EPIDEMIOLOGY OF EPIDEMIOLOGY OF RESPIRATORY RESPIRATORY

TRACT INFECTIONSTRACT INFECTIONS

RRespiratory tract is usually espiratory tract is usually divided into three segmentsdivided into three segments

• The Upper Respiratory tract: This The Upper Respiratory tract: This includes the nose, paranasal includes the nose, paranasal sinuses, and throat.sinuses, and throat.

• The Respiratory Airways: This The Respiratory Airways: This includes the trachea, bronchi, and includes the trachea, bronchi, and bronchioles.bronchioles.

• The Lungs: This includes the The Lungs: This includes the respiratory bronchioles, alveolar respiratory bronchioles, alveolar ducts, alveolar sacs, and the ducts, alveolar sacs, and the alveoli. alveoli.

The following defense mechanisms in The following defense mechanisms in the alveoli protect the parenchymal the alveoli protect the parenchymal

cells from invasion by microorganismscells from invasion by microorganisms– Alveolar macrophages (the most important)Alveolar macrophages (the most important)– Complement componentsComplement components– Alveolar lining fluid containing surfactant, Alveolar lining fluid containing surfactant,

phospholipids, neutral lipids, IgG, IgE, IgA, phospholipids, neutral lipids, IgG, IgE, IgA, secretory IgA, certain complement secretory IgA, certain complement components, Factor B, and other unidentified components, Factor B, and other unidentified agents that maybe important in activation of agents that maybe important in activation of alveolar macrophagesalveolar macrophages

– B cells, T cells, and null cells that can elicit a B cells, T cells, and null cells that can elicit a localized immune response to infectionlocalized immune response to infection

– Lymphoid tissue associated with the lungsLymphoid tissue associated with the lungs

Mechanisms used to avoid Mechanisms used to avoid

phagocytosisphagocytosis – Capsule productionCapsule production. (. (S. pneumoniae, H. influenza, B. S. pneumoniae, H. influenza, B.

anthracis, N. meningitidis, K. pneumoniaeanthracis, N. meningitidis, K. pneumoniae))

– Toxin productionToxin production. These toxins could include cytotoxins, . These toxins could include cytotoxins, leukocidins, and exotoxins. (examples; leukocidins, and exotoxins. (examples; S. aureus S. aureus produces produces leukocidins and cytotoxins.leukocidins and cytotoxins. P. aeruginosa P. aeruginosa produces exotoxin produces exotoxin A which destroys cells much like the diphtheria toxin does.)A which destroys cells much like the diphtheria toxin does.)

– Being Being too largetoo large to phagocytize. Parasites and fungi are often to phagocytize. Parasites and fungi are often too large for the phagocyte to engulf.too large for the phagocyte to engulf.

– Replication inside cellsReplication inside cells. Viruses and . Viruses and ChlamydiaChlamydia sp. are sp. are obligate intracellular parasites that replicate inside the cells obligate intracellular parasites that replicate inside the cells of the lung avoiding the phagocyte.of the lung avoiding the phagocyte.

– MimicryMimicry. Some parasites produce surface proteins which are . Some parasites produce surface proteins which are very similar to host proteins or acquire host proteins and very similar to host proteins or acquire host proteins and appear to the phagocyte as self. Some bacteria produce appear to the phagocyte as self. Some bacteria produce proteins that cause host proteins to bind to their surfaces proteins that cause host proteins to bind to their surfaces (ex. protein A/(ex. protein A/Staphylcoccus aureusStaphylcoccus aureus))

Mechanisms used to survive in the Mechanisms used to survive in the phagocyte phagocyte

Inhibition of lysosome fusion with the phagosome. Inhibition of lysosome fusion with the phagosome. ((Toxoplasma gondii, Aspergillus sp., Chlamydia psittaciToxoplasma gondii, Aspergillus sp., Chlamydia psittaci))

Escape from the phagosome. (Escape from the phagosome. (Mycobacterium leprae, Mycobacterium leprae, Trypanosoma cruziTrypanosoma cruzi, Influenza virus escapes the , Influenza virus escapes the phagolysosome)phagolysosome)

Resistance to killing and digestion in the Resistance to killing and digestion in the phagolysosome. (phagolysosome. (Mycobacterium tuberculosis, Nocardia Mycobacterium tuberculosis, Nocardia sp., Yersinia pestis)sp., Yersinia pestis)

Growth in the phagocytic cell. (Growth in the phagocytic cell. (M. tuberculosis, M. tuberculosis, Legionella pneumophilaLegionella pneumophila, Cytomegalovirus), Cytomegalovirus)

Entry into the phagocyte other than by phagocytosis. Entry into the phagocyte other than by phagocytosis. Some organisms avoid destruction by getting into the Some organisms avoid destruction by getting into the phagocyte's cytoplasm. No phagosome-lysosome fusion phagocyte's cytoplasm. No phagosome-lysosome fusion occurs and the organisms can survive in the phagocyte. occurs and the organisms can survive in the phagocyte. ((Toxoplasma gondiiToxoplasma gondii, some enveloped viruses), some enveloped viruses)

Nonbacterial Agents that Cause Upper Nonbacterial Agents that Cause Upper Respiratory Tract Infections of ManRespiratory Tract Infections of Man

Agents Human Serotypes Nucleic Acid Types

Date of Discovery

Myxoviruses

Influenza A, B, C RNA 1933-1949 

Parainfluenza  1, 2, 3, 4  RNA 1953Respiratory Syncytial Virus 1 (maybe 2)  RNA  1956

Coronaviruses  1 RNA  1965 

Picornaviruses

Rhinoviruses- most common cause. > 100 types RNA  1960s 

Coxsackie virus A  24 (perhaps only A21 causes respiratory illnesses)  RNA  1948

Coxsackie virus B 6 (perhaps only B4, B5 cause respiratory illnesses)  RNA  1948 

Echoviruses  31 (perhaps only types 11, 20, 25 cause respiratory illnesses)  RNA 1950s

Adenoviruses 34 (types 1, 2, 3, 5, 7, 14, 21 are responsible for respiratory illnesses)  DNA  1953 

Mycoplasma pneumoniae 1  DNA +

RNA  1944

Flu and other Flu and other respiratory tract respiratory tract

infectionsinfections

Main nosologic formsMain nosologic forms

InfluenzaInfluenza;; Parainfluenza;Parainfluenza; RSV infectionsRSV infections;; rhinovirus rhinovirus

infectionsinfections;; adenovirus adenovirus

infectionsinfections..

((Flu, influenzaFlu, influenza)) - -

Acute viral illness with the direct Acute viral illness with the direct mechanism of transmission of mechanism of transmission of agent, distribution epidemic agent, distribution epidemic and pandemic; it is characterized and pandemic; it is characterized by the infection of respiratory by the infection of respiratory tracts, expressed intoxication, tracts, expressed intoxication, fever and moderate catarrhal fever and moderate catarrhal phenomena.phenomena.

Key factsKey facts Influenza is an acute viral infection that Influenza is an acute viral infection that

spreads easily from person to person.spreads easily from person to person. Influenza circulates worldwide and can affect Influenza circulates worldwide and can affect

anybody in any age group.anybody in any age group. Influenza causes annual epidemics that peak Influenza causes annual epidemics that peak

during winter in temperate regions. during winter in temperate regions. Influenza is a serious public health problem Influenza is a serious public health problem

that causes severe illnesses and deaths for that causes severe illnesses and deaths for higher risk populations.higher risk populations.

An epidemic can take an economic toll An epidemic can take an economic toll through lost workforce productivity, and through lost workforce productivity, and strain health services.strain health services.

Vaccination is the most effective way to Vaccination is the most effective way to prevent infection.prevent infection.

Flu agents–RNA-containing Flu agents–RNA-containing virions, size varying from 80 virions, size varying from 80

to 120 nmto 120 nm

Different viral antigens of Different viral antigens of influenza A:influenza A:

19181918 A.D A.D– – H1N1;H1N1;

1957A.D– H2N2;1957A.D– H2N2;

1968A.D– H3N2;1968A.D– H3N2;

1977A.D– H3N2 and1977A.D– H3N2 and H1N1.H1N1.

INFLUENZA VIRUS INFLUENZA VIRUS

FORMULAFORMULA::

А/А/SingaporeSingapore/1/57//1/57/H2N2H2N2А/А/HonkongHonkong/1/68//1/68/H3N2H3N2А/А/VictoriaVictoria/35/72//35/72/H3N2H3N2A/Texas/36/91/H1N1A/Texas/36/91/H1N1

SOURCES OF INFECTIONSOURCES OF INFECTION::

Healthy person in the latent periodHealthy person in the latent period;;

Patient during whole periodPatient during whole period

Disease lasting -7 daysDisease lasting -7 days

Recovery– it is proved that in Recovery– it is proved that in individuals a virus can be conserved up individuals a virus can be conserved up to 14-15 daysto 14-15 days

BirdsBirds. .

Epidemiology: • zoonotic• source of infection – poultry • mechanism of transmission – droplet?, fecal-oral?

contact? • receptivity: mostly children

Infectious agent: H5N1, H7N7, H9N2

Clinic: Flu-like symptoms:

fever, sensitivity to cold, headache, pain in muscles and throat symptoms of eyes infection pneumonia

History: in 1997 in to Hong Kong, virus H5N1 (18 people became ill, 6

died); in 1999 in to Hong Kong, virus H9N2 (became ill 2 children); in 2003 in to Hong Kong, virus H5N1 and H9N2 (became ill 3

persons, a 1 man died);in 2003 in Netherlands the virus H7N7 (89 people became ill, a 1 person

died);in 2004 – flash of bird flu H5N1 among people in China, Thailand,

Vietnam (35 persons died).Features of virus of bird flu 2004: The virus became more virulent, that testifies to his mutation The virus overcame an inter-specific barrier from birds to the man,

however while there are no proofs of that an exciter is passed straight from a man to the man (all sick people had the direct contact with the infected birds)

The virus will strike children mainly the source of exciter and ways of distribution of virus are not certain, that

does a situation with distribution of virus not by practically controlled one

measures on prevention to distribution – complete elimination all total number of birds of livestock

Classification of fluClassification of flu ((J10J10))

SerologicSerologic typetypess of virus: A (H1N1), of virus: A (H1N1), (H2N2), (H3N2), (H2N2), (H3N2), BB, , CC..

Clinical forms: typical, atClinical forms: typical, atypicalypical (afebril(afebrilee, acatar, acatarrhrhal, al, hyper-acutehyper-acute).).

Degree of Degree of severityseverity: : mildmild, , moderatemoderate, , severesevere, , very severevery severe..

Complication: pneumonia, otitis, Complication: pneumonia, otitis, sinusinussitiitiss, tonsillitis, encephalitis, , tonsillitis, encephalitis, meningmeningoeoenncephalitiscephalitis, , pyelonephritis, ppyelonephritis, pyyeloelocystitiscystitis, , ccholangitholangitisis and and othersothers..

Clinical differences of flu and other ARIClinical differences of flu and other ARI

DiseaseDisease BeginningBeginning Body Body TemperatureTemperature

IntoxicatioIntoxicationn

Damage of respiratory pathwaysDamage of respiratory pathways

Other damagesOther damages

OftenOften Rare Rare

Influenza (flu)Influenza (flu) Acute Acute Febrile Febrile (3-5 (3-5 daysdays))

DevelopedDeveloped Trachitis Trachitis BronchitisBronchitis --

Para-influenzaPara-influenza Progressive, Progressive, rarely acuterarely acute

Sub-febrile Sub-febrile ((tilltill 2 2 weeksweeks))

ImmeasuraImmeasurable ble LaryngitisLaryngitis

Rhino-Rhino-pharyngitis, pharyngitis,

trachitistrachitis--

Adenoviral Adenoviral infectioninfection

Progressive, Progressive, acuteacute

Febrile Febrile ((may may present > 5 present > 5

daysdays, , minimum minimum 5 5 daysdays))

Mild Mild PharyngitisPharyngitis, , rhinitisrhinitis Pneumonia Pneumonia

Kerato-conjuctivitisKerato-conjuctivitis, , lymphoadenopathy, lymphoadenopathy,

hepato-hepato-splenomegaly.splenomegaly.

Respiratory Respiratory synctal viral synctal viral

infectioninfection

Acute and Acute and progressiveprogressive

Sub-febrileSub-febrile, , rarely highrarely high (1-2 (1-2

weeksweeks))Mild Mild Bronchiolitis Bronchiolitis

Rhino-Rhino-pharyngitis, pharyngitis, laryngitis, laryngitis, bronchitisbronchitis,, pneumoniapneumonia

Rhinoviral Rhinoviral infectioninfection Acute Acute Normal or sub-Normal or sub-

febrilefebrile (1-3 (1-3 daysdays))Absent Absent

Rhinitis, Rhinitis, serous serous

secretionssecretions-- --

Differential Differential diagnosis:diagnosis:

tonsillitistonsillitis;;

ornitoornitosissis;;

measles;measles;

enterovirous illness;enterovirous illness;

typhoid;typhoid;

viral hepatitis;viral hepatitis;

pneumonia;pneumonia;

inflammation of additional inflammation of additional cavities of nose.cavities of nose.

TreatmentTreatment

amantadineamantadine rimantadinerimantadine Zanamivir Zanamivir (Relenza) (Relenza) oseltamiviroseltamivir (Tamiflu) (Tamiflu) ribavirinribavirin

WHO recommends annual WHO recommends annual vaccination for (in order of vaccination for (in order of

priority)priority)

nursing-home residents (the elderly or nursing-home residents (the elderly or disabled)disabled)

elderly individualselderly individuals people with chronic medical conditionspeople with chronic medical conditions other groups such as pregnant women, other groups such as pregnant women,

health care workers, those with health care workers, those with essential functions in society, as well essential functions in society, as well as children from ages six months to as children from ages six months to two years. two years.

Influenza vaccines are Influenza vaccines are available in two forms:available in two forms:

an intramuscular preparation an intramuscular preparation containing formalin-inactivated containing formalin-inactivated virus and purified surface virus and purified surface antigenantigen

an intranasal spray containing an intranasal spray containing live attenuated viruseslive attenuated viruses

VaccinesVaccines :: The “VaThe “Vaxxigrip” firms of Paster Marigrip” firms of Paster Markk ““FlFluuoriorixx” firms Smit” firms SmithhClyayn BichemClyayn Bichem ““Influvac” firms Solvey FarmaInfluvac” firms Solvey Farma Influenza vaccine “Influvac”Influenza vaccine “Influvac”:: components components

A/Sydney/455/97/H3N3A/Sydney/455/97/H3N3, , A/Beijing/263/95/H1N1 and B/Beijing/184/93A/Beijing/263/95/H1N1 and B/Beijing/184/93..

It is intended for adults children. Enter It is intended for adults children. Enter intramuscular or deeply hypodermic. A intramuscular or deeply hypodermic. A protective effect is achieved in 10 days after protective effect is achieved in 10 days after introduction. Proceeds during 1 year.introduction. Proceeds during 1 year.

This preliminary negative stained transmission This preliminary negative stained transmission electron micrograph depicts some of the electron micrograph depicts some of the

ultrastructural morphology of the A/CA/4/09 swine ultrastructural morphology of the A/CA/4/09 swine flu virus.flu virus. Courtesy of CDC/ C. S. Goldsmith and A. Balish. Courtesy of CDC/ C. S. Goldsmith and A. Balish.

Phase 6 criteria: In addition to the criteria defined in Phase 6 criteria: In addition to the criteria defined in Phase 5, the same virus has caused sustained Phase 5, the same virus has caused sustained

community-level outbreaks in at least one other community-level outbreaks in at least one other country in another WHO region. Courtesy of the country in another WHO region. Courtesy of the

WHO. WHO.

AdenovirusAdenovirus

Conjunctivitis duringConjunctivitis during adenoviral infections:adenoviral infections:

Pharyngo-conjunctivit is Pharyngo-conjunctivit is feverfever

TreatmentTreatment:: Bed regimenBed regimen milk-vegetable vitamin dietmilk-vegetable vitamin diet inhalations with addition in the inhalations with addition in the

aerosol of lemon acid 1:1000 or aerosol of lemon acid 1:1000 or juice of lemon, boric acid 1:100juice of lemon, boric acid 1:100

reflex-therapy and laser-therapyreflex-therapy and laser-therapy antiviral preparations: remantadin, antiviral preparations: remantadin,

leucocytic interferon, amixin, leucocytic interferon, amixin, cycloferon, amizoncycloferon, amizon

Indication for antibiotic Indication for antibiotic therapytherapy

Very severe flu (hyper toxic form Very severe flu (hyper toxic form with the phenomena of encephalitis, with the phenomena of encephalitis, beginning from pneumonia)beginning from pneumonia)

flu in children the first 2 years of flu in children the first 2 years of life, pregnant, very weakened, life, pregnant, very weakened, persons senile and old agepersons senile and old age

bacterial complicationsbacterial complications accompanying chronic diseasesaccompanying chronic diseases

Prophylaxis of flu and other Prophylaxis of flu and other ARI:ARI:

Seasonal Seasonal measuresmeasures

Increasing the Increasing the resistance of personsresistance of persons, , reflexotherapy, UV-reflexotherapy, UV-raysrays

Inductors of Inductors of interferon secretioninterferon secretion

adaptogens adaptogens ((extract extract eleoterococa, tincture eleoterococa, tincture arali, gin-singarali, gin-sing))

Urgent Urgent measuresmeasures

Antiviral drugsAntiviral drugs ImmunostimulatorsImmunostimulators ointment of oxolineointment of oxoline Leukocytic interferonLeukocytic interferon Anti-influenza Anti-influenza

immunoglobulinimmunoglobulin