hospitalized case of pandemic flu represents 2.7 total hospitalized cases (90% range, 1.9-4.3)
- The estimated median number of hospitalizations is 14,000 (range, 9000-21,000).
- The estimated ratio of hospitalizations to total symptomatic cases is 0.45% (90% range, 0.16%-1.2%).
- The estimated median incidence of hospitalizations in persons <5 years of age is 13.0/100,000.
- The ratio of deaths to hospitalizations was 6%.* (Note: This value was not derived from the model).
- The estimated median number of deaths is therefore 800 (90% range, 550-1300).
"Because this [death] assumption has several limitations," the authors conclude, "more sophisticated models are also being developed to better understand the severity of the US epidemic in the spring of 2009, including intensive care unit admissions and deaths."
RT-PCR = reverse transcriptase polymerase chain reaction.
* Therefore the overall estimated death rate (although this value is not provided in the article) is 0.027%—which is within the range provided by one of the authors, Harvard epidemiologist Marc Lipsitch, to Reuters in September.
Update: From the AP by way of the CDC—At least 114 American children have now died of complications due to the 2009 H1N1 virus.
Bill Maher, put this in your glass pipe and smoke it.
A total of 86 children have now died of H1N1 illness in the United States, according to the latest data from the CDC. Nearly half (47%) of the deaths were reported to the CDC after August 30th, and 11 of these deaths occurred during the last week. Among the most recent deaths (n = 43), 19 (44%) occurred in preteens or teenagers (12-17 years of age).
For all practical purposes, H1N1 activity is now widespread in the United States.
Like white on rice, rational bloggers have been all over Bill Maher's goofy ideas about vaccines and vaccination. It's too bad, though, that the man has a nationally televised show, HBO's "Real Time With Bill Maher," which affords Maher an opportunity to influence potentially gullible viewers in front of (like many a talk/variety/comedy show) an audibly fawning studio audience.
Nevertheless, begrudging props may be given to Maher for inviting retired Republican Senator and physician Bill Frist on Friday to discuss vaccination. In this segment, it's not entirely clear that Maher "gets schooled" by Frist about vaccines (despite the clip's title). Schooling requires that Maher's thick skull be penetrable. And schooling requires time—much more time than television typically allows.
But a blog provides an enduring, leisurely format for dissecting and refuting some of the utterly fallible anti-vaccine statements that Maher made on Friday and that Frist didn't have the chance to challenge.
Maher comment #1: Conservatives always say, about healthcare especially: You gonna let the government run healthcare? They screw everything up. So why would you let them stick a disease into your arm? I would never get a swine flu vaccine or any vaccine. I don't trust the government, especially with my health. [Applause.] And that seems to be a conservative opinion: not to trust the government.
Dissection: The usually liberal Maher tries to create a bit of oh-gosh irony here by aligning himself with traditionally government-distrusting conservatives. He then jumps to make a very broad and loose association between government incompetence and government-recommended vaccination. However, if Maher were familiar with the monumental benefits of historical vaccination programs (eg, against smallpox and polio), the association actually supports organized intervention into healthcare (whether instigated by a government or some other authoritative entity, like the World Health Organization).
At the same time, Maher indicates that vaccination is a process whereby "disease" is injected into the body. First "disease" is a clinical manifestation of bodily dysfunction; it is not something that can be confined in a syringe. But we sort of know what Maher's means here, so we'll give him a pass on this semantic point. What Maher is really implying is that disease-causing virus is injected during vaccination. But that idea is also false.
With respect to the injected 2009 H1N1 (swine flu) vaccine, the inoculant is a killed (actually chemically "split") virus—which is incapable of causing infection (but is capable of inducing protective immunity). The nasal-spray vaccine from MedImmune contains live, attenuated H1N1 virus. The attenuated virus is engineered (ie, cold adapted and temperature sensitive) so that it can replicate in the cooler confines of the nose to induce immunity, without causing influenza-like illness.
Maher indicates that he would never get the swine flu vaccine, which is fine (assuming that Maher isn't at baseline risk for influenza complications and doesn't care for an infant younger than 6 months of age*). The 53-year-old isn't a CDC-recommended candidate for the 2009 H1N1 vaccine (although he should get a seasonal flu shot).
Maher comment #2 (in response to a Frist anecdote about a patient dying of swine flu): I cannot believe that a perfectly healthy person died of swine flu. That person was not perfectly healthy. Medical—Western medicine misses a lot.
Dissection: Maher's just flat-out wrong here. Regardless of what he believes, serious H1N1-related disease preferentially affects persons younger than 65 years of age, and about 45% of Americans who have died of swine flu were healthy, according to the CDC. With his last sentence, Maher also betrays a broad, inherent distrust of Western (really, allopathic) medicine.
Maher comment #3: Let me read you a quote from the former control officer at the US FDA. His name is Dr. J. Anthony Morris. He said, "There is no evidence that any influenza vaccine thus far developed is effective in preventing or mitigating any attack of influenza. The producers of these vaccines know they are worthless, but they go on selling them anyway."
Dissection: By quoting J. Anthony Morris, Maher reveals a lazy reliance on an ostensibly authoritative source, about which he probably knows nothing.
Finding reliable information on Morris (at least on the web) is a challenge; at first blush, he appears to be a quotable favorite among anti-vaccinationists—probably because of the specious appeal-to-authority angle (ie, Morris reportedly has/had a PhD in bacteriology and was an FDA employee). An archived newspaper search reveals that Morris was a virologist in the Division of Biologic Standards, which was part of the NIH until 1972 when the division was transferred to the FDA.
In the fall of 1971, Morris made news by arguing to Congress that influenza vaccines were not just useless, but dangerous (see Lyons RD. Influenza shots held ineffective. NYT. October 15, 1971). He claimed that "not only has there been little or no benefit from the use of influenza vaccine in man, but harm has resulted." However, a federally appointed, 12-person scientific committee rejected Morris's claims of incompetence within his NIH division; although the committee did concede, in ho-hum fashion, that "inactivated influenza vaccines are imperfect instruments for the prevention of influenza." (The committee may have been referring to subpotent lots of influenza vaccine that were distributed in the 1960s.) The committee then proceeded to reject Morris's claims that influenza vaccines are harmful (see Lyons RD. Charges of poor vaccine regulation rejected. NYT. November 30, 1971).
A related news story in June 1972 indicates that Morris had been demoted within his division, which was now (presumably) a part of the FDA. But later news reports indicate that Morris was appointed director of the Slow and Temperate Virus Branch of the agency.
In July 1976, Morris, then 57, was finally fired from the FDA for "insubordination" and "inefficiency." Morris claimed that he was sacked from his $35,000-a-year job because he opposed President Ford's swine flu vaccination program. FDA officials acknowledged, at the time, that it was very unusual for an FDA employee to be fired, but the process that led to Morris's departure began long before anybody recognized the swine flu threat. Later Morris showed up on fear-mongering talk shows like "Phil Donahue" and provided anti-vaccine quotes to news reporters as recently as 1988.
A phrase search of various archived newspapers fails to return a source for the exact quote cited by Maher, except in 1 instance: Donald Harte, in a November 2007 editorial for the Marin Independent Journal ("Is there a vaccine that protects against non-science?") requotes Morris from a citation in a contemporary issue of Health & Fitness magazine. The quote was described as being 30 years old, but the original source was not identified.
Morris, if alive this year (and I haven't been able to confirm whether he's alive or dead), would be about 90.
Maher comment #4: But a virus is always mutating. You would agree with that? [Frist: Yeah.] So, so the vaccine that they produce back in March—that's not really what's gonna prevent what's, what's going on now. Because—I know a lot of people on the conservative side don't believe in evolution—but—and you can't see evolution in advanced species, but you can see—[Frist interrupts: We know this vaccine is 98% effective...]
Dissection: Here Maher tries to discount the efficacy of the swine flu vaccine by implying that the virus has mutated so much since the creation of the vaccine (in March) that it will evade whatever immunity is produced by inoculation. However, on October 9 (the same day that Maher's show aired), the CDC reported that the 2009 H1N1 viruses "have not undergone substantial antigenic change since they were first characterized in April 2009 and should be well-matched to the monovalent vaccine strain."
Last month, data published in the NEJM indicated that significant antibody titers were generated in 97% of adults after 1 dose of the inactivated vaccine. Rates of antibody production among children aged 6-35 months, 3-9 years, and 10-17 years were 25%, 36%, and 76%, respectively. These data are the foundation for recommending 2 vaccine doses in children younger than 10 years of age. The suboptimal immune response in younger children is probably related to their limited immune experience with influenza viruses and is clearly not the result of viral mutation.
There have been scattered reports of 2009 H1N1 virus that is resistant to oseltamivir (Tamiflu), but all of these isolates were susceptible to zanamivir (Relenza).
Maher comment #5: Dr. Jonas Salk: "Live virus vaccines against influenza and paralytic polio, for example, may in each instance cause the disease it's intended to prevent."
Dissection: Another appeal to authority by Maher. Salk, as everyone knows, was the creator of the inactivated polio vaccine. The quote cannot be confirmed and, again, appears to be a favorite among online anti-vaccinationists. An archived newspaper search fails to return relevant hits, and without context, it's useless to interpret a statement that Salk may or may not have made.
* And don't we all hope that's the case.
