2009 h1n1 influenza
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2009 H1N1 Influenza -- Just the Facts: Clinical Features and EpidemiologyJohn G. Bartlett, MD Posted: 09/25/2009; Updated: 11/23/2009
Editor's Note: This article will be updated frequently, so check back often for new information. On October 15, updates were made to weekly US influenza data (including college data) and reports of bacterial coinfections. Influenza hospitalization data were added as well. On October 27, updates were made about the declaration of a national emergency, weekly US and international H1N1 activity, deaths in children and pregnant women, and treatment outcomes. Updates made on November 5 include information on the true prevalence of H1N1, pediatric deaths, and underlying conditions in children hospitalized with H1N1 influenza. Updates made on November 16 include new information on the global H1N1 pandemic, the H1N1 situation on college campuses, the effect of sick-call policies on the spread of influenza, and characteristics of patients hospitalized with H1N1 infection. On November 23, updates were made about emergency use authority for pandemic supplies, guidance for homeless shelters, a summary of the article "One Killer Virus, Three Key Questions," studies on reduced deaths in patients receiving statins, and the role of cytokines in mediating the symptoms of influenza. For the latest information on 2009 H1N1 influenza, please go to the H1N1 Alert Center.
Novel Influenza A (H1N1) Timeline
February 24, 2009
Patient zero is said to be a 6-month-old girl from northern Mexico, according to Celia Alpuche of the Institute of Epidemiological Diagnosis and Reference in Mexico City. (Cohen J. Swine flu outbreak, day by day. ScienceInsider. July 17, 2009. Available at: http://blogs.sciencemag.org/scienceinsider/special/swine-flu-timeline.html Accessed September 16, 2009.)
March 3, 2009
Initial recognition of case in Mexico City with multiple cases reported on March 18.
April 6, 2009
Outbreak in La Gloria, Mexico, with attack rate of 60%.
April 15, 2009
First virologically defined cases and first recognized US case: 10-year-old boy in California with positive test for influenza H1 antigen but negative for seasonal H1 and H3.
April 26, United States declares public health emergency.
2009April 29, 2009
Mexican Ministry of Health reports 1-month total of 2155 patients with severe pneumonia and 100 deaths.
May 9, 2009 Global epidemic recognized with caseloads that matched international air-traffic patterns from Mexico City. (Khan K, Arino J, Hu W, Raposo P, et al. Spread of a novel influenza A (H1N1) virus via global airline transportation. N Engl J Med. 2009;361:212-214. Available at: http://content.nejm.org/cgi/content/full/361/2/212 Accessed September 16, 2009
June 11, 2009
Dr. Margaret Chan, Director General of the World Health Organization (WHO), declares phase 6 pandemic and calls 2009 H1N1 "unstoppable"; also notes that most patients in the world with 2009 H1N1 are younger than 25 years of age and that one third of serious cases are in previously healthy young people.
July 1, 2009 US cases appear in all states; estimated total is more than 1 million infected; 87% of deaths in persons 5-59 years of age.
July 17, 2009
WHO reports 94,512 virologically confirmed cases and 429 deaths, but considers this the "tip of the iceberg." A decision is made to stop counting cases.(World Health Organization. Chan M. World now at the start of 2009 influenza pandemic. June 11, 2009. Available at: http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html Accessed September 16, 2009
July 20, 2009
Chile reports 2009 H1N1 in turkeys, increasing sources of the virus and introducing the possibility of mixing with avian genes.
August 25, 2009
President's Council of Advisors anticipates that 2009 H1N1 may infect half of the US population, require 1.8 million hospitalizations, and result in 30,000-90,000 deaths. (President's Council of Advisors on Science and Technology. U.S. Preparations for 2009-H1N1 Influenza. August 7, 2009. Available at: http://www.whitehouse.gov/assets/documents/PCAST_H1N1_Report.pdf Accessed September 16, 2009
August 31, 2009
WHO predicts that within 2 years nearly one third of the world population will have been infected. (Chan M. Swine flu spreading at 'unbelievable' rate: WHO chief. Khaleej Times. August 29, 2009. Available at: http://www.khaleejtimes.com/displayarticle.asp?xfile=data/international/2009/August/international_August2077.xml§ion=international&col= Accessed September 25, 2009.) Seasonal flu is usually acquired by 5%-20% per season with 200,000 are hospitalized and an average of 36,000 die. (CDC. Key facts about seasonal influenza (flu). Available at: www.cdc.gov/flu/keyfacts.htm Accessed September 25, 2009.)
October 24, 2009
President Obama declares H1N1 influenza a state of national emergency. This declaration waives certain regulatory requirements for healthcare facilities in response to emergencies. (FluView. President Obama signs emergency declaration for H1N1 flu. October 24, 2009. Available at: http://www.flu.gov/professional/federal/h1n1emergency10242009.html Accessed October 26, 2009.)
Emergency Use Authority and 2009 H1N1 Influenza
(Sherman SE, Foster J, Vaid S. Emergency use authority and 2009 H1N1 influenza. Biosecurity Bioterrorism 2009;7:245-250.)
Purpose: To persuade the FDA to allow products to be introduced to interstate commerce without the usual regulatory requirements for approval, clearance or licensing. This emergency use authorization (EUA) is justified by a relevant emergency and lasts during the emergency.
Process: Step 1 -- Determination of an emergency by Secretary of HHS, Department of Homeland Security, or Department of Defense; Step 2 -- Declaration of emergency by Secretary of HHS; Step 3 -- Issuance of EUA; Step 4 -- The FDA Commissioner then exercises this authority after consulting with directors of the NIH and CDC.
Requesting an EUA: Any entity may request emergency use of a product under the EUA by a pre-EUA submission to the FDA. This may apply to products that are not FDA approved, cleared, or licensed, or this may apply to new use of an approved product.
EUAs for 2009 H1N1: On April 26, 2009, the HHS Secretary determined that this influenza was a public health emergency and there have subsequently been 3 EAUs for diagnostics, antivirals, and masks, as summarized below (Table 1).
Table 1. EAUs Related to H1N1
Product PurposeDiagnostics rRt-PCRCDC rRT-PCR Flu PanelFocus Diagnostics
Permitted CDC to distribute testCleared test for additional specimensPermitted this test by qualified labs
Antivirals Oseltamivir
Zanamivir
Authorizes use in children < 1 yr and dosing changes in children > 1 yrAllows use with 5 symptoms > 48 hrs
Allows use with symptoms > 48 hrs
Masks Disposable N95 respirators
Allows use of 15 types of N95 respirators from the National Stockpile by general public
Conclusion: The EUA permits use of new products necessary to respond efficiently to an emergency. Pandemic influenza is a good illustration of appropriate use.
Epidemiology and Impact
According to Dr. Tom Frieden, Director of the CDC, there is widespread H1N1 activity in 46 states. H1N1 influenza continues to be a disease primarily involving children and young adults. "Many millions" of cases and more than 1000 deaths have occurred. This influenza is expected to come in waves, and we are now in the second wave. This wave may continue through the seasonal flu season (which peaks in December-February) or there may be a third wave at that time. No increase in severity has been seen, resistance to antiviral agents is rare, and genetic mutations are minimal. (CDC Online Newsroom. Weekly 2009 H1N1 Flu Media Briefing. October 22, 2009. Available at: http://www.cdc.gov/media/transcripts/2009/t091023.htm Accessed October 26, 2009.)
Updated Influenza Data for United States, Based on CDC Surveillance Data
For the week ending November 7, 2009 (influenza season week 44):
Influenza activity in the United States decreased slightly.2849 influenza strains were subtyped: 2830 (99.4%) were A 2009
(H1N1) and 19 (0.6) were influenza B. Analysis of 319 strains of 2009 influenza A (H1N1) strains showed relatedness to the reference strain used in the 2009 A (H1N1) vaccine for all but 1 (99.7%).
Sensitivity testing of 2009 A (H1N1) strains collected since September 1, 2009 showed that 3/1076 were resistant to oseltamivir, 0/315 were resistant to zanamivir, and 152/152 were resistant to amantadines.
Pediatric deaths attributed to influenza since April 26, 2009 total 179, including 1 case attributed to seasonal influenza, 156 to 2009 A (H1N1), and 22 to influenza A-subtype unknown.
(CDC, Influenza Division. FluView. Available at:
http://www.cdc.gov/flu/weekly/ Accessed November 13, 2009)
Update: Influenza Activity – United States, Based on MMWR Reports
(CDC. Update: Influenza Activity – United States, Aug. 30-Oct. 31, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:1236-1241.)
Viral surveillance August 30-October 31, 2009. WHO and the US National Respiratory and Enteric Virus Surveillance System labs tested 163,123 respiratory specimens:
Number positive: 48,585 (30%)
Influenza A: 48,483 (99.8%)2009 (H1N1): 32,814 (99.8%)Seasonal H1: 18 (0.1%)Seasonal B: 35 (0.1%)
Antiviral resistance. The total number of 2009 A (H1N1) isolates in the United States with oseltamivir resistance is 14 (or about 0.4%). Of these, 12 were from patients with previous exposure to oseltamivir. One had no oseltamivir exposure and another is still being investigated.
Influenza-associated hospitalizations. Cumulative influenza hospitalization rates were substantially elevated for this time of year (Table 2).
Table 2. Influenza-Associated Hospitalizations
AgeRate/
10,000 pop0-4 yrs
7.3
5-17 yrs
2.9
18-49 yrs
1.2
50-64 yrs
1.2
> 65 1.1
yrs
Pneumonia and influenza related mortality. Pneumonia or influenza was the reported cause of 7.4% of all deaths for the week ending October 31, 2009, which is above the epidemic threshold of 6.7% for the fifth consecutive week.
Pediatric mortality. Eighty-five deaths have been attributed to influenza during this period, including 12 in children younger than 2 years, 9 in those age 2-4 years, 30 in those age 5-11, and 34 in those age 12-17 years. Of the 85, 78 (92%) had medical histories reported, showing that 56 (72%) had risks for influenza complications. Note that the number of pediatric deaths attributed to influenza during the past 5 influenza seasons has ranged from 46 to 153, with an average of 82/year. The US data for April 26-October 31 shows 145 pediatric deaths, including 129 (89%) attributed to 2009 A (H1N1) and 16 (11%) attributed to seasonal influenza.
Antiviral usage. Rates of antiviral usage in hospitals is disappointing. Recent reports indicate that 21%-25% of hospitalized patients with laboratory-confirmed 2009 A (H1N1) influenza have not received antivirals, and those who did often had a 1- to 2-day postadmission delay in receiving antivirals. (Louie JK, Acosta M, Winter K, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A (H1N1)infection in California. JAMA. 2009;302:1896-1902; Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June, 2009. N Engl J Med. 2009;361:935-944.)
BRFSS report. The Behavioral Risk Factor Surveillance System, established in 1984 at the CDC, is the largest telephone health survey in the world, with interviews of more than 400,000 adults yearly. Data collected from October 1 to October 11, 2009 indicated that 7% of the US adult population and 20% of children reported an influenza-like illness, although this system cannot distinguish among viral causes which may include respiratory syncytial virus, rhinovirus, and adenovirus, as well as influenza. (CDC. Behavioral Risk Factor Surveillance System. Available at: http://www.cdc.gov/BRFSS/ Accessed October 27, 2009.)
International Situation Update
Keiji Fukuda, MD, MPH, Special Advisor on Pandemic Influenza to the WHO Director-General, reported on November 5:
20 countries have started 2009 H1N1 vaccination programs. Side effects of H1N1 vaccination "may actually be lower than what is seen with seasonal flu shots."
The H1N1 virus shows minimal mutations to date, but this is expected to change as the epidemic progresses.
Norway's decision to make anti-influenza drugs available over-the-counter was considered "innovative and prudent" to relieve the overburdened health system.
Pandemic H1N1 influenza is the dominant influenza strain in the world and comprises 99% of North American strains. In areas where seasonal flu has occurred, such as East Asia, it is predominantly influenza A (H3N2). Pandemic H1N1 is "crowding out" seasonal influenza A (H1N1). This viral replacement has been seen in previous epidemics. (WHO. November 5, 2009 press conference. Available at: http://www.who.int/mediacentre/multimedia/swineflupressbriefings/en/index.html Accessed November 10, 2009.)
WHO reports 375,000 confirmed cases of H1N1 influenza infection and 4500 deaths. The number confirmed is a small fraction of the total. The virus spread throughout the world in 6 weeks and "is now everywhere." (WHO, Pandemic H1N1 2009 -- update 69. October 4, 2009. Available at: http://www.who.int/csr/don/2009_10_09/en/index.html Accessed October 22, 2009.)
On October 23, WHO reported viral subtype determinations of 17,225 isolates from 759 US labs for which subtyping results were available. The distribution was:
2009 influenza A (H1N1): 17,108 cases (99.5%);Influenza A (H1N1): 15 cases;Influenza A H3N2: 34 cases; andInfluenza B: 68 cases.
(CDC. 2009-2010 influenza season week 41 ending October 17, 2009. FluView. Oct 23, 2009. Available at: http://www.cdc.gov/flu/weekly/ Accessed October 26, 2009.)
The Harvard iPhone. Harvard Medical School now offers an influenza iPhone application for $1.99. Features include basic information about 2009 H1N1 influenza, such as a "health map" that indicates the state of the epidemic in your location and other locations. There is also: (1) an interactive section that helps individuals to recognize 2009 H1N1 flu; (2) advice regarding when to contact a physician; (3) hotlines; (4) videos; and (5) emergency numbers. (Rao L. Harvard Medical School launches swine flu iPhone app. Washington Post. October 26, 2009.)
Colleges. The American College Health Association (ACHA) reports that for the week ending October 30, 274 colleges and universities have had 9128 new cases of ILI. This represents a 2% increase over the previous week and includes 25 hospitalizations and no deaths. The total for this academic year for 3 million students is > 65,000 cases of ILI and 123 hospitalizations. (ACHA. Pandemic influenza surveillance. influenza-like illness in colleges and universities. Weekly Case Data for the period October 17-23, 2009. Available at: http://www.acha.org/ILI_surveillance.cfm Accessed November 10, 2009.)
Sick leave. About 39% of private sector workers do not receive paid sick days according to the Bureau of Labor Statistics. The CDC has encouraged employers "to develop nonpunitive leave policies." When employees at Walmart, for example, call in sick they receive "no pay" for the first sick day (but Walmart does allow it to be taken as a vacation or personal leave day). When workers miss 1 or more days they get a demerit point; 4 points over 6 months can result in warnings for possible dismissal. A survey by the National Opinion Research Center at the University of Chicago found that 68% of those not eligible for paid sick days said that they had gone to work with a contagious illness compared with 53% who were eligible for paid sick time. The survey also found that 11% said that they lost their job as a result of time taken off for themselves or a sick family member, and 13% said that they were warned about the possibility of losing their jobs. (Greenhouse S. Lack of paid sick days may worsen flu pandemic. New York Times. November 2, 2009. Available at: http://www.nytimes.com/2009/11/03/business/03sick.html?_r=1 Accessed November 10, 2009.)
Businesses. A national survey of 1057 randomly selected businesses in 6 categories (small, medium, large; critical or noncritical) was conducted by the Department of Homeland Security and the Harvard School of Public Health The study was funded by the CDC and took place between July 16 and August 12, 2009. Key findings from the survey of businesses (Harvard Opinion Research Program, Harvard School of Public Health. Business Preparedness: Novel Influenza A (H1N1). July 16-August 12, 2009. Available at: http://www.hsph.harvard.edu/news/press-releases/2009-releases/businesses-problems-maintaining-operations-significant-h1n1-flu-outbreak.html Accessed September 16, 2009.):
74% provide paid sick leave; 34% offer leave to care for others; 21% provide sick leave to care for children;
67% would note operational problems if 50% of workforce was off more than 2 weeks;
Paid sick leave is offered by 74% and 35% allow paid sick leave to care for family members;
A doctor's note is required for sick leave by 43%, and 69% that offer sick leave require a doctor's note to return after a contagious illness (relevance is concern about physician access in a pandemic);
Strategies to decrease person-person contact (like staggered shifts) could be implemented by 50% for 1-2 weeks.
Click here for information about business planning for influenza.
Nursing homes. No outbreaks of the 2009 H1N1 virus have been reported to the CDC. This is attributed to the advanced ages of most persons in chronic care facilities, which is a reduced risk for this virus.
Hospitals. Many anticipate a surge of H1N1 influenza cases in the coming influenza season based on the experience in the Southern hemisphere. The President's Advisors estimate that there will be a 30%-50% attack rate this winter with 1.8 million hospitalizations, which will pose extreme challenges for hospitals. A 2006 Institute of Medicine report indicated that emergency medicine nationwide was "at the breaking point" in both finances and capacity. (Committee on the Future of Emergency Care in the United States Health System, Institute of Medicine. Emergency Medical Services: At the
Crossroads. Washington, DC: National Academies Press; 2007.)
An analysis by the Center for Biosecurity at the University of Pittsburgh Medical Center estimated that a severe pandemic would require 4.6-fold more ICU beds and 2-fold more hospital beds. (Bartlett JG, Borio L. Healthcare epidemiology: the current status of planning for pandemic influenza and implications for health care planning in the United States. Clin Infect Dis. 2008;46:919-925.)
New York City. Thomas Farley, MD, MPH, New York City Health Commissioner, said, "We're seeing essentially no (flu) disease transmitted in the City. We had 750,000 to 1 million sick people last spring. We were the hardest hit city then, so we have a lot of immune people now." (Hartocollis A, McNeill DG Jr . Areas hit hard by flu in spring see little now. New York Times. October 8, 2009;sect A1.)
The cat. The American Veterinary Association has reported a laboratory-confirmed case of H1N1 in a cat. The infection was presumably acquired from a household member, because the cat did not go outdoors. The diagnosis was made by a bronchial lavage. The cat was treated with fluids and antibiotics and recovered. The cat was described by the veterinarian as "charming with a lot of personality." (Parker-Pope T. The cat got swine flu. The New York Times. November 5, 2009. Available at: http://well.blogs.nytimes.com/2009/11/05/the-cat-who-got-swine-flu/ Accessed November 19, 2009.)
Homeless persons and homeless shelters. (Scott M. Pandemic influenza guidance for homeless shelters and homeless service providers, 2009. Available at: www.nhchc.org/flumanual.pdf Accessed November 18, 2009.)
The guidance is for homeless shelters and homeless service providers.
Isolation recommendations:
House the sick person in a single room: (1) Do not allow group activity; (2) The sick person must wear a mask when leaving the room; (3) No visitors until the sick person is afebrile for 24
hours; (4) Have meals delivered or have meals at a different time or place; and (5) Provide access to fluids, tissues, wastebasket, and hand sanitizer.
If a single room is not available, house the sick person in a large, well-ventilated room with the fewest number of other residents and: (1) Try to separate the sick person from residents who have risks for influenza complications; (2) Increase spacing between beds to 6 feet; (3) Use sheets or curtains to create barriers; (4) Provide access to water, soap, hand sanitizer, etc. and (5) Teach hand hygiene and cough etiquette.
Clinical Features of H1N1 Influenza
Typical Signs and Symptoms
The incubation period for H1N1 influenza is 1-4 days, possibly as long as 7 days. The clinical features of influenza are well known and include:
Sudden onset of fever (usually high);Headache;Extreme tiredness;Dry cough;Sore throat;Runny nose; andMuscle aches and stomach symptoms -- more common in children.
(CDC. Interim guidance for clinicians on identifying and caring for patients with swine-origin influenza A (H1N1) virus infection. June 2009. Available at: http://www.cdc.gov/h1n1flu/identifyingpatients.htm Accessed September 16, 2009.)
The symptoms of pandemic H1N1 influenza of 2009 are essentially the same as the seasonal flu, although some have noted an increased frequency of gastrointestinal symptoms, including vomiting and diarrhea, and others have noted the absence of fever in a significant number with virologically proven cases.
The CDC defines cases as influenza-like illness (ILI) if there is fever of ≥100° F (37.8° C) plus cough and/or sore throat in the absence of a known cause other than influenza. Another category is acute
respiratory illness (ARI), defined by the presence of 2 of the following 4 symptoms: fever, cough, sore throat, or rhinorrhea. In the outbreak of pandemic influenza in New York City, 95% of virologically proven cases satisfied the ILI definition. (CDC. Swine-origin influenza A (H1N1) virus infections in a school -- New York City, April 2009. MMWR Morb Mortal Wkly Rep Dispatch. 2009;58:1-3. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0430a1.htm Accessed September 25, 2009.)
Patients with 2009 influenza A H1N1 infections have higher rates of gastrointestinal symptoms and lack of fever compared with those who have seasonal flu. Most patients have mild symptoms, but a small subset of previously healthy young adults have severe pulmonary disease that progresses to acute respiratory distress syndrome (ARDS); this may occur with or without underlying conditions. CDC epidemiologist Tim Uyeki notes that about 12% do not have fever and that many report diarrhea and vomiting.
Symptoms in virologically confirmed cases. During an outbreak of H1N1 in a New York City high school, a sample of New York City school students (median age, 15 years) with virologically confirmed cases were interviewed about their symptoms by telephone. They reported:
Cough (98%);Subjective fever (96%);Fatigue (89%);Headache (82%);Sore throat (82%);Abdominal pain (50%);Diarrhea (48%);Dyspnea (48%); andJoint pain (46%).
The measured mean peak fever in this group was 102.2° F. (CDC. Swine-origin influenza A (H1N1) virus infections in a school -- New York City, April 2009. MMWR Morb Mortal Wkly Rep Dispatch. 2009;58:1-3. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0430a1.htm Accessed September 25, 2009.)
Swine Flu: 1 Killer, 3 Questions
(Maher B, Butler D. Swine flu: One killer virus, three key questions. Nature. 2009;462:154-157.)
An article in Nature featured onsite interviews with leading investigators in 3 distinct research areas. Here is a summarization:
Question 1: How does it kill? Sherif Zaki from the CDC answered, saying that pandemic A H1N1 binds the receptors in the terminal alveoli of the lungs. This is not a characteristic of seasonal flu, which preferentially infects upper airway cells. The pattern of 2009 A (H1N1) is often seen with avian influenza (H5N1), but it is described as more severe with H1N1 -- "like avian flu on steroids."
Question 2: How does it transmit? Authorities Peter Palese, John Steel, and Anice Lowen at Mount Sinai School of Medicine reviewed their data (published in Journal of Virology last month) based on guinea pig experiments. Infected animals in wire cages transmitted the virus to previously uninfected guinea pigs in adjacent cages, indicating aerosol transmission as with seasonal flu.
Question 3: What could it turn into? This was asked of Bruno Lina from Université Claude Bernard Lyon, working at the Biosecurity Level-4 laboratory at INSERM (National Medical Research Institute) in Paris. The researchers want to test reassortants to find determinants of virulence and transmissibility, but this work requires rigorous scientific review to determine public health justification. One aim is to determine the reassortment potential for combining the virulence of H5N1 and the transmissibility of H1N1.
Case Definitions for H1N1 Influenza
(CDC. Interim guidance for clinicians on identifying and caring for patients with swine-origin influenza A (H1N1) virus infection. June 2009. Available at: http://www.cdc.gov/h1n1flu/identifyingpatients.htm Accessed September 16, 2009.)
Confirmed case: Patient with ILI plus laboratory evidence confirmed by real-time RT-PCR or viral culture;
Probable case: ILI plus laboratory test positive for influenza A and negative for human H1 and H3 by RT-PCR; and
Optional: ILI without negative H1N1 test and (1) previously healthy person > 65 years hospitalized for ILI; (2) epidemiologic link to confirmed or probable case in past 7 days; or (3) ILI plus travel to a state or country with confirmed or probable cases.
Complications of H1N1 Influenza
Exacerbation of underlying chronic disease;Complications related to the upper airways, including sinusitis or
otitis;Pulmonary complications, including bronchitis, asthma (sometimes
with status asthmaticus), and acute exacerbations of chronic bronchitis; and
Miscellaneous conditions, including cardiac (myocarditis and pericarditis), myositis, rhabdomyolysis, central nervous system complications (encephalopathy, encephalitis, seizures), toxic shock syndrome, and secondary bacterial pneumonia.
Bacterial coinfections. CDC investigators reviewed clinical records and pathology reports from 77 lethal cases of pandemic H1N1 infection. (CDC. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - US, May - August 2009. MMWR Morb Mortal Wkly Rep. 2009;58: early release) The tissue specimens were examined by tissue Gram stain, Warthin-Starry silver stain, various microbe-specific immunohistochemical assays, and PCR that targeted the 16S ribosomal DNA in tissue blocks. Bacteria were detected in 22 of 77 cases (29%). Major pathogens were Streptococcus pneumoniae (10), Staphylococcus aureus (7), Streptococcus pyogenes (6), Streptococcus mitis (2), and Haemophilus influenzae (1); 4 cases had more than 1 pathogen. The study authors emphasize the importance of bacterial superinfection in patients with influenza. During the 1918-19 pandemic, most deaths were associated with bacterial superinfection. (Morens DS, Taubenberger JK, Fauci AS. Prominent role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness J Infect Dis. 2008;198:962-970.)
Severe complications of H1N1 Influenza. In June 2009, the University of Michigan reported severe pulmonary complications of 2009 H1N1 influenza infection in 10 patients with a median age of 49 years. All 10 patients were referred for severe hypoxemia, ARDS, and
inability to oxygenate with conventional ventilation methods. All had severe multilobar pneumonia on x-ray, none had evidence of bacterial pneumonia, and 4 had CT scan-confirmed pulmonary embolism. Lab findings included leukocytosis in 5 (median WBC 9500/mm3), elevated AST levels (41-109 IU/L) in all 10, and elevated CPK levels (51-6572 IU/L) in 6; none had evidence of disseminated intravascular coagulation. The major risk factor was obesity in 9 and morbid obesity (BMI > 40) in 7. All 10 required advanced mechanical ventilation with high-frequency oscillatory or bilevel ventilation with mean airway pressures of 32-55 cm H2O. Two required veno-venous extracorporeal membrane oxygenation (ECMO) support and 6 required dialysis. At the time of the report, 3 had died, 1 was still on ECMO, 1 was still on mechanical ventilation, and 5 had been transferred back to referring institutions. (CDC. Intensive care patients with severe novel influenza A (H1N1) virus infection -- Michigan, June, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:749-752.)
Neurologic complications. Neurologic complications were reported in 4 child-ren ages 7-17 years with 2009 H1N1 influenza A. Findings included seizures in 2 children, encephalitis in 2, and ataxia in 1. All recovered without neurologic sequelae. The editorial comment in this report noted that the neurologic disease in these 4 patients was less severe than what has been described in previous reports of seasonal flu. (CDC. Neurological complications associated with novel influenza A (H1N1) infection in children -- Dallas, Texas, May 2009. MMWR Morb Mortal Wkly Rep. 2009;58:773-778.; Maricich SM, Neuf JL, Lotze TE, et al. Neurologic complications association with influenza A in children during the 2003-2004 influenza season in Houston, Texas. Pediatrics. 2004;114:e626-e633.; Morishima T, Togashi T, Yokota S, et al. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis. 2002;35:512-517.)
Related Risk for Infection, Hospitalization, and Lethal Outcome
Age-related risk. These data are shown in Table 3.
Table 3. Rates for H1N1 for May-July 2009 by Age
Age Cases/100,000 Hospitalization/100,000
0-4 yrs 235-24 yrs 2725-49 yrs 750-64 yrs 4> 65 yrs 1.3
a % of total deaths. Age data not available for 15%. Rate expressed /100,000 population
US age data
(Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; 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;360:2605-2615.)
Median age of confirmed cases: 12 yearsMedian age of hospitalized cases: 20 yearsMedian age of lethal cases: 37 years
A comparison of the H1N1 outcome and seasonal flu outcome in elderly individuals is shown in Table 4.
Table 4. Age-Related Outcome With 2009 H1NI Influenza
Compared With Seasonal Influenza in the United States*
HospitalizedAge > 65 yrs Seasonal flu2009 H1N1
60%5%
*CDC. Use of influenza A (H1N1) 2009 monovalent vaccine --- recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Morb Mortal Wkly Rep. 2009;58(RR-10):1.CDC. Update: Swine-origin influenza A (H1N1) virus --- United States and other countries. MMWR Wkly. 2009;58:421.
The unusual age distribution of 2009 H1N1 virus infection is attributed to studies showing that persons who were exposed to the 1918 influenza virus have antibody to 2009 H1N1 strains. Related H1N1 influenza strains circulated until 1957, suggesting that people born before this time were likely to be exposed to common antigens. H1N1 viruses re-emerged in 1977 and were antigenically related to
viruses circulating in the 1950s, but there is not good evidence of protection from the 2009 H1N1 virus. (Itoh Y, Shinya K, Kiso M. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009;460:1021-1025.)
Estimates of the prevalence of pandemic (H1N1). (Reed C, Angulo FJ, Swerdlow DL, et al. Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July, 2009. Emerg Infect Dis. 2009 Dec. [Epub ahead of print] Available at: http://www.cdc.gov/eid/content/15/12/pdfs/09-1413.pdf Accessed November 4, 2009.) Previous reports of the prevalence of H1N1 seriously underestimated the true number of laboratory-confirmed cases. In the current study, investigators from the CDC used "a simple multiplier model" to correct for this. Using this approach, the new estimate is 79 cases for every laboratory-confirmed case, with a 90% probability range of 47-148. The median estimate for the United States during the period April-July 2009 was 3 million symptomatic cases (range, 1.8-5.7 million). For hospitalized patients the multiplier was 2.7, yielding a median of 14,000 (9000-21,000), with a 90% probability range of 1.9-4.3. Cases and rates by age are provided in Table 5.
Table 5. Estimated Cases and Rates of 2009 Influenza A (H1N1) in the United States for April-July 2009
Age Cases (Median)
Rate/100,000 Population(Median)
Cases(x
1000)*
Hospitalized
(x 1000)*Case
sHospitalize
dTotal 3052 13 997 4.50-4 years
397 2.7 1870 13.0
5-24 1820 4.9 2196 6.0
years25-49 years
612 3.4 577 3.2
50-64 years
180 1.9 319 3.4
≥ 65 years
42 0.6 107 1.7
*Numbers rounded for table (Reed C, Angulo FJ, Swerdlow DL, et al. Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July, 2009. Emerg Infect Dis. 2009 Dec. [Epub ahead of print] Available at: http://www.cdc.gov/eid/content/15/12/pdfs/09-1413.pdf Accessed November 4, 2009.)
Pediatric Hospitalizations
Data from a review of 465 pediatric hospitalizations for the period April 15- August 31, 2009 are summarized in Table 6.
Table 6. Underlying Conditions in Children Hospitalized for H1N1 Influenza
Condition N (%)> 1 underlying condition
465 (62%)
Asthma 166 (36%)Developmental delay 33 (7%)Hemoglobinopathy 31 (7%)Seizure disorder 27 (6%)Prematurity 27 (6%)Neuromuscular disease
24 (6%)
Chronic lung disease 23 (5%)Immunosuppression 21 (4%)Cardiovascular disease
20 (4%)
Chronic metabolic disease
14 (3%)
(CDC. Information on H1N1 influenza and H1N1 vaccination and treatment for children. Clinician Outreach and Communication Activity Conference Call. October 28, 2009.)
Pediatric Deaths
For influenza week 42 (ending October 24, 2009):
To date, the CDC data for pediatrics show 74 pediatric deaths from influenza in the 2009-2010 season. Comparative data for 2006-2007, 2007-2008, and 2008-2009 seasons show that the total number of pediatric deaths was 117, 88, and 78, respectively. (CDC. 2009-2010 influenza season week 42 ending October 24, 2009. FluView. Available at: http://www.cdc.gov/flu/weekly/ Accessed November 1, 2009.)
Ages of patients hospitalized for influenza (all types) for the period September 1, 2009-October 24, 2009 appear in Table 7.
Table 7. Age of Patients Hospitalized for Influenza
AgeInfluenza Rate(per 10,000)
0-4 years 2.7 (4.9)5-17 years 1.3 (2.5)18-49 years 0.9 (0.8)50-64 years 1.0 (0.9)> 65 years 0.8 (0.7)
During the period May 11-October 11, 2009, Quest Diagnostics tested 76,500 specimens from hospitalized patients, by far the largest source of H1N1 testing data. Results show that 53% of patients were younger than 25 years of age, and 7% of patients were older than 65 years of age. There was a sharp rise in school-age children with influenza in September, and several weeks later influenza increased in the elderly, persons 50-64 years of age, and children younger than 5 years of age. This temporal relationship suggests what might be expected epidemiologically in upcoming weeks. The report emphasizes the need to vaccinate children for their own health and to slow the epidemic. (Fox M. Tests show flu spreads from schools. Reuters. October 21, 2009. Available at: http://www.reuters.com/article/healthNews/idUSTRE59K3S920091021 Accessed November 4, 2009.
Risks for serious disease requiring hospitalization or causing death
Pregnancy and 2009 influenza A (H1N1). One hundred pregnant women with swine flu have been hospitalized in ICUs; 28 of these women died. (CDC Press Briefing Transcripts. Weekly 2009 H1N1 Flu Media Briefing. October 1, 2009. Available at: http://www.cdc.gov/media/transcripts/2009/t091001.htm Accessed October 22, 2009.)
Pregnancy: A review of 34 confirmed cases of 2009 H1N1 influenza in pregnant women, reported to the CDC from 13 states, showed that 11 women were hospitalized and 6 died. All 6 deaths were in previously healthy women who developed viral pneumonia and ARDS requiring mechanical ventilation. None of the 5 infants born to these women had evidence of influenza. (Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009;374:451-458.)
Other previously defined risks (chronic underlying disease or immunosuppressed) in 117/179 (65%) of hospitalized patients;
Obesity: 30%-35% of hospitalized patients are obese (BMI ≥ 30) or morbidly obese (BMI > 40). Note that 25% of adults in the United States are obese by this definition and that most of the obese patients hospitalized with H1N1 had other predisposing illnesses. Nevertheless, a rodent model showed excessive mortality in a group of mice fed with a high-fat diet. (Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA. Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology. 2009;126:268-279.)
Patients hospitalized with 2009 H1N1 influenza in the United States. The CDC reviewed the medical records from 272 of the 1082 patients hospitalized with influenza as reported to the CDC for the period May 1, 2009 to June 9, 2009. (Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June, 2009. N Engl J Med. 2009 361:935-944.) Important observations from this review:
ICU patients fall into 3 categories:
Primary influenza pneumonia with severe gas exchange abnormalities;
Invasive bacterial superinfection usually caused by S aureus (including methicillin-resistant S aureus), S pneumoniae, and group A streptococcus; and
Worsening organ dysfunction as a result of poor cardiopulmonary reserve as a consequence of comorbidities.
Age distribution: median age: 21 years; 14 patients were older than 65 (5%);
Symptoms: vomiting or diarrhea: 39%;Associated conditions: any: 198 (73%); asthma: 76 (28%);
immunosuppression: 40 (15%); pregnancy: 18 (7%); morbid obesity in adults 26/100 (26%);
Lab: x-ray showing pneumonia: 100/249 (40%) including 60/100 with bilateral infiltrates; anemia: 87/238 (37%); leukopenia: 50/246 (20%); bacteremia: 3/272 (1%);
ICU admission: 67 (25%);Mortality: 19 (7%) -- all were ICU patients given mechanical
ventilation; median age was 26 years; median time from onset to death was 15 days; underlying disease present in 13/19 (68%);
Antimicrobials: antiviral agents were given to 201/268 (75%) starting at a median of 3 days after onset of illness; antibiotics were given to 79%;
Neuraminidase inhibitor treatment has been associated with increased survival;
The report notes that oseltamivir or zanamivir is recommended for patients hospitalized with influenza and for those at high risk for complications, even if started later than 48 hours after onset of symptoms. (McGeer A, Green KA, Plevneshi A, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45:1568-1575.)
Surveillance of patients hospitalized with H1N1 influenza
Most adults have associated risks, especially asthma, chronic lung or heart disease, or immunosuppression;
Most children have associated risks such as asthma, chronic lung disease, neurologic disease, or sickle cell disease; and
6% were pregnant womenFactors associated with death or hospitalization from
pandemic 2009 influenza A (H1N1) infection in California.
Background: Pandemic influenza A (H1N1) emerged rapidly in April 2009. The preliminary impression is that, compared with seasonal flu, it affected younger people and was usually mild.
Goal: Describe the clinical and epidemiologic features of this influenza that led to death or hospitalization.
Method: Enhanced public health surveillance of California residents who were hospitalized or died with laboratory-confirmed infection with 2009 Influenza A (H1N1) from April 23, 2009 to August 11, 2009.
Results: Data are based on 1088 cases of hospitalization or death reported in 41 of 61 local health jurisdictions, with most occurring in the first wave during June and July.
See Table 8.
Table 8. Characteristics and Comorbid Conditions of Hospitalized and Fatal Cases of 2009 Influenza A (H1N1) in California
Age 0-17
years Age ≥ 18 years
VariableTotal
n = 1088Fatal
8
Nonfatal
336Fatal110
Nonfatal
634Signs/symptoms FeverDyspneaChillsDiarrheaNausea/vomiting
89%56%20%20%35%
100%
38%0%25%50%
95%33%7%19%38%
83%81%25%18%20%
87%63%27%20%37%
Laboratory Positive rapid flu testInfiltrates (x-ray)
66%66%
83%80%
85%60%
44%97%
59%62%
Hospital Care ICUMechanical ventilationAntiviral therapy
31%25%79%4%
75%88%63%13%
25%10%77%2%
80%93%73%14%
26%19%82%4%
Bacterial infectionAssociated conditions Chronic lung diseaseAsthmaDiabetesPregnancyImmunosuppressive drugsHIV/AIDS
Other premorbid conditions BMI > 30BMI > 40Chronic heart disease
748 (68%)37%24%11%10%14%2%
370 (34%)48%43%15%
6 (75%
)38%13%0%0%25%0%
2 (25%
)0%----
25%
199 (59%)38%29%1%2%13%0%
45 (13%)19%----7%
83 (75%)41%16%18%6%26%4%
69 (63%)66%50%23%
453 (71%)36%22%14%15%13%3%
254 (40%)52%40%18%
BMI = body mass index
Important observations from this study:
GI symptoms were noted in > 35% compared with < 5% in those who had seasonal flu;
There was a high rate of severe disease, with 31% requiring ICU care and 25% requiring mechanical ventilation;
Mortality was 11% and usually was attributed to viral pneumonia or acute respiratory distress syndrome;
Bacterial pneumonia was diagnosed in only 4%;Highest rate of hospitalization by age was infants < 1 year of age
(11.9/100,000) vs 2.8/100,000 for all age groups and 1.5/100,000 for persons > 70 years of age;
The highest fatality rate was 18% in persons > 50 years of age;Morbid obesity was noted in 43% vs 4.8% in the US population;32% did not have a comorbid illness.
(Louie JK, Acosta M, Winter K, Jean C, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California JAMA. 2009;302:1896-1902.)
Individuals should seek emergency medical care if they have dyspnea, chest pain or pressure, confusion or seizures, persistent
vomiting, or bluish lips. (CDC. H1N1 flu (swine flu): general information, 2009. Available at: http://www.cdc.gov/h1n1flu/general_info.htm Accessed September 16, 2009.)
Risk Reduction Recommendations for Specific Patient Groups
(Flu.gov. People with health conditions. Available at: http://pandemicflu.gov/individualfamily/healthconditions/index.html Accessed October 26, 2009.)
Asthma
Get vaccinated for seasonal flu as soon as the vaccine is available. Children ages 6 months to 8 years who have never had seasonal flu vaccine need 2 doses.
Persons 6 months to 64 years of age should get the 2009 H1N1 vaccine by injection as soon as it is available where they live
Persons with asthma should not take the intranasal (FluMist) vaccine.
Oseltamivir is recommended for patients with asthma who get 2009 H1N1 infection; it should be started within 48 hours of onset of symptoms if possible.
Diabetes
Patients with diabetes should get both seasonal flu vaccine and H1N1 vaccine.
Diabetes care: Continue insulin or oral hypoglycemics even if the patient cannot eat; monitor blood glucose every 4 hours and record; drink extra calorie-free liquids; weigh daily.
Health provider should be alerted for temperature > 100°F, blood glucose < 60 mg/dL or > 300 mg/dL, moderate or large amount of urine ketones, change in mental status, dyspnea, weight loss of 5 lbs or more, or onset of severe diarrhea.
Pregnancy
Pregnant women are at high risk for serious influenza complications.
Pregnant women should get both seasonal flu vaccine and 2009 H1N1 flu vaccine, both by IM injection when the vaccines become available. Pregnant women should not get the
intranasal LAIV (FluMist) vaccine.Pregnant women with established or suspected influenza should be
treated with oseltamivir or zanamivir, preferably within 2 days of the onset of symptoms.
Statins and reduced death from influenza. (Vandermeer M, Thomas A, Kamimoto L, et al. Program and abstracts of the 47th Infectious Diseases Society of America Annual Meeting; October 29-November 1, 2009; Philadelphia, Pennsylvania. Abstract 706.) The authors reviewed 2800 patients older than 18 years who were hospitalized with influenza during the 2007-2008 season, using a surveillance system that covered 10 states. The mortality rate was reduced by 54% in patients who received statins for cardiovascular disease. (See next review)
Treating the "cytokine storm" of influenza. (Fedson DS. Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: Why they are needed and how they might work. Influenza Other Respi Viruses. 2009;3:129-142). The author reviews data from multiple sources supporting the thesis that acute lung injury that is associated with influenza is caused by excessive release of cytokines, the "cytokine storm." This is seen with the experimental models of the 1918-1919 pandemic strain, H5N1 (avian) influenza, and 2009 (H1N1). Agents that inhibit cytokine production may be logical therapeutic agents and have demonstrated benefit in the mouse model of H5N1 influenza. (Zheng BJ, Chan KW, Lin YP. Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc Natl Acad Sci U S A. 2008;105:8091-8096.) It is noted that 3 classes of drugs that work in this fashion (by inhibiting cell-signaling pathways in cytokine production) are statins, glitazones, and fibrates. Multiple studies have shown that the mortality rate of bacterial pneumonia is reduced by about 50% in patients receiving statins. (Chopra V, Flanders SA. Does statin use improve pneumonia outcomes? Chest. 2009;136:1381-1388.)
Outcomes of Treatment in Severely Ill Patients
Australia and New Zealand Extracorporeal Membrane Oxygenation for 2009 Influenza A (H1N1) Acute Respiratory Distress Syndrome
(Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA. 2009 Oct 12. [Epub ahead of print])
The investigators review their experience in 15 ICUs in Australia and New Zealand with 68 patients with 2009 influenza A (H1N1) infection who developed acute respiratory distress syndrome (ARDS) and required ECMO:
Patients: mean age, 34 years; children (3 children younger than 15 years of age)
Predisposing conditions: BMI > 30 (34 patients), asthma (19), diabetes (10), pregnancy or postpartum (10)
Bacterial superinfection was found in 19 patients (28%), including S pneumoniae in 10 and S aureus in 4
Severity of illness: median values for lowest PaO2: 56; highest positive end expiratory pressure (PEEP): 18 cm H2O; lowest pH: 7.2; highest FiO2: 1.0; median acute lung injury score: 3.8; highest pCO2: 69 mm Hg; highest peak airway pressure: 36 cm H2O
Course: infectious complications in 42 (62%) included respiratory tract: 42; bacteremia: 14; ECMO cannulae: 7; and non-ECMO-related: 13
Median duration of care modalities: mechanical ventilation: 25 days; hospitalization: 37 days; ICU stay: 27 days; ECMO: 10 days
Outcome: survival and ICU discharge: 48 (71%); survival and hospital discharge: 32 (47%); still in hospital: 16 (24%); died: 14 (21%) [cause of death: respiratory failure: 4; intracranial hemorrhage: 6; hemorrhage: 4; infection: 1 (some had multiple infections)]
Comments:
All of the patients satisfied the CESAR criteria for ECMO (see below);
The 21% end-of-study mortality rate in this study is low compared with previous reports; the authors attribute this to the relatively young age of patients and several training and technical attributes of their consortium of ECMO sites;
On the basis of their experience, the investigators project that the
ECMO needs for the United States and Europe for the 2009-2010 influenza season will be 800-1300 patients.
Rate of ECMO use for H1N1 influenza was 2.6 cases/million population in 2009 vs 0.15 cases/million for seasonal influenza in 2008.
CESAR Trial Comparing ECMO and Conventional Ventilation
A study was designed to determine the safety, efficacy, and cost-effectiveness of ECMO compared with conventional ventilation in the treatment of adults with severe acute respiratory failure. There were 120 adults with potentially reversible respiratory failure and Murray score > 3.0 or pH < 7.2. The 6-month survival was 57/90 (63%) for patients allocated to consideration of treatment by ECMO vs 41/87 (47%) for patients allocated to conventional treatment (P = .03). (Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;Sep 15 [Epub ahead of print].)
Critically Ill Patients in Canada
Kumar and colleagues present a prospective observational study of 168 patients critically ill with 2009 influenza A (H1N1) cared for in 38 adult and pediatric ICUs in Canada during April 16-August 12, 2009. All patients were evaluated by a standardized protocol.
Demographics. Mean patient age was 32 years, with 50 (30%) under 18 years of age. There were 16 nosocomial cases. Chronic preexisting conditions of the sample included:
Chronic lung disease: 69 (41%), including asthma (38 [23%]) and COPD (16 [10%]);
Obesity: 56 (33%); morbid obesity with BMI > 40: 28 (24%);Immune suppression: 33 (20%), including chronic steroids (26
[16%]) and HIV (2 [1%]);Neurologic disease: 26 (16%);Cardiac disease: 25 (15%);Pregnancy: 13 (8%);Malignancy: 6 (4%); andChronic renal disease: 12 (7%).
Symptoms
Fever: 91%;Myalgias: 56%;Suspected bacterial infection: 32%;Hypotension: 14%;Altered consciousness:10%;Renal failure: 7%;Median duration of symptoms prior to hospitalization: 4 days;Median duration of hospitalization prior to ICU: 1 day.
Physical exam and laboratory data (day 1 of hospitalization):
Chest x-ray (bilateral infiltrates: 71%; 4-quadrant involvement: 41%; lung injury "at onset": 73%);
Vital signs (mean pulse: 119; lowest mean systolic BP: 95 mmHg; mean SOFA score: 6.8);
Lab results (mean WBC: 9400/mL; median CPK: 243).Treatment
Mechanical ventilation:136 (81%) on day 1;Treatment for O2 failure included neuromuscular blockade in 47
(28%), inhaled nitric oxide in 23 (14%), high-frequency oscillatory ventilation in 20 (12%), ECMO in 7 (4%), and prone-position ventilation in 5 (3%);
Drugs: vasopressors or inotropes: 55 (33%); antivirals:152 (91%); antibacterials: 166 (99%); corticosteroids: 85 (51%).
(Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009 Oct 12. [Epub ahead of print])
Epidemiology of 2009 H1N1
Virus. 2009 H1N1 influenza virus is a quadruple reassortment with gene products from pigs (Europe and Asia origin), avian influenza, and human influenza strains. This virus is antigenically unrelated to H1N1 influenza viruses in circulation since 1957. (Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197-201.; Zimmer SM, Burke DS. Historical perspective -- emergence of influenza A (H1N1) viruses. N Engl J Med. 2009;361:279-285.)
As of September 1, 2009, the H1N1 viruses are similar, showing minimal mutation by sequential analysis and by geographic distribution. (CDC. Pneumonia hospitalizations among young children before and after introduction of pneumococcal conjugate vaccine --- United States, 1997-2006. MMWR. Morb Mortal Wkly Rep. 2009;58:1-4.)
Laboratory studies show that in the rodent model, compared with seasonal H1N1 strains, the 2009 H1N1 virus replicates in lungs more efficiently, causes different proinflammatory cytokine responses, and results in more lung damage and more death. (Itoh Y, Shinya K, Kiso M. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009;460:1021-1025.)
Transmission rates
Reproduction ratio (RO) = 1.4Secondary attack rates in households are 8%-18%; the rate is 8%-
12% for ILI and 18%-19% for ARI.Case fatality rate
Case fatality is reported to be 0.4% (compared with 0.3% in Europe and 2.4% for the 1918-19 influenza pandemic). The death rate of 0.4% compares to a rate of 0.1% for seasonal flu.
The highest death rate is in persons 50-64 years.A New York City telephone survey found ILI in 250,000 of 8.3 million
people; case-fatality rate was 0.0008%. (New York City Department of Health and Mental Hygiene. Prevalence of flu-like illness in New York City: May 2009. Available at: http://www.nyc.gov/html/doh/downloads/pdf/cd/h1n1_citywide_survey.pdf Accessed September 16, 2009.)
Data based on confirmed cases are flawed by selected use of testing that favors seriously ill patients. (Garske T, Legrand J, Donnelly CA, et al. Assessing the severity of the novel influenza A/H1N1 pandemic. BMJ. 2009;339:b2840.)
Projected cases and impact in the United States
On August 25, 2009, the President's Council of Advisors projected that H1N1 may infect up to half of the US population, with hospitalization of 1.8 million and lethal outcome in 30,000-90,000.
Mortality: Media emphasized the 90,000 figure; Thomas R. Frieden, MD, MPH, Director of the CDC, emphasized the 30,000 figure.
Impact: The President's Council of Advisors estimates that 50% of 60-120 million will seek medical care.
ICU burden of H1N1 disease: The Advisory Panel to President Obama projected that as many as 300,000 patients could require intensive care and occupy up to half of all ICU beds in affected regions.
CDC Report on US Influenza A (H1N1) Infections
The CDC has 1600 people dedicated to the influenza effort, according to CDC Director Frieden. The CDC currently estimates that there are 48,000 influenza A (H1N1) infections in the United States and more than 600 deaths. The initial vaccine supply of 2.2 million doses of the nasal spray, the live attenuated virus vaccine, has started to arrive. The CDC is emphasizing the safety of the vaccine to counter the campaign that vaccines are harmful. (McHugh R, Fortuna R, McCarthy K. Swine flu ground zero: a rare look into CDC. ABC News. October 13, 2009. Available at: http://abcnews.go.com/m/screen?id=8778094&pid=4380645 Accessed October 13, 2009.)
Experience in New Zealand With H1N1 Influenza
This experience is valuable because New Zealand has good surveillance systems and is in the Southern hemisphere, so the country's winter flu season with simultaneous seasonal flu and pandemic H1N1 flu is largely over. (CDC. Surveillance for the 2009 pandemic influenza A (H1N1) virus and seasonal influenza viruses --- New Zealand, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:918-921.)
Sentinel GP surveillance system in New Zealand. Defines ILI activity based on reports of volunteer general practitioners. Rates of 50-249/100,000 population/week are considered average for normal seasonal flu activity. Rates > 400/100,000 define epidemic levels. The highest rate was 287 consultations/100,000 population for July 13-19, 2009; this is 3 times the peak rate of 95/100,00 in 2008.
Virology. Analysis of 527 influenza virus isolates in the sentinel surveillance labs (527 strains) and the nonsentinel labs (3931 strains) showed that 2009 H1N1 influenza A accounted for about
65% of identified strains.
Patients. The ILI rates (expressed per 100,000 population) in rank order: children 1-4 years (154); infants < 1 year (110); 15-17 years (97); 20-34 years (96); 35-49 years (66); 50-64 years (57); and ≥ 65 years (23).
Australia
Like New Zealand, Australia represents a model of what may occur in the northern hemisphere because it represents a southern hemisphere country with good surveillance and recent simultaneous epidemics of 2009 H1N1 and seasonal flu. Highlights of a recent influenza report from this country:
Case counts: Confirmed cases: 35,936 (underreported); hospitalized: 4649; deaths: 169 (3.6% of hospitalized patients, Table 9)
Table 9. Influenza Outcomes in Australia
Severe Cases HospitalizedMedian age (yrs)ComorbidityPregnancy
3164%a 4%a
a % of hospitalized patientsb ICU patients: 75% required mechanical ventilation and 14% required ECMO.(Dwyer DE. Mini Lecture. Pandemic influenza (H1N1)09 activity in Australia - implications for the northern hemisphere. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, California. Abstract V-1269a.)
Issue of transplantation of non-lung organs: single case with no transfer of infection. Viremia is rare compared with influenza due to H5N1, and autopsies in 13 cases showed no extrapulmonary infected sites.
Dominant seasonal influenza strain that cocirculated was H3N2 influenza A, but 2009 H1N1 "pushed out seasonal influenza"; 2009 H1N1 accounted for 76% of ILI patients in ICUs.
Resource List
ACHA. Pandemic influenza surveillance. influenza-like illness in colleges and universities. Weekly Case Data for the period
October 17-23, 2009. Available at: http://www.acha.org/ILI_surveillance.cfm Accessed November 10, 2009.
Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA. 2009 Oct 12. [Epub ahead of print]
Bartlett JG, Borio L. Healthcare epidemiology: the current status of planning for pandemic influenza and implications for health care planning in the United States. Clin Infect Dis. 2008;46:919-925. Abstract
CDC. 2009-2010 influenza season week 42 ending October 24, 2009. FluView. Available at: http://www.cdc.gov/flu/weekly/ Accessed November 1, 2009.
CDC. 2009-2010 influenza season week 41 ending October 17, 2009. FluView. Oct 24, 2009. Available at: http://www.cdc.gov/flu/weekly/ Accessed October 27, 2009.
CDC. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - US, May - August 2009. MMWR Morb Mortal Wkly Rep. 2009;58:early release.
CDC. Information on H1N1 influenza and H1N1 vaccination and treatment for children. Clinician Outreach and Communication Activity Conference Call. October 28, 2009.
CDC. Behavioral Risk Factor Surveillance System. Available at: http://www.cdc.gov/BRFSS/ Accessed October 27, 2009.
CDC. H1N1 flu (swine flu): general information. Available at: http://www.cdc.gov/h1n1flu/general_info.htm Accessed September 16, 2009.
CDC. Hospitalized patients with novel influenza A (H1N1) virus infection --- California, April-May. MMWR Morb Mortal Wkly Rep. 2009;58:536-541. Abstract
CDC. Intensive care patients with severe novel influenza A (H1N1) virus infection -- Michigan, June 2009. MMWR Morb Mortal Wkly Rep. 2009;58:749-752. Abstract
CDC. Interim guidance for clinicians on identifying and caring for patients with swine-origin influenza A (H1N1) virus infection. June 2009. Available at: http://www.cdc.gov/h1n1flu/identifyingpatients.htm Accessed September 16, 2009.
CDC. Key facts about seasonal influenza (flu). Available at:
www.cdc.gov/flu/keyfacts.htm Accessed September 25, 2009.CDC. Neurological complications associated with novel influenza A
(H1N1) infection in children -- Dallas, Texas, May 2009. MMWR Morb Mortal Wkly Rep. 2009;58:773-778. Abstract
CDC Online Newsroom. Weekly 2009 H1N1 Flu Media Briefing. October 22, 2009. Available at: http://www.cdc.gov/media/transcripts/2009/t091023.htm Accessed October 26, 2009.
CDC Online Newsroom. Weekly 2009 H1N1 Flu Media Briefing. October 9, 2009. Available at: http://www.cdc.gov/media/transcripts/2009/t091009.htm Accessed October 22, 2009.
CDC. Pneumonia hospitalizations among young children before and after introduction of pneumococcal conjugate vaccine --- United States, 1997-2006. MMWR Morb Mortal Wkly Rep. 2009;58:1-4. Abstract
CDC Press Briefing Transcripts. Weekly 2009 H1N1 Flu Media Briefing. October 1, 2009. Available at: http://www.cdc.gov/media/transcripts/2009/t091001.htm Accessed October 22, 2009.
CDC. Surveillance for the 2009 pandemic influenza A (H1N1) virus and seasonal influenza viruses --- New Zealand, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:918-921. Abstract
CDC. Swine-origin influenza A (H1N1) virus infections in a school -- New York City, April 2009. MMWR Morb Mortal Wkly Rep Dispatch. 2009;58:1-3. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0430a1.htm Accessed September 25, 2009.
CDC. Update: Influenza activity – United States, Aug. 30-Oct. 31, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:1236-1241. Abstract
CDC. Update: Swine-origin influenza A (H1N1) virus --- United States and other countries. MMWR Wkly. 2009;58:421.
CDC. Use of influenza A (H1N1) 2009 monovalent vaccine --- recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Morb Mortal Wkly Rep. 2009;58(RR-10):1.
CDC, Influenza Division. FluView. Available at: http://www.cdc.gov/flu/weekly/ Accessed November 13, 2009.
Chan M. Swine flu spreading at 'unbelievable' rate: WHO chief.
Khaleej Times. August 29, 2009. Available at: http://www.khaleejtimes.com/displayarticle.asp?xfile=data/international/2009/August/international_August2077.xml§ion=international&col= Accessed September 25, 2009.
Chopra V, Flanders SA. Does statin use improve pneumonia outcomes? Chest. 2009;136:1381-1388.
Cohen J. Swine flu outbreak, day by day. ScienceInsider. July 17, 2009. Available at: http://blogs.sciencemag.org/scienceinsider/special/swine-flu-timeline.html Accessed September 16, 2009.
Committee on the Future of Emergency Care in the United States Health System, Institute of Medicine. Emergency Medical Services: At the Crossroads. Washington, DC: National Academies Press; 2007.
Dwyer DE. Mini Lecture. Pandemic influenza (H1N1)09 activity in Australia - implications for the northern hemisphere. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, California. Abstract V-1269a.
Fedson DS. Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: Why they are needed and how they might work. Influenza Other Respi Viruses. 2009;3:129-142. Abstract
Flu.gov. People with health conditions. Available at: http://pandemicflu.gov/individualfamily/healthconditions/index.html Accessed October 26, 2009.
FluView. President Obama signs emergency declaration for H1N1 flu. October 24, 2009. Available at: http://www.flu.gov/professional/federal/h1n1emergency10242009.html Accessed October 26, 2009.
Fox M. Tests show flu spreads from schools. Reuters. October 21, 2009. Available at: http://www.reuters.com/article/healthNews/idUSTRE59K3S920091021 Accessed November 4, 2009.
Garske T, Legrand J, Donnelly CA, et al. Assessing the severity of the novel influenza A/H1N1 pandemic. BMJ. 2009;339:b2840.
Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197-201. Abstract
Hartocollis A, McNeill DG Jr .Areas hit hard by flu in spring see little now. New York Times. October 8, 2009; sect A1.
Greenhouse S. Lack of paid sick days may worsen flu pandemic. New York Times. November 2, 2009. Available at: http://www.nytimes.com/2009/11/03/business/03sick.html?_r=1 Accessed November 10, 2009.
Harvard Opinion Research Program, Harvard School of Public Health. Business Preparedness: Novel Influenza A (H1N1). July 16-August 12, 2009. Available at: http://www.hsph.harvard.edu/news/press-releases/2009-releases/businesses-problems-maintaining-operations-significant-h1n1-flu-outbreak.html Accessed September 16, 2009.
Itoh Y, Shinya K, Kiso M. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009;460:1021-1025. Abstract
Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June, 2009. N Engl J Med. 2009;361:935-944.
Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009;374:451-458. Abstract
Khan K, Arino J, Hu W, Raposo P, et al. Spread of a novel influenza A (H1N1) virus via global airline transportation. N Engl J Med. 2009;361:212-214. Available at: http://content.nejm.org/cgi/content/full/361/2/212 Accessed September 16, 2009.
Kumar A, Zarychanski R, Pinto R, et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009 Oct 12. [Epub ahead of print]
Louie JK, Acosta M, Winter K, Jean C, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California JAMA. 2009;302:1896-1902.
Maher B, Butler D. Swine flu: One killer virus, three key questions. Nature. 2009;462:154-157. Abstract
Maricich SM, Neuf JL, Lotze TE, et al. Neurologic complications association with influenza A in children during the 2003-2004 influenza season in Houston, Texas. Pediatrics. 2004;114:e626-e633. Abstract
McGeer A, Green KA, Plevneshi A, et al. Antiviral therapy and
outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45:1568-1575. Abstract
McHugh R, Fortuna R, McCarthy K. Swine flu ground zero: a rare look into CDC. ABC News. October 13, 2009. Available at: http://abcnews.go.com/m/screen?id=8778094&pid=4380645 Accessed October 13, 2009.)
Morens DS, Taubenberger JK, Fauci AS. Prominent role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness J Infect Dis. 2008;198:962-970.
Morishima T, Togashi T, Yokota S, et al. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis. 2002;35:512-517. Abstract
New York City Department of Health and Mental Hygiene. Prevalence of flu-like illness in New York City: May 2009. Available at: http://www.nyc.gov/html/doh/downloads/pdf/cd/h1n1_citywide_survey.pdf Accessed September 16, 2009.
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; 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;360:2605-2615.
Parker-Pope T. The cat got swine flu. The New York Times. November 5, 2009. Available at: http://well.blogs.nytimes.com/2009/11/05/the-cat-who-got-swine-flu/ Accessed November 19, 2009.
Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;Sep 15 [Epub ahead of print].
President's Council of Advisors on Science and Technology. U.S. Preparations for 2009-H1N1 Influenza. August 7, 2009. Available at: http://www.whitehouse.gov/assets/documents/PCAST_H1N1_Report.pdf Accessed September 16, 2009.
Rao L. Harvard Medical School launches swine flu iPhone app. Washington Post. October 26, 2009.
Reed C, Angulo FJ, Swerdlow DL, et al. Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July, 2009. Emerg
Infect Dis. 2009 Dec. [Epub ahead of print] Available at: http://www.cdc.gov/eid/content/15/12/pdfs/09-1413.pdf Accessed November 4, 2009.
Schipoliansky C, Cox L. Swine flu cuts the kiss in Europe. ABC News, September 9, 2009. Available at: http://abcnews.go.com/Health/SwineFluNews/swine-flu-cuts-kiss-europe/story?id=8520227 Accessed September 16, 2009.
Scott M. Pandemic influenza guidance for homeless shelters and homeless service providers, 2009. Available at: www.nhchc.org/flumanual.pdf Accessed November 18, 2009.
Sherman SE, Foster J, Vaid S. Emergency use authority and 2009 H1N1 influenza. Biosecurity Bioterrorism. 2009;7:245-250.
Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA. Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology. 2009;126:268-279. Abstract
Vandermeer M, Thomas A, Kamimoto L, et al. Program and abstracts of the 47th Infectious Diseases Society of America Annual Meeting; October 29-November 1, 2009; Philadelphia, Pennsylvania. Abstract 706.
WHO. November 5, 2009 press conference. Available at: http://www.who.int/mediacentre/multimedia/swineflupressbriefings/en/index.html Accessed November 10, 2009.
World Health Organization. Chan M. World now at the start of 2009 influenza pandemic. June 11, 2009. Available at: http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html Accessed September 16, 2009.
World Health Organization. Pandemic H1N1 2009 -- update 69. October 4, 2009. Available at: http://www.who.int/csr/don/2009_10_09/en/index.html Accessed October 22, 2009.
Zheng BJ, Chan KW, Lin YP. Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc Natl Acad Sci U S A. 2008;105:8091-8096. Abstract
Zimmer SM, Burke DS. Historical perspective -- emergence of influenza A (H1N1) viruses. N Engl J Med. 2009;361:279-285. Abstract
Authors and Disclosures
Author(s)
John G. Bartlett, MD
Professor of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Director, HIV Care Program, Johns Hopkins Hospital, Baltimore, MarylandDisclosure: John G. Bartlett, MD, has disclosed the following relevant financial relationships:Served on the policy board for: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.Served as an advisor or consultant to: Pfizer Inc; Tibotec, Inc. Served on the data safety monitoring board for: Tibotec, Inc.Received honoraria from: Abbott Laboratories