Influenza 流行性感冒 教材 -4

上接:   Influenza 流行性感冒 教材-3

^{Deterrence/Prevention of Influenza}

^{Influenza vaccine provides good protection against immunized strains. The vaccination becomes effective 10-14 days after administration. With regard to vaccine efficacy, historic studies[43] show 50-60% efficacy for strain A and 70% for strain B each year in preventing clinical symptoms of influenza. For example, the vaccine effectiveness for season the 2012-2013 predominate strain A (H3N2) was 55% and for strain B (H3N2) was 70%.[60]}

^{Each year in the United States, a vaccine that contains antigens from the strains most likely to cause infection during the winter flu season is produced. For the trivalent formulation influenza vaccines, two strains of influenza A and one of influenza B are included. The quadrivalent vaccines contain an additional influenza B strain.[61] The trivalent 2013-2014 northern hemisphere vaccine contains the following components:}

^{·        A/California/7/2009 (H1N1)-like (same strain as was used for 2009 H1N1 monovalent vaccines)}

^{·        A/Texas/50/2012 (H3N2), replaces A/Victoria/361/2011}

^{·        B/Massachusetts/2/2012-like (B/Yamagata lineage), replaces B/Wisconsin/1/2010-like}

^{The quadrivalent influenza vaccines contain the following additional B strain in addition to the 3 viral strains listed above:}

^{·        B/Brisbane/60/2008-like (B/Victoria lineage)}

^{The vaccine is available in a variety of dosage forms. The intramuscular injection contains 45 mcg of hemagglutinin of influenza per 0.5 mL and utilizes a 1- to 1.5-inch needle. A microinjection system for intradermal delivery (Fluzone Intradermal) features an ultrafine needle that is 90% shorter than the typical needle used for IM injections. The intradermal dosage form contains 27 mcg/0.1 mL of influenza hemagglutinin. In both younger and older adults, AS03 adjuvant system improves immune response to inactivated 2009 H1N1 influenza vaccine. AS03 adjuvant system is well tolerated.[62]}

^{Influenza vaccine is also available as a quadrivalent nasal spray (FluMist Quadrivalent) for healthy children aged 2 years or older, adolescents, and adults aged younger than 50 years. Clinical trials are limited in scope regarding the protective effects of live vaccine. The live virus is attenuated by cold; therefore, only very limited viral replication occurs at temperatures of more than 95°F.}

^{A recombinant trivalent vaccine (Flublok) is also available for adults aged 18 years through 49 years. It is made from HA proteins that are not derived from egg or chick embryo.}

^{Specific recommendations for individuals who should be immunized can be obtained from the CDC, which publishes regular updates of this information (see Seasonal Influenza Vaccination Resources for Health Professionals). Groups recommended for immunization include elderly individuals, those with certain chronic diseases, and health care workers. The vaccination of high-risk pregnant patients also provides some protective immunity for newborns and reduces subsequent hospitalizations in the infants.[63]}

^{A recent CDC analysis stresses the importance of vaccinating pregnant women regardless of trimester and prompt treatment with a neuraminidase inhibitor (ie, within 2 d of symptom onset) if influenza occurs during pregnancy.[51]}

^{It is safe to administer attenuated influenza vaccine in children with cancer.[64]}

^{Early use of glucocorticoids}

^{Although glucocorticoids increase the risk of developing critical disease from viral infections, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk. In one retrospective study from China the absolute risk increase was 32% for critical illness in patients who received steroids. Using glucocorticoids to reduce fever and prevent pneumonia increases the risk for critical disease or death from pH1N1 infection.[65]}

^{Prevention in elderly persons}

^{In order to improve the immunogenicity of influenza virus vaccine in elderly adults, a high-dose trivalent inactivated influenza vaccine has been developed. In a multicenter, randomized, double-blind controlled trial in elderly adults (≥65 y), a statistically significant increase in seroconversion rate was found in those who received the high-dose vaccine (n=2575) compared with the standard-dose vaccine (n=1262).[66]}

^{The high-dose vaccine met superiority criteria for both strains of influenza A, and noninferiority criteria were met for influenza B strains. Seroprotection rates were higher for the high-dose vaccine compared with the standard-dose vaccine. The authors suggest that the high-dose vaccine may provide improved immunity for elderly adults.[66]}

^{Dual vaccination with pneumococcal and influenza vaccine is effective in protecting elderly persons with chronic illness from developing complications due to respiratory, cardiovascular, and cerebrovascular diseases, thereby reducing hospitalization, coronary or intensive care admissions, and death.[67, 68]}

^{Woods et al found that, in sedentary older adults, cardiovascular exercise extends influenza vaccine seroprotection. A randomized controlled trial in 144 sedentary but healthy older (age 69.9 +/- 0.4 y) adults who underwent either cardiovascular exercise or flexibility and balance training showed that peak (3 and 6 wk) postvaccine anti-influenza hemagglutination inhibition (HI) titers were similar in both groups, but participants randomized to cardiovascular exercise were significantly more likely to have seroprotective HI titers at 24 weeks, suggesting enhanced influenza seroprotection throughout the entire influenza season.[69]}

^{Prevention of avian influenza}

^{Some data from animal studies suggest that the standard inactivated influenza vaccine may confer some partial immunity toward avian influenza. Therefore, recommendations are that poultry workers receive annual influenza vaccination to prevent illness and to prevent viral reassortment through simultaneous infection with the two types of influenza.}

^{No avian influenza vaccine is currently available to the public, although various products are in clinical trials and appear immunogenic. One complication is that the highly pathogenic viruses cannot be easily grown using the traditional embryonated chicken egg method, as the embryos often die during incubation.}

^{Alternative methods for producing immunogenic particles include tissue culture and reverse-genetic approaches using recombinant viruses. One option for increasing the immunogenicity (and hence potentially lowering the dose needed to vaccinate) is to use an adjuvant agent such as aluminum hydroxide. All of these methods are being evaluated for an avian influenza vaccine.}

^{An H5N1 monovalent killed-virus vaccine produced by Sanofi-Pasteur has been approved by the FDA in the United States but is available only to government agencies and for stockpiles.[70] It is derived from the influenza A/Vietnam/1203/2004 strain isolated from humans, and is a formalin-inactivated/detergent-disrupted, purified virus grown in embryonated chicken eggs.}

^{The vaccine was approved based on a limited safety and immunogenicity study of 500 adults aged 18-64 years. Fewer than half of those receiving the highest dose of vaccine responded and achieved antibody titers expected to be fully effective (ie, hemagglutination inhibition antibody titers >1:40) based on experience with seasonal influenza. The vaccine contains thimerosal (unlike many other seasonal influenza vaccines) because of the need for multidose vials.[71]}

^{In a study of vaccination against Vietnamese- and Indonesian-origin H5N1 strains using a prime-boost strategy, which included 491 subjects, optimal antibody titers required at least a 14-day interval between doses, and results were no better at 28 days.[72]}

^{Some cross-reactivity was documented, but this was minimal at 1 month and was much better when 6 months had elapsed between doses. Although the use of a 6-month interval between vaccine doses is questionable in the setting of a pandemic, the authors suggest that priming at-risk individuals with an antigenically distant H5 influenza vaccine may have some effect in reducing the need for a 2-dose series later on.[72]}

^{A newer recombinant H5N1 vaccine is also available from the WHO.[73] The CDC provides additional information about Avian Influenza Vaccines.}

^{Avian influenza and travelers}

^{Because avian influenza is rare in humans, the CDC does not currently recommend against travel to any country affected by H5N1.}

^{Prophylactic antivirals are not indicated for patients who plan to travel to areas where avian influenza has been reported. Travelers who plan to travel to areas of the world affected by avian influenza outbreaks in birds and/or humans are advised to avoid close contact with poultry, especially diseased or dead birds, and to consume only adequately cooked meat.}

^{If contact with birds in enclosed spaces is unavoidable, an N-95 respirator mask (or equivalent), gloves, and goggles should be used to minimize contact with droplets or particulates. For additional information, see the Avian Flu Travel Information from the CDC.}

^{Controlling H5N1 influenza in birds}

^{At present, highly pathogenic H5N1 avian influenza is predominantly a disease of birds. However, controlling the disease in birds is important because of its potential economic effects on poultry farming. Control may also decrease the opportunity for a pandemic flu strain to emerge. In addition, control of the H5N1 strain in birds decreases the likelihood of direct human exposures to infected birds and, thus, zoonotic cases in humans.}

^{Control methods include the following:}

^{·        Culling of infected and exposed birds}

^{·        Sanitation}

^{·        Quarantine}

^{In the 1997 outbreak of H5N1 disease in Hong Kong, aggressive government-ordered culling of chickens is believed to have limited the initial expansion and spread of the virus. Vietnam is similarly praised for having more success than its adjacent countries in containing the disease with aggressive testing and culling of poultry.}

^{Proper disposal of carcasses and bird excrement are critical in limiting bird-to-bird and bird-to-human spread of disease. High concentrations of virus have been demonstrated in droppings obtained from chickens infected with H5N1. Bathing in water contaminated with droppings is suspected to be one mechanism of human exposure. In economically poor, rural settings, death of individual chickens is common, and H5N1 illness may be frequently unrecognized and unreported.}

^{In the past, strict quarantining of commercial farms has limited the spread of highly pathogenic avian influenza virus (HPAIV) strains other than H5N1. Today, the importation of any bird from affected countries is prohibited. Quarantines work relatively poorly in rural settings, where animals are allowed to run free among human living quarters and between farms. Furthermore, the presence of H5N1 in wild birds, especially migratory species, limits the extent to which quarantining can be effective over the long term.[25]}

^{Containing pandemic influenza}

^{Preparedness for pandemic influenza is widely considered to be grossly inadequate. The following 5 areas are important to managing a surge in severe illness[74] :}

^{·        Surveillance and diagnostic services}

^{·        Information sharing and dissemination}

^{·        Community support}

^{·        Hospital and physician capacity}

^{·        Availability of vaccines and drugs}

^{Even in the absence of a pandemic illness, the lack of capacity in US emergency departments has been described as a crisis by the Institute of Medicine. For more information about preparedness for epidemic influenza, see the WHO Global Influenza Preparedness Plan.}

^{Consultations}

^{Consultation with an infectious disease specialist is prudent in some cases of seasonal influenza. Intensive care specialists need to be involved to manage severe disease.}

^{In suspected H5N1 influenza, a pulmonary specialist, a critical care specialist, an infectious disease specialist, and the staff of the local public health department may all be consulted. Clinical laboratory personnel should also be informed before potential H5N1 isolates are sent to them. In addition, hospital infection-control officers should be involved early in the care of any patient who might have avian flu. Ultimately, the WHO and/or CDC should be contacted; the CDC can safely perform serotyping for suspected avian influenza strains.}

^{Early involvement of the local public health department and hospital infection control is necessary to contain any outbreaks.}

^{Long-Term Monitoring}

^{Patients with influenza who do not improve should return for further evaluation. Patients diagnosed with influenza should be educated about potential complications and encouraged to return for evaluation if concerned. This is especially true of patients with underlying chronic disease or those who are immunocompromised.}

^{Medication Summary}

^{The goals of pharmacotherapy are to reduce morbidity and to prevent complications.}

^{Agents include vaccines and antiviral drugs (eg, oseltamivir, zanamivir). Amantadine and rimantadine resistance has been widespread in recent years, and these agents are no longer recommended by the US Centers for Disease Control and Prevention.}

^{The uricosuric agent probenecid may be used as an adjunct to antiviral treatment.}

^{Antiviral Agents}

^{Class Summary}

^{Antiviral drugs indicated for treatment of influenza include neuraminidase inhibitors (eg, oseltamivir, zanamivir). Amantadine and rimantadine resistance has been widespread in recent years, and these agents are no longer recommended by the US Centers for Disease Control and Prevention. Neuraminidase inhibitors act directly on the viral proteins, decreasing the virulence of infection.}

^{View full drug information}

^{Oseltamivir (Tamiflu)}

^{Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, oseltamivir decreases the release of viruses from infected cells and thus, viral spread.}

^{Oseltamivir is effective for the treatment of influenza A or B. It must be administered within 48 hours of symptom onset. The sooner it is taken after symptom onset, the better the effect. Oseltamivir reduces the length of illness by an average of 1.5 days. (In a subgroup of high-risk patients, illness was reduced by 2.5 d.) In addition, the severity of symptoms is also reduced. This agent is available as capsules (75 mg, 45 mg, 30 mg) and oral suspension.}

^{Oseltamivir resistance emerged in the United States during the 2008-2009 influenza season. Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected.}

^{A second-line alternative is a combination of oseltamivir plus rimantadine rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.}

^{The efficacy of oseltamivir against avian influenza is not well established. CDC recommendations for the avian viral strain H7N9 include oseltamivir in confirmed, suspected, or in cases under investigation.}

^{View full drug information}

^{Zanamivir (Relenza)}

^{Zanamivir is an inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. This agent is effective against both influenza A and B; its efficacy against avian influenza is not well established. CDC recommendations for the avian viral strain H7N9 include zanamivir in uncomplicated confirmed, suspected, or in cases under investigation. The investigational IV dosage form is recommended for hospitalized patients unable to use oral oseltamivir.}

^{Zanamivir is inhaled through a Diskhaler oral inhalation device and therefore is not recommended for patients with airway disease (eg, asthma, COPD). Circular foil disks that contain 5-mg blisters of drug are inserted into the supplied inhalation device.}

^Vaccines

^{Class Summary}

^{Influenza A and B vaccine is administered each year prior to flu season. The CDC analyzes the vaccine subtypes each year and makes any necessary changes based on worldwide trends.}

^{In April 2007, the US Food and Drug Administration (FDA) approved the first vaccine for H5N1 influenza (ie, avian influenza or bird flu). It is available only to government agencies and for stockpiles.}

^{View full drug information}

^{Influenza virus vaccine trivalent (Afluria, FluLaval, Fluarix, Flucelvax, Fluvirin, Fluzone, Fluzone High-Dose, Fluzone Intradermal)}

^{Influenza vaccine is indicated for active immunization to prevent infection from influenza A and B viruses. The vaccine induces antibodies specific to virus strains contained in the vaccine. The US Public Health Service determines influenza vaccine contents annually. Typically, 3 live attenuated virus strains, which antigenically represent the influenza strains likely to circulate the next flu season, are included in the formulation each year. Fluzone is approved for children as young as 6 months, Fluarix for children aged 3 years or older, Fluvirin for children aged 4 years or older, and Afluria for children aged 5 years or older.}

^{View full drug information}

^{Influenza virus vaccine trivalent, recombinant (Flublok)}

^{This vaccine is made from recombinant HA proteins that are not derived from egg or chick embryo. Influenza vaccine is indicated for active immunization to prevent infection from influenza A and B viruses. The vaccine induces antibodies specific to virus strains contained in the vaccine. The US Public Health Service determines influenza vaccine contents annually. Typically, 3 live attenuated virus strains, which antigenically represent the influenza strains likely to circulate the next flu season, are included in the formulation each year. It is administered as an IM injection and approved for adults aged 18 through 49 years.}

^{View full drug information}

^{Influenza virus vaccine quadrivalent (Fluarix Quadrivalent)}

^{Quadrivalent vaccines contain two strains of influenza A and two of influenza B. The vaccine induces antibodies specific to virus strains contained in vaccine. Each year, the US Public Health Service determines which viral strains will be included in the seasonal influenza vaccine that will antigenically represent the viral strains most likely to circulate in the next flu season. It is administered as an IM injection and approved for adults and children 3 years or older.}

^{View full drug information}

^{Influenza virus vaccine quadrivalent, intranasal (FluMist Quadrivalent)}

^{Intranasal influenza vaccine is indicated for active immunization to prevent influenza A and B viruses in healthy children, adolescents, and adults. Quadrivalent vaccines contain two strains of influenza A and two of influenza B. The vaccine induces antibodies specific to virus strains contained in vaccine. Each year, the US Public Health Service determines which viral strains will be included in the seasonal influenza vaccine that will antigenically represent the viral strains most likely to circulate in the next flu season.}

^{Influenza virus vaccine (H5N1)}

^{The H5N1 inactivated virus vaccine induces antibodies against viral hemagglutinin, thereby blocking viral attachment to human respiratory tract epithelial cells. The vaccine is estimated to reduce the risk of contracting avian influenza by 45%. This vaccine is indicated for active immunization of adults at increased risk of exposure to the H5N1 influenza virus subtype.}

^{Uricosuric Agents}

^{Class Summary}

^{Agents that inhibit the tubular secretion of the active metabolite of the drug may be used as adjunctive therapy with the antiviral drug oseltamivir.}

^{View full drug information}

^Probenecid

^{This agent inhibits tubular secretion of the active metabolite of oseltamivir, reducing the clearance by approximately 50% and approximately doubling systemic exposure to oseltamivir.}

^{The appropriate dosing for combination therapy using probenecid and oseltamivir in the treatment of avian influenza has not been established.}