OS 213: Human Disease and Treatment 3 (Circulation and Respiration)

LEC 12: VIRAL AND FUNGAL DISEASES OF THE LUNG

Exam 2 | Maria Margarita Maiquez-Lota | January 25, 2013
PART ONE

VIRAL RESPIRATORY INFECTIONS

OUTLINE
I. Introduction
A. Respiratory Tract Infections
B. Laboratory Studies for
Respiratory Viruses
II. Upper Respiratory Tract Infections
A. Rhinovirus

B. Adenovirus
C. Coronavirus
III. Lower Respiratory Tract Infections
A. Influenza Virus
B. Respiratory Syncytial Virus

I. INTRODUCTION
A. Resiratory Tract Infections
Upper Respiratory Tract Infections (URTIs)
Involves nasal cavity, pharynx, larynx
Rhinovirus, coronavirus, enterovirus, adenovirus, EBV (EpsteinBarr virus)
More typical type of infections
Table 1.Common URTIs And Affected Areas
Areas Affected
Rhinitis
Nasal mucosa
Rhinosinusitis/
Nares,paranasal sinuses
Sinusitis
Rhinopharyngitis
Nares, pharynx, hypopharynx, uvula and tonsils
Pharyngitis
Pharynx, hypopharynx, uvula and tonsils
Epiglottitis/
Superior portion of the larynx,supraglottic area
Supraglottitis
Laryngitis
Larynx
Laryngotracheitis Larynx, trachea and subglottic area
Tracheitis
Trachea and subglottic area
Mostly inflammations
Sinusitis may involve all paranasal sinuses (frontal, ethmoid,
maxillary, sphenoid)
Common cold: Rhinopharyngitis
Supraglottitis is also caused by influenza B
Lower Respiratory Tract Infections
Trachea, bronchi, lungs
Influenza, parainfluenza, RSV (respiratory syncytial virus)
Very virulent pathogen, or patient is immunocompromised
Respiratory Invaders
Table 2. Types of Respiratory Invaders
Requirement
Adhesion to normal
mucosa

Professional
Invaders

Ability to interfere with

cilia
Ability to resist
destruction in alveolar
macrophages
Ability to damage local
tissues
Initial infection and
damage by respiratory
virus
Local defenses impaired

Secondary
Invaders

Chronic bronchitis
Depressed immune
responses
Depressed resistance

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Examples
Respiratory viruses,
S. pyogenes,
M. pneumoniae, M.
pneumoniae, Chlamydia
Bordatella pertussis, M.
pneumoniae, S.
pneumoniae
Legionella, M.
tuberculosis
C. diphtheria, S.
pneumoniae
S. aureus, S. pneumonia
S. aureus, Pseudomonas
H. influenzae,S.
pneumoniae
Pneumocytiscarinii,CMV
(cytomegalovirus),
M. tuberculosis
S. pneumoniae,S.
aureus,H. influenzae

Secondary invaders may also require local foreign bodies or

tumors
Common Respiratory Viruses
Table 3. Common Respiratory Viruses and Syndromes
More Commonly
Less Commonly
Syndrome
Associated Virus
Associated Virus
Influenza and
Coryza
Rhinovirus, coronavirus
parainfluenza virus,
enterovirus, adenovirus
Parainfluenza virus,
Influenza
Influenza virus
adenovirus
Influenza virus, RSV,
Croup
Parainfluenza virus
adenovirus
Influenza and
RSV (respiratory syncytial
Bronchiolitis
parainfluenza virus,
virus)
adenovirus
Parainfluenza virus,
BronchioInfluenza virus, RSV,
measles, VZV (varicella
pneumonia
adenovirus
zoster virus), CMV
Coryza: Cold
Croup: Hacking cough
Bronchopneumonia
o Not all pneumonias are due to bacteria
o Viral pneumonia or infection can cause mucopurulent discharge
rd
th
due to inflammation on the 3 to 5 day of illness
o Antibiotics are not recommended for all pneumonia patients
(viral etiologies should be ruled out first)
B. Laboratory Studies for Respiratory Viruses
For research purposes: Primary diagnosis is still clinical
Cerebrospinal Fluid
o Cell counting and typing
o Cell culture for respiratory viruses where indicated
Serum
o ELISA (enzyme-linked immunosorbent assay)
o Immunofluorescence microscopy
Others
o Nose and throat swab (pharyngeal washings: culture for
respiratory viruses)
o Fecal culture (culture for enteroviruses)
o Urine culture (culture for mumps virus)
Please see Appendix I for key morphologic characteristics of the
viruses that will be discussed below
II. UPPER RESPIRATORY TRACT INFECTIONS
A. Rhinovirus
Common Cold
Causes one of the most common illnesses to man
Leading cause of doctor visits and lost hours both at school and
the workplace
Belongs to family Picornaviridae
o Accounts for 1/3 to 1/2 of acute respiratory infections
o Rhinoviruses: 30-50% of common colds
o Coronaviruses: 10-30% of the cases
Other viruses: Adenovirus, enterovirus (Some patients may
present with diarrhea due to this probable systemic viral
infection), RSV, influenza and parainfluenza virus
Responsible for:
o About 70% of the cases where a virus has been found
o Around 35-50% of the total number of cases of common colds

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Picornaviridae

Enteroviruses: Poliovirus,coxsackievirus A and B, Echovirus,Enterovirus

Rhinoviruses: common colds
o Common colds
o Differences from other Picornaviridae
Unable to withstand acid condition
Able to grow in low temperature (33C), others thrive at 37C
Aphthoviruses: FMDV (foot-and-mouth disease virus)
Cardioviruses: murine viruses

Characteristics
Small, 18-30nm
Naked capsid
o Environmentally stable to: Temperature, acid, proteases,
detergents, drying
o Can be spread easily
o Can dry out and retain infectivity
o Can survive the adverse conditions of the gut
o Can be resistant to poor sewage treatment
(+)single stranded RNA with icosahedral symmetry
> 100 serotypes
o No cross-protection between different serotypes
o There is no vaccine against these viruses
Transmission
Aerosol or direct contact with contaminated secretions
Primary site of inoculation: Nasal mucosa(conjunctiva can also be
involved to a lesser extent)
Major human rhinovirus receptor: ICAM-1 (Intercellular adhesion
molecule 1)
o Binds endothelial cells with leukocytes at time of infection
o Aids in binding of endothelial cells with WBCs, facilitating viral
spread
o Virus upregulates ICAM-1 (ends up calling more rhinoviruses)
Optimal temperature for replication: 33-35C
Incubation period: approximately 2-4 days
Pathogenesis
1. Source of virus
2. Transmission to human host
3. Binding of capsid protein to ICAM-1
4. Virus then multiplies
5. Spread of infection to neighboring cells via surface secretions to
new sites on the mucosal surface of the respiratory tract
6. Damage to epithelial cells
7. Secretion of fluid containing inflammatory mediators such as
bradykinin
8. Cold-type symptoms: stuffiness, congestion
Cytopathic effect of rhinovirus: loss of fibroblasts
Viremia is absent
May lead to secondary bacterial infection

Classification
Table 4. Classification of Adenovirus
Representative
Subgroup
Target Organ
Viruses
A
12, 18, 31
GIT
Pharynx, lungs,
B
3, 7, 11, 21
urinary tract,
conjunctiva
C
1, 2, 5, 6
Pharynx
D
8, 9, 19
Eye
E
4
Upper RT
F
40, 41
GIT

Epidemiology
Endemic
Endemic
Latent throat
Epidemic
Epidemic
Endemic

B3, B7, C2, C5: Most common types of adenovirus

Subgroup B: Fever and pharyngitis/sore throat accompanied by
conjunctivitis or other ophthalmic infections
Pathogenesis
1. Source of virus
2. Transmission to human host (through inhalation of droplets)
3. Infection of epithelial cells lining the respiratory and enteric
organs by the virus(variations in target cell specificity due to
different viral attachment proteins)
4. Proliferation/ multiplication of virus
5. Viremia: Spread of virus to visceral organs and to lymphoid
tissues, i.e. adenoids, tonsils and Peyers patches
Histological hallmark: a dense intranuclear inclusion within the
infected cell
Transmission
Direct contact, respiratory droplet, airborne
o Very contagious because there is relatively high viral particles in
the sputum (100K-1M/mL)
o Those with no antibodies can acquire the disease by just
inhaling few viral particles (as few as 5 virions)
Indirect contact with articles
Fecal-oral route
Clinical Manifestations
Nasal congestion, coryza, cough and headache: If dry cough,
usually caused by adenovirus
Can cause exudative tonsillitis
o Exercise caution in prescribing antibiotics immediately
o Check for systemic symptoms bacteria would not cause such
Pharyngo-conjunctival fever (triad)
o Pharyngitis
o Non-purulent conjunctivitis
o CLAD (cervical lymphadenopathy)
Others: laryngotracheitis, bronchitis, pneumonia, pertussis-like
syndrome

Treatment
Symptomatic relief
Decongestants
o NaCl sprays, phenylpropanolamines, etc.
o Btter to take in lots of water
Antihistamines for atopy or allergic rhinitis
NSAIDs (non-steroidal anti-inflammatory drugs)
Do not give antibiotics
Antivirals: No role since infection is only mild and is self-limiting
(laboratory diagnosis not usually done)
Vaccines against respiratory viruses provide cross-protection

C. Coronavirus
Characteristics
Has projections that look like a crown
Enveloped, (+) single stranded RNA with loose helical
nucleocapsid
Narrow host range
Cause of SARS (severe acute respiratory syndrome)
Can also be found in birds (no cross-reactions across species
unlike the influenza virus)
SARS Coronavirus

B. Adenovirus
Characteristics

Doublestranded DNA with icosahedral symmetry

Naked virus:More virulent than enveloped viruses
Unique: Slender fiber projecting from vertices
47 human serotypes
Has predilection to adenoids, thus called adenovirus

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First surfaced in Southern China in late 2002; by early 2003, it has

spread to several countries in Asia, as well as Canada
WHO: 8,437 people were infected and 813 people died between
Nov 2002 and Aug 2003
Common symptoms
o Fever of 38C
o Persistent dry cough
o Malaise and body aches

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Can mutate which leads to a different antigen, i.e. previous vaccines
will not work anymore

o Serious shortness of breath

o Can sometimes cause cyanosis
Highly contagious(close to 10% mortality rate)

Influenza A and B have at least 8 segments each

Influenza C has at least 7 segments

Transmission
Very contagious: Can survive outside the body on a dry surface for
at least 3-4 hours
Droplet spread
Direct contact (can spread by any body fluid contact)
Laboratory Diagnosis
Serological testing
o IFA (indirect fluorescent microscopy)
o ELISA: Only for specimens obtained >21 days by fever
Molecular testing
o RT-PCR (reverse transcriptase polymerase chain reacion):
Mainstay of therapy
o Can detect infection within the first 10 days
Culture
o Difficult to do (requires biosafety level 3 laboratory)
o Use nasopharyngeal aspirates, throat swabs, others (feces)
Treatment
Isolation: quarantine
Supportive: fluids
Ribavirin (2015)
III. LOWER RESPIRATORY TRACT INFECTIONS
A. Influenza Virus
Belongs to theOrthomyxoviridae family
Ortho means true or regular
Myxo refers to the ability of the virus to attach to mucus
membrane
Types of Influenza Viruses
Table 5. Types of Influeza Viruses
Antigenic
Antigenic
Type
Drift
Shift
A
+
+
B
+

Can Cause
Pandemic
Epidemic

Act as the mixing vessel for human and avian flus (can come up with
novel strains from different sources of infection)
Swine flu or A(H1N1)

All pandemics are due to Influenza A

15 known HA serotypes and 9 known NA serotypes
Influenza B
Antigenic drift only
Infects humans only
Causes diseases that are not as severe as A types
Causes epidemics
No distinguishable serotype
Influenza C
Infects humans only
Relatively stable
Causes milder diseases
Viral Structure
Presence of an envelope
() single stranded RNA with segmented genome
Each segment:

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High frequency of variations caused by HA and NA results in new

serologic type; hence, the flu continues to evolve
HA protein
Responsible for binding to host receptor
Performs mechanisms that internalize the virus via membranefusion events (endosomal pathway)
Most abundant surface glycoprotein in the viral structure
(~80%)
Contains epitopes that are targeted by neutralizing antibodies
H1, H2, H3: Most commonly associated with human infections
NA protein
Hydrolyzes the mucus of the respiratory tract
Assists in viral budding and release of virion from cells
N1, N2: Most commonly associated with human infections
Influenza: Summary
Acute respiratory infection caused by influenza virus of any type
Viruses currently circulating in human populations include
o A(H3N2)
o A(H1N1)
o B strains
All known pandemics are caused by Influenza A
Animal influenza virus may affect human in special circumstances,
e.g. Avian flu A(H5N1)
Viral Reservoirs
Major reservoirs include birds, swine, horses, dogs, cats, domestic
poultry
Reservoirs provide new strains by recombination between
influenza viruses of man, mammals and birds (recall swine flu)
Changing Patterns in Influenza

Relatively
Stable

Subtypes are due to the antigenic variations of surface

glycoproteins HA (hemagglutinin) and NA (neuraminidase)
Influenza A
Antigenic shift and drift
Infects a wide variety of mammals (pigs, birds, horses, humans)
Wild birds act as natural host to all subtypes of Influenza A virus
Pigs

Encodes a different viral protein

Surface Glycoprotein

Enables influenza A viruses to cause annual epidemics, even

pandemics
Antigenic Drift
Causes epidemics
Minor mutations in HA antigen
Makes prior immunity less effective
Occurs primarily among influenza A viruses but type B viruses
may also acquire antigenic drift
Results in emergence of new variants of prevailing strains every
year
Antigenic Shift
causes pandemics
Occurs when two separate strains of influenza infect the same
cell simultaneously
Major changes occur in surface antigens
Occurs by mutation or by reassortment
Virus strains appear more different antigenically from
previously seen strains
Changes lead to emergence of potentially pandemic strains
Theories for the emergence of pandemic viruses
Genetic reassortment between human and animal viruses
Direct transfer of viruses between animals and humans
Re-emergence of viruses from unrecognized or unsuspected
reservoirs
Herd Immunity: Most if not all members of the population have
been vaccinated (decreased chance of spreading the virus)
Table 6. Influenza in the Past
Year
Virus
1918
A(H1N1)
1957
A(H2N2)
1968
A(H3N2)
2003
A(H5N1)

Name
Spanish Flu
Asian Flu
Hong Kong Flu
Avian/Bird Flu

Deaths
>20M
>2M
>2M

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Hong Kong Flu is due to antigenic shift in HA

Avian Flu
First human case in 1997
Human-to-human transmission is relatively inefficient and not
sustained

Because of antigenic drift, new vaccines have to be prepared

every year
Killed vaccine
Live-attenuated

Everyone is encouraged to get the annual flu vaccine,

particularly:

Flu Pandemic
The avian strain or A(H5N1) raised the concern of a new influenza
pandemic after it emerged in Asia in the 1990s (not considered a
pandemic back then)
Novel flu strain evolved that combined genes from human, pig
and bird influenza viruses: Swine flu or A(H1N1) emerged in
Mexico
World Health Organization officially declared the outbreak to be
pandemic on 11 June 2009
Confirmed case of A(H1N1)
Defined as a person with an acute febrile respiratory illness
with laboratory confirmed novel influenza A(H1N1) virus
infection at any WHO-approved laboratories via one or more of
the following:

o F (fusion) protein
Induce syncytia in cell culture
Also for virus penetration and spread

RT-PCR and ELISA

Clinical Manifestations of Influenza

Incubation period for 2 days (normal range: 1-4 days)
Abrupt onset of fever, myalgia, sore throat, non-productive
cough, headache
May present with associated gastrointestinal symptoms
Nausea
Vomiting
Diarrhea
May also present with joint and muscle pains
Severity of the illness depends on prior experience with related
variants, e.g. presence of concomitant illnesses, take Oseltamivir
Presentation can easily get confused with dengue fever
Immunity
Due to the continuous evolution of the strains, immunity must
always be developed
The quality of immunity to the current variant depends on the
immunity to the previous variant that circulated the population
and the relatedness of the two variants
Antibody against HA is productive while antibody against NA helps
modify virulence
Treatment Considerations
Mostly self-limiting
Hospitalizations involve
Isolation and observation
Treatment of the seriously ill
Symptomatic care includes antipyretics
e.g.paracetamol for fever or pain
Avoid ibuprofen or NSAIDs because if the case turns out to be
dengue, treatment will only cause further bleeding
Fluid rehydration
Antiviral Therapy
Involves NAIs (NA inhibitors),e.g.Oseltamivir and Zebanivir
Only for severe cases
If used on mild cases, virus may become resistant to medicine

Positive effects of early NAI administration

Reduction in the severity and duration of illness
Contributes to the prevention of the progression to severe disease
and the eventual death

Beneficial for:
Pregnant patients
Patients with progressing lower respiratory disease or pneumonia
Patients with underlying medical conditions

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B. Respiratory Syncytial Virus

Most common cause of bronchiolitis in childreb
Pleomorphic, enveloped with surface spikes
() single stranded RNA
Subtypes: A and B
Pneumovirus lack HA and NA proteins; contains glycoprotein
Protein structures
o G (glycoprotein) protein: Receptor for cell attachment
o M (matrix) protein
Also for attachment
Aids in virus penetration

Real Time Polymerase Chain Reaction (RT-PCR)

Viral culture
Four-fold rise in A(H1N1)-specific neutralizing antibodies
In the Research Institute of Tropical Medicine: Used to screen for
free especially for patients which high level of suspicion
During the Flu Scare, the same tests cost PhP 10,000 in Makati Med

Children below 2 years old

Elderly
Chronically ill
Institutionalized as well as healthcare professionals

Transmission

Respiratory droplets
Common habitat: human reservoir
Can also infect cattle, monkeys, goats, rodents
Common cold during cold weather (winter or rainy season)

Pathogenesis
1. Infects ciliated cells of respiratory tract
2. Disseminates locally
3. Inoculation occurs through the nose/eyes and spreads through
respiratory epithelium
4. Viral replication in the peribronchial tissue leads to edema,
proliferation and necrosis of bronchioles
5. Collection of sloughed epithelial cells leads to obstruction of small
bronchioles and air trapping (can produce a wheezing sound,
mistaken as bronchial asthma)
Epidemiology
Common (outbreaks during winter and fall)
High risk groups
o Very young infants (<6 weeks) especially preemies
o Older adults
o Mortality from RSV pneumonia can approach 20% in this group
o Children with bronchopulmonary dysplasia and congenital
heart disease
o Immunocompromised individuals
o SCID (severe combined immunodeficiency)
o Transplant recipients
o Hematologic malignancies
Clinical Presentation
Respiratory tract infections
o Bronchiolitis in children <1 year old
o Common cold in older children and adults
Complete recovery possible
RSV Bronchiolitis
Primary infection is usually symptomatic and lasts for 7-21 days
o Starts as URI with congestion, sore throat, fever
o Cough deepens and becomes more prominent
Lower respiratory tract involvement is heralded by increase in
respiratory rate and retraction of intercostal muscles (appears like
pneumonia)
Hospitalization rates can approach 40% in young infants
Reinfection occurs in adults and older children, but is rarely
asymptomatic, i.e. recovery is complete but immunity is not

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Laboratory Diagnosis

Clinical Manifestations

May demonstrate from nasopharyngeal secretions during the

acute phase
Immunofluorescence, enzyme immune assay or culture
Commercially available conjugate monoclonal antibody
Detection
Direct fluorescent antibody or EIA are used for the rapid detection
of viral antigen in respiratory secretions
RSV are very fragile and culture is difficult
Specimens must be processed quickly
Antibody detection is most often used to provide epidemiologic
evidence of past/recent infection
Histologic appearance: With multinucleated giant cells
Treatment
RSV immunoglobulin (passive immunity): Not available in the
Philippines (PhP40K-50K per vial)
Supportive care
Bronchodilators (Inhaled epinephrine more efficacious than
inhaled -agonist)
Ribavirin
PART TWO

FUNGAL RESPIRATORY INFECTIONS

OUTLINE
I. Histoplasmacapsulatum
II. Aspergillusfumigatus

III. Pneumocystis jiroveci

I. HISTOPLASMA CAPSULATUM
Histoplasmosis
Pulmonary infection resembling tuberculosis
o First recognized as a disease among patients who were x-ray
positive but tuberculin negative
o Intracellular mycotic infection of the RES (reticuloendothelial
system), i.e. lesions are not confined to the lungs
o Disease mainly affects the lungs with most patients often
showing minimal or no symptom
Pathogenesis: Inhalation of conidia from the fungus
Reservoir: Soil contaminated with bird or bat droppings
Agent Distribution
H.capsulatum is found among the major river valleys in North and
South America
Can also be found in some areas in Africa
Found in at least 50 countries in the temperate regions and the
tropics including the Philippines
Transmission
Exposure to contaminated soil with bird or bat droppings is
considered to be a risk factor
o Grows in bird or bat droppings (microconidia spores may be
inhaled and may settle in alveoli)
o Spores survive when phagocytosed by macrophages
o Cause edema, pneumonitis (similar picture to TB or primary
complex in children)
Once the human host is infected, T cell mediated immune
response will be activated, involving the RES
Histologically, it can mimic the appearance of the Ghons complex
From thereon, it can disseminate to other organs
~90% would be asymptomatic

Table 7.Clincal Manifestations of Histoplasmosis

Presentation
Features
Majority are asymptomatic
Presents with flu-like symptoms such as chills,
Acute
fever, headache, malaise, muscle pains
Pulmonary
May have difficulty in breathing, chest pain,
Histoplasmosis
cough and other associated respiratory
problems
Skin lesions and joint pain occur in 5-6%
Occurs mostly in patients with underlying lung
disease (only 5% move on to this)
Chronic
Presents with hemoptysis, malaise, weight loss,
Pulmonary
fever and difficulty in breathing
Histoplasmosis
Closely resembles tuberculosis with lung
involvement
Occurs mostly in patients with weakened
immune systems
Gastrointestinal, central nervous system and
Progressive
cardiac symptoms develop as the disease
Disseminated
progresses, eye (ocular histoplasmosis)
Histoplasmosis
50-60% of patients have mouth and gum pain
due to mucosal ulcers
Can be fatal if not treated
Approximately 1-10% of infected people in
endemic areas have eye involvement that is
Ocular
usually symptomless in its early stages
Histoplasmosis
In later stages, abnormal blood vessels in the
Syndrome
eye may develop and cause changes in vision
that may eventually lead to blindness
Laboratory Diagnosis
Not easily detected by direct mycological examination of organic
secretions even if special staining techniques are employed
Can be isolated from sputum or tracheobronchial secretion in 6085% of the cases in chronic pulmonary histoplasmosis
Direct Microscopy
o Skin scrapings, exudates and body fluids:10% KOH and Parker
ink or calcofluor white mounts
o Tissue
secretions:
PAS
(periodic
acid-Schiff),
GMS(Grocottsmethenaminesilver) or Gram stain
Culture
o SAB (Saborauds dextrose) agar and brain-heart infusion agar
supplemented with 5% sheep blood
o In room temperature (25-27C) exhibits filamentous growth
with hyphae, microconidia and tuberculatemacroconidia
o To confirm, fungus must change from mycelial form to parasitic
or yeast form (round, single-budding fungus), which usually
happens at 37C
Serology
o Immunodiffusion
o Complement fixation test
Analysis of the H. capsulatum var. capsulatum antigen
o Valuable tool for the diagnosis of patients with severe acute
histoplasmosis, who require early treatment
o Screening for the antigen is useful also for monitoring the
treatment and recurrence of the disease
Management
Monitoring among those with mild symptoms
Antifungal treatment for more severe cases (chronic or
disseminated)
o Ketoconazole andItraconazole
Prolonged or severe pulmonary symptoms
Cutaneous manifestations

o Amphotericin B
Severe acute pulmonary histoplasmosis
Chronic pulmonary and disseminated histoplasmosis

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II. ASPERGILLUS FUMIGATUS

Accounts for over 90% of all fungal infections caused by
Aspergillus
Grows in a wide range of temperature (up to 50C)
Inhibited by cycloheximide
An opportunistic parasite
Predisposing Factors
o Immunocompromised host
o Presence of other diseases
Modes of Transmission
o Respiratory
o Direct inoculation
o Ingestion of peanuts (aflatoxin)
Clinical Syndrome
Allergic aspergillosis: Affects asthma, cystic fibrosis and sinusitis
patients
Aspergilloma/ Acute invasive aspergillosis: Risk increases if
patient has weakened immunity such as some cancer patients and
those on chemotherapy
Disseminated invasive aspergillosis:Widespread in the body
Pathogenesis: Respiratory
The initial and most usual sites of infection include the paranasal
sinuses and lungs (respiratory tract)
Non-specific signs and symptoms of flu
Can disseminate to other sites from the initial point of invasion
o Aspergilloma
Fungus ball can be seen occupying a large pulmonary cavity as in TB
patients
Usually asymptomatic and the diagnosis of the ball is incidental

o Aspergillus looks for a pre-existing cavity and settles there

Laboratory Diagnosis
Specimen
o Sputum
o Tracheal aspirates
o Bronchial washings
o Tissue biopsies
Microscopic examination
o Prepare wet mounts of the sputum, washings and aspirates in
either 10% KOH and Parker ink or Calcofluor white and/or Gram
stain
o Tissue sections should be stained with H&E, GMS and PAS
digest
Characteristics
o Septate hyphae
o Dichotomous hyphae
o Spores
Culture
o Involves isolation of organism from tissues
o SAB agar is used
o Incubation is done at room temperature
o Identification: spores and fruiting body
Serology
o Not performed in the Philippines due to lack of facilities
o Allergy
Detection of specific IgE in serum
Perform skin test

o Invasive infection: Detection of galactomanan in antigen serum

(via ELISA)
Treatment
Allergic aspergillosis: Corticosteroids and Itraconazole
Invasive aspergillosis
o Amphotericin B
o Itraconazole
Aspergilloma
o Lobectomy may benefit some
o Amphotericin B

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III. PNEUMOCYSTIS JIROVECI

Formerly called Pneumocystis carinii
Once considered to be a member of the protozoan kingdom
o In 1988 its rRNA sequence was found to parallel the fungal
rRNA
o Recent gene sequence analysis studies suggest that it is a
fungus
o There is striking similarity of its mitochondrial RNA to that of
red yeast fungi
Epidemiology
PCP(Pneumocystis pneumonia)
o Result of transmission from human host
o Not a reactivation of dormant or latent infection
Evidence for the person-to-person transmission is underscored by
the peak of infections occurring about 4 months after the annual
winter virus season
Spread maybe from aerosolized secretions of persons with viral
secretions
Clustered outbreaks also support person-to-person transmission
Very little is known about most of its mechanisms
o Has not been cultured yet
o Nost of the knowledge regarding the fungus is based on
histopathologic studies
Characteristics

Obligate extracellular organism

Has not been cultured in vivo
Has different mammalian hosts
Genetically diverse, i.e. an isolated strain in one host will not grow
in another host
Three distinct morphologic stages
o Trophozoite(trophic form): Exists in clusters
o Sporozoite(precystic form)
o Cyst: Contains several intracystic bodies (spores)

Figure 1. Life cycle of P. jiroveci

Pathogenesis
1. Fungus is inhaled from another host by persons with weakened
immune system such as in AIDS
2. Organisms infect the lining of the alveoli
3. Thick walled cyst with at least 8 spores forms
4. Exchange of gas becomes impaired
o Leads to hypoxemia
o May present as acute respiratory distress syndrome
Laboratory Diagnosis
In chest radiograph, 80% of cases will show diffuse interstitial
infiltrates
Gold Standard: Microscopic examination
o BAL (broncho-alveolar lavage): Use fluorescent monoclonal
antibody stain
o Transbronchial biopsy shows alveolar spaces filled with foamy
materials composed of a mass of P. jiroveci
o Basis for diagnosis in >90% of patients

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OS 213

LEC 16: VIRAL AND FUNGAL DISEASES OF THE LUNG

Drugs used in Management of PCP

Mainstay of treatment
o Trimethoprim (Cotrimoxazole)
o Side effect: Stevens-Johnson syndrome
Pentamidine
Steroids (Prednisone)
Dapsone
Clindamycin
Atavoquone

END

Jio:
4 day weekend!! Then, 3 day weekend!! Use the free days wisely!! Btw, Im
making this trans with a broken letter a button on my laptop. So, every
time I need to type the letter a, I paste a copied letter a.
Pwedenamansanang q nalangyungnasira. Walalang. Just ranting. Halfway
through the semester!! 2 more months, sem break na! Lets go block B!
Nick:
I dont usually give greetings, but when I do
Jim:
Hi ****! Miss nakita. :piMed, paki-click yung Miranda Kerr link ni Terence. Iprint at ipakitakay Jer. Hello 14A04 club! Kamustanaang bouncer
niyongsiAlexeis?MSSR 2016, salirin kayo samga international conferences
next year: MM 2013 USA, AMSC 2013 Malaysia, AM 2013 Chile, APRM 2013
Indonesia at EAMSC 2014 Korea. :D Wag langsobrahanporket ICC year,
bakamasunogtayo. =))Vincen, nice labeneh. :pBalitakohindika raw
nabibigyanng hard copy ngtranses ah?

Bilina kayo ngChicharabao!! P50.00 lang :D

Appendix I. Summary of Key Morphologic Characteristics of Respiratory Viruses
Infections Caused
Upper Respiratory Tract
Virus
Rhinovirus
Adenovirus
Coronavirus
Family
Picornaviridae
Adenoviridae
Coronaviridae
Size
18-30nm
70-90nm
120-160nm
Enveloped or naked
Naked
Naked
Enveloped
Icosahedral
Yes
Yes
No
Nucleic acid makeup
ssRNA
dsDNA
ssRNA
Strand (if ssRNA)
Positive
Positive

BALMADRID, BARIT

Lower Respiratory Tract

Influenza
RSV
Orthomyxoviridae
Paramyxoviridae
80-120nm
120-300nm
Enveloped
Enveloped
No
No
ssRNA
ssRNA
Negative
Negative

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