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Friday, December 26, 2014

Influenza and Ebola - unrelated viruses but spreading infections

Finding Perspective: Influenza in the Shadow of Ebola

http://www.medscape.org/viewarticle/836401?src=wnl_cme_revw

Each year, an estimated 200,000 Americans are hospitalized for influenza and its complications; in 2014, 4 persons were hospitalized with Ebola. Influenza kills an average of 20,000 Americans each year, ranging from 3300 in a year with mild H1N1 infections to 49,000 in a year with severe H3N2 infections; 2 died of Ebola in the United States from the virus contracted in Africa.


As of December 4, 2014, Guinea, Liberia, and Sierra Leone have documented more than 17,000 cases and more than 6100 deaths. These figures almost certainly underestimate the true impact, and the unfolding tragedy in West Africa is far from over. Although signs of progress have appeared at long last -- the number of new cases is stable in Guinea and falling in Liberia -- the epidemic continues in Sierra Leone, and new foci have appeared in Guinea and Liberia. As long as the epidemic continues, so will the risk of spread to other resource-poor countries.

Medscape asked infectious disease expert Andrew T. Pavia of the University of Utah to provide perspective to emergency medicine physicians and nurses and other healthcare workers who see patients with influenza-like symptoms regarding the risk of Ebola virus disease and influenza. 

Cases of a potentially lethal viral diseases are increasing rapidly in the United States. Patients with high fevers crowd emergency departments and hospitals. Seven children have died between late September and December 6, 2014.[1]A mutated strain has been detected that may reduce vaccine effectiveness and worsen the epidemic.

This bad news about influenza arises in the midst of the largest outbreak of Ebola virus disease in history. As of December 4, 2014, Guinea, Liberia, and Sierra Leone have documented more than 17,000 cases and more than 6100 deaths. These figures almost certainly underestimate the true impact, and the unfolding tragedy in West Africa is far from over. Although signs of progress have appeared at long last -- the number of new cases is stable in Guinea and falling in Liberia -- the epidemic continues in Sierra Leone, and new foci have appeared in Guinea and Liberia. As long as the epidemic continues, so will the risk of spread to other resource-poor countries.

A small number of patients have acquired Ebola in Western countries or have been evacuated to Western countries for care. A nursing assistant in Spain was infected while caring for a dying priest evacuated from West Africa and recovered. Four cases have occurred in the United States -- 2 imported and 2 acquired domestically. In Dallas, Ebola was diagnosed in a Liberian man on September 30, 2014, and 2 nurses who provided intensive care for him before his death became infected. 

An American doctor became ill in New York City after returning from caring for Ebola patients in Guinea. The Liberian man died but the other 3 patients recovered, and none of the several hundred potential contacts, including the Liberian man’s family, have been infected.
A Public's Unhealthy Response

The somewhat dramatic and feverish response of the public and the media to the domestic Ebola cases peaked in October 2014, a time when physicians, nurses, and public health officials typically focus efforts on improving influenza awareness and immunization rates. In October, a Harvard School of Public Health poll reported that more than half of respondents were concerned there would be a large outbreak of Ebola in the United States, and almost 60% believed that sneezing and coughing readily spread Ebola.[2] In contrast, influenza was met with a yawn.

The reasons for this disparate response are not entirely clear. Ebola is an exotic threat and most Americans had previously paid no attention to it. Ebola virus disease is often lethal with a case fatality rate of more than 50%. However, the media response was nonstop and breathless. Politicians looking to the upcoming election inserted themselves into discussions of public health response. Some thoughtful voices, as well as accurate and informative reporting, were heard, but they were overwhelmed. Public health officials did not adequately prepare the public for the possibility that recommendations might be adjusted as the epidemic unfolded. Together, these factors may have fed into the public’s distrust of authority. But the public reaction in October also highlighted the less-than-rational -- yet very human -- way that we tend to think about risk. We overestimate the risk of rare or novel events. In contrast, we seem more likely to minimize risk that is familiar. 

We drive too fast and with our cell phones in use, and we ignore advice to exercise and eat sensibly; then, we obsess about plane crashes, terrorist attacks, and Ebola. Influenza clearly is a familiar threat, and we seem to be more comfortable with that threat.
Compare and Contrast

Healthcare providers also can sometimes focus on novel and emerging threats while minimizing those that are familiar. 

It is informative, then, to directly compare features of the 2 diseases from a US perspective. Each year, an estimated 200,000 Americans are hospitalized for influenza and its complications; in 2014, 4 persons were hospitalized with Ebola. Influenza kills an average of 20,000 Americans each year, ranging from 3300 in a year with mild H1N1 infections to 49,000 in a year with severe H3N2 infections; 1 has died of Ebola in the United States.[3,4]Thus, an American is more than 10,000 times more likely to die from influenza in the coming year than from Ebola.

Influenza is readily spread via large droplets and contaminated surfaces, aided by sneezing and coughing. Patients with influenza are infectious at least 24 hours before symptoms begin. In contrast, Ebola virus is spread via direct contact with infected blood and body fluids. There is no evidence of presymptomatic shedding or transmission, and virus is not detectable in blood until after symptoms begin. In fact, virus may not be detectable in some patients during the first 24 to 72 hours after symptom onset.[5]

Important potential overlaps exist in the presentations of the 2 diseases. As influenza begins to surge in the United States and the Ebola outbreak continues in West Africa, the public may become anxious and hospital emergency departments challenged. Both diseases begin with fever -- often high -- associated with myalgia, weakness, or headache. Onset of influenza is often sudden, whereas Ebola gradually worsens over several days. Vomiting and diarrhea are prominent symptoms later in Ebola infection but variably present early in disease; these can occasionally be seen with influenza.[6] Cough and sore throat are prominent features of influenza; sore throat can also occur with Ebola, but cough is uncommon until very late in disease. A moderately effective vaccine and antiviral agents are available for influenza. To date, similar countermeasures have not yet been demonstrated to be effective for Ebola.

Exposure history is the critical distinguishing factor.[7] Epidemiologic risk factors for Ebola include travel to an Ebola-affected country within the past 21 days or contact with blood or body fluids of an Ebola patient. Interestingly, 75% of inquiries to the CDC for Ebola testing in October were for persons with no identified risk factor. Since October 27, the CDC and state and local health departments have implemented risk-stratified active monitoring of all persons arriving from Ebola-affected countries. This means that most persons with risk factors who develop symptoms will have contacted the health department and be referred and transported to a hospital following protocols for persons under investigation (PUI) for Ebola.
The Influenza Situation

While this program of active monitoring will likely lessen the burden of unanticipated Ebola evaluations, recent surveillance data raise the real possibility that this will be a severe influenza season. Influenza cases are increasing rapidly in many regions of the country, and most isolates are influenza A (H3N2) with a small number of influenza B. In seasons where influenza A (H3N2) predominates, illness is typically more severe with higher rates of hospitalization and death, especially among the very young, older persons, and those at higher risk of complications from influenza because of immunosuppression and underlying medical conditions, including morbid obesity and pregnancy. In addition, more than 50% of H3N2 strains characterized by early December were antigenically different or “drifted” from the H3N2 strain used to produce the 2014-2015 vaccine. This type of mismatch occurs approximately every 10 years and results from having to select strains for the coming season’s vaccine many months in advance, typically during the preceding February. The drifted strain (A/Switzerland/9715293/2013) was first detected in very small numbers in March. The drifted strain makes it likely that vaccine effectiveness will be substantially lower this year than the average effectiveness of approximately 60%.
MANAGING THE GREATER THREAT

Although vaccine effectiveness for the current influenza season is likely to be less than optimum, it is still wise to encourage the use of influenza vaccine. All influenza B strains and 48% of influenza A (H3N2) strains are well matched to the vaccine, and the degree of cross-protection that the vaccine provides for drifted strains is unknown. There may also be some benefit by reducing febrile illness in a person for whom the presence of fever might prompt concern about Ebola, such as those with known exposure.
Antivirals

Antiviral medications can be an important adjunct to immunization in reducing the effect of influenza, and clinicians should be familiar with the benefits of antiviral medications for influenza and recommendations for their use.[9] The clinical benefit of antivirals is greatest when administered early, ideally within 48 hours of symptom onset. This is particularly true for otherwise healthy outpatients, because clinical trials have not shown any benefit from delayed antiviral therapy. There is, however, substantial evidence from observational studies of benefits from antiviral use for hospitalized patients or those with severe or progressive illness even when started more than 48 hours after illness onset.[10,11] It is important to educate patients at high risk of influenza complications to contact you or to seek care promptly if they develop symptoms of influenza.

Clinical trials in predominantly healthy adults and children demonstrated reductions of 1 to 1.5 days in total symptom duration and a modest reduction in otitis media and lower respiratory tract illness. No robust data from randomized trials address the effectiveness of antivirals in patients with more severe illness or at higher risk for complications. A large body of observational data has demonstrated benefits among hospitalized and severely ill patients, including reductions in intensive care unit admissions and mortality.[12-16]

CDC recommendations for using antiviral drugs emphasize early empiric use in patients at greatest risk of complications and most likely to have substantial benefits. Patients include those who are hospitalized or have severe progressive disease, as well as persons at increased risk for complications of influenza because of age (younger than 2 years or 65 years or older) or who have chronic pulmonary, cardiac, renal, metabolic, hematologic, or neurologic disorders. [See CDC Recommendations for Antiviral Use, below.] Others at increased risk include pregnant or postpartum women, those who are immunosuppressed due to medication or HIV infection, those who are morbidly obese, American Indian and Alaska native persons, and residents of nursing homes.

Initiating antiviral therapy in high-risk patients should not wait for laboratory confirmation of influenza. Rapid antigen detection tests (RIDTs) can give rapid results but have relatively low sensitivity. False-negative results are common when the probability of influenza is high, and a negative RIDT does not exclude influenza. One rapid molecular test for influenza and one rapid multiplex platform are currently FDA approved that can provide results within 1 to 2 hours with high sensitivity, but these may not be widely available.

The recommended drugs are the neuraminidase inhibitors oral oseltamivir and inhaled zanamivir. Oseltamivir is approved for treatment of people 2 weeks of age and older, while zanamivir is approved for those 7 years and older. Oseltamivir resistance has been problematic in strains of H1N1 circulating before 2009 and the development of resistance during treatment has occurred, especially among severely immunosuppressed patients. To date, oseltamivir resistance has been fairly rare with H3N2 strains.
Keeping Perspective

Emerging infections continue to threaten and surprise us. Influenza is both an old and familiar illness and an unpredictable emerging infection. Our current diagnostic tests, vaccines, and antivirals are far from perfect, but their effective use can have a major impact on our care of patients while we await better tools.

CDC Recommendations for Antiviral Use

Clinical benefit is greatest when antiviral treatment is administered early. When indicated, antiviral treatment should be started as soon as possible after illness onset, ideally within 48 hours of symptom onset. However, antiviral treatment might still have some benefits in patients with severe, complicated, or progressive illness and in hospitalized patients when started after 48 hours of illness onset.

Antiviral treatment with oseltamivir or zanamivir is recommended as early as possible for any patient with confirmed or suspected influenza who:
is hospitalized;
has severe, complicated, or progressive illness; or
is at higher risk for influenza complications. This list includes:
children aged younger than 2 years;
adults aged 65 years and older;
persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic disorders (including diabetes mellitus), or 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 [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury);
persons with immunosuppression, including that caused by medications or by HIV infection;
women who are pregnant or postpartum (within 2 weeks after delivery);
persons aged younger than 19 years who are receiving long-term aspirin therapy;
American Indians/Alaska Natives;
persons who are morbidly obese (ie, body mass index is equal to or greater than 40); and
residents of nursing homes and other chronic-care facilities.

Clinical judgment, on the basis of the patient’s disease severity and progression, age, underlying medical conditions, likelihood of influenza, and time since onset of symptoms, is important when making antiviral treatment decisions for high-risk outpatients. Decisions about starting antiviral treatment should not wait for laboratory confirmation of influenza.

Oseltamivir is approved for treatment of influenza in persons aged 2 weeks and older and for chemoprophylaxis to prevent influenza in people 1 year of age and older, while zanamivir is approved for treatment of persons 7 years and older and for prevention of influenza in persons 5 years and older.

Antiviral treatment also can be considered on the basis of clinical judgment for any previously healthy, symptomatic outpatient who is not considered “high risk” with confirmed or suspected influenza, if treatment can be initiated within 48 hours of illness onset.

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