MYCOLOGY

Medical Microbiology (Lecture)

BS Biology 4-5 | Dr. Diaz | 1st Sem 2023-2024

C. YEASTS VS. MOLDS

I. MYCOLOGY
● Yeasts
A. CHARACTERISTICS ○ Exists as unicellular and budding
○ Morphology:
● Eukaryotic ■ Unicellular
○ Ribosome - 80s ■ Round
■ Non Filamentous
Form Fungi Bacteria ○ Capable of forming Pseudohyphae
○ Colonies:
Cell type Eukaryotic Prokaryotic ■ Moist, creamy or buttery with an alcohol like
odor
Cell membrane Sterols present Sterols absent ○ Can be identified by Biochemical Test
(Ergosterols) (except in ○ Presence of:
Mycoplasma) ■ Blastospores
■ Chlamydospore
Cell wall Chitin present Peptidoglycan ➢ Also called as “Resting spore”
present ➢ In times of drought or low nutrients, fungi
can survive by using the chlamydospore.
● Mykes
○ Study of fungi
● Thallophytes Unique Structure Definition

● Nonmotile Pseudohyphae Seen in Candida albicans

● Rigid cell wall when grown at 20℃
○ Chitin
○ Sterol cell membrane Germ tube Seen in Candida albicans
● Heterotrophic & Non-photosynthetic or when grown at 37℃
Achlorophyllous
○ Not having any chlorophyll ● Molds
○ Unable to engage with photosynthesis ○ Consists of hyphal elements
● Mostly obligate or facultative aerobes ○ Morphology:
■ Multicellular
● Dimorphism ■ Filamentous
○ Fungi can exist either as yeast or molds ○ Capable of forming Hyphae
■ Depending on the temperature and the needs ○ Colonies:
of the environment ■ Dry with velvety surface
○ Can be identified by the appearance of spores
■ Yeast form and hypha
➢ Range of temperature is 35-37℃
➢ Resembles human body temp
■ Mold form
➢ Range of temperature is 25℃ II. FUNGAL STRUCTURES
➢ Resembles room temp
A. SPORES
○ Dimorphic Switching
● Can be formed through sexual process (via meiosis)
■ Switching from yeast form to mold form and
or asexual process (via mitosis)
vice versa
● Important feature for speciation of a certain fungal
organism
B. CELL WALL AND MEMBRANE
● Contains a phospholipid bilayer like bacteria ● Sexual spores
● Contains ergosterol instead of cholesterol ○ Ascospores: Phylum Ascomycota
○ Antifungal drugs targets this sterol to penetrate ○ Basidiospores: Phylum Basidiomycota
the cell wall and cell membrane ○ Zygospores: Order Mucorales
● Composed of mannoproteins, ɑ- and β-glucan, and
chitin ● Asexual spores
○ Differentiating factor: size or method of production
■ Via size differentiation:
➢ Microconidia: small spores
➢ Macroconidia: large or multicellular
■ Via method of production
➢ Chlamydoconidia
★ From terminal or intercalary
hyphae.
➢ Phialoconidia
★ From vase-shaped conidiogenous
cells called Phialides.
➢ Blastoconidia
★ From budding yeast
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 ➢ Arthroconidia
III. FUNGAL REPRODUCTION
★ From fragmentation of hyphal cells
➢ Sporangiospores
★ Characteristic asexual spores of the
order Mucorales.

B. SPORANGIUM
● Receptacle or enclosure where spores are being
formed
● For asexual spore reproduction.

C. STOLON
● An occasionally septate hyphae
● Connects sporangiophores together

D. HYPHAE
● Filamentous elements or tube-like elements in the
fungal structure that make up the body of the fungus.
● Usually consists of chitin and glucan.
● Can be seen in molds which can grow in cold
environments (in bread, utensils, pillows, etc.), and in ● Sexual Reproduction
yeasts. ○ It involves the vegetative form of fungi or the
● Structural unit of most fungi. mycelium
○ Involves fusion of two mycelia
● Septate Hyphae ■ Haploid to diploid to spore formation
○ Divisions are seen in the hyphal structures
(septated) ● Asexual Reproduction
○ Seen in molds ○ The mycelium will enter mitosis producing the
spores and the spores will undergo germination
● Ceonocytic Hyphae
○ Divisions are not seen in the hyphal structures
○ Non-septated
○ Seen in molds IV. LABORATORY DIAGNOSIS

A. SPECIMEN COLLECTION AND HANDLING

● Pseudohyphae
○ “Not hyphae”
● BSC II
○ Ellipsoid in shape that can be described as that
buds off a true hypha.
● 10% KOH
○ Seen in many yeast species.
○ KOH dissolves any tissue cells.
○ Makes the highly refractory fungal cells more
● Hyaline Hyphae
visible.
○ Nonpigmented or lightly pigmented hyphae.
■ Dissolve keratin to easily visualize fungal
elements.
● Dematiaceous (Phaeoid) Hyphae
○ Initial examination of keratinized tissues.
○ Darkly pigmented due to the presence of
melanin in the cell wall.
○ Preparation:
■ Add a small amount of specimen to one gram
of KOH (press cover slip)
■ Warm the slide to hasten clearing
➢ Hair samples can be examined if
infection is endothrix or ectothrix.

B. STAINING

● India Ink
E. SPORES
○ Also known as Nigrosin
● Conidiospores ○ Used “negative staining”
○ The head is the conidiospore ■ Highlight the heavily thickened capsule of
○ The stalk is the conidiophore Cryptococcus neoformans.
○ One conidiospore is capable of producing one ○ Used for capsule demonstration.
mycelium
● Gomorimethenamine silver (GMS)
● Blastospores ○ Stains fungal cell wall black
○ Also called new yeast bud ○ Used to stain Pneumocystis carinii
○ Spores attached to pseudohyphae
● Mucicarmine stain
● Chlamydospore (Resting spore) ○ Stains fungal capsule red
○ In times of drought or low nutrients, the fungi ○ Used to stain Cryptococcus neoformans
can survive using the chlamydospore

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● Giemsa or Wright Stain
Hyphae (nonseptate) Mucormycosis (species of
○ Best for filamentous fungi and yeasts
Rhizopus, Lichtheimia,
○ Recommended stain for Histoplasma
Cunninghamella, etc.)
■ Found in blood and bone marrow
Hyphae (septate); brownish Phaeohyphomycosis
● Calcofluor White
cell walls (species of Bipolaris,
○ Stains fungal cell wall and makes it fluorescent
Cladosporium, Curvularia,
○ Binds to the components of cell wall specifically
Exserohilum, etc.)
the chitin and cellulose
○ Upon using wood’s lamp, it will fluoresce
Yeasts and pseudohyphae Candidiasis (species of
○ Best in detecting viable fungal elements
Candida)

C. AGAR Yeasts and Hyphae in skin Pityriasis versicolor

scrapings
● Sabouraud’s Dextrose Agar (SDA)
○ Fungal infections need requests for culture to Spherules Coccidioidomycosis
determine the specific fungi that cause the
disease. Sclerotic cell (brownish cell Chromoblastomycosis
○ The standard culture for isolation of fungal agents. walls)
○ Different fungi appear differently in SDA.
Sulfur granules Mycetoma
○ Candida albicans
■ Pasty opaque, slightly dome, smooth and Arthroconidia in hair Dermatophytosis
cream or white colonies
○ Aspergillus flavus Conidia in pulmonary cavity Hyalohyphomycosis
■ Yellow green powdery on front and pale (species of Aspergillus,
yellowish on reverse (plate flipped on the Fusarium, etc.)
other side)
○ Aspergillus fumigatus Cysts (asci) in pulmonary Pneumocystis jirovecii
■ Bluish green powdery colonies on front and specimens
pale yellow on the reverse

● Inhibitory Mold Agar (IMA)

○ Used to enhance the recovery of fungi from V. FUNGAL PATHOGENESIS
clinical experiments

● Two types of host response

D. OTHER TESTS
○ Granulomatous
○ Pyogenic
● Serological Testing
○ Helpful among immunocompetent ● Some can be detected by using skin tests for delayed
○ Positive antibody test hypersensitivity reaction
■ May confirm the diagnosis ● Reduced cell-mediated immunity predisposes to
○ Negative antibody test disseminated disease
■ May exclude the diagnosis
● Mycotoxins
● Molecular Methods ○ Exotoxins produced by fungi
○ PCR ■ Aflatoxins
○ MALDI-TOF-MS ➢ Produced by Aspergillus flavus
■ Matrix-assisted laser desorption ■ Ergot alkaloids
ionization-time of flight mass spectrometry ➢ Produced by Claviceps purpurea
■ For rapid diagnosis of fungal organisms ➢ Causes ergotism
➢ St. Anthony's Fire or Holy Fire
E. KEY FUNGAL STRUCTURES OBSERVED ★ Immediately feel burning sensation
that will result to gangrene
Predominant Morphology formation in the limbs
★ Caused by ingestion of rye bread
Yeasts (single or multiple Blastomycosis, Erysipelas
buds) Histoplasmosis, ■ Psychotropics
Paracoccidioidomycosis, ➢ Amanitin and Phylloidin
Penicilliosis,
Sporotrichosis A. OVERVIEW OF FUNGAL DISEASES

Yeasts with capsules Cryptococcosis ● Fungal Allergies

Hyphae (septate) Hyalohyphomycosis
(species of Aspergillus,
Fusarium, Geotrichum,
Trichosporon, et al.)
Hyphae (septate in skin or Dermatophytosis
nail specimens)
○ Sick building syndrome
■ From molds
○ Farmer’s lung
■ From thermophilic actinomycetes
○ Allergic bronchopulmonary aspergillosis
■ Aspergillus fumigatus IgE-mediated
hypersensitivity
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● Mycotoxicoses ○ Unable to grow in 37℃ or in the presence of
○ May result from ingestion of fungal-contaminated serum, hence, no deep infections
food ○ Caused by a group of at least 40 related fungi
belonging to the following genera:
○ Aflatoxin
■ Aspergillus flavus
■ May cause liver cancer
Genera Skin Hair Nails
○ Amanitin & Phylloidin
■ Amanita mushroom
Trichophyton X X X
■ Causes liver necrosis
➢ Dose-related disease called mycetismus
Microsporum X X No
infection
● Fungal Infections (Mycoses)
○ Range from superficial to overwhelming systemic
Epidermophyton X No X
infections that are rapidly fatal in the compromised
infection
host
○ Increasing in prevalence because of increased
use of antibiotics, corticosteroids, and cytotoxic
drugs ● Pathogenesis
○ Chronic infections often locate in the warm, humid
● All fungal diseases are not infective to other areas of body
organisms except for cutaneous mycoses. ○ Forms ringworms
○ Humans are dead-end hosts. ■ Raised circular lesions
● Infective vs Infectious ○ May also cause hypersensitivity causes
○ Infective refers to communicable diseases dermatophytid reactions
○ Infectious is the nature of the disease which is ■ Inflammatory reaction to dermatophytosis at
microbial in origin. a cutaneous site distant from the primary
infection

VI. FUNGAL DISEASES

FORMS OF DERMATOPHYTOSIS BASED ON
LOCATION ON THE BODY

Dermatophytosis Features

Tinea pedis Involves the feet

(Athlete’s foot)
Most prevalent of all
dermatophyses

Tinea unguium Involves the nails

(Onychomycosis)
Most difficult to treat

Requires months of oral

azole or terbinafine as well
as surgical removal of nail

Tinea corporis Involves the body

Tinea cruris Involves the groin area

(Jock itch)
A. CUTANEOUS MYCOSES
Tinea manus Involves the hands
● Involves the skin, hair, and nails.
● This is the only classification of mycoses that is Tinea capitis Involves the scalp
infective to other organisms.
● This group is the most prevalent mycoses in the Ectothrix - formation of
world. dense sheaths of spores
● Source / Habitat: around the hair (Microsporum
○ Usually resides in soil or on vegetation. sp.)
● Transmission
○ Agents may enter the subcutaneous tissue via Endothrix - formation of
traumatic inoculation. spores within the hair shaft
○ You will observe in the patient granulomatous in (T. tonsurans, T. violaceum)
nature and (+) positive with lymphatic spread.
Tinea barbae Involves the areas with facial
● Dermatophytes hair
○ Dermatophytoses (Ring Worms)
○ Secrete the enzyme keratinase
■ Digests keratin
➢ Infect only superficial keratinized
structure)
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 ■ (+) yellow fluorescence on Wood’s lamp
CLINICAL FEATURES OF DERMATOPHYTE INFECTIONS
➢ Certain species of Microsporum will
fluoresce under ultraviolet light
Skin Location Clinical Fungi most
disease of features frequently
● Treatment
lesions responsible
○ Local antifungal creams (e.g. topical imidazole)
○ Oral Griseofulvin
Tinea Non-hairy, Circular Trichophyton
■ For tinea unguium and tinea capitis
corporis smooth patches with rubrum
○ Oral terbinafine
(ringworm) skin advancing red,
○ Keep skin dry
vesiculated Epidermophyton
border, and floccosum
● Cutaneous fungi (detailed)
central scaling.
○ Trichophyton (genus)
■ 2 to 3 weeks to grow in culture
Pruritic
■ Microconidia
➢ The characteristics structures of the
Tinea pedis Interdigita Acute: itching, T. rubrum,
genus Trichophyton
l spaces red vesicular.
■ Macroconidia
on feet of E.
➢ Smooth, thin-walled septate
persons Chronic: floccosum,
➢ Composed of 0 to 10 septa
wearing itching,
➢ Pencilshaped
shoes scaling, Trichophyton
➢ The colonies are loose aerial mycelium
fissures mentagrophytes
scereting pigments in variety of
Tinea cruris Groin Erythematous T. rubrum,
○ Trichophyton rubrum
scaling lesion
■ Colonies on front:
in E.
➢ Flat to slightly raised, white to cream,
intertriginous floccosum,
suede-like
area.
■ Colonies on reverse
Trichophyton
➢ Pinkish red
Pruritic mentagrophytes
➢ Downy type
Tinea Beard Edematous, T. rubrum, ★ Yellow-brown to wine-red on
barbae hair erythematous reverse
lesion Trichophyton
mentagrophytes,

Trichophyton
verrucosum

Tinea Scalp Circular bald Trichophyton

capitis hair. patches with mentagrophytes,
Endothrix: short hair
fungus stubs or Microsporum
inside hair broken hair canis,
haft. within hair ■ Numerous clavate to pyriform microconidia
Ectothrix: follicles. Trichophyton formed evenly on hyphae
fungus on tonsurans ➢ Resembling “birds on a wire”
the Kerion rare.
surface of
hair Microsporum
infected hairs
fluoresce.

Tinea Nail Nails No fungi present

unguium thickened or in lesion.
crumbling
distally, May become
discolored; secondarily
lusterless. infected with
bacteria
Usually
associated ■ Moderate numbers of smooth thin-walled
with tinea multiseptate, pencil-shaped macroconidia
pedis ■ Present strains of downy type
➢ Few microconidia and no macroconidia
● Diagnosis
○ 10% KOH ○ Trichophyton tonsurans
■ Septate hyphae ■ Major causative agent of tinea capitis
■ Colonies
○ Sabouraud dextrose agar (SDA) ➢ Suede-like to powdery
■ Hyphae and conidia ➢ Flat with a raised center or folded
➢ Often with radial grooves
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 ○ Others:
■ Malassezia furfur
■ Cladosporium werneckii
■ Trichosporon beigelii

B. SUBCUTANEOUS MYCOSES

● Sporthrix shenckii
○ Causes Sporotrichosis
○ Dimorphic fungus that lives on vegetation
○ Occurs most often in gardeners, especially those
who prune roses
■ Color varies from buff to yellow (sulfureum
form) to dark brown ○ Histopathology
■ The reverse varies from yellow-brown to ■ (+) cigar shaped yeasts, asteroid bodies
red-brown to mahogany
■ Numerous microconidia along the hyphae or ○ Transmission
on a short conidious spores ■ Via thorn prick
■ Varies in size and shape from long clavate to
broad pyriform, at right angles to the hyphae ○ Treatment
(match stick shape) ■ Itraconazole, potassium iodide for cutaneous
➢ May enlarge into balloon forms form
■ Occasional smooth thin-walled clavate ■ Amphotericin B for systemic disease
microconidia in some culture
● Other Subcutaneous Mycoses
○ Chromoblastomycosis (CMB)
■ Agent
➢ Phialophora verrucosa
➢ Fonsecaea pedrosoi
➢ Fonsecaea compacta
➢ Rhinocaldiella aquaspera
➢ Cladosporum carrionii

■ Features
➢ Sclerotic cell walls
➢ Cauliflower-like lesions

○ Trichophyton interdigitale ○ Mycetoma

■ Anthropomorphic species ■ Agent
■ Cause of tinea pedis ➢ Pseudallescheria boydii
■ Colonies ➢ Madurella mycetomatis
➢ Flat white to cream color ➢ Madurella grisea
➢ Powdery to suede-like surface. ➢ Exophiala jeanselmei
■ Reverse is yellowish and pinkish brown, ➢ Acremonium falciforme
becoming red-brown with age
■ Features
➢ Sulfur granules from interconnecting
draining sinuses

○ Phaeohyphomycosis
■ Agent
➢ Phialophora richardsiae
➢ Exophiala jeanselmei
➢ Bipolaris spicifera
➢ Wangiella dermatitidis
➢ Exserohilum rostratum
➢ Alternaria
■ Sub-spherical to pyriform microconidia, ➢ Curvularia
occasional spiral hyphae and spherical
chlamydoconidia ■ Features
■ Occasional slender, clavate, smooth walled ➢ Darkly pigmented septate hyphae in
multiseptate macroconidia tissue

C. ENDEMIC/SYSTEMIC MYCOSES

● Mode of Transmission
○ Inhalation of infective stage of fungi.

● Disease: Pneumonia
● Endemic in certain geographic regions

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 ○ Usually present as asymptomatic among ➢ Fluconazole
immunocompetent individuals.
○ There will be a widespread systemic presentation ○ Coccidioides immitis
in the immuno-compromised population. ■ Epidemiology
➢ Southwestern US
● Caused by a Dimorphic Fungi ➢ California
○ Caused by thermally dimorphic fungi
geographically restricted to specific areas of ■ Transmission
endemicity ➢ Inhalation of spores from soil, rodents

● General pathogenesis ■ Diagnostic feature

○ Inactivation of inhaled spores via alveolar ➢ Presence of spherules (filled with
macrophages endospores)
■ Initiation of antibody and cell-mediated
immunity ■ Clinical features
➢ Valley fever / San Joaquin Valley fever /
● Clinical presentation Desert rheumatism
○ Most infections are asymptomatic or mild and ★ Self-limited, influenza-like illness,
resolve without treatment malaise, cough, arthralgia
○ A small but significant number develop pulmonary
disease (pulmonary form) and may disseminate to ■ Remarks
other organs (disseminated form) ➢ Filipinos are most susceptible

● Examples: ■ Treatment
➢ Amphotericin B
○ Histoplasma capsulatum ➢ Itraconazole
■ Epidemiology ➢ Fluconazole
➢ Global distribution
➢ Mississippi ○ Paracoccidioides brasiliensis
➢ Ohio River valleys ■ Epidemiology
➢ Latin America
■ Transmission
➢ Inhalation of spores from avian and bat ■ Transmission
habitats (guano) ➢ Inhalation of spores
➢ Alkaline soil ➢ Unknown (soil)

■ Diagnostic feature ■ Diagnostic feature

➢ Presence of macrophage filled with ➢ With large, multiply budding yeasts
Histoplasma oval yeasts ★ Mariner’s wheel or captain’s wheel

■ Clinical features ■ Clinical features

➢ Pancytopenia, oral ulceration, ➢ South American blastomycosis or
splenomegaly Brazilian blastomycosis
➢ Erythema nodosum ★ Ulcerated granulomas, lytic bone
lesions
■ Treatment
➢ Amphotericin B ■ Treatment
➢ Itraconazole, ➢ Amphotericin B
➢ Fluconazole ➢ Itraconazole
➢ Fluconazole
○ Blastomyces dermatitidis
■ Epidemiology
Summary of Endemic Mycoses
➢ Eastern and Central US
➢ Great Lakes
Mycosis Etiology Tissue Form
■ Transmission Histoplasmosis Histoplasma Oval yeasts, 2 x 4 µm,
➢ Inhalation of spores capsulatum intracellular in
➢ Unknown (riverbanks) macrophages

■ Diagnostic feature Coccidioido- Coccidioides Spherules, 10 – 80 µm,

➢ With broad-based budding yeasts mycosis posadasii containing endospores, 2 –
4 µm
■ Clinical features Coccidioides
➢ Ulcerated granulomas immitis
➢ Lytic bone lesions
Blastomycosis Blastomyces Thick-walled yeasts with
dermatitidis broad-based, usually
■ Remarks single, buds, 8 – 15 µm
➢ Mimicker of squamous cell carcinoma
Paracoccidioido Paracoccidioides Large, multiply budding
■ Treatment -mycosis brasilensis yeasts, 15 – 30 µm
➢ Amphotericin B
➢ Itraconazole

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 D. OPPORTUNISTIC MYCOSES ➢ Fungal culture

● Will appear on those patients who have low immune ■ Treatment

system or immunocompromised ➢ Amphotericin B
○ Elders ➢ Flucytosine
○ Those who are infected with human ➢ Chemoprophylaxis: Fluconazole
immunodeficiency virus (HIV)
○ Pneumocystis jirovecii
● They are ubiquitous fungi. ■ Characteristics
○ To which, healthy people are exposed but usually ➢ Indeterminate organism
they are resistant.
■ Diagnosis
● In general, to say that you are prone to having ➢ Cannot be cultured
opportunistic mycoses, you need to request a CD4 ➢ Diagnosed by staining BAL washings
Count. with the following stains:
○ CD4 Count of less than 200 cells/uL = increases ★ Methenamine silver stain – (+)
the susceptibility to opportunistic fungi. disc-shaped yeast with cysts and
trophozoites
● Examples ★ Quantitative PCR may be useful in
distinguishing between colonization
○ Candida albicans and active infection
■ Characteristics
➢ Member of the normal flora of URT, GIT, ■ Pathogenesis
and female GUT ➢ Transmission occurs by inhalation of
cysts
■ Diagnostic features ➢ Cysts in alveoli induce an inflammatory
➢ With pseudohyphae (at room response consisting plasma cells
temperature) ★ Frothy exudate that blocks oxygen
➢ With germ tubes (at body temperature) exchange

■ Spectrum of Disease ■ Spectrum of Disease

➢ Immunocompetent ➢ Pneumonia usually occurs when CD4
★ Oral thrush count <400
★ Vulvovaginitis → curd-like ➢ Most common AIDS-defining illness
discharge
★ Intertrigo ■ Gold Standard Imaging
★ Skin infections → satellite lesions ➢ CT SCAN
★ Onychomycosis ★ Diffuse interstitial pneumonia with
ground glass infiltrates bilaterally in
➢ Immunocompromised 100% mortality if untreated
★ Esophagitis
★ Subcutaneous nodules ■ Treatment and Prevention
★ Right-sided endocarditis ➢ Prophylaxis
★ When CD4 count is less than 200
○ Cryptococcus neoformans ★ TMP-SMX or Aerosolized
■ Characteristics pentamidine
➢ Oval yeast with narrow based bud ➢ Drug of choice
surrounded by a wide polysaccharide ★ TMP-SMX
capsule ★ Pentamidine isethionate
➢ India ink preparation
➢ Positive latex agglutination test (CALAS) ○ Aspergillus fumigatus
■ Characteristics
■ Transmission ➢ Exist only as molds
➢ Grows abundantly in soil containing bird ➢ Septate hyphae that form V-shaped
(especially pigeon) droppings (dichotomous) branches at acute angles
➢ Transmission by inhalation of airborne
yeast cells ■ Transmission
➢ Widely distributed in nature
■ Spectrum of Disease ➢ Inhalation of airborne conidia
➢ Asymptomatic lung infection
➢ Meningitis, encephalitis ■ Pathogenesis
★ Most common cause of ➢ Infections
meningoencephalitis in HIV patients ★ Wounds, burns, the cornea,
external ear, sinuses
■ Diagnosis ➢ Aspergilloma (fungus ball) in lung
➢ India ink (clear halo) cavities
➢ Mucicarmine (red inner capsule) ➢ Allergic bronchopulmonary
➢ Cryptococcal Antigen Latex aspergillosis (ABPA)
Agglutination System (CALAS) of the ★ Asthmatic symptoms with
CSF expectoration of brownish bronchial
★ Detects polysaccharide capsular plugs
antigen and is more specific. ★ Most common etiologic agent

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 Radiologic Description Diagnosis Flucytosine Blocks nucleic acid synthesis by
Feature inhibiting DNA and RNA polymerases

Monod sign Gas surrounding Aspergilloma Griseofulvin Interferes with microtubule function
the aspergilloma in dermatophytes and may also
inhibit the synthesis and
Air crescent Presence of Invasive polymerization of nucleic acids
sign crescent-shaped aspergilloma
space between
mass and lung Bronchogenic E. SUPERFICIAL MYCOSES
cavity carcinoma
● Diseases affecting the outermost layer of the skin
(stratum corneum), or rowing along hair shafts
■ Diagnosis
➢ Allergic bronchopulmonary aspergillosis ● Pityriasis versicolor (tinea versicolor or An-an)
★ High level of IgE (IgE level > 1000 ○ Most common, causes patches of hypo-orhyper
IU/dL) pigmentation of the neck, shoulders, chest and
★ Sputum culture back.
★ Wheezing patient and chest X-ray ○ Malassezia furfur
with fleeting infiltrates ■ May cause fungemia in premature infants on
★ Increased level of eosinophils IV lipid supplements because it is lipophilic
★ Skin test: immediate ➢ There is a degradation of lipids that
hypersensitivity reaction leads to the production of acids and
eventual destruction of melanocytes that
■ Treatment can be found in the skin.
➢ Drug of choice ★ Hypopigmented macules/patches in
★ Amphotericin B dark skin
★ Hyperpigmented macules/patches
➢ Allergic bronchopulmonary aspergillosis in fair skin
★ Corticosteroids ➢ Associated with seborrheic dermatitis
➢ Aspergilloma
★ Removal via thoracic surgery ■ Diagnostic Features
➢ Invasive aspergillosis ➢ “Spaghetti and meatballs” appearance.
★ Voriconazole ➢ Sometimes called “bacon and eggs”
appearance in 10% KOH preparation.
○ Rhizopus oryzae and Mucor spp. ➢ Coppery-orange under Wood’s lamp
■ Mucormycosis
➢ Saprophytic molds with nonseptate
hyphae and branches ranches at right
angles (90 Degrees) Other Superficial Mycoses
➢ Can present as rhino-orbital-cerebral
infection with eschar formation Mycosis Agent Feature
★ Especially among patient with
diabetic ketoacidosis, burns, Tinea nigra Hortaea Dark (brown to
leukemia werneckii black) discoloration
of the palm/soles
○ Others (Exophiala
■ Pneumocystis pneumonia werneckii) Caused by a
■ Penicilliosis dematiaceous fungi

Black Piedra Piedraia hortae Small, firm/hard

Common Drug of Choice for Fungal Infection black nodules on
hair shaft
Drugs Mechanism of Action
White Piedra Trichosporon Soft, beige/white
Polyenes Binds to ergosterol in fungal cell nodules on the
Amphotericin B membranes, forming leaky pores distal ends of hair
shafts
Azoles Inhibit fungal P450-dependent
Ketoconazole enzymes (lanosterol
Fluconazole 14-a-demethylase) blocking
Itraconazole ergosterol synthesis
Posaconazole
Voriconazole Resistance can occur with long-term
use

Terbinafine Inhibits epoxidation of squalene

Echincandins Inhibit B-glucan synthase

Caspofungin decreasing fungal cell wall synthesis
Micafungin
Anidulafungin

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 VIROLOGY
Medical Microbiology (Lecture)
BS Biology 4-5 | Dr. Diaz | 1st Sem 2023-2024

C. VIRAL ENVELOPE
I. VIRAL STRUCTURE
● Enveloped viruses are less stable and more easily
A. STRUCTURE inactivated
● All enveloped viruses acquire their envelope from the
● Genome consists of DNA or RNA plasma membrane except herpes virus (from the
nuclear membrane)
● Capsid
○ Protein shell or coat that encloses the nucleic acid
genome Naked DNA Virus Naked RNA Virus
○ Maybe helical, icosahedral, or complex
○ Composed of protein subunits called Papillomavirus Calicivirus
capsomeres.
○ Protects nucleic acid, enabling viruses to attach to Adenovirus Picornavirus
and enter the host cell.
● Nucleocapsid Parvovirus Reovirus
○ The genome and its protein coat together (nucleic
acid genome + capsid) Polyomavirus Hepevirus
● Virion
○ Complete viral particle
○ Infectious unit II. VIRAL GENETICS
● Envelope
○ Lipid-containing membrane that surrounds some A. VIRAL GENOME
viruses acquired by budding through the cell
membrane ● All viruses are haploid except retroviruses
● Genomes can be either single-stranded or
○ Naked viruses double-stranded
■ Non-enveloped viruses ● Genomes of RNA viruses can be either
■ Ether resistant positive-polarity or negative-polarity
○ Enveloped viruses ● Some RNA viruses have a segmented genome
■ Ether sensitive (BOAR)

RNA Virus # of Segments

Bunyaviruses 3

Orthomyxoviruses 8
(influenza)

Arenaviruses 2

Reoviruses 10 or 11

B. MORPHOLOGY
B. RNA VS DNA VIRUS
● Helical, icosahedral, or complex
● All helical viruses are enveloped ● Positive-stranded RNA Viruses
● Icosahedral viruses can be enveloped or naked ○ RNA is just like a messenger RNA (mRNA)
● All DNA viruses are icosahedral except Poxvirus ○ When a positive-stranded RNA virus enters a host
● Only RNA viruses have helical symmetry cell, its RNA can immediately translate by the
○ Most assume a helical shape except host’s ribosomes into protein
rhabdoviruses, which have a bullet-shaped
capsid. ● Negative-stranded RNA viruses
● RNA viruses that have icosahedral symmetry instead: ○ Must transcribe (–) strand → (+) strand before
○ Flaviviruses translation
○ Caliciviruses ○ Virion brings its own RNA-dependent polymerase
○ Reoviruses needed for transcription of the negative strand
○ Picornavirus ○ Viruses: (Always Bring Polymerase Or Fail
○ Togaviruses Replication)
○ Hepevirus ■ Arenaviruses
■ Bunyaviruses
■ Paramyxoviruses
■ Orthomyxoviruses
■ Filoviruses
■ Rhabdoviruses

● DNA Viruses
○ Unlike RNA, DNA cannot be translated directly
into proteins.

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 ○ It must be transcribed into mRNA with a E. RECEPTORS USED BY VIRUSES
subsequent translation of mRNA into structural
proteins and enzymes
○ Most DNA viruses have both a negative strand Virus Receptors
and a positive strand except
■ Parvoviruses, which have single-stranded CMV Integrins (heparan sulfate)
DNA genome
○ Negative strand EBV CD21
■ Refers to the DNA strand that is read
■ Used as a template for transcription into HIV CD4, CXCR4, CCR5
mRNA,
○ Positive strand Parvovirus B19 P antigen on RBCs
■ Ignored
Rabies Nicotinic AChR

C. VIRAL REPLICATION Rhinovirus ICAM-1

● Called the infectious cycle
● Only happens within a host cell
F. UNCOATING OF AN ENVELOPED VIRUS
● Adsorption
○ Attachment of virus to host cell receptor
● Penetration
○ Virus enters host cell by direct penetration,
endocytosis or fusion with cell membrane
● Uncoating
○ Loss of capsid, genome enters cytoplasm (for
most RNA viruses or nucleus for most DNA
viruses)
● Macromolecular Synthesis
○ Production of nucleic acids and protein polymers
● Viral Assembly
○ Structural proteins, genomes, viral enzymes are
assembled into viral particles. III. LABORATORY DIAGNOSIS
○ Envelopes acquired during viral budding from host
cell membrane A. PRESUMPTIVE IDENTIFICATION
● Release ● Cytopathic effect
○ Occurs after cell lysis (lytic virus) or by virus ● Hemadsorption
particle budding from cytoplasmic membranes ○ Attachment of RBCs to surface of infected cells
● Interference
○ Interference with CPE by another virus
● Decrease in acid production by infected, dying cells
○ Using phenol red

B. DEFINITIVE DIAGNOSIS
● Complement fixation
● Hemagglutination inhibition
● Neutralization
● Fluorescent antibody assay
● Radioimmunoassay
● Enzyme-linked immunosorbent assay (ELISA)

D. VIRAL LIFE CYCLE AND PHARMACOTHERAPY
Replication stage
1 Adsorption
2 Penetration, uncoating
3 Viral nucleic acid synthesis
4 Viral protein synthesis
5 Assembly
C. SEROLOGIC TESTS
● Seroconversion
○ Finding antibody in one who previously had none
● Presence of IgM
Drugs available ○ Can be used to diagnose current infection
● Presence of IgG
Fusion inhibitors ○ Cannot be used to diagnose current infection
○ Antibody may be due to an infection in the past
Amantadine
D. DETECTION OF VIRAL ANTIGENS
Acyclovir, Zidovudine,
Lamivudine, Nevirapine,
Ribavirin ● Presence of viral proteins, commonly used in
diagnosis
Interferons ● Example: p24 of HIV and HBsAg
● Presence of viral DNA or RNA of the gold standard in
Protease inhibitors viral diagnosis

6 Release -

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 ○ Only virus with fibers
IV. DNA VIRUSES
○ 41 antigenic types
A. OVERVIEW
● Transmission
○ Aerosol droplet
○ Fecal-oral
○ Direct contact

● Spectrum of Disease
○ Upper Respiratory Tract
■ Pharyngitis
■ Conjunctivitis
■ Coryza
○ Lower Respiratory Tract
■ Bronchitis
■ Atypical pneumonia
○ Gastrointestinal Tract
■ Acute gastroenteritis
○ Urinary Tract
B. NAKED DNA VIRUSES ■ Hemorrhagic cystitis
1. PARVOVIRIDAE
○ Histopathology
■ Cowdry type B intranuclear inclusions
● Parvovirus B19 (Fifth Disease)
➢ Intranuclear and basophilic
➢ Circumscribed and multiple
● Characteristics
○ Naked virus with icosahedral symmetry
○ Single-stranded DNA genome
○ One serotype

3. PAPOVAVIRIDAE

● Human Papilloma Virus (HPV)

● Characteristics
● Transmission ○ Naked viruses with double-stranded circular
○ Respiratory droplets and transplacental DNA
○ Icosahedral nucleocapsid
● Spectrum of Disease ○ At least 100 types
○ Erythema Infectiosum (Fifth Disease) ○ More than half of cancers are due to HPV 16
■ Bright red cheek rash (slapped cheeks) with (high-risk HPV)
fever, coryza, and sore throat
○ Aplastic crisis ● Transmission
■ Interferes with erythroid progenitor cells ○ Direct contact
■ Transient but severe aplastic anemia in ○ Sexually
children sickle cell anemia, thalassemia or
spherocytosis ● Pathogenesis
○ Fetal Infections ○ Infect squamous cells and induce formation of
■ 1st trimester: fetal death cytoplasmic vacuole (koilocytes)
■ 2nd trimester: hydrops fetalis ○ Genes E6 and E7
○ Arthritis ■ Inactivation of tumor suppressor genes
■ Immune-complex arthritis of small joints ■ E6 inhibits p53
○ Chronic B19 Infection ■ E7 inhibits Rb
■ Pancytopenia in immunodeficient patients
● Spectrum Of Disease
○ HPV-1 to 4
2. ADENOVIRIDAE ■ Skin and plantar warts
○ HPV-6 and 11
● Adenovirus ■ Genital warts (condyloma acuminata)
■ Respiratory tract papilloma
● Characteristics ■ Most common viral STD
○ Naked viruses with double-stranded linear DNA ○ HPV-16, 18, 31, 33
○ Icosahedral nucleocapsid ■ Carcinoma of cervix, penis, and anus
● Treatment
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 ○ Genital warts ○ Large, pink to purple intranuclear inclusions
■ Podophyllin (Cowdry type A)
○ Skin warts ■ Variable and granular
■ Liquid nitrogen
○ Plantar warts
■ Salicylic acid

● Prevention
○ Vaccine for HPV-6, 11, 16 and 18
○ Cervarix
■ 16 and 18
○ Gardasil
■ 6, 11, 16, and 18

● JC Polyoma Virus
○ Only causes disease in immunocompromised ● Spectrum of Disease
hosts ○ Herpes Simplex Virus Type 1
○ Causes progressive multifocal ■ Gingivostomatitis
leukoencephalopathy (PML) in patients with AIDS ■ Keratoconjunctivitis
○ Demyelinating disease that affects ■ Temporal lobe encephalitis
oligodendrocytes ➢ Often with characteristic necrosis
■ Characterizedby deficits in speech, ■ Cold sores
coordination, and memory ➢ Herpes labialis (lips)
➢ Herpetic whitlow (fingers)
● BK Polyoma Virus ➢ Herpes gladiatorum (trunk)
○ Only causes disease in immunocompromised ○ Herpes Simplex Virus Type 2
hosts ■ Genital herpes
○ Causes hemorrhagic cystitis and nephropathy in ➢ Painful anogenital vesicles
patients with solid organ (kidney) and bone ■ Neonatal herpes
marrow transplants ➢ Contact within birth canal
■ Aseptic meningitis

C. ENVELOPED DNA VIRUSES ● Treatment

1. HERPESVIRIDAE ○ Drug of Choice is Acyclovir
■ Shortens the duration of the lesions
● Herpes Simplex Viruses (HSV 1 and 2) ■ Reduces the extent of shedding of the virus
■ No effect on the latent state
● Characteristics
○ Enveloped virus with linear double-stranded
DNA ● Varicella-Zoster Virus (VZV)
○ Icosahedral nucleocapsid
○ Most commonly diagnosed cause of acute ● Characteristics
sporadic encephalitis in the US ○ Enveloped virus with linear double-stranded
DNA
● Transmission ○ Icosahedral nucleocapsid
○ HSV-1 ○ Remains latent in sensory nerve ganglia
■ Saliva or direct throughout the body after infection
➢ Mucous membranes
➢ Breaks in skin ● Transmission
○ HSV-2 ○ Respiratory droplets (airborne)
■ Sexual or transvaginal ○ Direct contact with lesions

● Pathogenesis ● Pathogenesis
○ Vesicle filled with virus particles and cell debris ○ Infects URT, then spreads via the blood to the skin
○ Site of latency ○ Becomes latent in the dorsal root ganglia
■ HSV-1: trigeminal ganglia ■ May reactivate as zoster
■ HSV-2: lumbosacral ganglia ○ Histopathology
○ Multinucleated giant cells are seen on Tzanck ■ Multinucleated giant cells with intranuclear
smear inclusions

● Spectrum of Disease
○ Varicella
■ “Chickenpox”
■ Incubation period of 14–21 days
■ Vesicular centripetal rash
➢ “Dewdrop on a rose petal” appearance
■ Complications:
➢ Pneumonia
➢ Encephalitis
➢ Reye syndrome

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 ○ Zoster ● Treatment
■ “Shingles” ○ DOC is Ganciclovir
■ Painful vesicles along dermatomal ○ CMV is largely resistant to Acyclovir
distribution
■ Debilitating pain
➢ Postherpetic neuralgia ● Epstein-Barr Virus (HHV-4)

○ Ramsay Hunt Syndrome ● Characteristics

■ Involvement of geniculate ganglion causes ○ Enveloped virus with linear double-stranded
facial nerve paralysis DNA
○ Icosahedral nucleocapsid
● Treatment ○ Monospot-positive / Heterophil-positive
○ Mild
■ No treatment ● Transmission
○ Moderate to severe ○ Saliva
■ Acyclovir ○ Airborne
■ Shortens the duration of the lesions ○ Close contact
○ Mucous membranes

● Cytomegalovirus (CMV) ● Pathogenesis

○ Infects mainly lymphoid cells, primarily B
● Characteristics lymphocytes
○ Enveloped virus with linear double-stranded ○ Elicits EBV-specific antibodies and nonspecific
DNA heterophil antibodies
○ Icosahedral nucleocapsid ○ Differential WBC count will show elevated
○ Cultured in shell tubes “atypical lymphocytes” > Downey Cells
○ Negative heterophil test

● Transmission
○ Close contact (perinatal, venereal)
○ Body fluids
○ Transplacental
○ Transfusion
○ Organ transplantation

● Pathogenesis
○ Immediate early proteins
■ Translated from premade mRNAs
■ Impair assembly of the MHC class I–viral
peptide complexes
○ Histopathology ● Spectrum of Disease
■ Giant cells with owl's-eye nuclear inclusions ○ Infectious Mononucleosis
■ “Kissing disease”
■ Fever, sore throat, lymphadenopathy, and
splenomegaly
■ Splenic rupture is a rare complication
➢ Rapid increase in size produces a tense,
fragile splenic capsule
○ Malignancies
■ Oncogenicity associated with expression of
latency-associated membrane protein 1
(LMP-1)
■ B-cell lymphomas
■ African people
➢ Burkitt lymphoma
● Spectrum of Disease ■ Chinese people
○ Congenital CMV infection ➢ Nasopharyngeal carcinoma
■ Most common cause of congenital ■ AIDS patients
abnormalities ➢ Hairy leukoplakia
➢ One of the TORCH pathogens ➢ CNS lymphoma
■ Causes teratogenic symptoms in fetus ○ Post-transplant lymphoproliferative disease
➢ Microcephaly, seizures, deafness, ○ Encephalitis
jaundice, and purpura
■ Most common when mother infected in 1st
trimester ● Human Herpesvirus-6 (HHV-6)
○ Heterophil-negative mononucleosis
■ Lymphadenopathy ● Characteristics
■ Fever, lethargy, and abnormal lymphocytes in ○ Enveloped virus with linear double-stranded
PBS DNA
○ Systemic CMV infections ○ Icosahedral nucleocapsid
■ Pneumonitis, hepatitis, colitis, retinitis ○ 90% of all humans are infected by age 3
■ In immunocompromised patients (particularly ■ Usually benign course
transplant recipients)
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● Transmission ○ Largest viruses
○ Saliva ○ Brick-shaped poxvirus containing linear
double-stranded DNA
● Spectrum of Disease
○ Roseola / Exanthem Subitum / Sixth Disease ● Transmission
■ Caused by adenopathy ○ Aerosol
■ Rose-colored macules appear on body after ○ Contact
several days of high fever
■ Can present with febrile seizures; usually ● Pathogenesis
affects infants ○ Histopathology
■ Guarnieri bodies or intracytoplasmic
○ Nagayama spots eosinophilic inclusions
■ Erythematous papules on soft palate and
base of the uvula

○ Hepatitis

● Human Herpesvirus-8 (HHV-8)

● Characteristics
○ Enveloped virus with linear double-stranded
DNA
○ Icosahedral nucleocapsid

● Transmission
○ Sexual ● Spectrum of Disease
○ Body fluids ○ Incubation period: 7–14 days
○ Prodrome of fever and malaise followed by
● Spectrum of Disease centrifugal rash
○ Kaposi sarcoma (KS)
■ A rare type of cancer that can affect both the
skin and internal organs ● Molluscum Contagiosum Virus
■ Primary infection asymptomatic
■ Causes purpuric, raised skin lesions ● Characteristics
■ Most common symptoms ○ Pinkish, papular skin lesions with an umbilicated
➢ Red or purple patches on the skin. center

■ Classified into: ● Transmission

➢ AIDS-related Kaposi sarcoma ○ Direct contact
➢ Endemic African Kaposi sarcoma
★ Widespread common cancer in ● Pathogenesis
parts of Africa with high levels of ○ Histopathology
HIV ■ Henderson-Paterson bodies
➢ Classic Kaposi sarcoma ➢ AKA Molluscum bodies
★ Non-AIDS-related KS. ➢ Intracytoplasmic eosinophilic inclusions
★ Rare
★ Mostly affecting middle-aged and
elderly men of Mediterranean or
Ashkenazi Jewish descent
➢ Transplant-related Kaposi sarcoma
★ Uncommon side effect when the
immune system is weakened after a
transplant

2. POXVIRIDAE
● Characteristics
○ Largest DNA viruses
○ The only DNA virus that is complex ● Treatment
■ Not icosahedral ○ Cidofovir
○ The only DNA virus that replicates in the
cytoplasm
■ Not in the nucleus 3. HEPADNAVIRIDAE

● Hepatitis B Virus
● Variola Virus (Smallpox)
● Characteristics
● Characteristics ○ Enveloped virus with incomplete circular
○ Only disease that has been eradicated from the double-stranded DNA
face of the Earth

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● Transmission
Time Period HBsAg Anti-HBs Anti-HBc HBeAg
○ Blood
○ During birth
Incubation + - - +
○ Sexual
period
● Memory Aid:
Acute + - + +
○ The VOWELS (A and E) hit your BOWELS.
infection IgM
■ Hepatitis A and E cause enteric infections
Window - - + -
HEPATITIDES period IgM

Hepatitis A Asymptomatic Hepatitis Complete - + + -

recovery IgG
Hepatitis B Blood-borne Hepatitis
Chronic + - + -
Hepatitis C Chronic, Cirrhosis, carrier IgG
Carcinoma, Carriers
Hepatitis Chronic + - + +
active IgG
Hepatitis E Enteric, Expectant
mothers, Epidemics Vaccinated - + - -

● Serological Evolution
○ Surface antigen
■ Describes whether the patient is diseased or
immune
■ HBsAg
➢ Having this antigen means the patient
has the disease
★ Chronic, acute, or asymptomatic
carrier
➢ Precedes onset of symptoms and
elevation of liver enzymes
■ Anti-HBsAg
➢ Presence of this antibody indicates that
patient is immune and/or cured
➢ NO active disease present
● Memory Aid:
○ The only positive during window period
■ Anti-HBc IgM
○ The only positive among vaccinated patients
■ Anti-HBs
○ What can differentiate chronic active (+)
infection from chronic carrier (-)
■ HBeAg
○ Chronic infection is characterized by:
■ Persistence of HBsAg for at least 6 months
■ Persistence of HBsAg is the principal marker
of risk for developing chronic liver disease
and liver cancer (hepatocellular carcinoma)
later in life.

○ Core antigen ● Spectrum of Disease

■ Tells us how long the infection has been
present
■ HBcAg
➢ The antigen of the core of the virus
★ HBsAg removed
➢ Antibodies are not protective but yield
information about the state of infection
➢ Positive antibodies seen during the
"window period"
★ A period of active infection
■ IgM anti-HBcAg ● Treatment
➢ New infection is present
➢ Most specific marker for diagnosis of
acute HBV infection
★ Because it persists during the ● Prevention
window period
■ IgG anti-HBcAg
➢ Old infection is present
➢ The soluble component of the core
antigen tells us how infective the patient
is
■ HBeAg
➢ A soluble component of the viral core
➢ Presence connotes high infectivity
★ "e" = "enfectivity"
■ Anti-HBeAg
➢ Presence connotes low infectivity
○ Incubation period: 10–12 weeks
○ Fever, anorexia and jaundice
○ Dark urine, pale feces, and elevated transaminase
levels
○ Cirrhosis and hepatocellular carcinoma
■ Liver cell hyperplasia via HBx protein that
interferes with p53
○ Associated with autoimmune vasculitides
(polyarteritis nodosa)
○ Interferon-a
○ Lamivudine
○ Vaccination
■ First vaccine to prevent a human cancer
○ HBV vaccine and cancer reduction
■ Chronic HBV is related to approximately
60%-90% of hepatocellular carcinomas
(HCC) in adults and nearly 100% of
childhood HCC in areas endemic for HBV
infection

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 ● Polio vaccine
V. RNA VIRUSES

A. OVERVIEW Attribute Killed Live

(Salk) (Sabin)

Interrupts transmission & No Yes

spread

Secondary protection No Yes

(prevents spread)

Induces humoral IgG Yes Yes

protection

Induces intestinal IgA No Yes

protection

Reversion to virulence No Yes (rare)

Disease-causing in the No Yes

immunocompromised

Route Injection Oral

Refrigeration requirement No Yes

Immunity duration Shorter Longer

GENERALITIES ON RNA VIRUSES

All are haploid except Retrovirus ● Coxsackie Virus

All have a SS RNA except Reovirus & Rotavirus ● Characteristics

All replicate in the cytoplasm
except
○ Naked nucleocapsid with single-stranded, positive
Influenza & Retrovirus polarity RNA (1SS+)
● Transmission
○ Oral-fecal

B. NAKED RNA VIRUSES ● Spectrum of Disease

1. PICORNAVIRIDAE ○ Herpangina
■ Fever, sore throat, and tender vesicles in the
● Poliovirus oropharynx.
○ Hand-foot-and-mouth disease
● Characteristics ■ Vesicular rash on hands and feet
○ Naked nucleocapsid with single-stranded, positive ■ Ulcerations in the mouth.
polarity RNA (1SS+) ○ Hemorrhagic conjunctivitis
○ Pleurodynia
● Transmission ■ Fever and severe pleuritic-type chest pain
○ Oral-fecal ■ Pain due to an infection of the intercostal
○ LReplicates in motor neurons in the anterior horn muscles (myositis), not of the pleura.
of the spinal cord, causing paralysis. ○ Myocarditis and Pericarditis
■ Most common cause of fever, chest pain, and
● Pathogenesis signs of congestive failure.
○ Histopathology ○ Aseptic meningitis
■ Cowdry type B intranuclear inclusions ■ Coxsackie virus, poliovirus, and echovirus
are enteroviruses.
● Spectrum of Disease ■ Most common cause of aseptic meningitis.
○ Inapparent, asymptomatic infection

○ Abortive poliomyelitis ● Echovirus

■ Most common clinical form
■ Mild, febrile illness with headache, sore ● Characteristics
throat, nausea, and vomiting. ○ Enteric Cytopathic Human Orphan
○ Nonparalytic poliomyelitis ○ Called “orphans” because they were not initially
■ Aseptic meningitis associated with any disease
○ Paralytic poliomyelitis
■ Flaccid paralysis ● Transmission
■ Permanent motor nerve damage ○ Fecal-oral route

● Spectrum of Disease
○ Now known to cause:

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 ■ Aseptic meningitis
■ Upper respiratory tract infection ● Transmission
■ Febrile illness with and without rash ○ Oral-fecal route
■ Infantile diarrhea
■ Hemorrhagic conjunctivitis ● Spectrum of Disease
○ Viral Gastroenteritis
○ Most common cause of non-bacterial diarrhea in
● Rhinovirus adults.
○ Sudden onset of vomiting and diarrhea
● Characteristics accompanied by fever and abdominal cramping.
○ Naked nucleocapsid with single-stranded, positive
polarity RNA (1SS+)
○ More than 100 serotypes 3. REOVIRIDAE
● Transmission ● Rotavirus (Norovirus)
○ Aerosol droplets
○ Hand-to-nose contact ● Characteristics
○ Right Out The Anus
● Pathogenesis ■ ROTAvirus causes diarrhea
○ Replicated better at 33°C than at 37°C ○ Naked double-layer capsid with 10 or 11
■ Affect primarily the nose and conjunctiva segments of double-stranded RNA
rather than the lower respiratory tract.
○ Acid-labile ● Spectrum of Disease
■ Killed by gastric acid when swallowed ○ Viral Gastroenteritis
■ Do not infect the gastrointestinal tract, unlike ○ Most common cause of childhood diarrhea
the enteroviruses.
■ Host range is limited to humans and ● Treatment
chimpanzees. ○ Oral Rotavirus Vaccine
■ RotaTeq (Pentavalent RV5)
● Spectrum of Disease ➢ 3 doses (2, 4, 6 months)
○ Common colds ■ Rotarix (Monovalent RV1)
➢ 2 doses (2, 4 months)
● Hepatitis A Virus ■ Given at a minimum age of 6 weeks with a
○ Characteristics minimum interval of 4 weeks between doses
■ Naked nucleocapsid with single-stranded, ■ The last dose should be given not later than
positive polarity RNA (1SS+) 32 weeks of age (PidsPhil)
■ Also known as Enterovirus 72
■ Only 1 serotype
■ No antigenic relationship to HBV or other
hepatitis viruses C. NEGATIVE ENVELOPED RNA VIRUSES
■ Anti-HAV IgM is the most important test. 1. ORTHOMYXOVIRIDAE

○ Transmission ● Influenza Virus

■ Fecal-oral route
● Characteristics
○ Spectrum of Disease ○ Enveloped virus with a helical nucleocapsid and
■ Self-limited hepatitis segmented, and SS-negative RNA (SS-)
➢ Children is the most frequently infected
● Transmission
○ Respiratory droplets
2. CALICIVIRIDAE
● Pathogenesis
● Hepatitis E Virus ○ Enveloped
■ Two different types of spikes (H and E)
● Characteristics
○ No chronic carrier state ○ Hemagglutinin (H)
○ No cirrhosis ■ Binds to the cell surface receptor (neuraminic
○ No Hepatocellular Carcinoma acid, sialic acid) to initiate infection of the cell
■ The target of neutralizing antibody
● Transmission
○ Fecal-oral route ○ Neuraminidase (N)
■ Cleaves neuraminic acid (sialic acid) to
● Spectrum of Disease release progeny virus from the infected cell.
○ High mortality in pregnant women ■ Degrades the protective layer of mucus in the
respiratory tract which enhances the access
to respiratory epithelial cells.
● Norwalk Virus (Norovirus)
○ Zoonosis
● Characteristics ■ Aquatic birds (waterfowl) are a common
○ Icosahedral nucleocapsid and one piece of single source of these new genes
stranded, positive-polarity RNA (1SS+)
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 ➢ Reassortment event leads to the new ● Measles Virus
human strains occurring in pigs.
■ Pigs serve as the “mixing bowl” within which ● Characteristics
the human, avian, and swine viruses ○ Enveloped virus with helical nucleocapsid and
reassort. one piece of single-stranded negative polarity
RNA (SS-)
Antigenic Shift Antigenic Drifts
● Transmission
(Pandemics) (Epidemics)
○ Respiratory droplets
Major changes based on Minor changes based on
● Pathogenesis
the reassortment of mutations in the genome
○ Infects URT, then spreads to reticuloendothelial
segments of the genome RNA.
cells
RNA.
○ Can transiently depress cell-mediated immunity
○ Histopathology
Example: When human
■ Warthin-Finkeldey bodies
influenza A virus recombines
➢ Multinucleated giant cells
with swine influenza A virus

1. Sudden change in the 1. Slow and progressive

molecular structure of change in the composition of
microorganism microorganisms
2. New strain 2. Altered immunological
3. Little or no acquired responses and susceptibility
immunity to those novel
strains
4. New epidemics or
pandemics

● Spectrum of Disease
ADDITIONAL INFO ○ Incubation period
■ 10-14 days
● Sudden Shift is more deadly than graDual Drift ○ Pathognomonic Koplik spots
■ Bright red lesions with a white, central dot on
buccal mucosa (mouth)
● Spectrum of Disease
○ Maculopapular rash
○ Influenza A
■ Face-trunk-extremities palms and soles
■ Worldwide epidemics (pandemics)
■ Patients are contagious from 4 days before
■ Each year, influenza is the most common
the rash to 4 days after the appearance of the
cause of respiratory tract infections.
rash.
○ Influenza B
● Complications
■ Major outbreaks of influenza
○ Most common
■ Does not lead to pandemic
■ Otitis media
■ Only humans infect humans
○ Most life-threatening
■ No animal source of new RNA segments
■ Bacterial pneumonia
○ Influenza C
○ Complications in 1 month
■ Mild respiratory tract infections but does not
■ Post-infectious encephalomyelitis
cause outbreaks of influenza.
○ Complications in 1-10 months
■ Measles inclusion body encephalitis
● Treatment
○ Complications in 1-15 years
○ Oseltamivir or Zanamivir
■ Subacute Sclerosing Panencephalitis
○ Influenza A
(SSPE)
■ Amantadine or Rimantadine
● Cardinal Manifestations of Measles (3Cs)
● Prevention
○ Cough
○ Yearly vaccination
○ Coryza
○ Conjunctivitis

2. PARAMYXOVIRIDAE ○ Koplik spots

Virus Hemagglutinin Neuraminidase Fusion ● Prevention

Protein ○ Infection confer lifelong immunity
○ Vitamin A reduces severity
Measles + - + ○ Prevented by giving live-attenuated vaccine

Mumps + + +

RSV - - +

Parainfluenza + - +

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 ● Mumps Virus ● Parainfluenza Virus 1 & 2

● Characteristics ● Spectrum of Disease

○ Enveloped virus with helical nucleocapsid and ○ Laryngotracheobronchitis (group)
one piece of single-stranded negative polarity ■ Characterized by inspiratory stridor
RNA (SS-) ➢ Cough
➢ Hoarseness.
● Transmission
○ Respiratory droplets ■ Steeple sign on X-Ray
➢ Also called the wine bottle sign
● Pathogenesis ➢ Refers to the tapering of the trachea on
○ Initially infects URT a frontal chest radiograph reminiscent of
○ Spreads to local lymph nodes and via the a church steeple.
bloodstream to parotid glands, testes, ovaries,
meninges, and pancreas.

● Spectrum of Disease
○ Incubation period
■ 18-21 days
○ Parotitis
■ Tender swelling of the parotid glands
■ The period of maximum communicability was
considered to be several days before and
parotitis onset
○ Resolves within 1 week
○ Complications
■ Orchitis
■ Meningitis

○ Virus is shed in the saliva from about 3 days

before to 9 days after the onset of salivary glands
swelling. 3. RHABDOVIRIDAE

● Prevention ● Rabies Virus

○ Infection confers lifelong immunity
○ Prevented by giving live-attenuated vaccine ● Characteristics
○ Bullet-shaped enveloped virus with a helical
nucleocapsid and one piece of single-stranded,
ADDITIONAL INFO negative-polarity RNA (SS-)
Mumps makes your parotids & testes as big as POM-poms ● Transmission
● Parotitis ○ Animal reservoir
● Orchitis ■ Dogs
● Meningitis (aseptic) ■ Cats
■ Skunks
■ Raccoons
■ Bats
● Respiratory Syncytial Virus (RSV) ○ Transmission by animal bite
● Characteristics ● Pathogenesis
○ Humans are the natural hosts of RSV. ○ Multiplies locally at bite site, infects sensory
neurons and moves by axonal transport to CNS.
● Pathogenesis
○ Surface spikes ○ Histopathology
■ Fusion proteins ■ Negri body
■ Not hemagglutinins or neuraminidases.
○ Fusion protein
■ Causes cells to fuse
➢ Forming multinucleated giant cells
(syncytia)

● Spectrum of Disease
○ Viral Pneumonia
■ Most important cause of pneumonia and
bronchiolitis in infants
■ Severe disease in infants due to immunologic

● Treatment
○ Ribavirin

QUIAMBAO, LMB | 11
 ● Clinical Manifestations D. POSITIVE ENVELOPED RNA VIRUSES
○ Prodromal period 1. CORONAVIRIDAE
■ Symptoms suggestive of rabies:
➢ Paresthesia
● Coronavirus
➢ Fasciculations at around the bite
○ Encephalitic phase
● Characteristics
■ Excessive motor activity, excitation and
○ Enveloped virus with helical nucleocapsid and one
agitation
piece of single-stranded positive-polarity RNA
■ Periods of mental aberration are
(SS+)
interspersed with lucid intervals.
○ Prominent club-shaped spikes form a “corona”
■ Prominent brainstem dysfunction
○ Displays high frequency of recombination
○ Coma or death
○ Four main sub-groupings of coronaviruses:
■ Alpha
● Diagnosis
■ Beta
○ Fluorescent antibody testing (direct and
■ Gamma
indirect)
■ Delta
■ Occurrence of rabies antibodies in the CSF is
diagnostic for rabies a
● Structure
➢ Antibodies from vaccination do not cross
○ Made up of 4 structural proteins:
the blood-brain barrier.
■ Spike (S)
■ Antibodies in serum and CSF develop late in
■ Membrane (M)
the clinical course and may be undetectable
■ Envelope (E)
in the acute phase.
■ Nucleocapsid (N)
○ RT-PCR on fresh saliva
■ Viral shedding precedes signs

○ Skin biopsy sample

■ Direct Fluorescent Antibody testing or PCR
○ Brain is an optimal sample for definitive
post-mortem diagnosis
○ Rabies is ruled out in an animal only by direct
fluorescent antibody test of brain tissue.
○ The absence of Negri bodies does not rule out
rabies.

● Treatment and Prevention

○ Pre-exposure (PREP)
■ Vaccine
○ Post-exposure (PEP)
■ Vaccine ○ S protein
■ Immunoglobulin ■ Important for host attachment and
➢ Only vaccine that is routinely used penetration
post-exposure ■ Composed of two functional subunits
➢ S1: binding to host cell receptor
WHO GUIDELINES FOR PEP ➢ S2: fusion of viral and host cellular
membranes
Category I Touching or feeding No treatment
animals ● Transmission
Licks on the skin ○ Respiratory droplet and aerosol transmission
○ Virus binds to ACE-2 receptor
Category II Nibbling of uncovered Vaccine ■ Highly expressed on pulmonary epithelial
skin cells
Minor scratches without ○ Enters host through endocytosis or membrane
bleeding fusion
Licks on broken skin
● Spectrum of Disease
Category III Single or multiple Vaccine + ○ Common colds
transdermal bites or Immunoglobulin ■ Alpha coronavirus
scratches ➢ 229E
Contamination of ➢ NL63
mucus membrane with ■ Beta coronavirus
saliva from licks ➢ OC43
Exposure to bat bites or ➢ HKU1
scratches
○ Severe Acute Respiratory Syndrome (SARS)
■ Emerged in 2002 in China
■ Most likely originated in horseshoe bats,
amplified in palm civets then transmitted to
humans
■ Incubation period: 2-10 days
■ Atypical pneumonia rapidly progressing to
ARDS
QUIAMBAO, LMB | 12
 ■ Chest X-ray ■ Tourniquet Test
➢ Non cavitary “ground-glass” infiltrates ➢ Inflate the BP cuff between systolic and
diastolic blood pressure
○ Middle East Respiratory Syndrome (MERS) ➢ Keep cuff inflated for 5 minutes
■ Beta coronavirus ➢ >20 petechiae in one-inch square
■ Originated in bats, became widespread in indicates capillary fragility
dromedary camels, then transmitted to
humans ● Spectrum of Disease
■ Emerged in 2012 in Arabian Peninsula ○ Breakbone fever
■ Causes severe pneumonia and respiratory ■ Influenza-like syndrome with maculopapular
failure rash and severe pains in muscles and joints
○ Coronavirus disease-2019 (COVID-19)
■ Severe acute respiratory syndrome CoV-2 ○ Labs
(SARS-CoV-2) ■ Leukopenia
■ A novel Beta coronavirus belonging to the ■ Thrombocytopenia
subgenus Sarbeco virus ■ Increased hematocrit count
■ Emerged in Wuhan in late 2019
○ Hemorrhagic shock due to cross-reacting antibody
● Clinical Presentation during 2nd dengue infection.
○ Mode of transmission
■ Direct person-to-person ● Prevention
■ Via respiratory particles ○ Insecticides
○ Draining stagnant water
○ Incubation period ○ Mosquito repellant
■ 5-6 days
■ But can be up to 14 days ● Warning Signs
○ Period of infectiousness ○ Abdominal pain or tenderness
■ Starting a few days prior to the development ○ Persistent vomiting
of the symptoms ○ Clinical signs of fluid accumulation
■ Transmission after 7 to 10 days of illness is ○ Mucosal bleeding
unlikely ○ Lethargy, restlessness
○ Liver enlargement
○ Quarantine ○ Laboratory
■ Preferred period is 14 days ■ Increase in hematocrit
○ May be asymptomatic ■ Decrease in platelet count
■ Fever
■ Body aches
■ Breathlessness ● Hepatitis C Virus
■ Malaise and dry
■ GI Symptoms: ● Characteristics
➢ Abdominal pain ○ Enveloped virus with one piece of single-stranded,
➢ Vomiting positive-polarity RNA (SS+)
➢ Loose stools ○ Hypervariable region in envelope glycoprotein
○ 6 serotypes
○ The complications mostly due to the cytokine ○ Most prevalent blood-borne pathogen
storm
■ Acute respiratory distress syndrome ● Transmission
■ Acute respiratory failure ○ Major mode
■ Sepsis ■ Blood-borne
■ Disseminated intravascular coagulation ■ Setting
■ Acute liver and kidney injury ➢ IV drug abusers
■ Pulmonary embolism ○ Minor modes
■ Needle-stick injury
■ Vertical transmission
2. FLAVIVIRIDAE ■ Sexual

● Dengue Virus ● Diagnosis

○ Anti-HCV
● Characteristics ○ HCV RNA
○ Flavivirus family
○ Enveloped virus with icosahedral nucleocapsid ● Pathogenesis
and one piece of single-stranded, positive-polarity ○ Replication in liver enhance by liver-specific
RNA (SS+) microRNA
○ 4 serotypes ○ Hepatocellular injury due to immune attack
■ Alcoholism greatly enhances rate of
● Transmission hepatocellular CA
○ Transmitted by Aedes aegypti mosquito ○ Chronic carriage of HCV is much higher than HBV
○ Diagnosed using dengue IgM
● Spectrum of Disease
● Diagnosis ○ Incubation
○ Positive tourniquet test, but is nonspecific ■ 8 weeks
○ Clinical presentation resembles hepatitis B

QUIAMBAO, LMB | 13
 ○ Autoimmune reactions 4. RETROVIRIDAE
■ Thyroiditis
■ Autoantibodies ● Distinguished from all other RNA viruses by the
■ MPGN presence of an unusual enzyme
■ Porphyria cutanea ○ Reverse transcriptase
■ TARDA ■ Converts a single-stranded RNA viral
■ DM genome into double-stranded viral DNA.
○ Main cause of essential mixed
cryoglobulinemia
● Human Immunodeficiency Virus (HIV)
● Treatment
○ Acute hepatitis C infection ● Characteristics
■ Interferon ○ Enveloped with two copies (diploid) of a
○ Chronic hepatitis single-stranded, positive-polarity, RNA genome
■ Peginterferon ○ Most complex of the known retroviruses
■ Ribavirin
○ Liver transplantation for severe cirrhosis ● Structural and Regulatory Genes
■ Most common indication for liver
transplantation
○ New antivirals against Hepatitis C Structural Genes
■ Simeprevir
■ Sofosbuvir Gene Protein Function
■ Ledipasvir
p24, p7 Nucleocapsid
gag
p17 Matrix
3. TOGAVIRIDAE
reverse Transcribes RNA genome into
● Rubella Virus transcriptase DNA

● Characteristics pol protease Cleaves precursor polypeptides

○ Enveloped virus with an icosahedral nucleocapsid
and one SS-positive-RNA (SS+) integrase Integrates viral DNA into host cell
DNA
● Transmission
○ Respiratory droplet gp120 Attachment to CD4 protein
Antigenicity changes rapidly
● Spectrum of Disease env
○ German Measles gp41 Fusion with host cell
■ Incubation period
➢ 14-21 days
■ Prodrome followed by 3-day maculopapular Regulatory Genes
rash and posterior auricular
lymphadenopathy Gene & Protein Function
➢ Face – trunk – arms/legs
➢ Immune-complex polyarthritis in adults tat Activation of transcription of viral genes

○ Congenital Rubella Syndrome ref Transport of late mRNAs to cytoplasm

■ Infected during the 1st trimester
➢ Associated abnormalities nef CD4 and class I MHC proteins
➢ Patent ductus arteriosus
➢ Congenital cataracts vif Enhances hypermutation
➢ Sensorineural deafness
➢ Mental retardation vpr Transport in nondividing cells

● Prevention vpu Enhances virion release

○ Infection confers lifelong immunity
○ Prevented by giving life-attenuated vaccine
● Structure and Genome
■ Should not be given to immunocompromised
patients or pregnant women

ADDITIONAL INFO

5 Bs of Congenital Rubella Syndrome

● Bulag (cataracts)
● Bingi (sensorineural deafness)
● Brain damage (mental retardation)
● Butas ng puso (PDA or patent ductus arteriosus)
● Blueberry muffin baby

QUIAMBAO, LMB | 14
 < 200 P. jiroveci PCP pneumonia

T. gondii Cerebral toxoplasmosis

C. neoformans Meningoencephalitis

C. immitis Coccidioidomycosis

C. parvum Chronic diarrhea

< 50 M. avium Invasive pulmonary

disease

H. capsulatum Histoplasmosis

CMV CMV retinitis

● Transmission
○ Original source
■ Chimpanzees ● Diagnosis
○ Transfer of body fluids ○ Presumptive diagnosis
○ Transplacental and perinatal ■ Detection of antibodies by ELISA
○ Needlestick ➢ There are some-false positive results
with this test
● Pathogenesis ○ Definitive diagnosis
○ Preferentially infects and kills helper (CD4+) ■ Western blot analysis
T-lymphocytes ■ If antibodies are present, they will bind to the
■ Loss of cell-mediated immunity viral proteins
■ High probability of opportunistic infections ➢ Predominantly to the gp41 or p24
○ Main immune response consists of cytotoxic protein.
(CD8+) lymphocytes
ELISA Western Blot
● Stages of Infection
Presumptive diagnosis Definitive diagnosis

Phase 0 HIV acquired through sexual Sensitive Specific

Infection intercourse, blood, or perinatally
High false positive rate Low false positive rate
Phase 1 Rapid viral replication HIV test is
Window Period negative Low threshold High threshold

Phase 2 Peak of viral load Rule out test Rule in test

Seroconversion Positive HIV test
Mild flu-like illness
○ Polymerase chain reaction (PCR)
Lasts 1-2 weeks
■ Very sensitive and specific
■ To detect HIV DNA within infected cells
Phase 3 Asymptomatic
■ Amount of viral RNA in the plasma (i.e., the
Latent Period CD4 goes down
viral load) can also be determined using
Lasts 1-15 years
PCR-based assays
Phase 4 CD4 500 to 200
● Treatment
Early Symptomatic Lasts 5 years
○ Highly active antiretroviral therapy (HAART)
Mild mucocutaneous, dermatologic
■ Often initiated at the time of HIV diagnosis
and hematologic illness
■ Strongest indication for patients presenting
with:
Phase 5 CD4
➢ AIDS defining illness
AIDS
➢ Low CD4+ cell counts (<500
cells/mm3),
➢ High viral load
● AIDS-Defining Illnesses ○ Regimen consists of 3 drugs to prevent
resistance:
■ 2 NRTIs
CD4 Count Etiology Clinical Syndrome
➢ Zidovudine
➢ Lamivudine
< 500 M. tuberculosis Disseminated
■ Protease inhibitor
tuberculosis
➢ Indinavir
HSV HSV esophagitis

C. albicans Esophageal candidiasis

HHV-8 Kaposi's Sarcoma

QUIAMBAO, LMB | 15
 E. MISCELLANEOUS VIRUSES
VI. COVID-19
● Human T-Cell Lymphotropic Virus (HTLV) A. OVERVIEW

● Characteristics ● Defined as an illness caused by a novel coronavirus

○ Retrovirus causing adults’ T-cell leukemia and a
HTLV-associated myelopathy
● Histopathology
○ Malignant T cells with flower-shaped nucleus
● Now called severe acute respiratory syndrome
coronavirus 2
○ SARS-CoV-2
○ Formerly called 2019-nCoV
● Postulated to have originated in a large animal and
seafood market
○ Huanan Seafood Wholesale Market

B. CORONAVIRUS FAMILY

● Characteristics
○ Enveloped, non-segmented, positive-sense RNA
viruses
○ Club-like spikes that project from their surface
■ Defining feature of the virion
■ Gives the appearance of a solar corona
○ Are the largest group of viruses belonging to the
Nidovirales order
■ Coronaviridae
■ Arteriviridae
■ Mesoniviridae
● Ebola Virus ■ Ronivirida

● Characteristics
○ Belongs to the Filoviruses
○ “Threadlike” viruses
○ Longest viruses
○ Natural hosts
■ Fruit bats

● Transmission
○ Direct contact with body fluids
○ Fomites
■ Including dead bodies
○ Infected bats
○ Primates

● Spectrum of Disease
○ Ebola Hemorrhagic Fever
○ Abrupt onset of flu-like symptoms, diarrhea,
vomiting, high fever, myalgia ● 4 genera of CoVs
○ Can progress to ○ Alphacoronavirus (alphaCoV)
■ Disseminated intravascular coagulation (DIC) ○ Betacoronavirus (betaCoV)
■ Diffuse hemorrhage ○ Deltacoronavirus (deltaCoV)
■ Shock ○ Gammacoronavirus (gammaCoV)
○ Mortality rate can be as high as 100%
● Spectrum of Disease
○ Some cause disease in animals
● Japanese B Virus ■ Enteritis in cows, and pigs
■ URT in chickens
● Characteristics
○ Member of the flavivirus family ■ Severe acute respiratory syndrome (SARS)
○ Most prevalent in Southeast Asia and Middle East respiratory syndrome
(MERS) is also caused by coronaviruses that
● Transmission “jumped” from animals to humans
○ Culex tritaeniorhynchus mosquitoes
● Variants of Concern (VOCs)
● Pathogenesis ○ Potential to cause enhanced transmissibility or
○ Thalamic infarcts on CT scan virulence

● Spectrum of Disease ○ Alpha (B.1.1.7)

○ Japanese B Encephalitis ■ First variant of concern
○ Most common cause of epidemic encephalitis ■ United Kingdom (UK) in late December 2020
○ Beta (B.1.351)
■ First reported in South Africa in December
2020

QUIAMBAO, LMB | 16
 ○ Gamma (P.1) ○ Coronaviruses are also known for their ability to
■ First reported in Brazil in early January 2021 recombine using both homologous and
○ Delta (B.1.617.2) nonhomologous recombination
■ First reported in India in December 2020
○ Omicron (B.1.1.529) ● Assembly and Release
■ First reported in South Africa in November ○ The viral structural proteins, S, E, and M are
2021 translated and inserted into the endoplasmic
reticulum (ER)
C. CORONAVIRUS LIFE CYCLE ○ These proteins move along the secretory pathway
into the endoplasmic reticulum–Golgi intermediate
compartment (ERGIC)
○ Viral genomes encapsidated by N protein bud into
membranes of the ERGIC
■ Containing viral structural proteins
■ Forming mature virions

D. EPIDEMIOLOGY

● As of December 1, 2023 in the Philippines per DOH

data,
○ 4,079,167 total cases reported
○ 4,009,326 recoveries
○ NCR as the top region with total case of 1,320,782
○ 17.2% bed occupancy reported in NCR
○ New cases in the last 14 days are reported at 677
in NCR

● On May 5, 2023, WHO Director General announced

that COVID-19 no longer constituted a public health
emergency

● On July 22, 2023, PBBM lifted the state of public health

emergency throughout the nation
○ But evidently, the fight for SARS COV-2 still exist
as positive cases are still reported everyday

E. PATHOPHYSIOLOGY
1. TRANSMISSION

● Via respiratory droplets from coughing, and sneezing

● Virus released in respiratory secretion can infect other
individuals via direct contact with mucous membranes.
● Droplets usually cannot travel more than 6 feet.
● Reproduction number (R0 - Rnaught) = 2.2
○ Estimated that an infected individual is likely to
spread the disease to an average of 2.2 people

● Attachment and Entry 2. INCUBATION PERIOD

○ Interaction of virus S protein with host receptor
○ Host Receptors ● Symptoms develop 2 days to 2 weeks following
■ SARS-CoV exposure to the virus
➢ Angiotensin Converting Enzyme 2 ● In a study, the mean incubation period was 5.1 days
Receptor ○ 97.5% of individuals who developed symptoms did
■ MERS-CoV so within 11.5 days of infection.
➢ Dipeptidyl dipeptidase 4
○ Fusion with acidified endosomes, or plasma 3. RISK FACTORS
membrane
○ Release of viral genome into cytoplasm ● Include (but are not limited to)
○ Advanced age
● Replicase Protein Expression ○ Immunocompromised state
○ Translation (mRNA to protein synthesis) of ○ Diabetes
replicase gene from virion genomic RNA ○ Cardiovascular disease
○ Hypertension
● Replication and Transcription ○ Chronic pulmonary disease
○ The leader and body transcription regulatory ○ Chronic renal disease
segments (TRS) fuse during production of ○ Liver disease
sub-genomic RNAs ○ Malignancy
■ Most novel aspect of coronavirus replication ○ Severe obesity

QUIAMBAO, LMB | 17
● Occupational Risk ■ Deteriorating sensorium
○ Employees of seafood and wet animal wholesale ■ Multi-organ failure
markets in Wuhan ■ Thrombosis
○ Healthcare workers
○ Frontliners
3. UPDATED PROTOCOLS
4. EFFECT ON RESPIRATORY SYSTEM
Protocols
● Increased vascular permeability and subsequent
development of pulmonary edema in patients with
Asymptomatic close No need to quarantine
severe COVID-19 are explained by multiple
contact exposed to
mechanisms.
confirmed Wear a well-fitted face mask for
● These mechanisms include
COVID-19-positive 10 days
○ Endotheliitis
individual
■ Result of direct viral injury and perivascular
inflammation leading to microvascular and
Asymptomatic but Home isolation for 5 days or until
microthrombi deposition
confirmed afebrile (fever-free) for at least 24
○ Dysregulation of RAAS
COVID-19-positive hours without using antipyretics
■ Due to increased binding of the virus to the
case (Paracetamol) and with an
ACE2 receptors
improvement of respiratory
○ Activation of the kallikrein-bradykinin pathway
symptoms
■ The activation of which enhances vascular Confirmed
permeability COVID-19-positive Wear a well-fitted face mask for
○ Enhanced epithelial cell contraction case with mild 10 days
■ Causes swelling of cells and disturbance of symptoms
intercellular junctions
Isolation may be shortened as per
○ Binding of SARS-CoV-2 to the Toll-Like Receptor Individuals with acute a healthcare provider
(TLR) respiratory symptoms
■ Induces the release of pro-IL-1β
➢ Mediates lung inflammation until fibrosis.
Isolation for at least 10 days from
onset of signs and symptoms
F. CLINICAL MANIFESTATIONS following the advice of attending
physician, including whether to be
1. SIGNS AND SYMPTOMS Confirmed
admitted in a healthcare facility
COVID-19-positive
● Ranges from asymptomatic or mild symptoms to case with moderate to
Wear a well-fitted face mask for
severe illness and mortality severe symptoms
10 days
○ Fever
○ Cough Immunocompromised
For severe and
○ Shortness of breath immunocompromised,
○ Malaise discontinue isolation only upon
○ Myalgia the advice of healthcare provider
○ Fatigue
○ Respiratory distress or Dyspnea

2. CASE SEVERITY CLASSIFICATION FOR ADULTS G. LABORATORY DIAGNOSIS

1. POLYMERASE CHAIN REACTION (PCR)
● Moderate
○ With risk factors ● Real-time reverse transcription–polymerase chain
■ Elderly age >60 reaction (rRT-PCR) assay
■ Comorbidities
● Sample to be used
● Moderate COVID-19 with pneumonia ○ Nasopharyngeal swabs (NPS) and Oropharyngeal
○ With pneumonia but no difficulty of breathing or swabs (OPS)
shortness of breath ○ Sputum, endotracheal aspirate, or
bronchoalveolar lavage fluid as appropriate.
● Severe
○ With pneumonia and any one (1) of the following: ○ Nasal swabs
■ Signs of respiratory distress ■ Contain the most virus.
■ Oxygen saturation
➢ SpO2 <94% at room air ○ URT specimens have a smaller viral load than
■ Respiratory rate of >30 breaths per minute LRT specimens
■ Requiring oxygen supplementation
● Materials for Sample Collection
● Critical ○ Healthcare workers should wear the following
○ With pneumonia and any of the following: PPE
■ Impending respiratory failure requiring high ■ Eye protection
flow oxygen ■ Surgical mask
➢ Non-invasive or invasive ventilation ■ Double gloves
■ Acute Respiratory distress syndrome
■ Sepsis or shock
QUIAMBAO, LMB | 18
 ■ Disposable impermeable, breathable, ○ Aseptically, cut or break applicator sticks off near
long-sleeved, laboratory gown fastened at the the tip to permit tightening of the cap.
back ○ Label the vial with the:
■ If the specimen is collected with an ■ Patient’s name
aerosol-generating procedure ■ Specimen type
➢ Staff should wear a particulate respirator ■ Date collected
at least as protective as a: ■ Other required information.
★ NIOSH-certified N95
★ An EU standard FFP2 ○ If specimens will be examined within 48 hours
★ Or the equivalent after collection
■ Keep specimen at 4C
○ Procedure for collecting respiratory specimens ■ Ship on wet ice or refrigerant gel-packs
■ Use sterile Dacron or rayon viral swabs for ■ Otherwise, store frozen at ≤ 70C and ship on
collecting upper respiratory tract specimens dry ice.
from both the nasopharynx and the ■ Avoid freezing and thawing specimens.
oropharynx.
■ Do not use calcium alginate swabs ○ Specimens should be packaged using the triple
packaging system detailed below
● Collecting Oropharyngeal Swabs ■ Primary Receptacle
○ Insert the swab into the posterior pharynx and ➢ Seal using Parafilm
tonsillar areas. ➢ Wrap the primary receptacle with an
○ Rub the swab over both tonsillar pillars and absorbent material
posterior oropharynx ★ E.g., gauze
■ Avoid touching the tongue, teeth, and gums. ■ Secondary Container
○ Do not sample the tonsils ➢ The second container should be durable
and leak-proof.
■ Outer Container
➢ E.g., ice box.
➢ Ensure that the required temperature is
maintained in the outer container
through the use of wet ice or refrigerant
packs.

● Collecting Nasopharyngeal Swabs

○ Insert flexible wire shaft swab through the nares
parallel to the palate (not upwards)
■ Until resistance is encountered or
■ The distance is equivalent to that from the
ear to the nostril of the patient indicating
contact with the nasopharynx
○ Gently, rub and roll the swab.
○ Leave the swab in place for several seconds to
absorb secretions before removing.
○ Do not sample the nostrils.
● Specimen Handling
○ Place swabs immediately into a sterile vial
■ Containing 2mL of viral transport media
without antibiotics
■ Both swabs can be placed in the same vial
2. RAPID ANTIGEN TEST KIT
● Collecting Nasal Swabs
○ Wash your hands thoroughly with warm water and
soap for at least 30 seconds.
○ The kit comes with two tests
■ Each contains three main items
➢ A collection swab
➢ A test strip
➢ A small vial of liquid.
■ Place them all on a clean surface.
○ Open the collection swab and insert it into each
nostril
■ Rotating five times against the inner wall.
■ You should insert the swab ½ to ¾ of an
inch into the nostrils.
○ Tap the bottom of the vial of liquid three times on a
hard surface.
○ Open the large cap and insert your swab into the
vial
■ Stir the swab 15 times
○ Squeeze the sides of the vial against the swab as
you pull it out.
■ Put the cap back on the vial.
○ Open the test strip.

QUIAMBAO, LMB | 19
 ○ Open the smaller, top cap on the vial of liquid
■ Squeeze three drops of your sample into the
collection area of the strip.
○ Set a timer for 15 minutes.
■ Don’t disturb the test strip during this time.
○ Read your test.

● Collecting Saliva

5. ANTIBODY TESTING

● A qualitative immunoglobulin M (IgM) and

immunoglobulin G (IgG) antibody test for SARS-CoV-2
using:
○ Serum
○ Plasma
■ Ethylenediamine Tetraacetic Acid (EDTA)
■ Citrate)
○ Venipunctured whole blood

● IgM antibodies
○ Detectable days after initial infection
● IgG antibodies
○ Detected later

6. VIRAL CULTURE

● Virus isolation in cell culture or initial characterization of

viral agents recovered in cultures of specimens is not
3. CHEST RADIOGRAPH (X-RAY) recommended for biosafety reasons
● Consolidation
○ Commonly bilateral and of lower zone distribution 7. BLOOD TESTS
● Ground-glass opacities
● Pulmonary infiltrates ● Leukopenia, or Leukocytosis
● Pleural effusion was an uncommon finding. ● Neutrophilia
● Severity on chest radiography peaked 10-12 days ● Lymphopenia
following onset.
● Decreased Hemoglobin
● Decreased platelet

● Increased ALT/AST

● Elevated CRP
● Elevated BUN
● Elevated Procalcitonin
● Elevated D-Dimer

H. MANAGEMENT AND PREVENTION

● Practice proper hand hygiene.

● Practice cough etiquette
○ Cover your mouth with your arm rather than your
4. CT SCAN hand when coughing
● Avoid going into mass gatherings or crowds.
● Ground-glass opacities, possibly with consolidation ● Make it a point to clean your gadgets.
● Usually bilateral, involve the lower lobes, and have a ● Wear a face mask if you have any respiratory
peripheral distribution symptoms or if your occupation requires you to handle
● Pleural effusion, pleural thickening, and possible individuals with flu-like symptoms.
lymphadenopathy have also been reported, but with ● Avail vaccines when accessible
less frequency ● Improve indoor ventilation
● May have findings in apparently asymptomatic ● Be vigilant for signs and symptoms of COVID-19, avail
individuals OTC test kits

QUIAMBAO, LMB | 20