respiratory tract diseases final

8/2/2019 Respiratory Tract Diseases Final

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RESPIRATORY TRACTDISEASES


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UPPER RESPIRATORY TRACT DISEASES

The respiratory tract is the most common site of

infection by pathogens. Each year, children acquire between two and five

upper respiratory tract infections and adults acquireone or two infections.

The respiratory tract is a frequent site of infectionbecause it comes in direct contact with the physicalenvironment and is exposed to airbornemicroorganisms.

A wide range of organisms can infect the respiratorytract, including viruses, bacteria, fungi, and parasites(Table -1).


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Table R-1. Common Causes of Various Respiratory Diseases by LocationDisease Location Disease Group of Pathogen CommentsUpper respiratory tractNasal passages Common cold Viruses Most common cause

rhinovirusNasal sinuses Rhinosinusitis Viruses

Bacteria

Viruses are most

common cause of

rhinosinusitisPharynx Pharyngitis Viruses

Streptococcus

pyogenes and

Corynebacterium

diphtheriae

Viruses cause 90% of

these infections

Respiratory airways

Epiglottis Epiglottitis Bacteria Usually Haemophilus

influenzae type bTrachea and bronchi Bronchitis,

tracheobronchitis,

croup, laryngitis

Viruses Usually caused by

viruses

Bronchioles Bronchiolitis Viruses Most common causeis respiratory

syncytial virusLower respiratory tractAlveoli and alveolar

sacs

Pneumonia Bacteria Most common cause

in adults is

Streptococcuspneumoniae


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Most of the surfaces of the upper respiratory tract(including nasal and oral passages, nasopharynx,oropharynx, and trachea) are colonized by normalflora, which are regular inhabitants and rarely causedisease.

The normal flora of the upper respiratory tract hastwo main functions that are important in maintainingthe healthy state of the host: (1) These organisms

compete with pathogenic organisms for potentialattachment sites, and (2) they can producesubstances that are bactericidal and preventinfection by pathogens.

There are no resident bacteria in the lowerrespiratory tract.

Organisms that manage to enter the alveoli areusually eliminated by alveolar macrophages.

Most bacteria (e.g., Streptococcus pneumoniae,Klebsiella pneumoniae, Haemophilus influenzae) that


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Protective Mechanisms Normal flora: Commensal organisms Limited to the upper tract Mostly Gram positive or anaeorbic Microbial antagonist (competition)

Clearance of particles and organisms from the

respiratory tractCilia and microvilli moveparticles up to the throatwhere they are swallowed.

Alveolar macrophagesmigrate and engulf particlesand bacteria in the alveolideep in the lungs.


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Other Protective Mechanisms

Nasal hair, nasal turbinates Mucus Involuntary responses (coughing) Secretory IgA

Immune cells


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There are two main obstruction a bacterium or virus mustovercome in order to initiate an infection in therespiratory tract.

The microorganism must avoid being caught up in the

mucus layers of the upper respiratory tract, beingtransported to the back of the throat, and eventuallybeing swallowed.

If the invader has avoided the physical defense

mechanisms of the upper respiratory tract, and isdeposited in the lower respiratory tract or lung, it musteither avoid phagocytosis, or be able to survive andmultiply in the phagocytic cell.

Mechanisms Used By Respiratory Tract Pathogens ToInitiate Disease A. Before a respiratory disease can be established, the

following conditions need to be met. There must be a sufficient number or sufficient "dose"

of micob.


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B. Once a respiratory tract pathogen is in the respiratorytract, it is essential that it colonize these surfaces before ican cause obvious disease.

Most microorganisms cause disease by only a fewpathogenic mechanisms. A few of these mechanisms,especially those used by respiratory tract pathogens arediscussed below.

Bacterial adherence factors = F and M proteins ofStreppyogenes, Hemagglutinins ofB. pertussis. Extracellular toxins = diphtheria toxin; pertussis toxin. Growth in host tissue = viruses, chlamydia sp. Evasion of host defense mechanism = capsules of

Strep. pyogenes (also M protein), S. pneumoniae and H.influenzae by inhibiting phagocytosis.


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Respiratory Tract Pathogens = Wide Ranges ofOrganisms

Viruses = Rhinoviruses, RSV, Adenoviruses,Influenza, Parainfluenza

Group A streptococci = pharyngitis Other streptococci = S. pneumoniae = sinusitis,

Group B = pneumonia of infants Other microorganisms = C. diphtheriae, M.

pneumoniae, Fungi Parasites Upper Respiratory Tract Pathogens

Common cold = mostly viruses Acute otitis media = viral, bacterial, or fungal

pathogens Sinusitis = Bacteria = S. pneumoniae, H. influenza

Pharyngitis = 90% viruses, important bacteria = S.o enes and C. di htheriae

I Th C C ld


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I. The Common Cold The common cold is caused by a multitude of

organisms; about 90% of cases are due to viruses. Etiology Most cases of the common cold are caused by

rhinoviruses; there are at least 100 immunologicallydistinct rhinoviruses. Other causes of the common coldare listed in Table -2.Table URI-2. Some Infectious Agents that Cause the Common ColdAgents* Human Serotypes

Myxoviruses

Influenza A, B, C

Parainfluenza 1, 2, 3, 4

Respiratory syncytial virus 1 (possibly 2)

Human metapneumovirus 1

Coronaviruses 1

Picornaviruses

Rhinoviruses (most common cause) > 100 types

Coxsackievirus A 24

Coxsackievirus B 6

Echoviruses31 (only types 11, 20, and 25 may cause

respiratory illnesses)

Adenoviruses 34 (types 1, 2, 3, 5, 7, 14, and 21 areresponsible for respiratory illnesses)


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Diagnosis Diagnosis of the common cold is dependent on the

patients symptoms, localization of the disease process,

time of year. Laboratory culture of the viruses and serologic testing

is rarely performed. Therapy and Prevention

The studies on the use of zinc acetate lozenges andnasal gel containing zinc gluconate are mixed.

Others say they are of no help in treating patients withthe common cold.

Regular intake of large doses of vitamin C (0.2 gm/day)may shorten the duration of the illness and decreasethe severity of symptoms of the common cold.

Handwashing and disinfecting contaminated objectscan help to avoid acquiring the common cold as well asavoiding contact with others during the cold season.


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Pharyngitis Pharyngitis (sore throat) can be caused by many

different microorganisms; however, 90% of sorethroats in adults and 6075% of sore throats inchildren are caused by viruses (Table -3). S

pyogenes (-hemolytic group A Streptococcus) isthe most common bacterial cause of acutepharyngitis.

Table URI-3. Some Viral Causes of Pharyngitis*

Virus Associated Disorder or Symptom Occurrence in Pharyngitis

Rhinovirus Common cold Common

Coronavirus Common cold CommonAdenovirus Pharyngoconjunctival fever and acute

respiratory disease

Common in military recruits and boarding

schools

Herpes simplex virust ypes 1 and

2

Gingivostomatitis Common

Parainfluenza virus Cold and croup Common in children

Coxsackie virus A Herpangina (high fever, vomiting, diarrhea,

abdominal pain) and hand-foot-and-mouthdisease

Common

Influenza A and B viruses Influenza Common during flu season

Respiratory syncytial virus Bronchiolitis and croup Common in children

Epstein-Barr virus Infectious mononucleosis Common in adolescents during winter

Cytomegalovirus CMV mononucleosis Less common

Human immunodeficiency virus Primary HIV infection Infrequent (homosexual males and

heterosexual females at highest risk)*Viruses are the most common cause of pharyngitis.


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Pathogenesis In viral pharyngitis, viruses gain access to the

mucosal cells lining the nasopharynx and replicate inthese cells.

Damage to the host is often caused by damage to thecells where the viruses are replicating.

In bacterial pharyngitis, S pyogenes attaches tothe mucosal epithelial cells using M protein,lipoteichoic acid, and fibronectin-binding protein(protein F). It has a capsule composed of hyaluronicacid that prevents phagocytosis.

Rheumatic fever and glomerulonephritis still occurfollowing throat infections caused by S pyogenes.

An autoimmune reaction occurs in some patients


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Streptococcus pyogenes

Gram positivestreptococci

Carried andtransmitted from the

throat In Respiratorysecretions


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Group A Strep

Capsule -resistant tophagocytosis Enzymes damage

host cells M protein adhesin

The M protein has many antigenic varietiesand thus, different strain ofS.pyogenescause repeat infections


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Strep Throat

Fever Tonsillitis

Enlarged lymphnodes

Middle-ear

infection


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Infected

Middle Ear(otitis media)


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Diagnosis Viral infections of the throat are rarely cultured

because of the mild self-limiting.

There are fewer cases of bacterial infections of thethroat (compared to viral pharyngitis); however,delaying treatment ofS pyogenes pharyngitis beyond 9days after symptoms begin increases the patientschances of developing rheumatic fever .

Therefore, strategies for diagnosis of acute pharyngitisinfections are primarily directed at identifying patientswith S pyogenes pharyngitis who require antimicrobialtherapy.

The best means of determining which etiologic agentis causing the pharyngitis is to swab the patientsthroat, culture the sample on blood agar plates, anddemonstrate the growth of -hemolytic colonies thatare catalase-negative, gram-positive cocci and aresensitive to bacitracin. S pyogenes rapid antigen

Therap and Pre ention


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Therapy and Prevention Viral pharyngitis is treated with analgesics (e.g.,

acetaminophen), and warm saline gargles. These treatments will help lessen the pain Susceptible persons should be encouraged to limit

contact with infected persons. An adenovirus vaccine isavailable for military personnel, but it is not permit foruse in the general population.

S pyogenes pharyngitis requires the use of anantimicrobial agent Penicillin remains the drug ofchoice to treat S pyogenes pharyngitis; erythromycin is

the drug of choice for patients allergic to penicillin.Patients should be encouraged to limit contact withuninfected persons.

DIPHTHERIA


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DIPHTHERIA Diphtheria is a bacterial disease that is now rarely seen

because of successful universal vaccination. Thevaccine does not affect the ability of the bacteria to

colonize the oropharynx, however, but rather inducesantibody production to inhibit diphtheria toxin.

Etiology Corynebacterium diphtheriae is irregularly staining

gram-positive, rod-shaped bacteria. Only strains ofCdiphtheriae that have toxin-producing lysogenicbacteriophage (b phage) can cause diphtheria.

Manifestations

Diphtheria results in pharyngeal pain, formation of apseudomembrane seen on the tonsils and back of theoropharynx, regional lymphadenopathy (bull neckappearance), edema of the surrounding tissues, fetidbreath, low-grade fever, and cough. Airway obstruction

can occur.


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Diphtheria Transmitted by droplets or fomites Infects the upper respiratory tract Begins with severe sore throat, low-grade fever and

swollen lymph nodes or with skin rash, 1-6 days afterinfection


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Corynebacterium diphtheriae

Aerobic Gram + bacillusToxin inhibits protein

synthesis of cells to which itbinds

Destroyed cells and WBC

form "pseudomembrane"which blocks airways


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Diphtheria


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An AB toxin

B = bindingsubunit

A = activesubunitwhich binds to

and inhibits a

eucaryoticribosomaltranslation factor

Vaccine isdi htheria toxoid


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Diagnosis Diagnosis of diphtheria includes observation of a

pseudomembrane and bleeding upon removal of the

membrane and severe cervical lymphadenopathy. The oropharynx should be swabbed and samples

cultured for C diphtheriae. The C diphtheriae strainisolated by culture should be assayed for diphtheriatoxin production using the Elek test (immunodiffusion

assay) or by polymerase chain reaction (PCR). Treatment and Prevention A patient with diphtheria should be hospitalized, placed

in isolation, and immediately treated with antiserum to

the toxin. The second most immediate task is antimicrobial

treatment with penicillin or erythromycin. The patientshould also be given diphtheria vaccine to ensure

immunity to the disease. Active immunization with theDTP vaccine for children and the DT vaccine for adults


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Bacterial Pneumonia

Bacterial, viral or fungal infection can causeInflammation of the lung .


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Pneumomoccal Pneumonia


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Pneumococcal Pneumonia

Streptococcuspneumoniae Diagnosis by culturing

bacteria Penicillin is drug of choice Leading cause of

meningitis Often secondary

infection following

influenza virus


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Legionella pneumophila: Gram-negative rod L. pneumophila is found in water Transmitted by inhaling aerosols, not transmitted from

human to human Pontiac fever is a less deadly form of legionellosis Diagnosis: culturing bacteria Treatment: Erythromycin

Legionellosis


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Bordetella pertussis

Gram negativecocco-bacillus

Capsule Adherence to

ciliated cells

Pertussis toxin is A-B toxin


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Pertussis (Whooping Cough)

Cough Violent coughing

followed by whoopingsound Vaccine it is made of

purified components

Not lifelong immunity adult carriers


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Mycobacterium tuberculosis

Thick lipid coat

of Mycolic fatty acids

Grows very slowly Resists killing by

macrophages and

grows in them


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Tubercule formation

A tubercle in the lung is a

granulomaconsisting of a central core of TBbacteria inside an enlargedmacrophage, and an outer wall

of fibroblasts, lymphocytes,and neutrophils


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Tuberculosis

Primary Lung tubercles, caseous, tuberculin skin

reaction Secondary (reactivation)

Consumption: Coughing and chronicweight loss

Dissemination Extrapulmonary TB (lymph nodes, kidneys,

bones, genital tract, brain, meninges)


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Tuberculosis

Elimination requires longantibiotic treatment withcocktail of antibioticsbecause of the resistance

that develops. The two antibiotics most

commonly used arerifampicin and isoniazid.

TB requires much longerperiods of treatment(around 6 to 24 months) tocompletely eliminatemycobacteria from thebody
http://en.wikipedia.org/wiki/Rifampicinhttp://en.wikipedia.org/wiki/Isoniazidhttp://en.wikipedia.org/wiki/Isoniazidhttp://en.wikipedia.org/wiki/Rifampicin


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TB Skin Test


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Virus infections

Respiratory syncytial virus (RSV) Influenza virus

Fungal InfectionsCoccidiodomycosis (Valley Fever)

Coccidioides immitis Histoplasma capsulatumOpportunistic fungi involved in respiratory disease:

AspergillusRhizopusMucor


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Respiratory Syncytial Virus

Enveloped (membrane) RNA virus Spread by respiratory droplets Community outbreaks in late fall to spring Upper respiratory tract infection epithelial cells

May be fatal in infants Common in infants; 4500 deaths annually Causes cell fusion (syncytium) in cell culture Symptoms: coughing Diagnosis by serologic test for viruses and

antibodies Treatment: Ribavirin

Influenza Virus


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Influenza VirusIn virus classification influenza viruses are RNA virusesthat make up three of the five genera of the familyOrthomyxoviridae:

InfluenzavirusAInfluenzavirusBInfluenzavirusC

Chills, fever, headache, muscle pain (no intestinalsymptoms)1% mortality due to secondary bacterial infections

Treatment: AmantadineVaccine for high-risk individuals

Influenza Virus
http://en.wikipedia.org/wiki/Virus_classificationhttp://en.wikipedia.org/wiki/RNA_viruseshttp://en.wikipedia.org/wiki/Generahttp://en.wikipedia.org/wiki/Orthomyxoviridaehttp://en.wikipedia.org/wiki/Influenzavirus_Ahttp://en.wikipedia.org/wiki/Influenzavirus_Ahttp://en.wikipedia.org/wiki/Influenzavirus_Bhttp://en.wikipedia.org/wiki/Influenzavirus_Bhttp://en.wikipedia.org/wiki/Influenzavirus_Chttp://en.wikipedia.org/wiki/Influenzavirus_Chttp://en.wikipedia.org/wiki/Influenzavirus_Chttp://en.wikipedia.org/wiki/Influenzavirus_Chttp://en.wikipedia.org/wiki/Influenzavirus_Bhttp://en.wikipedia.org/wiki/Influenzavirus_Bhttp://en.wikipedia.org/wiki/Influenzavirus_Ahttp://en.wikipedia.org/wiki/Influenzavirus_Ahttp://en.wikipedia.org/wiki/Orthomyxoviridaehttp://en.wikipedia.org/wiki/Generahttp://en.wikipedia.org/wiki/RNA_viruseshttp://en.wikipedia.org/wiki/Virus_classification


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New human strains everyyear

MutationsPandemic strainsGenetic RecombinantViruses1957 Asian Flu H2N2

1968 Hong Kong Flu H3N21977 Russian Flu H1N1Bird FluDirectly from birds?? H5N1

H1N1, which caused Spanish Flu in 1918, and Swine Flu in 2009H2N2, which causedAsian Flu in 1957H3N2, which caused Hong Kong Flu in 1968H5N1, which caused Bird Flu in 2004H7N7, which has unusual zoonotic potentialH1N2, endemic in humans, pigs and birds

H9N2 H7N2 H7N3 H10N7
http://en.wikipedia.org/wiki/H1N1http://en.wikipedia.org/wiki/Spanish_Fluhttp://en.wikipedia.org/wiki/Swine_Fluhttp://en.wikipedia.org/wiki/H2N2http://en.wikipedia.org/wiki/Asian_Fluhttp://en.wikipedia.org/wiki/H3N2http://en.wikipedia.org/wiki/Hong_Kong_Fluhttp://en.wikipedia.org/wiki/H5N1http://en.wikipedia.org/wiki/Bird_Fluhttp://en.wikipedia.org/wiki/H7N7http://en.wikipedia.org/wiki/Zoonotichttp://en.wikipedia.org/wiki/H1N2http://en.wikipedia.org/wiki/H9N2http://en.wikipedia.org/wiki/H7N2http://en.wikipedia.org/wiki/H7N3http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H7N3http://en.wikipedia.org/wiki/H7N2http://en.wikipedia.org/wiki/H9N2http://en.wikipedia.org/wiki/H1N2http://en.wikipedia.org/wiki/Zoonotichttp://en.wikipedia.org/wiki/H7N7http://en.wikipedia.org/wiki/Bird_Fluhttp://en.wikipedia.org/wiki/H5N1http://en.wikipedia.org/wiki/Hong_Kong_Fluhttp://en.wikipedia.org/wiki/H3N2http://en.wikipedia.org/wiki/Asian_Fluhttp://en.wikipedia.org/wiki/H2N2http://en.wikipedia.org/wiki/Swine_Fluhttp://en.wikipedia.org/wiki/Spanish_Fluhttp://en.wikipedia.org/wiki/H1N1


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Influenza

Antigenic shift Changes in H and N spikes Probably due to genetic recombination between

different strains infecting the same cell

Reason for deadly outbreaks Antigenic drift

Mutations in genes encoding H or N spikes May involve only 1 amino acid

Allows virus to avoid mucosal IgA antibodies

C C ld Fl

Common Cold vs Flu
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Common Cold Flu

Causative Organism:adenoviruses,coronaviruses orrhinoviruses

Influenza virus

Chills: Rare CommonFatigue: Mild Moderate to severe

Aches: Slight Usual and often severe

Fever: Rare Usually present

Vaccination possible: No Yes

Severity:Usually does not causesevere health problems

Serious healthproblems, such aspneumonia, bacterialinfections, orhospitalizations canoccur.

Sore throat: Common Rare

Stuffy nose: Common Rare

Can be diagnosed: No Yes

Headache: Rare Common

Chest discomfort: Mild to moderate Often severe

Sneezing: Common Rare

Coughing: Hacking, productive Dry, unproductive
http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7


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Coccidioides immitis

Soil fungus inAmericanSouthwest

Cause of ValleyFever Highly infectious
http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7


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Coccidioides immitis Life Cycle
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Coccidioides immitis

Valley Fever usually aflu-like illness Can spread to bones,

skin, meninges Transmitted by airborne

arthrospores Diagnosis by serological

tests or DNA probe Treatment: amphotericin

B

Hi t l i
http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7


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Histoplasmosis

Figure 24.17

Histoplasma capsulatum, dimorphic fungus

(a) 37 (a) >35

Opportunistic fungi involved in
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Aspergillus Rhizopus Mucor

Opportunistic fungi involved in

respiratory disease:

Mucor rouxii
http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7http://en.wikipedia.org/wiki/H10N7

respiratory tract diseases final

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