Influenza 流行性感冒 教材 -2

[上接:  Influenza 流行性感冒 教材-1  ]

History

The presentation of influenza virus infection varies; however, it usually includes many of the symptoms described below. Patients with influenza who have preexisting immunity or who have received vaccine may have milder symptoms.

The onset of symptoms can occur suddenly over the course of a day, or it can progress more slowly over the course of several days. The symptoms listed below are not necessarily in order of prevalence.

Cough and other respiratory symptoms may be initially minimal but frequently progress as the infection evolves. Patients may report nonproductive cough, cough-related pleuritic chest pain, and dyspnea. In children, diarrhea may be a feature.

Fever may vary widely among patients, with some having low fevers (in the 100°F range) and others developing fevers as high as 104°F. Some patients report feeling feverish and a feeling of chilliness.

Sore throat may be severe and may last 3-5 days. The sore throat may be a significant reason why patients seek medical attention.

Myalgias are common and range from mild to severe.

Frontal/retro-orbital headache is common and is usually severe. Ocular symptoms develop in some patients with influenza and include photophobia, burning sensations, and/or pain upon motion.

Some patients with influenza develop rhinitis of varying severity, but it is generally not the chief symptom.

Weakness and severe fatigue may prevent patients from performing their normal activities or work. In some cases, patients with influenza may find activity difficult and may require bedrest. Patients report needing additional sleep time.

Acute encephalopathy has been associated with influenza A virus infection. In a case series of 21 patients, Steininger et al described clinical, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electroencephalographic (EEG) findings.^[34] Clinical features included altered mental status, coma, seizures, and ataxia. Of patients who underwent further testing, most had abnormal CSF, MRI, and EEG findings.

The incubation period of influenza averages 2 days, but it may range from 1 to 4 days. Because of aerosol transmission, and the possibility (albeit less likely) of transmission by asymptomatic persons and contaminated surfaces, the patient may be unaware of exposure to the disease.^[5]

2009 H1N1 pandemic influenza

In the 2009-2010 H1N1 influenza pandemic, initial symptoms included high fever, myalgias, rhinorrhea, and sore throat. Nausea, diarrhea, and vomiting were also reported. For more information, see the article H1N1 Influenza (Swine Flu).

Avian influenza

The key history component that should prompt consideration of avian influenza as a possible diagnosis is exposure to sick, dead, or dying poultry or humans with avian influenza. Many cases involve close contact, such as plucking or gutting of dead birds, removing infected carcasses, or ingesting incompletely cooked bird meat or blood. Some patients have had no history of exposure to sick birds, suggesting that spread from asymptomatic birds is possible or that the virus can be transmitted environmentally on fomites.

The mean time from exposure to onset of illness is 2-4 days, but can be as long as 8 days.^[35] About 94-100% of cases begin with a typical influenza syndrome, including high fever (temperature >38°C) and lower respiratory tract symptoms (cough and pleuritic pain). Headache, myalgia, and fatigue are also common.^{[36, 35]}

Dyspnea is reported in 76-100% of cases.^[35] Lower respiratory tract involvement appears to occur earlier with avian flu than with seasonal influenza. Dyspnea, shortness of breath, hoarseness, and copious sputum production may be presenting complaints.^[23] The sputum is sometimes bloody.

Upper respiratory findings of sore throat or rhinorrhea occurred in only about half of confirmed cases.^[35]

GI symptoms, including diarrhea, nausea, and abdominal pain, are common early complaints occurring in 10-50% of patients.^[35] Nonbloody, watery diarrhea appears to be more common with avian flu than with human seasonal influenza.^[23]

Encephalitis may occur.^[37] Two persons in Vietnam presented with encephalitis only.^[38]

The incidence of asymptomatic or mild cases is uncertain. Seroprevalence studies demonstrated exposure in poultry workers but little exposure to health care workers caring for patients with avian influenza.^[36]

^{Physical Examination}

^{The general appearance varies among patients who present with influenza. Some patients appear acutely ill, with some weakness and respiratory findings, while others appear only mildly ill. Upon examination, patients may have some or all of the following findings:}

^{·        Fever of 100-104°F; fever is generally lower in elderly patients than in young adults}

^{·        Tachycardia, which most likely results from hypoxia, fever, or both}

^{·        Pharyngitis - Even in patients who report a severely sore throat, findings vary from minimal infection to more severe inflammation}

^{·        Eyes may be red and watery}

^{·        Skin may be warm-to-hot, as reflected by the temperature status. Patients who have been febrile with poor fluid intake may show signs of mild volume depletion with dry skin}

^{·        Pulmonary findings during the physical examination may include dry cough with clear lungs or rhonchi and focal wheezing}

^{·        Nasal discharge is absent in most patients}

^{·        Appearance of fatigue}

^{Avian influenza}

^{High fever (temperature >38°C), tachypnea, and hypoxia may be noted at presentation. Pulmonary rales may be heard early. Wheezes are occasionally apparent. Patients typically have a productive cough, occasionally with blood-tinged sputum.}

^{Diarrhea is relatively common. Abdominal pain and vomiting are relatively infrequent.}

^{Signs of upper respiratory tract infection, including coryza, conjunctivitis, and pharyngitis, may be noted, but these findings are not necessarily present. Conjunctivitis appears to be less common with H5N1 infection than with seasonal influenza or with infection due to other strains of avian influenza in humans. Case reports have described other occasional signs (eg, bleeding gums, always in the presence of viral pneumonia).[39]}

^{Complications}

^{Primary influenza pneumonia is characterized by progressive cough, dyspnea, and cyanosis following the initial presentation. Chest radiographs show bilateral diffuse infiltrative patterns, without consolidation, which can progress to a presentation similar to acute respiratory distress syndrome (ARDS).}

^{Risks for viral pneumonia involve numerous complex host immune responses and viral virulence. Women in the third trimester of pregnancy are at higher risk, as they are for other complications of influenza A and B. Elderly individuals, especially nursing home patients, and those with cardiovascular disease usually constitute the highest risk groups; however, particular influenza strains may target younger persons. For example, in the 1918-1919 epidemic, many young adults died of a pneumonia that some experts believe was caused directly by the virus.}

^{Secondary bacterial pneumonia can occur from numerous pathogens (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae). The most dreaded complication is staphylococcal pneumonia, which develops 2-3 days following the initial presentation of viral pneumonia. Patients appear severely ill, with hypoxemia, an elevated WBC count, productive bloody cough, and a chest radiograph showing multiple cavitary infiltrates.}

^{A study from Israel compared H1N1 to non-H1N1 bacteremia in children and adults. Results show significant increases in S areus and S pyogenes infections in both groups during pandemic H1N1 influenza seasons. The highest increase was in S pneumoniae infections among children. There was not a marked increase in S pneumonia among adults.[40]}

^{Methicillin-susceptible S aureus( MSSA) and methicillin-resistant S aureus (MRSA) pneumonias have occurred following influenza pneumonia. MRSA pneumonia may be severe and difficult to treat, and deaths have occurred within 24 hours of presentation of pneumonia symptoms.}

^{S pneumoniae or H influenzae pneumonia, if occurring as a complication, usually develops 2-3 weeks after the initial symptoms of influenza and can be managed as a community-acquired pneumonia, following standard antibiotic and admission/discharge guidelines.}

^{Myositis is a rare complication. This group of patients may develop frank rhabdomyolysis, with elevated creatine kinase levels and myoglobinuria. Myocarditis and pericarditis have been associated with influenza infections.}

^{A review of avian influenza cases in 4 countries found that the clinical course progressed to ARDS and respiratory failure in 70-100% of patients.[38] The mean time to the development of ARDS was 6 days. Lymphopenia at presentation is a significant predictor of the progression to ARDS and death.[41]}

^{Severe cases of avian influenza may progress to multiorgan failure. In a study of 12 hospitalized patients with confirmed H5N1 influenza, 75% had respiratory failure, 42% had cardiac failure, and 33% had renal failure.[38]}

^{Diagnostic Considerations}

^{Accurately diagnosing influenza A or B infection based solely on clinical criteria is difficult because of the overlapping symptoms caused by the various viruses associated with upper respiratory tract infection (URTI). In addition, several serious viruses, including adenoviruses, enteroviruses, and paramyxoviruses, may initially cause influenzalike symptoms.}

^{The early presentation of mild or moderate cases of flavivirus infections (eg, dengue) may initially mimic influenza. For example, some cases of West Nile fever acquired in New York in 1999 were clinically misdiagnosed as influenza.}

^{Like influenza, URTIs from these viruses are more common in the winter. As a result, during the winter, clinics and emergency department waiting rooms fill with patients who have influenza or other URTIs.}

^{Influenza pneumonia must be differentiated from other forms of viral pneumonia, bacterial pneumonia, and noninfectious causes of respiratory distress, such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), pulmonary edema, and aspiration pneumonitis.}

^{Avian influenza}

^{Risk factors or features that should raise the index of suspicion include the following:}

^{·        Travel to (within the last 2 wk) or location in a country with known avian influenza cases in animals or humans}

^{·        Unusual comorbidities such as encephalopathy or diarrhea}

^{·        History of exposure to birds, especially living in close proximity to birds, contact with sick or dying birds, or consumption of incompletely cooked bird meat}

^{·        History of exposure to individuals with known avian influenza, especially family, or to sick people in a country with known human cases of avian influenza}

^{The situation can be complicated during outbreaks of severe respiratory disease not due to avian influenza. The first case of laboratory-confirmed avian influenza infection was documented during the severe acute respiratory syndrome (SARS) outbreak and was mistakenly misdiagnosed as SARS.[17]}

^{Although a small percentage overall, several cases in which respiratory disease was limited or not apparent (with even normal chest radiography findings) have been described.[39] The primary presenting illness has been encephalitis and/or diarrhea.}

^{Differential Diagnoses}

^{·        Acute Respiratory Distress Syndrome}

^{·        Adenoviruses}

^{·        Arenaviruses}

^{·        Cytomegalovirus}

^{·        Dengue Fever}

^{·        Echoviruses}

^{·        Hantavirus Pulmonary Syndrome}

^{·        HIV Disease}

^{·        Legionnaires Disease}

^{·        Parainfluenza Virus}

^{Approach Considerations}

^{The criterion standard for diagnosing influenza A and B is a viral culture of nasopharyngeal samples and/or throat samples. Rapid diagnostic tests are available, but because of cost, availability, and sensitivity issues, most physicians diagnose influenza based on clinical criteria alone.}

^{Findings of standard laboratory studies such as a complete blood cell count (CBC) and electrolyte levels are nonspecific but helpful in the workup of influenza. Leukopenia and relative lymphopenia are typical findings in influenza. Thrombocytopenia may be present.}

^{Rapid Diagnostic Tests}

^{The US Food and Drug Administration (FDA) has waived federal Clinical Laboratories Improvement Act (CLIA) requirements and cleared for marketing 7 rapid influenza diagnostic tests that directly detect influenza A or B virus–associated antigens or enzyme in throat swabs, nasal swabs, or nasal washes and can produce results within 30 minutes.[40] The following 3 of these tests are considered low complexity and may be used in physicians’ offices:}

^{·        QuickVue Influenza A+B test (Quidel)}

^{·        ZstatFlu (ZymeTx)}

^{·        QuickVue Influenza test (Quidel)}

^{The QuickVue tests provide results in 10 minutes or less; the ZstatFlu test provides results in 20 minutes. Nasal swabs need to be deeply inserted and swirled to attach the influenza virus. Specificity is high, in the range of 90% for many of these bedside tests. However, sensitivity is in the 50-60% range and dependent on collection technique and the skill of the person performing the test.}

^{In September 2011 the FDA approved a new CDC-developed test to diagnose influenza infections, including avian influenza. The Human Influenza Virus Real-Time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is an in vitro laboratory diagnostic test that can provide results within 4 hours. It is the only in vitro diagnostic test for influenza that is cleared by the FDA for use with lower respiratory tract specimens and will be given at no cost to qualified international public health laboratories. Other older bedside rapid diagnostic tests are available, but because of cost, availability, and sensitivity issues, most physicians diagnose influenza based on clinical criteria alone.}

^{Viral Culture}

^{The criterion standard for diagnosing influenza A and B is a viral culture of nasopharyngeal samples and/or throat samples. In 2011 the FDA approved a new kit developed by the CDC for diagnosing human infections with seasonal influenza viruses and novel influenza A viruses with pandemic potential.}

^{The Human Influenza Virus Real-Time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is an in vitro laboratory diagnostic test that can provide results within 4 hours. It is the only in vitro diagnostic test for influenza that is cleared by the FDA for use with lower respiratory tract specimens and will be given at no cost to qualified international public health laboratories.}

^{Consisting of 3 modules, the kit can:}

^{·        Identify and distinguish between influenza A and B viruses,}

^{·        Classify influenza A viruses by subtype, and}

^{·        Detect highly pathogenic avian influenza A (H5N1) virus infection in human respiratory tract specimens.}

^{Obtain samples with Dacron swabs and send the samples in appropriate viral transport media (eg, multimicrobe [M4] transport media) to the laboratory to be cultured in several lines of cells.}

^{A laboratory diagnosis of influenza is established once specific cytopathic effect is observed or hemadsorption testing findings are positive. Staining the infected cultured cell lines with fluorescent antibody confirms the diagnosis.}

^{Polymerase chain reaction (PCR) tests}

^{Most laboratories and hospitals now offer nucleic acid (PCR)–based studies. A nasal swab is submitted in special transport media to the laboratory, and results are reported within 24 hours. Some laboratories are able to differentiate between seasonal versus pandemic H1N1. Sensitivity for influenza is greater than 90%. These studies may be offered as respiratory panels, and they provide information on the presence of other viruses, such as respiratory syncytial virus (RSV) and adenovirus.}

^{Direct Immunofluorescent Tests}

^{Some laboratories offer direct immunofluorescent tests on fresh specimens, but these tests are labor-intensive and are less sensitive than culture methods. These tests require specially trained laboratory personnel for interpretation, and these personnel generally are not available during all shifts, even in large medical centers}

^{Serologic Testing}

^{In order to overcome the expensive and time-consuming obstacle of culturing, several serologic tests have become available. In reality, many of these are not bedside tests; generally, 30-60 minutes are required to perform the test's multiple steps. Test sensitivities generally range from 60-70%}

^{Testing for Avian Influenza}

^{The standard commercially available rapid influenza A tests do not detect H5N1 avian influenza.[8] A rapid test from nasopharyngeal swab specific to H5N1 influenza (Arbor Vita Corporation) was approved by the FDA in 2009.[9]}

^{Hematology (CBC) may be more clinically useful in avian influenza than in seasonal influenza disease. Leukopenia (white blood cell count of 454-4900 cells/µL), especially lymphopenia, is common and is observed in 50-80% of patients.[37] In at least one study, lymphopenia at presentation (absolute lymphocyte count < 1500 cells/µL) was a significant predictor of the progression to ARDS.[42] More than half of patients will have mild-to-moderate thrombocytopenia.}

^{Liver function tests (LFTs) may be useful in differentiating illness from other febrile tropical diseases. Aminotransferase levels are elevated in more than half of all patients with avian influenza H5N1 infection.[25]}

^{In addition to thrombocytopenia, some patients with severe disease will develop disseminated intravascular coagulation (DIC), as shown on coagulation studies.[25]}

^{A basic metabolic panel is generally required in the care of all seriously or critically ill patients. Abnormalities in renal function may herald the progression to organ failure.}

^{According to the 2009 CDC Recommendations,[41] clinicians should attempt to specifically identify avian H5N1 influenza in the patients with ALL of the characteristics listed below. Testing may be considered in discussion with public health authorities in patients who have only some of these characteristics. All testing should be discussed with local public health departments.}

^{·        Severe illness requiring hospitalization or fatal, and}

^{·        Temperature >38°C (100.4°F), and}

^{·        Radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which an alternative diagnosis has not been established, and}

^{·        At least one potential exposure within 7 days of symptoms onset}

^{The CDC defines potential exposure as follows:}

^{·        Close contact with an individual with confirmed or suspected H5N1 influenza infection, or}

^{·        Working with H5N1 virus in laboratory, or}

^{·        Travel to country where H5N1 influenza has been identified in birds or humans, and direct contact with a well or ill birds (poultry or wild); direct contact with surfaces with poultry parts or feces; consumption of raw or incompletely cooked poultry; or contact with H1N1 viral specimens or persons with suspected infection}

^{If avian influenza is suspected, cultures should not be ordered without guidance from a public health laboratory. Many laboratories are not equipped to deal with the isolation needed to safely contain avian influenza (biosafety category 3+ containment, higher than that used for HIV). If a sample is sent, the laboratory may need to be shut down for decontamination.}

^{Samples from patients with suspected avian influenza should be sent to a dedicated central reference laboratory such as at the Center for Disease Control and Prevention (CDC). The CDC laboratory can perform antiviral sensitivity testing, as well as subtyping of the virus.}

^{The best specimens are material collected with oropharyngeal swabs, material from bronchoalveolar washes, or tracheal aspirates. Specimens from nasopharyngeal swabs are acceptable, but they may contain a low quantity of the virus. Specimens should be collected in the first 3 days of illness.}

^{Pneumatic tubing is not recommended for transport; hand transport using a leak-proof specimen bag is preferred. The specimen should be clearly labeled as "suspected AI," and the person who transports the specimen should use appropriate protective equipment.}

^Radiography

^{In elderly or high-risk patients with pulmonary symptoms, perform chest radiography to exclude pneumonia. Early radiographic findings include no or minimal bilateral symmetrical interstitial infiltrates. Later, bilateral symmetrical patch infiltrates become visible. Focal infiltrates indicate superimposed bacterial pneumonia.}

^{With avian influenza, pulmonary infiltrates are seen in almost all patients. The wide variety of radiographic characteristics range from diffuse or patchy infiltrates to lobar multilobar consolidation. Effusions and lymphadenopathy are also observed, as well as cystic changes (see the image below).}

^{Chest radiograph of severe lung disease in a patient with avian influenza.}

^{In avian influenza, the severity of radiologically apparent disease is a good predictor of mortality, including findings consistent with acute respiratory distress syndrome (ARDS), such as a diffuse, bilateral ground-glass appearance.}

^{Other Tests}

^{Alveolar-arterial gradient}

^{Severe hypoxemia is present in severe cases of influenza. The alveolar-arterial (A-a) gradient may be increased (>35 mm Hg).}

^{Lumbar puncture}

^{Patients with physical examination findings compatible with meningitis should undergo lumbar puncture.}

^{Prehospital Care}

^{Prehospital care is predominantly supportive. Supplemental oxygenation to manage respiratory symptoms or objective hypoxia may be needed. Ventilatory support with a bag-valve-mask device and/or with field intubation may be required if the patient is in respiratory failure. Intravenous access should be obtained, and a bolus of a crystalloid can be administered to support hemodynamic stability.}

^{Attention should be given to the appropriate use of personal protective equipment (PPE) by the prehospital providers and advance notification should be given to the hospital regarding the potential need for patient respiratory isolation. General guidelines in low-risk areas are that patients with fever and respiratory complaints should wear a standard mask, if tolerated, to decrease airborne droplets.}

^{Inpatient Care}

^{Most frequently, hospitalization is necessary when influenza exacerbates underlying chronic diseases. Some patients, especially elderly individuals, may be too weak to care for themselves alone at home.}

^{On occasion, the direct pathologic effects of influenza may require hospitalization. Most commonly, this is influenza pneumonia.}

^{Approach Considerations}

^{As with other diseases, prevention of influenza is the most effective strategy. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) publishes recommendations for high-risk groups, including all health care personnel, who should be vaccinated.}

^{Public health measures are effective in limiting influenza transmission in closed environments.[12] Enhanced surveillance with daily temperature taking and prompt reporting with isolation through home medical leave and segregation of smaller subgroups decrease the spread of influenza. In one study, symptomatic illness attributable to influenza decreased from 12% to about 4% with the use of these measures.[13]}

^{The ACIP also publishes recommendations on the use of antiviral agents for prevention and treatment of influenza.[43]}

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