Global & Disaster Medicine

Archive for the ‘Influenza’ Category

Research that could make flu viruses more dangerous, and that the government suspended in 2014 because of safety concerns, has been approved to begin again.

NYT

“…..some scientists…oppose the research because they say it could create mutant viruses that might cause deadly pandemics if they were unleashed by lab accidents or terrorism……”

 


Influenza anti-virals

CDC

CDC recommends antiviral medications for treatment of influenza, regardless of a patient’s influenza vaccination status. Antiviral treatment has been shown to have clinical and public health benefit in reducing illness and severe outcomes of influenza based on evidence from randomized controlled trials, meta-analyses of randomized controlled trials, and observational studies during past influenza seasons and during the 2009 H1N1 pandemic [2–9]. Influenza antiviral medications are most effective in treating influenza and reducing complications when treatment is started early (within 48 hours of illness onset). However, some studies suggest clinical benefit among hospitalized patients and young children with febrile illness even when treatment starts three to five days after illness onset [10–16].

Recommendations

  1. All Hospitalized, Severely Ill, and High-Risk Patients with Suspected or Confirmed Influenza Should Be Treated with Antivirals
    Antiviral treatment is recommended as early as possible for any patient with suspected or confirmed influenza who:1) Is hospitalized—treatment is recommended for all hospitalized patients;2) Has severe, complicated, or progressive illness—this may include outpatients with severe or prolonged progressive symptoms or patients who develop complications such as pneumonia but who are not hospitalized;3) Is at high risk for influenza complications but not hospitalized—this includes
    1. Adults 65 years and older.
    2. Children younger than two years. Although all children younger than five years are considered at higher risk for complications from influenza, the highest risk is for those younger than two years.
    3. People with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic disorders (including diabetes mellitus).
    4. People with neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury).
    5. People with immunosuppression, including that caused by medications or by HIV infection.
    6. Women who are pregnant or postpartum (within two weeks after delivery).
    7. People younger than 19 years who are receiving long-term aspirin therapy.
    8. American Indians and Alaska Natives.
    9. People with extreme obesity (i.e., body-mass index is equal to or greater than 40).
    10. Residents of nursing homes and other chronic-care facilities.
  2. Antivirals in Non-High Risk Patients with Uncomplicated Influenza
    Antiviral treatment can benefit other individuals with influenza. While current guidance focuses on antiviral treatment of those with severe illness or at high risk of complications, antiviral treatment may be prescribed for any previously healthy (non-high risk) outpatient with suspected or confirmed influenza who presents within two days after illness onset. Clinical judgment—considering the patient’s disease severity and progression, age, likelihood of influenza, and time since onset of symptoms—is important when making antiviral treatment decisions for outpatients who are not at increased risk for influenza complications.
  3. Choice of Antiviral Medication
    Four influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2018-2019 influenza season. Three drugs are chemically related antiviral medications known as neuraminidase inhibitors that block the viral neuraminidase enzyme and have activity against both influenza A and B viruses: oral oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), inhaled zanamivir (trade name Relenza®), and intravenous peramivir (trade name Rapivab®). The fourth drug is oral baloxavir marboxil (trade name Xofluza®), which is active against both influenza A and B viruses but has a different mechanism of action. Baloxavir is a cap-dependent endonuclease inhibitor that interferes with viral RNA transcription and blocks virus replication. Recommended ages for treatment and prevention with antiviral medications are summarized in the table below. Dosing and more detailed treatment considerations can be found in the Summary of Influenza Antiviral Treatment Recommendations for Clinicians (http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm).
  4. Antiviral Route Treatment Chemoprophylaxis Most Common Adverse Events (Recommended Age)
  5. Oseltamivir oral and enteric any age >3 months nausea, vomiting, headache*
  6. Zanamivir inhaled >7 years >5 years bronchospasm
  7. Peramivir intravenous >2 years n/a diarrhea
  8. Baloxavir oral >12 years n/a none more common than placebo *Nausea and vomiting are generally transient and can be mitigated if oseltamivir is taken with food n/a = not applicable
  9. For outpatients with acute uncomplicated influenza, oral oseltamivir, inhaled zanamivir, intravenous peramivir, or oral baloxavir may be used for treatment.
    The recommended treatment course for uncomplicated influenza is
    • Two doses per day of oral oseltamivir for five days, or
    • Two doses per day of inhaled zanamivir for five days, or
    • One dose per day of intravenous peramivir for one day, or
    • One dose per day of oral baloxavir for one day.
    • Oral or enterically-administered oseltamivir is the only recommended antiviral medication for treatment of hospitalized patients with suspected or confirmed influenza and patients with severe or complicated illness with suspected or confirmed influenza (e.g., pneumonia, exacerbation of underlying chronic medical condition) who are not hospitalized.  There are insufficient data for inhaled zanamivir, intravenous peramivir, and oral baloxavir in patients with severe influenza disease.
    • Oral oseltamivir is preferred for treatment of pregnant women. Pregnant women are recommended to receive the same antiviral dosing as non-pregnant people. Baloxavir is not recommended for the treatment of pregnant women or breastfeeding mothers, as there are no available efficacy or safety data.
  10. Timing of Treatment and Implications for Patient Evaluation, Treatment, and Testing
    Clinical benefit is greatest when antiviral treatment is administered as early as possible after illness onset. Therefore, antiviral treatment should be started as soon as possible after illness onset and should not be delayed, even for a few hours to wait for the results of testing. Ideally, treatment should be initiated within 48 hours of symptom onset. However, antiviral treatment initiated later than 48 hours after illness onset can still be beneficial for some patients. Because of the importance of early treatment, decisions about starting antiviral treatment should not wait for laboratory confirmation of influenza. Therefore, empiric antiviral treatment should be initiated as soon as possible when there is known influenza activity in the community. A history of current season influenza vaccination does not exclude a diagnosis of influenza in an ill child or adult. High-risk patients should be advised to call their provider promptly if they have symptoms of influenza.

References

  1. Belongia EA, Simpson MD, King JP, et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis 2016; 16:942–951. https://www.sciencedirect.com/science/article/pii/S1473309916001298?via%3DihubExternal
  2. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med 2018; 379:913–923. https://www.nejm.org/doi/full/10.1056/NEJMoa1716197External
  3. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis 2018; 68:e1–e47. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciy866External
  4. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. The Lancet 2015; 385:1729–1737. https://www.sciencedirect.com/science/article/pii/S0140673614624491?via%3DihubExternal
  5. Malosh RE, Martin ET, Heikkinen T, Monto AS, Brooks WA, Whitley RJ. Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual Patient Data Meta-analysis of Randomized Controlled Trials. Clin Infect Dis 2018; 66:1492–1500. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cix1040External
  6. Hsu J, Santesso N, Brozek J, et al. Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies. Influenza Other Respir Viruses 2013; 7 Suppl 2:76–81. https://onlinelibrary.wiley.com/doi/full/10.1111/irv.12085External
  7. Doll MK, Winters N, Kraicer-Melamed H, Boikos C, Quach C, Gore G. Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: a systematic review of systematic reviews and/or meta-analyses. J Antimicrob Chemother 2017; 72:2990–3007. https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkx271External
  8. Venkatesan S, Myles PR, Leonardi-Bee J, et al. Impact of Outpatient Neuraminidase Inhibitor Treatment in Patients Infected With Influenza A(H1N1)pdm09 at High Risk of Hospitalization: An Individual Participant Data Metaanalysis. Clin Infect Dis 2017; 64:1328–1334. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cix127External
  9. Muthuri SG, Venkatesan S, Myles PR, et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2014; 2:395–404. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(14)70041-4/fulltextExternal
  10. Lee N, Choi KW, Chan PKS, et al. Outcomes of adults hospitalised with severe influenza. Thorax 2010; 65:510–515. https://thorax.bmj.com/content/65/6/510External
  11. Lee N, Cockram CS, Chan PKS, Hui DSC, Sung JJY, Choi KW. Antiviral Treatment for Patients Hospitalized with Severe Influenza Infection May Affect Clinical Outcomes. Clin Infect Dis 2008; 46:1323–1324. https://academic.oup.com/cid/article/46/8/1323/364997External
  12. Lee EH, Wu C, Lee EU, et al. Fatalities Associated with the 2009 H1N1 Influenza A Virus in New York City. Clin Infect Dis 2010; 50:1498–1504. https://academic.oup.com/cid/article/50/11/1498/507049External
  13. Louie JK, Yang S, Acosta M, et al. Treatment With Neuraminidase Inhibitors for Critically Ill Patients With Influenza A (H1N1)pdm09. Clin Infect Dis 2012; 55:1198–1204. https://academic.oup.com/cid/article/55/9/1198/435273External
  14. 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. https://academic.oup.com/cid/article/45/12/1568/303324External
  15. Siston AM, Rasmussen SA, Honein MA, et al. Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States. JAMA 2010; 303:1517–1525. https://jamanetwork.com/journals/jama/fullarticle/185713External
  16. Fry AM, Goswami D, Nahar K, et al. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect Dis 2014; 14:109–118. https://www.ncbi.nlm.nih.gov/pubmed/2426859External

Antiviral agents

Antiviral RouteTreatmentChemoprophylaxisMost Common Adverse Events
(Recommended Age)
Oseltamiviroral and entericany age>3 monthsnausea, vomiting, headache*
Zanamivirinhaled>7 years>5 yearsbronchospasm
Peramivirintravenous>2 yearsn/adiarrhea
Baloxaviroral>12 yearsn/anone more common than placebo
*Nausea and vomiting are generally transient and can be mitigated if oseltamivir is taken with food n/a = not applicable

WHO launches new global influenza strategy

WHO

WHO launches new global influenza strategy

11 March 2019

News Release
Geneva

WHO today released a Global Influenza Strategy for 2019-2030 aimed at protecting people in all countries from the threat of influenza. The goal of the strategy is to prevent seasonal influenza, control the spread of influenza from animals to humans, and prepare for the next influenza pandemic.

“The threat of pandemic influenza is ever-present.” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “The on-going risk of a new influenza virus transmitting from animals to humans and potentially causing a pandemic is real.   The question is not if we will have another pandemic, but when.  We must be vigilant and prepared – the cost of a major influenza outbreak will far outweigh the price of prevention.”

Influenza remains one of the world’s greatest public health challenges. Every year across the globe, there are an estimated 1 billion cases, of which 3 to 5 million are severe cases, resulting in 290 000 to 650 000 influenza-related respiratory deaths. WHO recommends annual influenza vaccination as the most effective way to prevent influenza. Vaccination is especially important for people at higher risk of serious influenza complications and for health care workers.

The new strategy is the most comprehensive and far-reaching that WHO has ever developed for influenza.  It outlines a path to protect populations every year and helps prepare for a pandemic through strengthening routine programmes. It has two overarching goals:
 

  1. Build stronger country capacities for disease surveillance and response, prevention and control, and preparedness. To achieve this, it calls for every country to have a tailored influenza programme that contributes to national and global preparedness and health security.
  2. Develop better tools to prevent, detect, control and treat influenza, such as more effective vaccines, antivirals and treatments, with the goal of making these accessible for all countries.

“With the partnerships and country-specific work we have been doing over the years, the world is better prepared than ever before for the next big outbreak, but we are still not prepared enough,” said Dr Tedros. “This strategy aims to get us to that point. Fundamentally, it is about preparing health systems to manage shocks, and this only happens when health systems are strong and healthy themselves.”

To successfully implement this strategy, effective partnerships are essential.  WHO will expand partnerships to increase research, innovation and availability of new and improved global influenza tools to benefit all countries.  At the same time WHO will work closely with countries to improve their capacities to prevent and control influenza.

The new influenza strategy builds on and benefits from successful WHO programmes.  For more than 65 years, the Global Influenza Surveillance and Response System (GISRS), comprised   of WHO Collaborating Centres and national influenza centres, have worked together to monitor seasonal trends and potentially pandemic viruses. This system serves as the backbone of the global alert system for influenza.

Important to the strategy is the on-going success of the Pandemic Influenza Preparedness Framework, a unique access and benefit sharing system that supports the sharing of potentially pandemic viruses, provides access to life saving vaccines and treatments in the event of a pandemic and supports the building of pandemic preparedness capacities in countries through partnership contributions from industry.

The strategy meets one of WHO’s mandates to improve core capacities for public health, and increase global preparedness and was developed through a consultative process with input from Member States, academia, civil society, industry, and internal and external experts.

Supporting countries to strengthen their influenza capacity will have collateral benefits in detecting infection in general, since countries will be able to better identify other infectious diseases like Ebola or Middle East respiratory syndrome-related coronavirus (MERS-CoV).

Through the implementation of the new WHO global influenza strategy, the world will be closer to reducing the impact of influenza every year and be more prepared for an influenza pandemic and other public health emergencies.


2018-2019 Influenza Season Week 10 ending March 9, 2019: Influenza activity decreased slightly, but remains elevated in the United States.

CDC

INFLUENZA Virus Isolated

national levels of ILI and ARI

INFLUENZA Virus Isolated

Click on image to launch interactive tool

 


CDC estimates that, from October 1, 2018, through March 9, 2019, there have been:

person coughing icon25.5 million – 29.3 million flu illnesses

 

11.8 million – 13.8 million flu medical visits

 

 327,000 – 394,000 flu hospitalizations

 

 21,500 – 35,500 flu deaths

Preliminary Cumulative Estimates of Hospitalizations in the U.S. 2018-2019 Flu Season


2018-2019 Influenza Season Week 9 ending March 2, 2019: Influenza activity remains elevated in the United States.

CDC

“…..According to this week’s FluView report, overall influenza activity remains elevated and is similar to activity reported last week. 48 states and Puerto Rico continue to report widespread flu activity and 32 states are experiencing high influenza-like-illness (ILI) activity levels. While cumulatively influenza A(H1N1)pdm09 viruses remain predominant for this flu season, during the weekend ending March 2, influenza A(H3) were reported more frequently nationally for the second week. Severity indicators continue to increase as expected but remain substantially lower than what was observed last season. This week another eight flu-related pediatric deaths occurring during the 2018-2019 season were reported to CDC, bringing the total to 64 flu-related deaths for the season.

CDC expects flu activity to remain elevated for a number of weeks……”

INFLUENZA Virus Isolated

INFLUENZA Virus Isolated

Click on image to launch interactive tool


FDA’s Critical Role in Ensuring Supply of Influenza Vaccine

FDA

The flu vaccine you get at your doctor’s office or pharmacy is the year-round work of highly skilled microbiologists, epidemiologists, physicians and other public health experts.

Sound complicated? It is.

The U.S. Food and Drug Administration (FDA) and the U.S. Department of Health and Human Services (HHS) are working toward developing new and better technologies for producing flu vaccines. As new strains of flu viruses emerge, the FDA works in close coordination with sister agencies, such as the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), encouraging manufacturers to develop vaccines that will successfully protect us from influenza disease, which can be a very serious illness.

The more diverse the influenza vaccine supply, the better we can respond to flu public health emergencies in a timely manner. All U.S. licensed flu vaccines have been evaluated and determined to be safe and effective by the FDA.

There is often more than one type of influenza virus circulating each season, so influenza vaccines are formulated to target three or four of the most likely influenza viruses of the season: two influenza A types (H1N1 and H3N2) and one (trivalent vaccine formulation) or two (quadrivalent vaccine formulation) types of influenza B.

Influenza Vaccines and How They Are Made

Influenza (flu) vaccine works by triggering your immune system to produce antibodies that help the body prevent the flu.

Most of the U.S. influenza vaccine supply is made using an egg-based production process. In this method of making influenza vaccines, manufacturers use fertilized eggs to grow flu viruses. After about six months of laboratory work and manufacturing, those viruses are incorporated into that season’s flu vaccine. While this method produces safe and effective vaccines, FDA, HHS, and manufacturers have been working on different technologies to increase the influenza vaccine supply, making sure to still maintain safety and effectiveness. Some technologies have the potential to produce these vaccines faster and less labor-intensively.

For example, more recent approvals include influenza vaccines that do not use an egg-based production process for manufacturing. In addition, quadrivalent vaccines, which protect against two influenza A strains and two influenza B strains, have been available for several years. Quadrivalent vaccines provide protection against the two lineages of influenza B strains, both of which circulate each flu season. This is important, particularly for preschool and school-age children who get Influenza B more often than adults do. Influenza B also causes more complications and fatalities in children than adults.

In addition, the FDA has approved a high-dose and an adjuvanted vaccine specifically for people ages 65 and older, who typically bear the greatest burden of severe influenza disease and account for most of influenza-related hospitalizations and deaths. Adjuvants are incorporated into some vaccine formulations to enhance the immune response of the vaccinated individual.

Making the Flu Vaccine: A Year-Round Effort

The job of producing a new vaccine for the next flu season starts well before the current flu season ends. For the FDA, it’s a year-round initiative.

The composition of vaccines for the prevention of other infectious diseases stays the same year after year. In contrast, flu viruses are constantly evolving. And the flu viruses that circulate causing disease in people, often change from one year to another. So, every year, there is a need for a new flu vaccine. To that end, FDA, World Health Organization (WHO), CDC, and other partners collaborate by collecting and reviewing data on the circulating strains of influenza from around the world to identify those likely to cause the most illness in the upcoming flu season.

In late February/early March — well before the new flu season begins — an FDA advisory committee reviews data about which flu viruses have caused disease in the past year, how the viruses are changing, and disease trends so they can recommend the three or four flu strains to include in the trivalent and quadrivalent influenza vaccines for the U.S in the upcoming flu season.

Once the strains are selected, vaccine manufacturers begin the manufacturing process to include the newly selected flu strains in their FDA-approved vaccines. The different flu virus strains are combined to formulate the vaccine into standard dosages. The vaccine is then filled into vials, syringes and, for the nasal vaccine, sprayers. Both egg-based and non-egg-based manufacturing methods for FDA-approved flu vaccines require high-tech processes and manufacturing facilities that have been inspected by the FDA. Vaccine manufacturers must submit applications to the FDA to include the new flu strains in their FDA-approved vaccines.

In its own laboratories, the FDA also produces materials that are critical for making the vaccine. These include generating candidate vaccine virus strains suitable for further vaccine manufacture and producing the critical potency reagents, which are materials needed to test the vaccines for potency and identity (to ensure standardization) before the FDA approves the new formulation of the approved seasonal influenza vaccines for U.S. distribution.

The FDA is also responsible for ensuring that released lots of influenza vaccines meet appropriate standards. Each vaccine undergoes quality control tests, including testing for sterility. Manufacturers submit the results of their testing, along with sample vials from each lot to the FDA for “lot release.” The FDA typically begins releasing lots of flu vaccines in late summer. Lot release can continue into early fall. Once lots are released, manufacturers distribute the vaccine throughout the United States for use by the public.

Flu seasons and severity are unpredictable. Annual vaccination is the best way to prevent the flu for people ages 6 months and older.

An annual immunization with flu vaccine is the most effective and safest way for most of us to reduce our risk of getting the flu and spreading it to others. When more people get vaccinated, it is less likely that the flu viruses will spread through a community, making us all healthier.

Updated: March 1, 2019


2018-2019 Influenza Season Week 8 ending February 23, 2019: Influenza activity remains elevated in the United States.

CDC

INFLUENZA Virus Isolated

national levels of ILI and ARI

Click on graph to launch interactive tool

INFLUENZA Virus Isolated

Click on image to launch interactive tool


2018-2019 Influenza Season Week 7 ending February 16, 2019: Influenza activity continues to increase in the United States.

CDC

national levels of ILI and ARI

INFLUENZA Virus Isolated

Click on image to launch interactive tool


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