Influenza Virus: Everything About The Virus

Influenza is a communicable acute infectious disease that is caused by RNA-containing viruses and is characterized by the specific symptoms of intoxication and catarrhal signs of the upper respiratory tract.

Etiology:  Influenza viruses are negative-strand RNA viruses (ortomyxoviruses) of three major antigenic types - A, B, C. All have the property hemagglutination and possess the enzyme neuraminidase.

Epidemiology:

·       Source of infection is ill person with typical or atypical influenza.

·       Way of spreading - droplet with infected drops produced by coughing and sneezing.

·       Susceptible organisms – people of all age groups.

During periods of epidemic or pandemic spreading, respiratory infections by influenza may exceed all other etiology. Influenza infections have marked seasonality; epidemic occurs almost exclusively in winter month.

Pathogenesis:

1.     Inoculation of virus in upper respiratory tract epithelial cells.

2.     Destruction and necrosis of epithelial cells.

3.     Immune response.

4.     Viremia.

5.     Toxic influence of cardiovascular and central nervous systems.

6.     Depression of immunity response – bacterial complication.

7.     Allergy to viral parts – autoallergic complication.

Clinical criteria:

The incubation period of influenza ranges from few hours to 1-2 days, if contact transmission – up to 7 days, but is commonly 2 to 3 days.  The symptoms and signs of ''classic" influenza in older children include abrupt onset, with fever and associated flushes face, chills, headache, myalgia and malaise. The temperature range is from 39º C to 41º C. Although a dry cough and corryza are also early manifestation of influenza. A sore throat occurs in over half the cases and is associated with nonexudative Pharyngitis. Ocular symptoms include tearing, photophobia, burning, and pain with eye movement [ophthalmodynia]. In severe cases signs of toxic capillaritis with petechia on the face, chest, or hemorrhages into sclera may be present (photo 87, 88). In uncomplicated illness, the fever usually persists for 2 to 3 days, but may last up to 5 days. By the second to the fourth days, respiratory symptoms become more prominent, and the systemic complaints begin to subside. The cough is dry and hacking, and usually persists for 4 to 7 days. In young children laryngotracheitis, bronchitis, bronchiolitis, pneumonia, and the common cold all occur. Affected children appear moderately toxic, with clear nasal discharge, cough and irritability. Pharyngitis is usually present, with diffuse erythema and boggy, enlarged tonsilar tissue. Gastrointestinal symptoms have been noted in young children. Febrile convulsion may be in several studies. Acute laryngotracheitis [croup] has been noted as a prominent feature of influenza A.

Petechia on the face

Hemorrhage into sclera

Classification of influenza, diagnostic criteria

Etiology	Diagnostic Criteria	Severity	Severity Criteria	Course
flu А flu В flu С	1.   Epidemic growth of morbidity 2.     Expressed syndromes of intoxication. 3.     Acute beginning, fever, headache, muscular pain and poorly expressed catarrhal phenomena; neurotoxicosis, convulsive syndrome, encephalitic reactions 4.   Characteristic changes in the respiratory system (bronchitis, segmentary lung's edema, croup syndrome, hemorrhagic lung's edema) 5.     Positive immune-fluorescence and immune-enzyme tests	Mild (also subclinical)	body t° is normal or up to 38,5 °С, the toxic syndrome is slightly expressed or is absent	1. Smooth, without complications. 2. With the origin of virus-associated complications (encephalitis, serous meningitis, neuritis) 3. With the origin of bacterial complications (pneumonia, otitis, purulent-necrotizing laryngotracheitis)
		Moderate	bodу t° is 38,5-39,5°С, infectious toxicosis is expressed, probable: croup, segmental lung's edema of lights, abdominal or other signs
		Severe	t° 40-40,5 °С short loss of consciousness, delirium, cramps, hallucinations, vomit
		Hypertoxic	Hyperthermia, meningeal- encephalitic, hemorrhagic syndromes

By the type:

 ––  typical forms (catarrhal, subtoxic, toxic, toxic-catarrhal)

–– atypical forms (subclinical, hypertoxic)

Variants (by the main syndrome):

·                                        Croup syndrome,

·                                        Obstruction syndrome,

·                                        Primary lung’s damage,

·                                        Segmentary  lung’s damage,

·                                        cerebral syndrome,

·                                        abdominal syndrome,

·                                        hemorrhagic syndrome,

Peculiarities in infants:

·       less acute beginning,

·       less intoxication,

·       small respiratory  symptoms,

·       rare croup syndrome,

·       often dyspeptic syndrome (vomiting, diarrhea),

·       poor feeding,

·       decrease of body weight,

·       bacterial infection complications [otitis, pneumonia] and mortality appear more often.

Complications:    

1.     Viral: encephalitis, meningitis, neuritis.

2.     Bacterial: pneumonia, otitis, laryngotracheitis.

3.     Reye's syndrome.

   

Laboratory work-up:

·       Identifying of virus antigens in nasopharyngeal smears by immunefluorescence reaction.

·       Serologic diagnosis to find antibodies against viruses (CBR, DHAR) with fourfold increasing of antibodies title in 10-14 days may be used.

Diagnosis example: Influenza A, typical catarrhal form: tracheitis, moderate degree

Differential diagnosis between other respiratory viruses as parainfluenza, RS-infection, adenovirus infection and group A streptococcal diseases [angina, scarlet fever], typhoid fever, enterovirus infection, intestinal infections (shigella, salmonella, rotavirus ets.), meningococcal infection, pertussis, measles, viral hepatitis A.

  

Treatment: 

Hospitalization for patients with:

1. Flu-like diseases that are accompanied:

-         by cyanosis;

-         by dyspnea;

-         by physical changes in lungs;

-         by hemorrhagic displays: hemorrhagic rash, hemathemesis;

-         multiple vomit and diarrhea (over 3 times per day);

-         bradycardia as compared to an age-old norm; arrhythmia of other character;

-         by hypotension on 30% below the norm;

-         by violation of consciousness, cramps, surplus excitation or expressed languor.

2. Flu-like syndrome in children with concomitant diseases, which are risked to develop complications:

-         chronic pulmonary diseases, as bronchial asthma;

-         endocrine pathology – excessive weight more than 30%; severe diabetes mellitus;

-         immunedefficiencies – hemolytic anemia, primary immunedefficiencies, asplenia, hemoglobinopathies, HIV-infection, prolong immunosuppressive therapy, oncologic and oncohemathologic diseases, decompensated chronic cardio-vascular diseases; kidneys insufficiency.

3. Hospitalization by epidemiologic evidences:

-         children, that are in the closed child's collectives;

-         children from social risky families.

Treatment of patients with the severe flu mast be in hospital in the isolated boxes.

Basic therapy (for all patients independantly from the disease severity):

1.     Bed rest up to the normalization of body temperature.

2.     Vitaminized milk-vegetable food.

3.     Adequate rehydration with oral fluids (lemon tea, raspberry tea, warm alkalic drinks).

4.     Control of fever and myalgia (when the temperature is more than 38.5 °C in children elder 3 months); in children before 3 months and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is more than 38 °C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 5-10 mg/kg per dose, not often than every 6 hours. For better effect those two drugs may be given in order one by another with 4 hours interval between them (paracetamol 10 mg/kg, ibuprophen 5 mg/kg per dose). Acetylsalicylic acid medicine as antipyretic is contraindicated because of possible complication by the Reye’s syndrome!!!

5.     Nasal drops (in infants before 6 mo – only physiologic saline solutions as Salin; in elder children – decongestants: naphtizin, rhinasolin, nasivin for children 1-2 drops 3 t.d. in the nostrils, not more than 3-5 days).

6.     In case of dry cough - cough suppressors (such as dextramethorphan, synecod).

7.     Mucolytics in case of the moist nonproductive cough (ambroxol, acetylcystein etc.), are not recommended for the infants before 1 year.

8.     Histamine blockers of the 1st generation (2nd and 3rd are ineffective) as chlorpyramine (suprastin) 1-3 mg/kg decrease cough and sneezing. They should be used not more than 3-5 days because of the sleepiness effect.

• Combined mucolytics and antihystamines are not recommended before 6 years, and it is better not to use them in 6-12 years.

Before hospitalization to the department in severe cases SpO2 is measured:

·        If it is less than 90 % – an inhalation of 100 % O2 for an hour:

-         If it becomes normal – hospitalisation to the infectious department,

-         If it is still less than normal – hospitalisation to the intensive care unit.

·        If it is normal – hospitalisation to the infectious department.

Antiviral treatment (specific for influenza virus)

Antiviral treatment of severe, complicated forms, for the children with the chronic respiratory or cardiovasculary diseases, immune defficit, diabetes mellitus or obesity, children before 5 years, with chronic decompensated liver and kidneys diseases:

1. Oseltamivir (Tamiflu) – is effective against influenza A and B. It is given for children elder than 12 years 75 mg/dose in capsules 2 times a day, for children 1-12 years – in oral solution:

to 15 kg – 30 mg twice a day

15-23 kg – 45 mg twice a day

23-40 kg – 60 mg twice a day

* Solution is prepared according the instruction.

This medicine is appointed at first 48 hours from the disease beginning for 5 days.

2. Zanamivir (Relenza) is effective against influenza A and B – in inhalations from 5 years as medicine of the 2nd row (could provoke bronchial obstruction).

Broad spectrum Antiviral therapy (for mild and moderate forms in children elder than 5 years without concomitant diseases)

1. Arbidolum from 2 years (2-6 years 50 mg 4 times per day, 6-12 years 100 mg 4 times per day) for 5 days.

2. Remantadin is effective against seasonal influenza A, is given for children elder than 7 years for 3-5 days.

3. Inosini pranobex 50-100 mg/kg/daily in 3-4 doses for 5 days.

4. Synthetic interferon inductors: tiloron (amixin) from 7 years, cycloferon from 4 years, amizonum from 6 years.

Virus of influenza А (H1N1 California) is stable to Amantadine or Remantadine,

Amizonum.

Antiviral therapy of influenza А (H1N1 California) is indicated in severe cases

For mild and moderate forms antiviral therapy is not used.

Antiviral therapy influenza А (H1N1 California) also is indicated to people who are risked to develop complications.

Oseltamivir - to the children elder than 13 years is appointed in capsules 75 mg 2 times a day during 5 days. This medicine is appointed at first 48 hours from the disease beginning.

for children from 1 year and elder – in solution:

to 15 kg – 30 mg twice a day

15-23 kg – 45 mg twice a day

23-40 kg – 60 mg twice a day

* Solution is prepared according the instruction.

Virus of influenza А (H1N1 California) is stable to amantadine or remantadine.

Virus of influenza А (H1N1 California) is stable to Amizon.

Antibiotics are appointed

1. In case of complications caused by bacteria, micoplasm or chlamydia, as:

• Middle otitis

• Sinusitis

• Acute tonsillitis

• Bronchitis

• Pneumonia

2. At suspicion of secondary bacterial infection, children that are risky for bacterial infection development, with body temperature > 38 °C more than 3 days, leucocytosis more than 15 x 10⁹/l. Antibiotics from the following groups are used:

• Macrolydes (clarythromycin, azithromycin, spiramycin);

• Aminopenicillines protected by clavulanic acid (amoxacillin clavulanate);

• Cefoperason in combination with sulbactam (cefuroxim, cefpodoxim);

• Cephalosporines of 3rd-4th generation also are used;

• At presence of the methycillinresistant staphylococcus – vancomycin,

·        in case of nosocomeal pneumonia carbapenems are appointed.

Prevention specific

1.     Special prevention by immunization .Only inactivated influenza vaccines are licensed for use [whole virus vaccines and split-product]. Influenza vaccine is specially recommended for children 6 months of age and older. First time vaccineers less than 9 year of age need to receive two doses of vaccine separated by a 1-month interval.

2.     Remantadin, arbidol, recombined interpheron during 10-14 days.

An evidences to the obligatory vaccination of children:

-         Children with chronic broncho-pulmonary diseases;

-         Children with cardiac diseases with the changed hemodynamics;

-         Children with hemolytic anemia;

-         Children with diabetes mellitus;

-         Children, which receive immunosuppressive therapy;

-         Children with metabolic diseases;

-         Children with the chronic kidneys’ diseases;

-         Children, which get Acetylsalicylic acid therapy because of rheumatoid arthritis, and others like that;

-         Children with HIV-infection;

-         Children, which are in the closed child’s establishments.

A vaccine must be entered 1-1,5 months prior to the seasonal growth of influenza morbidity (in September-November).

All other people vaccination against influenza can be done because of necessity or at pleasure.

Prophylaxis of influenza (nonspecific):

-         To avoid a contact with people which have displays of influenza infection;

-         To limit visits of places with large accumulation of people;

-         To ventilate an apartment oftenly;

-         To teach children to wash hands with soap during 20 seconds;

-         To teach children to cough and sneeze in a serviette;

-         To aim not to touch eyes, nose or mouth by unwashed hands;

-         To avoid cuddles, kisses and greeting by hands;

-         To cover a nose and mouth at a sneeze or cough by nasal serviette which at once it is needed to throw out after the use;

-         To teach children not to stay with the patients nearer than on one and a half – two meters;

-         Ill children must stay at a home (not to visit preschool establishments and schools);

-         The moist cleaning up of apartments is needed not less than two times a day.

Key words and phrases: influenza, acute respiratory infection, way of spreading,

susceptible organism, inoculation of the virus, incubation period, flushed face, chills, dry

cough, corryza, ocular symptoms, ophthalmodynia, boggy, croup, Reye’s syndrome.

Key words and phrases: viral upper respiratory tract infections, common cold, Croup,

mist tent, humidification, Ribavirine, parainfluenza, adenovirus, RS-virus, rhinovirus.

References

Main:

1.     Ambulatory pediatric care\ edited by Robert A. Derchewitz;-2- nd ed. Lippincot-Raven, 1992.- P.602-605, 611-615, 618-623, 753-755.

2.     Current therapy in pediatric infections disease-2\ edited by D.Nelson, M.D.-B.C.Decker Inc. Toronto. Philadelphia, 1988- P. 38-40, 44-45, 49-51.

3.     Principles and Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry K. Pickering, Charles G. Prober, Philadelphia, Pa: Churchill Livingstone; 1997. – 1921 p.

Additional:

1.     Textbook of Pediatric Nursing.  Dorothy R. Marlow; R. N., Ed. D. –London, 1989.-661p.

2.     Pediatrics ( 2^nd edition, editor – Paul H.Dworkin, M.D.) – 1992. – 550 pp.