Methodical indicating for students on preparation to practical work.

1. THEME: “Influenza. Age features of clinical picture. Diagnostics, differential diagnostics. Complication, treatment. Common cold viral infections aninfluenzal etiology. Differential diagnostics. Treatment, prophylaxis. Mycoplasmal infection. Differential diagnostics. Viral croup, differential diagnostics with true croup, treatment. World Health Organization Programme on the treatment of ARI”.

2. AMOUNT OF CLASS PERIODS: 7 clocks

3. URGENCY OF THE THEME:

Influenza is one of the most contagious airborne infectious diseases. Patients frequently present to physicians with symptoms of influenza, the common cold, or a confusing combination of symptoms of both. In the Northern and Southern Hemispheres, these symptoms are more common in the winter months and result in clinics or emergency department waiting rooms becoming filled with patients who have flu or upper respiratory tract infections (URTIs).

Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold, typically a mild, self-limited, catarrhal syndrome of the nasopharynx, to life-threatening illnesses such as epiglottitis. Viruses account for most URIs. Physicians must be alert to signs of bacterial primary infection or superinfection, which may require targeted therapy.

The upper respiratory tract includes the sinuses, nasal passages, pharynx, and larynx, which serve as the gateways to the trachea, bronchi, and pulmonary alveolar spaces. Rhinitis, pharyngitis, epiglottitis, laryngitis, and tracheitis are specific manifestations of URIs.

Croup (laryngotracheobronchitis) is a contagious viral infection of the upper airways that causes cough and sometimes difficulty breathing, especially breathing in. Croup is a viral infection that causes swelling of the lining of the airways, particularly the area just below the voice box (larynx). Parainfluenza virus is the most common cause, but croup can be caused by other viruses, such as the respiratory syncytial virus or an influenza virus.. Croup primarily affects children 6 months to 3 years of age, although it occasionally affects those younger or older. Croup caused by an influenza virus may be particularly severe and is more likely to occur in children between the ages of 3 and 7.

THE EDUCATIONAL PURPOSES: to study the differential diagnosis influenza and others acute respiratory viral diseases, the differential diagnosis of croup syndrome, the main symptoms of mycoplasmal diseases, to learn the program of WHO – the therapy of acute respiratory viral diseases.

THE STUDENT SHOULD KNOW:

1. The main principles of the differential diagnosis influenza and others acute respiratory viral diseases, the differential diagnosis of croup syndrome;

2. The etiological structure of acute respiratory viral diseases;

3. The clinical picture of acute respiratory viral diseases (influenza, parainfluenza infection, adenoviral, enteroviral, rhinoviral infections), mycoplasmal pneumonia;

4. The complications of influenza and others acute respiratory viral diseases;

5. The program of WHO - the therapy of acute respiratory viral diseases

THE STUDENT SHOULD BE ABLE:

1. To keep ground rules of work at bed of the patient with influenza and others acute respiratory viral diseases in children, to gain the patient’s confidence and have a good bedside manner.

2. To collect the life history of the patient with influenza and others acute respiratory viral diseases in children.

3. To reflect the patient’s complaints, the history of present illness, the life history, the epidemiological history and data of general examination of patient in an educational history of the case.

4. To appoint the plan of laboratory investigations of the patient with influenza and others acute respiratory viral diseases in children.

5. To interpret the data of the laboratory examination.

6. To appoint treatment in the patient with influenza and others acute respiratory viral diseases in children.

7. To carry out the prophylactic measures and disinfection in an epidemic focus of influenza and others acute respiratory viral diseases in children.

5. QUESTIONS FOR PREPARATION TO PRACTICAL WORK :

а) On basic knowledge:

1. The etiological characteristics of causative agents influenza, others acute respiratory viral diseases, mycoplasmal diseases;

2. The definition of tha following syndromes: “rhinitis”, “laryngitis”, “tracheitis”, “bronchitis”, “mycoplasmal pneumonia” (the clinical features);

3. The methods of laboratory investigation of influenza’s, acute respiratory viral diseases’ patients;

b) On a theme of the present practical work:

1. The clinical features of influenza, parainfluenza infection, mycoplasmal pneumonia;

2. The clinical features of adenoviral, rhinoviral infections;

3. The clinical features of enteroviral infections;

4. The clinical features of respiratory syncytial virus infection (RS- infection);

5. The differential diagnosis influenza and others acute respiratory viral diseases, the differential diagnosis of croup syndrome;

6. The therapy of acute respiratory viral infections according to principles of WHO program;

7. The specific and nonspecific prophylactics of acute respiratory viral infections.

6. THE INFORMATIVE-DIDACTIC PART.

Influenza

Pathophysiology

Vaccines directed at critical viral surface antigens

· Hemagglutinin

· Neuraminidase

Antigenic drift

· Minor genetic mutations result in epidemics

· Influenza A most commonly involved

Antigenic shift

· Major genetic changes result in pandemic

· Major Pandemics

1. 1918: "Spanish flu" 20 Million deaths worldwide

2. 1957: Asian Flu

3. 1968: Hong Kong flu 34,000 deaths

· Recent Antigenic Shifts

1. 1976: Swine flu isolated

2. 1997: Hong Kong H5N1 (avian) influenza

Types

Influenza A

· Major outbreaks result from antigenic shifts

· Re-assortment of genomic expression

· Neuraminidase and Hemagglutinin

Influenza B

· Less variation than Influenza A

· Outbreaks in Schools and Military camps

Influenza C

Influenza results from infection with 1 of 3 basic types of virus, A, B, or C, which are classified within the family Orthomyxoviridae. These single-stranded RNA viruses share structural and biological similarities but vary antigenically.

The most common prevailing human influenza A subtypes are H1N1 and H3N2. Influenza A is generally more pathogenic than influenza B. Influenza A is a zoonotic infection, and more than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. This unique N1 neuraminidase is being studied in order to provide better insight into the N1 found in H5N1 bird flu.

Viral shedding

Viral shedding occurs at onset of symptoms or just before the onset of illness (0-24 h). Shedding continues for 5-10 days. Young children may shed virus longer, placing others at risk for contacting the virus.

Mortality/Morbidity

The CDC estimates that in excess of 20,000 deaths occur annually as a result of influenza virus when all years are averaged.

Sex

Women in the third trimester of pregnancy are at higher risk for complications of influenza A and B.

Epidemiology

§ Annual Periodicity

§ Temperate Climate

§ Onset as early as October

§ Peaks in late December to March

§ Tropical Climate: Occurs year round

Transmission

Small-large particle aerosol from cough and sneeze

Course

Incubation: 2-3 days (may be as long as 7 days)

Infectivity (Viral shedding)

§ Begins within 1 day of symptom onset

§ Peaks with illness severity

§ Declines over 4-5 days

Acute symptoms resolve in 4-5 days

Persistent symptoms may not clear for 3 or more weeks

§ Fatigue or malaise

§ Persistent non-productive cough

Attack rate:

§ Epidemics (antigenic drift): 20-30%

§ Pandemics (antigenic shift): 50%

Ages affected

§ Children

§ Highest attack rate

§ Elderly (over age 65 years)

§ Lowest attack rate

§ Highest risk of complication

§ Relative risk of hospitalization: 5-10

§ Relative risk of mortality: 5

Clinical

classification ofinfluenza

Mixt-infection.

History

The presentation of influenza virus infection can vary; however, it usually includes many of the symptoms described below. Patients with preexisting immunity or those who have received vaccine may have mild and less severe symptoms.

· Abrupt onset of illness is common. Many patients are able to report the time when the illness began.

· 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. Patients may report feeling feverish and a feeling of chilliness.

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

· Myalgias are a common symptom and range from mild to severe.

· Frontal/retroorbital headache is common and is usually severe. Ocular symptoms develop in some patients and include photophobia, burning sensations, pain upon motion, or a combination thereof.

· Rhinitis of varying severity is present in some patients but is generally not the overriding symptom.

· Weakness and severe fatigue may prevent patients from performing their normal activities or work. In some cases, patients may find activity difficult and require bedrest.

· 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.

· Acute encephalopathy has recently been described to be associated with influenza A virus. In a case series of 21 patients, Steininger et al described clinical, CSF, MRI, and EEG findings. Clinical features included altered mental status, coma, seizures, and ataxia. Of those who underwent further testing, most had abnormal CSF, MRI, and EEG findings.

• Symptoms
• Abrupt illness onset
• Viral prodrome
• High fever to 104 F (fever lasts 4-5 days)
• Chills
• Severe myalgias (lasts for first 3 days)
• Severe Headache (most severe in first 2 days)
• Eye
• Photophobia
• Red, Burning eyes
• Nose
• Coryza or profuse Nasal discharge (lasts 6-7 days)
• Often onset with fever and no other symptoms
• Rhinitis
• Nasal congestion or "stuffiness"
• Throat
• Sore Throat or dry throat (lasts for first 3 days)
• Chest
• Severe dry cough (lasts for first 3 days)
• Chest discomfort
• Other Constitutional symptoms
• Anorexia (may persist for first week)
• Fatigue persists weeks
• Severe Malaise (may persist for more than a week)
• Less common symptoms (20-40%)
• Nausea or Vomiting
• Dizziness
• Signs
• Fever up to 104 F (40⁰C)
• Non-exudative Pharyngitis
• Muscle tenderness
• Less Common Influenza signs
• Conjunctivitis
• Cervical adenopathy

Physical

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

· Fever may range from 100-104°F. The fever in elderly patients is not generally as high as that seen in young adults.

· Tachycardia most likely results from hypoxia, fever, or both.

· Pharyngitis may be present. Even in patients who report a severely sore throat, findings vary from minimal infection to more severe inflammation.

· Eyes may be red and watery.

· Nasal discharge is absent in most patients.

· 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 active cough, wheezing, rhonchi, or a combination thereof.

Lab Studies

• Complete Blood Count
• Leukopenia or slight Leukocytosis (up to 15,000)
• Relative Lymphopenia
• Virus Isolation (48-72 hours required for isolation)
• Nasopharyngeal swab
• Throat swab
• Sputum
• Rapid Influenza Test (Influenza Immunoassay)
• Sample site varies between products
• Serology (four fold rise over 10-14 days)
• Hemagglutination inhibition
• Complement fixation titers

· Viral culture

o The criterion standard for diagnosing influenza A and B is a viral culture of nasal-pharyngeal samples, throat samples, or both.

o Staining the infected cultured cell lines with fluorescent antibody confirms the diagnosis.

o The process may require 3-7 days, long after the patient has left the clinic, office, or ED and well past the time when drug therapy could be efficacious.

· Direct immunofluorescent tests

o Some laboratories offer direct immunofluorescent tests on fresh specimens, but these tests are labor-intensive and are less sensitive than culture methods.

Imaging Studies

· In elderly or high-risk patients with pulmonary symptoms, perform chest radiography (CXR) to exclude pneumonia.

Procedures

· Patients with physical examination findings compatible with meningitis should undergo lumbar puncture.

Treatment

Medical Care

· As with other diseases, prevention is the most effective strategy.

o The CDC has published recommendations for high-risk groups, including all health care personnel, who should be vaccinated.

o Amantadine and rimantadine have been approved for many years for use against influenza A. However, beginning with the 2005-2006 season, amantadine and rimantadine were no longer recommended by the CDC because significant resistance has evolved against these two drugs.

· Two new drugs have been marketed recently for treatment of influenza A and B. These are the neuraminidase inhibitors oseltamivir and zanamivir.

o Oseltamivir is taken orally (75 mg bid), and zanamivir is taken via an inhalation apparatus (10 mg bid for 5 d).

o The prophylactic dose is one half the acute treatment dose.

o Neuraminidase inhibitors have several advantages compared with amantadine, including less evolution of resistance, efficacy against influenza B, fewer adverse effects, and dramatic reduction in symptoms, even in patients who have a full course of flu.

o Advantages for prescribing these agents include significantly reducing illness severity and duration. Elderly and high-risk patients also have decreased secondary complications of influenza when treated with these agents.

o Disadvantages include potential adverse effects and costs. Adverse effects include potential bronchospasm with inhaled zanamivir and nausea, vomiting, and headache from oseltamivir.

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

Drug Category:

Antiviral agents

Drugs indicated for treatment of influenza include neuraminidase inhibitors (ie, oseltamivir and zanamivir) and amantadine and rimantadine.

Drug Category:

Vaccine.

Further Inpatient Care

· Hospitalization

o Most frequently, exacerbation of underlying chronic diseases by influenza may result in hospitalization. Some patients, especially elderly individuals, may be too weak to care for themselves alone at home.

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

Further Outpatient Care

· Patients who do not improve should return for further evaluation. Patients diagnosed with influenza infection 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.

Complications

• Primary Influenza Pneumonia (1% of adults)
• Increased risk with cardiac disease (Mitral Stenosis)
• Occurs 1 week after influenza symptom onset
• Occasionally fatal even in young adults
• Bacterial tracheobronchitis (occurs in 30% of adults)
• Increased risk in Tobacco smoking
• Acute Sinusitis (5-10%)
• Secondary Bacterial Pneumonia
• Occurs one week after influenza symptom onset
• Etiologies
• Streptococcal Pneumonia
• Staphylococcal Pneumonia
• Haemophilus Influenzae
• Risk factors
• Older than 65 years old
• Chronic renal disease
• Diabetes Mellitus and other endocrine disease
• Hematologic disease or Immunodeficiency
• Cardiopulmonary disease
• Rare Neurologic Complications
• Meningoencephalitis
• Transverse myelitis
• Reye's Syndrome
• Guillain-Barre Syndrome
• Myositis or Rhabdomyolysis
• Other rare complications
• Myoglobinuric Renal Failure
• Myocarditis
• Pericarditis
• Glomerulonephritis
• Parotitis

· Primary influenza pneumonia is characterized by progressive cough, dyspnea, and cyanosis following the initial presentation on the infection. CXRs show diffuse infiltrative patterns bilaterally, without consolidation, which can progress to a presentation similar to acute respiratory distress syndrome.

· Secondary bacterial pneumonia can occur from a number of bacteria (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae).

o The most dreaded is staphylococcal pneumonia, which develops 2-3 days following the initial presentation of viral pneumonia. Patients appear severely ill, with hypoxemia, an elevated white blood cell count, productive bloody cough, and a CXR showing multiple infiltrates. These patients are at risk for hypotension.

o 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. Because of increasing numbers of antibiotic-resistant staphylococcus emerging from the community, methicillin-resistant S aureus (MRSA) must be considered in any patient who develops pneumonia following an episode of influenza.

· 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.

Prognosis

· In patients without comorbid disease, the prognosis is very good, although some patients have a prolonged recovery time and remain weak and fatigued for weeks.

Rhinoviruses

Etioloogy

Rhinoviruses are in the Picornaviridae family, which includes the human pathogens, enteroviruses, and hepadnaviruses (notably, hepatitis A). Rhinoviruses are small, nonenveloped, positive (sense) stranded RNA viruses. Their structure is an icosahedral capsid of 12 pentamers containing the 4 viral proteins.

Rhinovirus infections are chiefly limited to the upper respiratory tract but may include otitis media and sinusitis. Rhinovirus plays a role in exacerbations of asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and patients who are immunocompromised.

Mortality/Morbidity:

Although not associated with fatal disease, rhinoviruses are associated with significant morbidity rates. Acute respiratory infections, predominantly rhinovirus infections, are estimated to cause 30-50% of time lost from work by adults and 60-80% of time lost from school by children. Complications of rhinovirus infections include otitis media, sinusitis, chronic bronchitis, and exacerbations of reactive airway disease in children and adults. These viruses are possibly involved in lower respiratory tract infections in elderly persons, infants, patients with cystic fibrosis, and patients who are immunosuppressed.

Age:

Disease occurs most frequently in children, with decreasing incidence as they approach adulthood. Children are instrumental in transmission of infection, commonly passing infection to family members after contracting the virus in nurseries, day care facilities, or schools.

Clinical

History:

Rhinoviral infections are typically indistinguishable from colds of other viral etiologies. Individual patients exhibit a wide variety of signs and symptoms.

· The incubation period is 12-72 hours, averaging 8-16 hours after viral inoculation of the nose. Symptomatic complaints 2 hours after viral inoculation have been described.

· Illness initially begins with a sore throat, which is frequently the most bothersome of the early symptoms. This is followed by nasal discharge, nasal congestion, and sneezing, which intensify over the next 2-3 days.

· Other associated complaints include headache, facial and ear pressure, and loss of smell and taste.

· Cough occurs in 30% of patients and hoarseness in 20%, both of which may persist up to a week, although they seldom become bothersome until nasal symptoms improve.

· Systemic signs and symptoms, such as fever and malaise, are unusual. If they are present, consider an alternative diagnosis.

· Symptoms generally last 7-11 days, although they persist up to 2 weeks in a quarter of patients. Rarely, patients may complain of lingering symptoms that last more than 30 days.

· Infants and toddlers may display only nasal discharge.

· Most patients have obstruction and mucosal abnormalities of sinuses, eustachian tubes, and middle ear, which causes a predisposition to secondary bacterial infection in up to 2% of patients.

· Infection may exacerbate underlying asthma and chronic pulmonary disease.

· People who smoke do not appear to have more frequent rhinovirus infections; however, their infections are more severe with longer duration of symptoms.

Physical:

The physical examination is typically unimpressive compared to the subjective complaints of the patient.

· Red nose with dripping nasal discharge may be present.

· Nasal mucous membranes have a glistening, glassy appearance without obvious erythema and edema. Yellow or green nasal discharge does not indicate bacterial infection because a large number of white blood cells migrate to the site of viral infection.

· If marked erythema, edema, exudates, or small vesicles are observed in the oropharynx or if conjunctivitis or polyps in the nasal mucosa occur, consider other etiologies, including adenovirus, herpes simplex virus, mononucleosis, diphtheria, Coxsackie A virus, or group A streptococcus (GAS).

· Auscultation of the chest may reveal rhonchi.

Lab Studies:

· Polymerase chain reaction (PCR) is currently available. This testing is faster and more sensitive than culture. Real-time PCR has been shown to be a rapid and effective way to detect rhinoviruses and has been proposed as the clinical method of detection. Furthermore, the use of nested PCR techniques have resulted in up to 20% of illnesses being attributed to more than one organism.

· Peripheral white blood cell counts may be elevated during the first 2-3 days of the infection, although use of common laboratory tests, such as complete blood count and erythrocyte sedimentation rate, are of virtually no benefit in managing rhinoviral infections.

Treatment

Drugs used in the symptomatic treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, and anticholinergic nasal solutions.

Drug Category:

Antihistamines -- These agents act by competitive inhibition of histamine at the H1 receptor.

Drug Category:

Anticholinergics -- These agents have antisecretory properties and, when applied locally, inhibit secretions from serous and seromucous glands lining the nasal mucosa.

Drug Category:

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- These agents have analgesic, anti-inflammatory, and antipyretic activities.

Deterrence/Prevention:

· Hand washing and avoidance of finger-to-eye and finger-to-nose contact are crucial to decreasing spread of infection. One study suggests that hand cleansers with salicylic acid and pyroglutamic acid prevent the transmission of rhinovirus as well as the number of patients who become clinically infected.

· Use of nasal tissue is encouraged because of possible aerosol spread of the virus.

Complications:

· Sinusitis: Viral infection of the sinus mucosa leads to alterations of sinus cavities, resulting in obstruction and entrapment of bacteria, such as Streptococcus pneumoniae and unencapsulated strains of Haemophilus influenzae, leading to bacterial sinusitis.

· Otitis media: Rhinoviruses have been suggested as both rare pathogens and as copathogens with bacteria in the etiology of otitis media. They have been recovered in middle ear fluid of people with otitis media and potentially allow secondary bacterial infection from obstruction secondary to mucosal changes in the eustachian tubes.

· Deep respiratory tract infections have been described in patients who are immunosuppressed, elderly persons, and infants and children with cystic fibrosis.

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