Step-by-step diagnostic approach

The diagnosis of 2009 H1N1 influenza should be suspected in a person who presents with an influenza-like illness (fever and cough or sore throat in the absence of any other known cause) in a community where H1N1 influenza is circulating. The presentation may range from a mild respiratory infection to severe pneumonia. In the outpatient setting, it may be appropriate to make a presumptive diagnosis of influenza in an otherwise healthy person who presents with the typical symptoms, without the need for additional tests, particularly if the illness is mild and the result of tests will not change medical management. Confirmatory tests are recommended for patients with lower respiratory tract illness, patients admitted to the hospital, those at risk for developing complicated infections, and patients residing in nursing homes and other institutions, particularly if this will guide treatment and infection control decisions. [41] [42]

History

The most common symptoms reported among patients with 2009 H1N1 influenza are fever (in 93%) and cough (in 83%). Other common symptoms are shortness of breath, fatigue or weakness, chills, myalgia, rhinorrhoea, sore throat, and headache. Unlike seasonal influenza, vomiting (29%) and diarrhoea (24%) are relatively common presenting symptoms. [11]

Reports have also emerged about the presentation of H1N1 in children and very young infants. [43] [44] Among children with confirmed 2009 H1N1 influenza, 95% complained of fever and cough, with 30% complaining of vomiting, 18% having abdominal pain, and 14% having diarrhoea. Among young infants, cough and fever are often, but not always, present. A few patients presented with apnoea. Thus, aside from more-frequent incidence of gastrointestinal symptoms, the presentation of H1N1 influenza appears to be similar to seasonal influenza.

Patients should be asked about ill contacts. Comorbid factors that place the patient at risk of influenza complications should be identified, including HIV or other immunocompromised states, diabetes, chronic lung disease, CVD, renal disease, hepatic disease, and neurological or neuromuscular disease. Patients should also be asked about smoking, pregnancy status, and whether they live in a nursing home or chronic-care facility, because these groups are at higher risk for complications. [45]

Physical examination

Findings on physical examination are variable. The patient may seem anything from mildly ill to severely ill. Commonly, patients have fever (temperature of ≥37.8°C [≥100°F]) and may have signs of dehydration. Complicated cases may have more physical examination findings, including tachypnoea, pallor, wheezing, and crackles. Infants and young children may seem lethargic and irritable, and may have altered mental status. [32] In addition, obesity has emerged as a risk factor for complicated influenza infection. [13] [46]

Rapid influenza test

Patients admitted to the hospital, patients in high-risk categories (children, adults >65 years, pregnant women, and those with comorbid conditions) and patients with regular close contact with high-risk patients should undergo additional laboratory testing for diagnosis. Rapid influenza tests (also known as 'point of care' tests) detect the influenza nucleoprotein antigen. Commercially available tests can provide results for the presence of influenza antigen within 15 to 30 minutes and can be performed on nasopharyngeal swab, nasal aspirate, or bronchial specimen. These tests come in several forms. Some detect both influenza A and B strains (but do not distinguish between them), some detect and distinguish between influenza A and B strains, and some detect influenza A only. Rapid influenza tests that detect the presence of influenza A cannot distinguish novel H1N1 swine influenza from seasonal influenza A. The sensitivity of this test is unknown, and reports have varied widely (10% to 70% compared with real-time reverse transcriptase [rRT]-PCR). [47] One study has reported a sensitivity of 51% for pandemic swine influenza confirmed by rRT-PCR. [48]

Given the low sensitivity, a negative test does not exclude the presence of 2009 H1N1 influenza. Hence, in the case of a negative rapid antigen test, clinical judgement should be used to determine whether to institute infection control measures and antiviral treatment or if additional confirmatory tests should be obtained. If the test is positive and swine influenza is known to be circulating, a probable case of swine influenza can be diagnosed.

Treatment should not be withheld in patients at high risk of influenza complications (children, adults >65 years, pregnant women, those with comorbid conditions) while awaiting test results.

Real-time reverse transcriptase (rRT)-PCR

Laboratory tests to diagnose 2009 H1N1 influenza, such as rRT-PCR, should be prioritised for hospitalised patients and immunocompromised persons with suspected influenza where rapid influenza testing is negative, or for determining influenza A virus subtype in patients who have died from suspected or confirmed influenza A virus infection. If additional testing is considered necessary, rRT-PCR is the test of choice for detecting H1N1 swine influenza infection. It can detect both live and dead viral particles and is the most sensitive test (viral culture can detect only live viruses). rRT-PCR can be performed directly on patient specimens (e.g., nasopharyngeal swab or aspirate, nasal wash and swab, bronchoalveolar lavage, or tracheal aspirate) or on cultured virus from patient specimens. If swabs are used to collect specimens for PCR, the tips should be made from synthetic material (e.g., polyester or Dacron) with an aluminium or plastic shaft. Specimens collected from swabs with cotton tips or made from calcium alginate or wood are not acceptable. [49]

Influenza culture

Viral culture (traditionally the definitive test) can be grown in Madin-Darby canine kidney (MDCK) cells or eggs. A positive culture is definitive for influenza infection, although confirmation of 2009 H1N1 influenza requires further molecular testing, such as PCR, on cultures. The polyclonal antibodies in the WHO influenza reagent kit specific for H1 subtypes of seasonal influenza viruses will not react with the 2009 H1N1 swine influenza haemagglutination inhibition assay, and therefore are not suitable for identifying H1N1. [50]