Influenza A H1N1

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Influenza A H1N1 2009, aka Swine Flu, is a new strain of influenza virus not previously seen. This strain is unusual in that it appears to be a cross between swine Influenza A H1N1 viruses found in North America, Asia, and Europe, as well as North American avian influenza viruses, and human influenza viruses .[1] To avoid misunderstandings, as of April 30, 2009, the World Health Organization is now referring to the virus as 2009 Influenza A H1N1. Although the virus does contain elements of swine Influenza, there is no documented risk from eating pork. To date, only those in close contact with swine (farmers/handlers) have ever contracted a Swine influenza infection from pigs themselves. [2]

Contents

Introduction

The virus was first identified in the US in two children on April 17. [3] It appears to have first occurred in La Gloria, Mexico in March, when there was a large outbreak of an unusual respiratory illness in the town. [4] Since then, it has now spread to and been identified in multiple countries, including the US, Canada, New Zealand, Hong Kong, China, and throughout Europe.

For perspective, as Dr Margaret Chan Director-General of the World Health Organization, observed, balancing information alerts can be a difficult challenge: "Last week, Mexican researchers published clinical profiles of early H1N1 cases in the New England Journal of Medicine. As noted, the full clinical spectrum of this disease is not yet fully understood. We do not fully understand the predictive factors for severe or fatal infections.

However, as more and more data become available, we are getting a better grip on warning signs that can signal the need for urgent medical care. Symptoms of concern include difficulty in breathing, shortness of breath, chest pain and severe or persistent vomiting.

In adults, a high fever that lasts for more than three days is a warning sign, particularly when accompanied by a general worsening of the patient’s condition. Lethargy in a child, that is, a child that has difficulty waking up or is no longer alert, or is not playing, is a warning sign.

For a pandemic of moderate severity, this is one of our greatest challenges: helping people to understand when they do not need to worry, and when they do need to seek urgent care. This is one key way to help save lives."[5]

Summary of Key Points for Protection

These are the essential points to understand to protect yourself and your community:

  • The mode of transmission of influenza viruses is thought to occur from person to person in respiratory droplets of coughs and sneezes. These infected droplets land on the mouth, nose or eyes of people nearby, or are spread when a person touches respiratory droplets on another person or an object and then touches their own (or another person's) mouth or nose (or rubs their eyes) before washing their hands. Influenza A H1N1 is not spread by pork or other food.
  • Masks will provide barrier protection against the large infective droplets that are believed to cause transmission. They are not effective against small viral particles that may be airborne. N-95 masks must fit tightly to work effectively. [6] Don’t panic if you do not have an N-95 surgical mask. An important part of prevention is to keep droplets away from your nose, mouth, and eyes. If you don't have a surgical mask, use a cloth bandana or similar to cover your nose and mouth. While there may be airborne transmission, droplets are probably a significant route and the one that individuals can best protect against through good hygiene practices.
  • The essence of protecting yourself: Practice good hygiene.
  • Keep your hands away from your face, or wash them first.
Wash with soap and water. Utilize hot water and scrub with soap for 30 seconds, including between fingers and under fingernails. Be sure to use a (paper) towel to turn off the faucet handles so as not to recontaminate your hands. The same applies to doorknobs. If you can't wash your hands, use an alcohol-based hand sanitizer with at least 60% alcohol.
Teach your family to cover their nose and mouth when they cough or sneeze, dispose of the used tissues promptly, and wash their hands (or use alcohol-based hand sanitizer) immediately, before they contaminate other surfaces with infective secretions.
  • "Social distancing"
Keep ill family members away from others in the home and at home unless they need medical care. If ill and you have to go out, wear a mask to catch coughs and sneezes and reduce the transmission of infective droplets to others.
In general, do not share drinks or eating utensils. Do not share towels. Color coding towels for different family members can help reduce spread, too.
  • Seek medical care promptly
if you have a serious underlying disease (see #Risk Factors), are pregnant, or become ill with severe flu-like symptoms or warning signs of more serious illness – such as:
  • Milder symptoms of influenza, including fever, generalized aches, sore throat, cough, runny nose, vomiting, and diarrhea, can be treated at home, symptomatically, since antiviral medication is no longer recommended except for high risk individuals or those developing complications. Take precautions if visiting your healthcare provider, including washing your hands frequently, using mask or cover over mouth and nose, and distancing yourself from others as much as possible to prevent further spread. See #Treatment.
  • Warning: Do not give aspirin (acetylsalicylic acid) to children or teenagers who have the flu; this can cause serious and possibly fatal Reye’s syndrome.[7] NSAIDS such as ibuprofen and acetominophen (Tylenol) are safe for symptomatic relief.

In this video, Dr. Joe Bresee, with CDC's Influenza Division, describes the symptoms of H1N1 (swine flu) and warning signs to look for that indicate the need for urgent medical attention.

Video at YouTube


More detailed information about swine flu follows.

Other Names

Influenza A(H1N1)

Swine influenza

Swine-origin influenza

In order to avoid further misunderstandings, as of April 30, 2009, the World Health Organization is now referring to the virus as 2009 Influenza A H1N1 rather than swine flu. Only those in close contact with swine (farmers and pig handlers) can be infected by pigs although pigs can be infected by humans [3]. There is no harm of contracting the virus from eating pork products.

Types

It is known that swine are "incubators" for influenza A, being susceptible to not only swine influenza, but avian and human also. When a swine is infected with multiple strains of virus, the genetic elements which make up the virus are able to recombine within individually infected cells. Thus, a virus can be packaged with a swine, human and/or avian elements or combinations thereof. As this recombination occurs, the resulting virus can be either more or less pathogenic (capable of causing illness). While various strains of influenza have previously been identified as combining swine, avian, and human elements, the 2009 Influenza A H1N1 appears to be an entirely new strain. While related to the human influenza H1N1 virus, it contains a novel combination of genetic material, including a cross of swine Influenza A H1N1 viruses found in North America, Asia, and Europe, as well as North American avian influenza viruses, and human influenza viruses.[5] This Influenza A H1N1 has not been previously recognized in either people or pigs. It is not yet clear where or how it arose nor how it was initially transmitted to humans. To reemphasize, Influenza A H1N1 does not require a prior exposure to pigs. It is not transmitted by eating pork products, and it is spread from person-to-person.

Causes and Transmission

H1N1 flu is an infection caused by a novel Influenza A strain, a cross between swine Influenza A H1N1 viruses found in North America, Asia, and Europe, as well as North American avian influenza viruses, and human influenza viruses.[8]

As with regular, seasonal influenza, transmission of Influenza A H1N1 is person to person, by spread of droplets from the respiratory secretions of infected individuals.

These can directly contact healthy people’s nose, mouth, or eyes, resulting in infection, or by contamination of surfaces with infective droplets. For more information, see #How Influenza A H1N1 is Spread.

How Influenza A H1N1 is Spread

Influenza viruses can be directly transmitted from pigs to people and from people to pigs. Human infection with flu viruses from pigs are most likely to occur when people are in close proximity to infected pigs, such as in pig barns and livestock exhibits housing pigs at fairs.

In this podcast, Dr. Joe Bresee of the CDC describes how to keep from getting the flu and spreading it to others

Video at YouTube


  • Droplet transmission
The main way that influenza viruses are thought to spread is from person to person in respiratory droplets of coughs and sneezes. This can happen when droplets from a cough or sneeze of an infected person are propelled through the air and deposited on the mouth or nose of people nearby. This is why masks are recommended if you are within 6 feet of an infected person. Influenza viruses may also be spread when a person touches respiratory droplets on another person or an object and then touches their own mouth, nose, or eyes (or someone else’s mouth, nose, or eyes) before washing their hands.
  • Direct and indirect contact transmission
"Direct contact transmission" means skin-to-skin contact (such as hand-to-hand) between an infected person and a susceptible person. "Indirect contact" is transmission by touching contaminated objects.

It is unclear how much transmission of swine flu occurs by these routes; primary transmission appears to be from droplets contacting the nose, mouth, or eyes of a susceptible person. Influenza A viruses can live for 24 to 48 hours on nonporous environmental surfaces and less than 12 hours on porous surfaces.[9]

  • Airborne transmission
Airborne transmission may occur with influenza viruses, but is not felt to be the primary mode of transmission. It is most likely to be of concern during aerosol generating procedures, such as intubation, suctioning, bronchoscopy, nebulizer treatments, or similar hospital or health care facility associated procedures.
There is no evidence to date of widespread airborne transmission as can occur with TB or chicken pox.[10]
  • Other transmission routes
It is not yet known if other routes, such as ocular, conjunctival, or gastrointestinal infections, can occur. Until more is known, it is recommended that all respiratory secretions and bodily fluids (including diarrheal stool) of novel H1N1 influenza cases should be considered potentially infectious.[11]
  • Incubation and Infectious Period
Adults with Influenza A H1N1 virus infection should be considered potentially contagious for up to 7 days following illness onset. Children, especially younger children, might potentially be contagious for longer periods.People are infectious for at least 24 hours prior to developing symptoms. Persons who continue to be ill longer than 7 days after illness onset should be considered potentially contagious until symptoms have resolved. The duration of infectiousness might vary by Influenza A H1N1 virus strain.
  • Prevention-Infection Control
Surgical masks will provide barrier protection against large droplets that are considered to be the primary route of influenza and SARS transmission. N-95 respirators provide additional protection against possible airborne transmission. Don’t panic if you don’t have an N-95 mask. The key to prevention is to keep droplets away from your nose, mouth, and eyes. If you don’t have a surgical mask, use a cloth bandana or similar to cover your nose and mouth. Change them frequently, launder and use hot dryer.
  • Keep your hands away from your face, or wash them first. Don’t share drinks or eating utensils.
Routine cleaning and disinfection strategies used during influenza seasons can be applied to the environmental management of Influenza A H1N1. More information can be found from the CDC. [12].

Appropriate hospital disinfectants include any one of the following, at the concentration respectively indicated:

  • ethanol diluted to 70% in water
  • Lysol diluted to 5% in water
  • bleach diluted to 10% in water


Household Infection Control Precautions

Lessening the Spread of Flu

"Social distancing" is important. Keep the sick person away from other people as much as possible.
  1. Remind the sick person to cover their coughs, and clean their hands with soap and water or an alcohol-based hand rub often, especially after coughing and/or sneezing.
  2. Have everyone in the household clean their hands often, using soap and water or an alcohol-based hand rub.
  3. Remind everyone to keep their hands away from their face, and to wash hands frequently or use a hand sanitizer (>60% alcohol based).
  4. Ask your health care worker if antiviral medications are indicated

If you are the caregiver

  • Avoid being face-to-face with the sick person.
  • When holding small children who are sick, place their chin on your shoulder so that they will not cough in your face.
  • Clean your hands with soap and water or use an alcohol-based hand rub after you touch the sick person or handle used tissues, or laundry.
  • Because you might become ill from your exposure, and can infect other people before you have any symptoms, wear a mask when you have to leave the home, to prevent further spread to others.
  • Ask your health care provider whether you should receive antiviral prophylaxis.

Household Infection Control Precautions: Cleaning, Laundry, and Waste Disposal

Clean surfaces in the patient's room and the bathroom fixtures used by the patient daily, with a household disinfectant. When cleaning, wear disposable gloves, and dispose of them after use. Or, use household utility gloves. Wash your hands or use sanitizer on them, before removing them if possible. Then wash your hands.

Use an EPA-reg household disinfectant labeled for activity against bacteria and viruses, or similar disinfectant or chlorine bleach solution, following label instructions. If a generic brand of chlorine is used, mix 1/4 cup of chlorine bleach with 1 gallon of cool water. The bleach should be mixed fresh daily. If you can't smell the chlorine, discard the solution and make a fresh mixture.

  • Throw away tissues and other disposable items used by the sick person in the trash. Wash your hands after touching used tissues and similar waste.
  • Keep surfaces (especially bedside tables, surfaces in the bathroom, and toys for children) clean by wiping them down with a household disinfectant according to directions on the product label.
  • Linens, eating utensils, and dishes belonging to those who are sick do not need to be cleaned separately, but importantly these items should not be shared without washing thoroughly first.
  • Wash linens (such as bed sheets and towels) by using household laundry soap and tumble dry on a hot setting. Avoid “hugging” laundry prior to washing it to prevent contaminating yourself. Clean your hands with soap and water or alcohol-based hand rub right after handling dirty laundry
  • Eating utensils should be washed either in a dishwasher or by hand with water and soap.[13]

Infection Control in Special Settings-Summer Camps

The CDC has expressed special concern regarding the potential for spread of influenza H1N1 in summer camps. Suggestions include pre-planning for dealing with sick campers and staff, planning in-camp cohorting and isolation for those who become ill, screening incoming campers, and planning how to transfer ill children home without infecting others enroute. [14]

Other Infection Control Recommendations

  • Masks and Respirators

While single use of masks (protective against droplets) or N-95 respirators (used when airborne transmission is suspected) is recommended, this is not always possible. Don’t panic if you don’t have an N-95 mask. The key to prevention is to keep droplets away from your nose, mouth, and eyes. If you don’t have a surgical mask, use a cloth bandana or similar to cover your nose and mouth. Change them frequently, launder and use hot dryer.

A study of 48 HCW with H1N1 infections was done by the CDC. Half were felt likely to have acquired the infection nosocomially, rather than through community exposure. Review showed only sporadic compliance with isolation precautions.[15]

  • Reuse of respirators and masks

While intended for single use, sometimes this is not practical and masks have to be reused. Drawn from experience with SARS, the following steps would allow a person to reuse a disposable N95 respirator if necessary. These steps are intended for reuse of a respirator by a single person:

  1. Wear a protective covering such as a medical mask or a clear plastic face shield—a loose-fitting barrier that does not interfere with fit or seal over the respirator.
  2. Remove the barrier upon leaving the patient’s room and perform hand hygiene. Surgical masks should be discarded; face shields should be cleaned and disinfected.
  3. Remove the respirator and either hang it in a designated area or place it in a bag. (Consider labeling respirators with a user’s name before use to prevent reuse by another individual.)
  4. Use care when placing a used respirator on the face to ensure proper fit for respiratory protection and to avoid contact with infectious material that may be present on the outside of the mask.[16]
  5. Perform hand hygiene after replacing the respirator on the face.

While these recommendations were developed for a different illness, Viral Hemorrhagic Fever, the CDC's site, [4], has excellent visuals and step-by-step instructions for infection control and for the use of masks and gowns (personal protective equipment), especially in resource-limited settings.[17]

Viral shedding

It is unclear at this time exactly when shedding begins or how long it lasts. Current estimates are based on the behavior of seasonal influenza. It is believed that shedding begins one day before the development of symptoms (contributing to person to person spread), and lasts for seven days in adults. Children are likely to shed virus and be infectious for a few days longer.

Incubation

Again, the precise incubation period is not yet known. It is likely 1 to 4 days, perhaps longer.

Chances of Developing Influenza A H1N1

The risk of developing illness after exposure is not yet known for certain. According to [World Health Organization|WHO] (reported in UpToDate), the H1N1 transmissibility appears substantially higher than that of seasonal influenza, with a secondary attack rate of the H1N1 strain estimated to be 22 to 33 percent, compared with 5 to 15 percent for seasonal influenza. The CDC has not confirmed the higher attack rate in the US.[18]

In this video, CDC's Dr. Joe Bresee describes how to prevent giving and getting novel H1N1 flu.

Video at YouTube


Risk factors

Risk factors are not yet known, other than exposure to pigs or people infected with Influenza A H1N1.

The current outbreak is atypical in that, thus far, the majority of the deaths from Influenza A H1N1 have occurred in Mexico. Furthermore, most have been in young adults. Regular influenza typically affects infants and the elderly the hardest.

With the H1N1, adults over the age of 60 may have protective immunity from prior related infection.

Pregnancy is being identified as a clear risk for more severe illness. (see #Complications and "#H1N1 in Pregnancy)

Other groups at higher risk of infection and complications from Influenza H1N1 include those with chronic lung disease (including asthma), cardiovascular disease, diabetes, and immunosuppression (including autoimmune disease), and morbid obesity.[19]

Signs and Symptoms

Symptoms of H1N1 flu are similar to the symptoms of regular influenza and generally include fever, cough, sore throat, body aches, headache, chills and fatigue.

In this video, Dr. Joe Bresee of the CDC describes the main symptoms of flu, including the new H1N1 flu, and when it is serious enough to seek medical help.

Video at YouTube


One thing that is different with this H1N1 flu is that some people have reported diarrhea and vomiting as well. About 12% of the patients in two Mexico City Hospitals experienced severe diarrhea, with loose stools multiple times per day. [20] Some reports from Mexico also note a cough that is more productive of phlegm than is typical.

One disturbing finding as of May 2009, is that about 1/3 of the patients at two Mexican hospitals had no fever when screened. This is troublesome, as doctors often use the presence of fever to help diagnose flu when screening patients. In fact, “textbooks say that in an influenza outbreak the predictive value of fever and cough is 90 percent,” Dr. Richard Wenzel, prominent epidemiologist and former president of the International Society for Infectious Diseases, noted. [21] The atypical symptoms with the H1N1 flu, with lack of fever being common, as well as the presence of diarrhea, both of which are unusual in seasonal influenza, are likely to confuse practitioners and lead to delays in diagnosis.

The symptoms of H1N1 flu have been a bit different in the 642 confirmed US cases from April 15th through May 5th that have been analyzed. Fever was the most common presenting symptom, (94% of ~394 patients for whom more complete information was available), followed by cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Hospitalization was required by 9%, almost half of whom had underlying immunocompromising conditions.[22]

As with regular influenza, H1N1 flu infections can be complicated by pneumonia and respiratory failure, and deaths have been reported. To date, a disproportionate number of deaths have been in Mexico (1.2%) and Argentina (2.4%) compared to the US (0.7%).[23] It is not known why the illness has been more severe in these countries thus far. (see #Controversy below). This outbreak has also thus far been different than seasonal influenza in that most of the deaths have been in young adults, rather than in young children, elderly, and otherwise immunosuppressed people.

Special Populations

H1N1 in Pregnancy

Symptoms of H1N1 in pregnancy are similar to the general population, and may include myalgia, dry cough, shortness of breath, low-grade fever, diarrhea, headache, dysphagia, and inspiratory chest pain. Pregnant women are one of the high-risk populations at risk for developing complications from seasonal influenza, such as pneumonia, respiratory distress, dehydration, and preterm delivery. It is now apparent that pregnancy is a risk factor for more serious complications and death from H1N1 infections, especially illness in the second or third trimesters.

Twenty cases of H1N1 (15 confirmed and 5 probable) have been reported by the CDC as of May 10, 2009. In the Morbidity and Mortality Weekly Report (MMWR) Dispatch, one case of maternal death in a 33-year old woman at 35 weeks gestation was presented. The patient presented initially with symptoms of myalgia, dry cough, and low-grade fever. Four days after presentation, the patient developed severe respiratory distress requiring intubation and cesarean delivery of a viable infant. Subsequent postpartum treatment with antivirals and broad-spectrum antibiotics was initiated. The patient died two weeks postpartum.[24]

Physiologic changes in pregnancy that account for increased complication rates include changes in the immune system, decreased functional residual capacity, increased baseline oxygen consumption, hypoalbuminemia predisposing to pulmonary edema, increased risk of aspiration, and increased cardiac output. Complication rates rise with increasing gestational age and with presence of co-morbidities such as asthma, diabetes, cardiac disease, immunosuppressive conditions, tobacco use, and other hisk-risk medical conditions. [25]

A review of cases reported in July, 2009 confirms the increased risk of complications in pregnant women. Because of this, they should begin treatment with the antiviral drug oseltamivir as soon as possible after symptom onset, even if later than the 48 hour optimal window for initiating therapy. WHO has also recommended that pregnant women be a priority group for immunization with the H1N1 vaccine in development.[26]

Complications

The complications of H1N1 flu are likely to be similar to those of seasonal influenza—most commonly pneumonia and respiratory failure. Pneumonia is expected to affect 10% of people with pandemic influenza. [27] It is important to note that staphylococcal pneumonia is a common cause of pneumonia following influenza. The rise in more severe and difficult to treat MRSA ([MRSA|methicillin-resistant staphylococcal aureus]) pneumonia is likely to result in more complications and deaths. Treatment guidelines are available from the Infectious Diseases Society of America (IDSA)[28] and the American Thoracic Society (ATS).[5]. [29]

Other complications of seasonal influenza include worsening of chronic underlying medical conditions, other respiratory tract infections (sinusitis, otitis, asthma), cardiac (myocarditis, pericarditis), neurologic (seizures, encephalitis), musculoskeletal (myositis, rhabdomyolysis) toxic shock.[30]

Groups at Higher Risk

As with seasonal influenza, groups at higher risk of complications from H1N1 include those with chronic lung disease (including asthma), cardiovascular disease, diabetes, and immunosuppression, hepatic, hematological, neurologic, or neuromuscular disorders. Pregnancy is increasingly being recognized as a risk factor for complications. Some studies suggest that extreme obesity may also be a risk factor for more severe disease.

Signs and symptoms of more severe illness warranting medical attention include:

  • shortness of breath or difficulty breathing, especially if the patient is turning blue
  • bloody or purulent sputum
  • chest pain (other than with coughing)
  • altered mental status
  • high fever that persists beyond 3 days
  • low blood pressure.

In children, danger signs include fast or difficult breathing, lethargy or lack of alertness, difficulty in waking up, and little or no desire to play.[31]

Expected Outcome

The outcome is too early to predict. The H1N1 flu reports initially more severe illness in Mexico, for unknown reasons (see # Controversy). In contrast, the US cases have been more mild, with fewer cases of pneumonia, respiratory failure, and death.[32]

For comparison, every year 5% to 20% of the population in the US becomes ill with influenza. More than 200,000 people are hospitalized from flu-related complications. The mortality from seasonal influenza in the US is estimated to be 36,000.[33]

Perspective is added by Dr. Richard Wenzel, expert epidemiologist and former President of the International Society for Infectious Diseases. He notes, "First let's look at the meaning of the deaths in context of the expected mortality rates. In the 1918-19 Avian flu pandemic, the mortality was 2.5% -- 25 times the rate we see with the seasonal arrival of flu each year of one in a thousand or 0.1%. If the 160 deaths in Mexico are truly related to swine flu and the disease is very virulent -- for example with a very high 1% mortality -- the real number of cases must be 16,000 -- not the 2,500 currently reported. On the other hand, if the new Swine flu is acting more like our seasonal flu, the real number of cases in Mexico is 160,000, 0.1% of which accounts for the 160 deaths."[34]

The World Health Organization Rapid Pandemic Assessment Collaboration has determined that approximately 23,000 Mexicans were infected with the virus by the end of April, 2009 [6]. Thus, the mortality rate for Influenza A H1N1 is 0.4%, higher then normal seasonal flu, but not as high as the 1918-1919 pandemic.

Diagnosis

Lab Diagnosis

Patients with symptoms suggesting H1N1 flu should have respiratory swab for influenza testing obtained and placed in a refrigerator (not a freezer). Swabs are usually obtained from the nasopharynx, though throat swabs, nasal wash or aspirate or bronchial wash or aspirate specimens are also suitable. Dacron or polyester-tipped swabs should be used. Cotton tipped swabs are not advised. Calcium alginate swabs are unacceptable. Ideally, the specimen should be placed in a collection vial containing viral transport media. A specimen that is unsubtypable influenza A will be sent by the lab to the Viral Surveillance and Diagnostic Branch of the CDC’s Influenza Division for further diagnostic testing. Rapid diagnostic tests have already been developed and distributed to state health departments by the CDC, based on real-time reverse transcriptase (RT)-PCR. Test results can be available within several hours.

Case Definitions

The CDC has the following case definitions for H1N1 flu: A confirmed case of H1N1 influenza A virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed Influenza A H1N1 virus infection at CDC by one or more of the following tests:

  1. real-time RT-PCR
  2. viral culture

A probable case of Influenza A H1N1 virus infection is defined as a person with an acute febrile respiratory illness who is:

  • positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or
  • positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case

A suspected case of Influenza A H1N1 virus infection is defined as a person with acute febrile respiratory illness with onset

  • within 7 days of close contact with a person who is a confirmed case of Influenza A H1N1 virus infection, or
  • within 7 days of travel to community either within the United States or internationally where there are one or more confirmed Influenza A H1N1 cases, or
  • resides in a community where there are one or more confirmed Influenza A H1N1 cases.[35]

Infectious period for a confirmed case of Influenza A H1N1 virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset.

Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of Influenza A H1N1 virus infection during the case’s infectious period.

Treatment

There are four influenza antiviral drugs approved for use in the United States (oseltamivir, zanamivir, amantadine and rimantadine). The Influenza A H1N1 virus that has been detected in humans in the United States and Mexico are resistant to amantadine and rimantadine so these drugs will not work against the Influenza A H1N1 virus. Laboratory testing on Influenza A H1N1 so far indicate that they are susceptible (sensitive) to neuraminidase inhibitor class of drugs, oseltamivir and zanamivir. Resistance to Tamiflu has been reported in patients from Denmark, Japan, Hong Kong, Canada, and the US (as of 8/11/2009).[36], [37], [38], [39]

Treatment for High Risk People:

For pregnant and other high-risk individuals, antiviral drugs should be started as soon as possible, and should be started within 48 hours of symptoms to be most effective. The drugs may make your illness milder and help you feel better faster. They may also prevent serious influenza complications, like pneumonia.

Because most of the illness in patients who are not considered “high risk” has been mild and self-limited, the CDC and WHO have revised their guidelines. They note that “persons with suspected novel H1N1 influenza who present with an uncomplicated febrile illness typically do not require treatment.” [40]

Priority access to antivirals should be given to patients at increased risk of complications due to underlying health problems and to hospitalized patients. Zanamivir (Relenza) or oseltamivir (Tamiflu) should be given for 5 days.

Treatment is recommended for:

  • Children younger than 5 years of age (particularly those less than 2 years of age)
  • Individuals 65 years of age or older
  • Individuals younger than 19 years of age who are receiving long-term aspirin therapy and who therefore might be at risk for Reye syndrome after influenza virus infection
  • Pregnant women
  • Individuals with chronic medical conditions requiring ongoing medical care, including:
    • Chronic pulmonary disease, including asthma (particularly if systemic glucocorticoids have been required during the past year)
    • Cardiovascular disease, except isolated hypertension
    • Active malignancy
    • Chronic renal insufficiency
    • Chronic liver disease
    • Diabetes mellitus
    • Hemoglobinopathies such as sickle cell disease
    • Immunosuppression, including HIV infection (particularly if CD4 <200 cells/microL), organ or hematopoietic stem cell transplantation, inflammatory disorders treated with immunosuppressants
  • Individuals who have any condition that can compromise handling of respiratory secretions (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, neuromuscular disorders, cerebral palsy, metabolic conditions)
  • Children with an underlying metabolic disorder, such as medium-chain acyl-CoA dehydrogenase deficiency, who are unable to tolerate prolonged fasting
  • Children with poor nutritional and fluid intake because of prolonged vomiting and diarrhea
  • Residents of nursing homes and other chronic care facilities [41]

Antiviral doses recommended for treatment of Influenza A H1N1 virus infection in adults or children 1 year of age or older are the same as those recommended for seasonal influenza and are available from the CDC.[42]

Antivirals

Each antiviral medication has pros and cons. The advantage of Oseltamivir (Tamiflu) is that it is administered orally and gives higher systemic levels. Oseltamivir is therefore the recommended treatment for lower respiratory tract complications. In contrast, Zanamivir (Relenza) is delivered by oral inhalation with low systemic absorption. The main side effect is that inhaled zanamivir has been temporally associated with bronchospasm and therefore patients with pre-existing airway disease (asthma or COPD) appear to be at increased risk for this severe adverse reaction.

Additionally, influenza A (H1N1) virus is resistant to amantadine and rimantadine. Therefore, where oseltamivir-resistant seasonal H1N1 influenza A virus is known to be circulating, Zanamivir is preferentially recommended.[43]

Video at YouTube
This video discusses the use of antiviral drugs for treating and preventing the H1N1 flu virus.


Treatment in Pregnancy

Cases of H1N1 influenza have been reported in pregnancy in the United States (Novel Influenza A (H1N1) Virus Infections in Three Pregnant Women --- United States, April--May 2009). With seasonal influenza, pregnant women are at increased risk of complications such as respiratory failure. It is now known that pregnant women with H1N1 infections are at higher risk of complications. Pregnant women who become ill with flu-like symptoms should contact their health care worker early in the course of illness to confirm the diagnosis of influenza and to determine if antiviral medications are indicated. The CDC is preferentially recommending oseltamivir at this time, because its systemic absorption may provide better protection against mother-to-child transmission.[44] Treatment should preferably be initiated within 48 hours of symptom onset but should be started even if later in the case of pregnant women. A 5 day course is recommended. Pregnant women with exposure to confirmed, probable, or suspected H1N1 influenza should consider taking a preventative course of oseltamivir or zanamivir for 10 days.[45] Illness with influenza is NOT a contraindication to nursing. Furthermore, pregnancy or nursing are NOT contraindications to taking antiviral zanamivir or oseltamivir.[46]

Fever

In addition to antiviral therapy, fever in pregnancy should be treated with acetaminophen to reduce the risk of complications for the infant—birth defects if fever occurs during the first trimester or, neonatal seizures, encephalopathy, cerebral palsy, and neonatal death if the fever occurs during labor.[47]

Antibiotics

Breastfeeding

Breastfeeding is acceptable in women affected by the H1N1 virus. Maternal antibodies may confer immunity to the breastfeeding neonate. However, current (8/11/09) recommendations are that the ill patient should consider avoiding close contact with her newborn until she has received antiviral medications for 48 hours, her fever has resolved, and she can control coughs and secretions. During this period, the newborn should be cared for in a separate room by another person who is well, and the patient should be encouraged to express her milk to be given to the newborn by a well individual. (See "#Breastfeeding" below). Once the patient begins contact with her newborn, she should be encouraged to wear a facemask, change to a clean gown or clothing, adhere to strict hand hygiene and cough etiquette, and begin breastfeeding, if possible. Protective measures should be continued for at least seven days after the onset of influenza symptoms; these measures might need to be continued until the patient is free of symptoms for 24 hours.[48]

Prevention: Antiviral drugs can also be given prophylactically, i.e., to prevent influenza when they are given to a person who is not ill, but who has been exposed to flu. When used to prevent the flu, these drugs are about 70% to 90% effective. The duration of treatment will vary depending on the person's health, or whether there is ongoing exposure, for example. Post-exposure prophylaxis is currently recommended only for those patients with underlying diseases or pregnancy. Post-exposure chemoprophylaxis is generally given for 10 days after the last known exposure to an ill confirmed case of swine flu.

Because of the concern that pregnant women may have a more severe illness, the CDC recommends that pregnant women who are in close contact with a confirmed, probable, or suspected case-patient receive a 10-day prophylactic course of antivirals.[49]

Vaccines:

The "flu shot" is intended to prevent seasonal influenza. It will not protect against 2009 Influenza A H1N1 flu.

No vaccine is yet available to prevent this disease. In testimony before Congress on 4/30/09, CDC and FDA officials projected that 600 million doses of an egg-based vaccine against 2009 Influenza A H1N1 could be available within 6 months.[50] After a new virus is identified, the seed strain is grown with a standard strain and attenuated in eggs. The virus is harvested from the egg whites and then killed with chemicals, and the outer proteins, or antigens, are further purified. The vaccine is then tested: a) for sterility, b) to confirm the protein concentration and ,c) for safety by testing in animals,before being tested in people.

Because the seasonal influenza vaccine has to be newly developed and produced each year, there is considerable experience with the development and production process. Nonetheless, the process takes a minimum of 6 months.[51] An H1N1 vaccine should be available by fall, 2009. Clinical trials of the new H1N1 vaccine began on 8/10/09 in the US. It can be given at the same time as the regular, seasonal "flu shot,” but it is anticipated that the new vaccine will require two separate injections.

Priorities in vaccination:

Because there will initially be limited supplies of vaccine, the CDC’s Advisory Committee on Immunization Practices (ACIP) has prioritized who should receive the vaccine as it becomes available. These key populations include pregnant women, people who live with or care for children younger than 6 months of age, healthcare and emergency services personnel, persons between the ages of 6 months and 24 years old, and people ages of 25 through 64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems. Current studies indicate the risk for infection among persons age 65 or older is less than the risk for younger age groups. Therefore, as vaccine supply and demand for vaccine among younger age groups is being met, programs and providers should offer vaccination to people over the age of 65.[52] One concern is the shortened development time available for vaccine production and testing. Between 409,000 to 970,000 people would need to be vaccinated to detect a risk at a level similar to that of the increased Guillain-Barre incidence that was associated with the 1976 immunization campaign for swine flu.[53]

This short video will help you understand how flu vaccines are made, why manufacturing and shipping vaccine take so long, and how you can find flu vaccines near you.

Video at YouTube

Warning

Do not give aspirin (acetylsalicylic acid) to children or teenagers who have the flu; this can cause serious and possibly fatal Reye’s syndrome.[54] NSAIDS (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil, and other) and naproxen (Aleve, Naprosyn, Anaprox and other), and acetominophen [Tylenol] are safe for symptomatic relief.


Controversy

  • Transmission

Seasonal influenza is thought to be spread primarily by droplets and therefore the CDC has previously advised regular masks or other avoidance of surfaces contaminated by droplets as standard preventive measures.[55]

Despite this, current H1N1 flu recommendations by many experts include airborne precautions in addition to contact precautions and the use of N-95 respirators rather than masks in healthcare settings, in particular, until more is known about the transmission of the H1N1 influenza A virus.[56]

  • Travel advisories

For updated information about travel advisories, see the United States Centers for Disease Control and Prevention website (http://wwwn.cdc.gov/travel/) and/or the World Health Organization website (http://www.who.int/csr/disease/swineflu/en/index.html).

There has been conflicting news about air travel. On the one hand some countries are urging travel bans or warnings, especially to Mexico. More commonsense recommendations have been given by experts such as Dr. Richard Wenzel. He noted, “that to put the influenza outbreak and air travel issue into perspective, if this were January and the US were in the midst of a widespread seasonal flu epidemic, no one would be talking about avoiding air travel or subways.

"This flu has an exotic name and origin, and diseases with exotic names and origins sometimes create extreme reactions," said Wenzel, who is chair of internal medicine at Virginia Commonwealth University in Richmond. "It creates a fear above and beyond the familiar."

Influenza spreads mostly through large droplets, which would typically spread within a foot or two of an infected traveler, Wenzel said, adding that newer, larger airliners generally recirculate about 50% of the air, which is generally clean and circulates in a laminar (top to bottom), unidirectional pattern.”[57]

  • Masks

“A surgical or procedure mask should be worn by health-care personnel who are in close contact (i.e., within 3 feet) with a patient who has symptoms of a respiratory infection, particularly if fever is present, as recommended for standard and droplet precautions.”[58]

“If supplies of N95 (or higher) respirators are not available, surgical masks can provide benefits against large droplet exposure, and should be worn for all health care activities for patients with confirmed or suspected pandemic-influenza.”[59]

Use of N-95 respirators are being recommended by the CDC until more is known about transmission of this new H1N1 flu.

Surgical masks have been distributed by the Mexican government to the public, and use has been widespread.

In contrast, the United Kingdom’s Health Protection Agency, recommends against mask use by the public.[60]

  • Mask efficacy studies

There have been two recent studies of the efficacy of masks in preventing viral transmission.

MacIntyre et. al. conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in Australian households during the 2006 and 2007 winter seasons. Intent to treat analysis showed no significant differences between the groups, but compliance with use of face masks was poor--<50% reported using the masks most of the time. The authors conclude however, that results would be expected to be better during an influenza pandemic, as there would be a higher perception of risk. They also observe, “During the height of the SARS epidemic of April and May 2003 in Hong Kong, adherence to infection control measures was high; 76% of the population wore a face mask, 65% washed their hands after relevant contact, and 78% covered their mouths when sneezing or coughing (28).” They estimate that there would be a relative reduction in risk of 60-80% with adherent mask use.[61] Cowling et. al. also conducted a randomized prospective trial, and also found that compliance with mask use was poor, meaning that conclusive recommendations were not possible. [62]

Recent news

  • Human transmission to swine

Preliminary reports suggest that the new H1N1 influenza virus has been transmitted from a farm worker in Alberta, Canada, to a herd of swine. The worker had developed a flu-like illness after traveling to Mexico in mid-April. He had contact with the pigs on April 14; 10% of the herd were noted to be ill on April 24. All involved are said to be recovering. The herd is quarantined. Transmission of flu from humans to pigs has occurred previously.[63] The major concern is whether infections in swine with this human H1N1, rather than the typical swine flu strains, will lead to reassortment of the different strains of influenza.

  • Antivirals

Which antiviral should be used, Relenza or Tamiflu?

According to a new study in PLOS, mathematical modeling by researchers at Harvard and the University of Hong Kong suggest that Relenza be used as first line therapy at this time, to reduce the likelihood of resistance to Tamiflu, which is in greater supply. Treating as few as 1% of patients with Relenza could significantly delay the emergence of resistance to Tamiflu. [64]Videos of the simulation are available at the site.[65]

  • Why has the illness been more severe in Mexico?

The initial H1N1 flu infections have been more severe in Mexico than in the US or other countries. There are several hypotheses: Malnutrition may be more widespread in the affected Mexican areas. There may be co-infections there with other organisms, resulting in more severe illness. Air pollution in Mexico city is a significant problem. Access to health care may be more limited or more delayed.

One striking feature in Mexico was that the mortality was highest in young adults, rather than in young children or the elderly, as with seasonal flu.[66] This pattern has been seen with deaths from Avian influenza as well, and in the 1918-1919 Spanish influenza epidemic. One hypothesis is that this is perhaps due to a more robust immunological response in young adults, called “cytokine storm,” and that the higher mortality is due to the inflammatory response to the infection rather than the infection itself. [67]


Epidemiology

Outbreaks

The current swine flu outbreak was detected in April, 2009. It appears that Mexico is the epicenter of the outbreak.

An association of influenza and pigs was noted in the 1918 pandemic; swine flu isolation from a human was identified first in 1974. An outbreak of swine influenza virus caused a respiratory illness among 13 soldiers in Fort Dix, New Jersey; no exposure to pigs was found there.

Regularly updated counts of U.S. human cases, are available at the CDC website at www.cdc.gov/swineflu/[68].

As of June 25, 2009, there have been almost 28,000 cases in the U.S., roughly half of the world's total, with 3065 hospitalizations and 127 deaths. Mathematical modeling from the CDC suggests that the new Influenza A (H1N1) has infected as many as 1 million in the U.S., and that 6% of some urban populations may have been infected.[69], [70]

Updated counts of international human cases, are available at the WHO website at http://www.who.int/csr/disease/swineflu/en/index.html [www.who.int/csr/disease/swineflu/en/index.html].

HealthMap is a reliable source of information with a frequently updated map showing the status of swine flu infections graphically.[71]

On June 11, 2009, the World Health Organization raised the threat level of Influenza H1N1 to Level 6, the highest alert level.[72] The announcement acknowledged that there is a pandemic, or widespread outbreaks of Influenza H1N1 throughout the world, underway.

Phase Description
Phase 1 No viruses in animals are found to have infected people.
Phase 2 Potential pandemic-an influenza virus in animals has infected people.
Phase 3 Limited human-to-human transmission, with isolated cases or small clusters of cases.
Phase 4 Sustained human-to-human transmission, able to cause community level outbreaks, with increased risk of a pandemic.
Phase 5 Widespread human-to-human infection, with spread to at least two countries in one region, indicating that a pandemic is imminent.
Phase 6 Widespread human infection with community level outbreaks in at least two regions; a pandemic is underway.
Post-Peak period This signifies that levels of disease appear to be dropping, but it is not yet known if there will be a recurrence, or second wave of infection. In previous pandemics, waves have occurred months after the initial outbreak.
Post-Pandemic period Influenza activity is back to its baseline seasonal level.

[73]

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Notable Experts

Organizations

World Health Organization (WHO, http://www.who.int/en/

Centers for Disease Control (CDC), http://www.cdc.gov/

Center for Infectious Disease Resource and Policy (CIDRAP) http://www.cidrap.umn.edu/

Infectious Diseases Society of America (IDSA) http://www.idsociety.org/


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External Links

World Health Organization (WHO)

Centers for Disease Control (CDC)

Center for Infectious Disease Resource and Policy (CIDRAP)

Infectious Diseases Society of America (IDSA)

International Society for Infectious Diseases

Influenza (Flu) Antiviral Drugs and Related Information (FDA)


Influenza Times & Swine Flu H1N1 News. http://knol.google.com/k/influenza-times-swine-flu-h1n1-news#

Influenza ( 2009 H1N1 ) " Swine Flu " Review. http://knol.google.com/k/influenza-2009-h1n1-swine-flu-review#

Influenza ( 2009 H1N1 ) Scientific & Medical Resources. http://knol.google.com/k/influenza-2009-h1n1-scientific-medical-resources#

Influenza ( 2009 H1N1 ) & Pregnancy: Vaccination and Treatment. http://knol.google.com/k/influenza-2009-h1n1-pregnancy-vaccination-and-treatment#

Peramivir: Rescue therapy during 2009 H1N1 Influenza Emergency. http://knol.google.com/k/peramivir-rescue-therapy-during-2009-h1n1-influenza-emergency#

Influenza ( 2009 H1N1 ) Vaccine Market. http://knol.google.com/k/influenza-2009-h1n1-vaccine-market#view

Influenza Antivirals Market 2009 http://knol.google.com/k/influenza-antivirals-market-2009#

Medpedia-logo.gif The basis of this article is contributed from Medpedia.com These articles are licensed under the GNU Free Documentation License It may have since been edited beyond all recognition. But we thank Medpedia for allowing its use.
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