Complications of Human Influenza 161

2 weeks. Second fever spikes are rare. The physical findings are summarised in table 3. Full recovery may take 1–2 weeks, or longer, especially in the elderly.

Table 3. Physical findings of uncomplicated influenza

Fever: rapidly peaking at 38–40°C (up to 41°C, especially in children), typically lasting 3 days (up to 4–8 days), gradually diminishing; second fever spikes are rare.

Face: flushed Skin: hot and moist

Eyes: watery, reddened Nose: nasal discharge Ear: otitis

Mucous membranes: hyperaemic

Cervical lymph nodes: present (especially in children)

Adults are infectious from as early as 24 hours before the onset of symptoms until about seven days thereafter. Children are even more contagious: young children can shed virus for several days before the onset of their illness (Frank 1981) and can be infectious for > 10 days (Frank 1981). Severely immunocompromised persons can shed influenza virus for weeks or months (Klimov 1995, Boivin 2002).

During non-epidemic periods, respiratory symptoms caused by influenza may be difficult to distinguish from symptoms caused by other respiratory pathogens (see Laboratory Findings). However, the sudden onset of the disease, fever, malaise, and fatigue are characteristically different from the common cold (Table 4).

Table 4. Influenza or common cold ?

Symptoms	Influenza	Cold
Fever	Usually high, lasts 3–4 days	Unusual
Headache	Yes	Unusual
Fatigue and/or weakness	Can last up to 2–3 weeks	Mild
Pains, aches	Usual and often severe	Slight
Exhaustion	Early and sometimes severe	Never
Stuffy nose	Sometimes	Common
Sore throat	Sometimes	Common
Cough	Yes	Unusual
Chest discomfort	Common and sometimes severe	Mild to moderate
Complications	Bronchitis, pneumonia; in severe	Sinus congestion
	cases life-threatening

Complications of Human Influenza

The most frequent complication of influenza is pneumonia, with secondary bacterial pneumonia being the most common form, and primary influenza pneumonia the most severe. In addition, mixed viral and bacterial pneumonia frequently occurs during outbreaks.

162 Clinical Presentation

Influenza may exacerbate heart or lung diseases or other chronic conditions. Influenza infection has also been associated with encephalopathy (McCullers 1999, Morishima 2002), transverse myelitis, myositis, myocarditis, pericarditis, and Reye’s syndrome.

Secondary Bacterial Pneumonia

Secondary bacterial pneumonia is most commonly caused by Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Typically, patients may initially recover from the acute influenza illness over 2 to 3 days before having rising temperatures again. Clinical signs and symptoms are consistent with classical bacterial pneumonia: cough, purulent sputum, and physical and x-ray signs of consolidation. Gram staining and culture of sputum specimens may determine the aetiology. Chronic cardiac and pulmonary disease predispose to secondary bacterial pneumonia, as does older age. Institution of an appropriate antibiotic regimen is usually sufficient for a prompt treatment response.

Primary Viral Pneumonia

Clinically, primary viral pneumonia presents as an acute influenza episode that does not resolve spontaneously. The clinical situation worsens with persistent fever, dyspnoea, and cyanosis. Initially, physical findings may be unimpressive. In more severe cases, diffuse rales may sometimes be present. At this stage, x-ray findings show diffuse interstitial infiltrates and acute respiratory distress syndrome (ARDS) with marked hypoxia. Viral titres are high in specimen cultures of respiratory secretions or lung tissue.

Primary influenza pneumonia with pulmonary haemorrhages was a prominent feature of the 1918 pandemic. In addition, pregnant women and individuals with cardiac disease (mitral stenosis) and chronic pulmonary disorders were found to be at increased risk during the 1957 pandemic.

Mixed Viral and Bacterial Pneumonia

Mixed influenza pneumonia has clinical features of both primary and secondary pneumonia. It most often occurs in patients with underlying chronic pulmonary or cardiovascular diseases. Some patients have a slowly progressive course, others may show a transient improvement in their condition, followed by clinical exacerbation. Treatment aims at eradicating the bacterial pathogens involved.

Exacerbation of Chronic Pulmonary Disease

Infectious pathogens have long been recognised as playing an important role in the pathogenesis of chronic respiratory disease (Monto 1978). In patients with chronic bronchitis, clinical influenza infection may lead to a permanent loss of pulmonary function. In children, influenza-induced asthma may continuously deteriorate during the first two days of illness and reconvalescence is typically longer (at least seven days) (Kondo 1991). Influenza virus is also implicated in the pathogenesis of asthma attacks in adults (Techtahl 1997).

Complications of Human Influenza 163

Croup

Croup is a typical complication of influenza infection in children. The clinical picture of croup caused by influenza viruses may be more severe than that caused by parainfluenza viruses (Peltola 2002).

Failure of Recovery

In epidemic influenza outbreaks, severely compromised elderly people are at particular risk. Pneumonia and influenza death rates have ranged from fewer than ten to more than 600 per 100,000 among healthy versus chronically ill adults. In one study, the highest death rates (870 per 100,000) occurred in individuals with both cardiovascular and pulmonary disease (Barker 1982). More importantly, the risk of death may extend well beyond the first weeks after influenza complications. Some people may simply never recover from influenza complications – and eventually die from deterioration of underlying pulmonary, cardiovascular, or renal function (Saah 1986).

Myositis

Myositis is a rare complication of influenza B virus infection, and to a lesser extent influenza A. It has mainly been reported in children, with boys being more commonly affected than girls. The median interval between the onset of influenza and the onset of benign acute childhood myositis is 3 days (Agyeman 2004). The calf muscles are involved alone or together with other muscle groups in 69 % and 31 % of cases, respectively. Blood creatine phosphokinase concentration is generally elevated (Hu 2004). Symptoms usually resolve within 3 days and may rarely persist for a couple of weeks. When myositis occurs in elderly patients, it is important to distinguish influenzal myositis from other forms of myopathy (Oba 2000).

Cardiac Complications

Myocarditis is a rare event during influenza infection. In an unselected cohort of patients with serologically confirmed acute influenza infection (n=152), the prevalence of elevated creatine kinase levels was 12 %. Of note, cardiac troponin I and T levels were not raised in any of the patients. The authors concluded that the prevalence of myocarditis during acute influenza infection is substantially lower than previously thought, whereas skeletal muscle injury is relatively common (Greaves 2003).

In a study determining the frequency, magnitude, and duration of myocardial dysfunction in previously healthy young adult patients, abnormal electrocardiogram findings have been noted in 53 %, 33 %, 27 %, and 23 % of patients on days 1, 4, 11, and 28, respectively, but none of the findings were considered to be clinically significant. No patients had significant changes in the ejection fraction or abnormal wall motions. None of the patients had an elevated CK-MB index or troponin I level (Ison 2005).

Toxic Shock Syndrome

Toxic shock syndrome (TSS) can occur as a complication of influenza (CDC 1986, MacDonald 1987, Tolan 1993). One of the hallmarks of the disease is rapidly de-