INFECTIOUS DISEASES

BRENDALYN A. GALLEBO, MD, DPSP

Categories of Infectious
Agents
PRIONS
PRIONS

 Abnormal forms of a normal host prion protein (PrP) –

modified host proteins
 Associated with NEURODEGENERATIVE DISEASES
(fatal familial insomia)

 Spongiform Encephalopathies:
-Kuru
-Creutzfeldt-Jakob disease
“mad cow disease”
PRIONS

 MECHANISM:

PrP = conformational (folding)

change that confers protease
resistance

protease-resistant PrP =
conversion of the normal protease-
sensitive PrP to abnormal form

spongiform encephalopathies
-neuronal damage and distinctive foamy
"spongiform" changes in the brain
MICROBIAL PATHOGENESIS
 HOST BARRIERS TO INFECTION

 Prevent microbes from entering the body

 Innate and Adaptive immune defenses
 Innate immunity
 1st line of defense
 phagocyticand natural killer (NK) cells, complement, and
inflammatory mediators
 Adaptive immune responses
 mediated by T and B lymphocytes
 Typically improve with successive contacts
 ROUTES OF ENTRY

1. SKIN:
 Intact Keratinized Epidermis – mechanical barrier
Mechanical injury – skin infections
2. GASTROINTESTINAL TRACT:
 Acidic gastric secretions, enzymes, defensins(IgA abs), Peristalsis,
Normal flora

3. RESPIRATORY TRACT:
 Trapped in the mucociliary blanket – Large particle
 Alveoli and Macrophages/Neutrophils- < 5 microns
 ROUTES OF ENTRY
4. UROGENITAL TRACT:
 Micturation, Obstruction or reflux of urine, pH environment, Epithelial lining
 Anatomy – female – high risk– (5 cm) distance between the urinary bladder and skin
5. VERTICAL TRANSMISSION:
 Mother to fetus or newborn child
 Placental-fetal transmission
 Rubella – 1st trimester – heart malformations, mental retardation, cataracts, deafness
 Rubella – 3rd trimester – little effect

6. TRANSMISSION DURING BIRTH:

 Through the birth canal: HSV; Papilloma
7. POSTNATAL TRANSMISSION IN MATERNAL MILK:
 CMV, HIV, HBV
IMMUNE EVASION BY MICROBES

1. ANTIGENIC VARIATION:
 Expression of different surface antigens – scape recognition
 Antigenic drifts and shifts – influenza viruses
 Mutation – generate genetic variants

2. RESISTANCE TO ANTIMICROBIAL PEPTIDES:

 Changes in net surface charge and membrane hydrophobicity –
prevent peptide insertion and pore formation
 Secretion of proteins – inactivate the peptides
 IMMUNE EVASION BY MICROBES

3. RESISTANCE TO KILLING BY PHAGOCYTES:

 Capsule – carbohydrate, sialic acid
 Protein A – inhibit phagocytosis

4. EVASION OF APOPTOSIS AND MANIPULATION OF HOST CELL METABOLISM

-Resistance to cytokine-, chemokine- and complement-mediated host defense
-Immunoregulatory mechanisms (Downregulation) anti-microbial T cell
responses
-Evade the recognition by CD4+ helper T cells and CD8+ cytotoxic T cells
 Mechanism of Bacterial Injury

 Ability of bacteria to cause disease (VIRULENCE)

depends on their ability to:

- ADHERE to host cells

- INVADE cells and tissues
- DELIVER TOXINS that damage cells and tissues
Mechanism of Bacterial Injury

 BACTERIAL ADHERENCE TO HOST CELL

 Adhesins – bacterial surface proteins
 Pili – filamentous proteins

 VIRULENCE OF INTRACELLULAR BACTERIA

 Evade Opsonization by macrophages

 BACTERIAL TOXINS
 Endotoxins- lipopolysaccharide (outer membrane of G- bacteria)
 Exotoxins – secreted bacterial proteins
 PATTERNS of Inflammatory Responses to Infection

 SUPPURATIVE INFLAMMATION
 acute tissue damage
 increased vascular permeability and leukocytic exudates
 neutrophils - liquefactive necrosis - abscesses
 Patterns of Inflammatory Responses to Infection

 MONONUCLEAR AND GRANULOMATOUS INFLAMMATION

Acute viral hepatitis Secondary syphilis in the Granulomatous

characterized by a dermis with
PERIVASCULAR inflammation in
predominantly
lymphocytic LYMPHOPLASMACYTIC response to
infiltrate and tuberculosis
infiltrate
endothelial proliferation
 Patterns of Inflammatory Responses to Infection

 CYTOPATHIC-CYTOPROLIFERATIVE RESPONSE

 cytopathic response- cell death

 cytoproliferative response)
 inclusion bodies (e.g., CMV, HSV, HBV)
 venereal warts - HPV
 molluscum contagiosum: umbilicated papules
 Patterns of Inflammatory Responses to Infection

 NECROTIZING RESPONSE

 potent toxins - rapid and severe necrosis ( C. perfringens)

 E. histolytica - colonic ulcers and liver abscesses
 Patterns of Inflammatory Responses to Infection

 Chronic inflammation and

scarring

 M. tuberculosis
 Schistosomiasis

Schistosoma haematobium infection

with numerous calcified eggs
(arrows) and extensive scarring
 SPECIAL TECHNIQUES for Diagnosing
Infectious Agents
TECHNIQUE ORGANISMS
1. Gram stain Most bacteria
2. Acid fast stain Mycobacteria and Nocardia
3. Silver stain Fungi, Legionella, Pneumocystis

4. Periodic acid schiff stain Fungi and Amoeba

5. Mucicarmine stain Cryptococci
6. Giemsa stain Campylobacteria, Leishmaniae, Malaria

7. Antibody probes Viruses, Rickettsiae

8. Culture All classes
9. DNA probes Viruses, Bacteria, Protozoa
VIRAL INFECTIONS
Acute (Transient)
Infections
MEASLES

 Rubeola Virus
 Paramyxovirus family - ssRNA virus
 Mumps,RSV,
Parainfluenza and Human
Metapneumovirus
 Transmitted RESPIRATORY DROPLETS
MORPHOLOGY:

 Rash of Measles Virus

 blotchy, reddish brown
 dilated skin vessels, edema, and a moderate, nonspecific,
mononuclear perivascular infiltrate
 “Koplik spots”-
Ulcerated mucosal lesions
 MEASLES
 WARTHIN-FINKELDEY CELLS

 multinucleated giant cells with eosinophilic nuclear and

cytoplasmic inclusion bodies
 pathognomonic - lung and sputum
 MUMPS

 Paramyxovirus family
 Primarily infects the salivary glands
 Pathogenesis: Inhalation of droplets

 Salivary gland- classic pain and swelling of mumps

 other sites (CNS, testis and ovary, and pancreas)
 Aseptic Meningitis
-most common extrasalivary gland complication
-approx.10% of cases
 Mumps
MORPHOLOGY
1. MUMPS PAROTITIS
 bilateral - 70% of cases

2. MUMPS ORCHITIS
 testicular swelling
 Sterility - scars and atrophy of the testis after
resolution of viral infection

3. PANCREAS
 parenchymal and fat necrosis and neutrophil-rich
inflammation

4. MUMPS ENCEPHALITIS
 perivenous demyelination and perivascular
mononuclear cuffing
 POLIOVIRUS
 Spherical, Unencapsulated RNA virus of the ENTEROVIRUS GENUS
 Transmission: FECAL-ORAL ROUTE
 Virus infects humans CD155
 1 of 100 infected persons

 Invades the CNS and replicates in:

-Motor neurons of the spinal cord =Spinal poliomyelitis
-Brain stem = Bulbar poliomyelitis
 Secondary to viremia or occur by retrograde transport of the
virus along axons of motor neurons
 WEST NILE VIRUS

 Arthropod born virus of FLAVIVIRUS GROUP

 Transmission: mosquitos to birds to mammals
 Humans – incidental host
 Skin dendritic cells infects the lymph nodes (replication)
to bloodstream and some crosses the BBB
 Usually Asymptomatic
 20% of infected individuals - fever, headache,
myalgia, fatigue, anorexia, and nausea
 50% of infected indv’ls - maculopapular rash
 West Nile Virus

 CNS complications:
-meningitis
-encephalitis
-meningoencephalitis

 Immunosuppressed and elderly individuals

 Survivors may exhibit long term cognitive and
neurologic impairment
VIRAL HEMORRHAGIC FEVERS
 SYSTEMIC INFECTIONS
 Enveloped RNA viruses in 4 different families:
 ARENAVIRUSES, FILOVIRUSES, BUNYAVIRUSES, AND
FLAVIVIRUSES
 Some cause HEMORRHAGIC FEVER (EBOLA, MARBURG, LASSA)
 mild acute disease
 fever, headache, myalgia, rash, neutropenia,
THROMBOCYTOPENIA
 severe, life-threatening condition - sudden hemodynamic
deterioration and shock
VIRAL HEMORRHAGIC FEVERS

 Pathogenesis:
 Damage to blood vessels – endothelial cells
 Infection of macrophages and dendritic cells – production
of inflammatory cytokines
 Hemorrhagic manifestations
 Petechiae - combination of thrombocytopenia or platelet
dysfunction
 Endothelial injury
 Cytokine-induced disseminated intravascular coagulation
 deficiency of clotting factors - hepatic injury
VIRAL HEMORRHAGIC FEVERS

Petechiae (1-2 mm) Purpura (>3 mm)

Latent Infections
(Herpesvirus
Infections)
 HERPESVIRUSES
 Large encapsulated viruses with double-stranded
DNA genomes

 8 types:
 α-group viruses - HSV-1, HSV-2, and VZV
 Lymphotropic β-group viruses - CMV, HHV-6 and HHV-7
 γ-group - EBV and KSHV/HHV-8
 HERPES SIMPLEX VIRUS (HSV)

MORPHOLOGY

 HSV- large, pink to purple

intranuclear inclusions
(COWDRY TYPE A)

 inclusion-bearing multinucleated
syncytia

Glassy intranuclear
herpes simplex inclusion
bodies
 HERPES SIMPLEX VIRUS (HSV)

 GINGIVOSTOMATITIS- encountered in
children-HSV-1

 GENITAL HERPES -more often by HSV-2

 HSV-2- transmitted to neonates

Gingivostomatitis
Herpes Labialis
 HERPES SIMPLEX VIRUS (HSV)

 CORNEAL LESIONS:
 Herpes epithelial keratitis
 Herpes stromal keratitis

 HOSPITALIZED PATIENTS – disseminated herpes infections

 Herpes simplex encephalitis
 Herpes esophagitis
 Herpes bronchopneumonia
 Herpes hepatitis
VARICELLA-ZOSTER VIRUS (VZV)

2 conditions:
1. Chickenpox = Acute infection with VZV
2. Shingles (herpes zoster) = reactivation of latent VZV
(Dewdrop on a rose petal)
Varicella-Zoster Virus (VZV)
SHINGLES
- reactivation OF THE LATENT VIRUS IN THE DORSAL ROOT GANGLIA

 Intense itching, burning, or sharp pain (Radiculoneuritis)

 Pain is severe when TRIGEMINAL NERVES are involved

 RAMSEY HUNT SYNDROME

– INVOLVED geniculate nucleus
- facial paralysis (rare)
 CYTOMEGALOVIRUS (CMV)

 Β-GROUP HERPESVIRUS
 Most common opportunistic pathogen in AIDS

 Infects monocytes and their bone marrow progenitors

 Infected cells exhibit gigantism of both the entire cell
and its nucleus

Within the nucleus - large inclusion surrounded by a

clear halo (OWL'S EYE)
 CYTOMEGALOVIRUS (CMV)
 TRANSMISSION :

• Transplacental transmission -(“congenital CMV”)

• Neonatal transmission (“perinatal CMV”)
• Saliva and respiratory secretions
 Fecal-oral route
• Organ transplants or blood transfusions
 CYTOMEGALOVIRUS (CMV)

 CONGENITAL INFECTION - NEONATAL CMV

 Cytomegalic inclusion disease – resembles erythroblastosis fetalis
 IUGR, jaundice, hepatosplenomegaly, anemia, bleeding encephalitis
 Brain - microcephaly with calcification
 PERINATAL INFECTIONS:
 Interstitial pneumonitis, failure to thrive, rash, or hepatitis

 CYTOMEGALOVIRUS MONONUCLEOSIS:
 infectious mononucleosis-like illness - fever, atypical lymphocytosis,
lymphadenopathy, and hepatitis (hepatomegaly and abnormal liver function tests)
 CHRONIC
PRODUCTIVE
INFECTIONS
 HEPATITIS B VIRUS

 HEPADNAVIRUS FAMILY

 significant cause of acute and chronic liver disease

 Transmission:
 Percutaneously (IV drug use or blood transfusion)
 Perinatally
 Sexually

 Effective Cytotoxic T-lymphocyte (CTL) response

 major determinant if a person clears the virus or becomes a chronic carrier
TRANSFORMING
INFECTIONS
Epstein-Barr Virus (EBV)
 INFECTIOUS MONONUCLEOSIS

 Benign, self-limited lymphoproliferative disorder

 Associated with certain neoplasms :
LYMPHOMAS AND NASOPHARYNGEAL CARCINOMA)
 Clinical manifestations:
-fever
-generalized lymphadenopathy
-splenomegaly
-sore throat
-appearance in the blood of atypical activated T lymphocytes (mononucleosis cells)

 Late adolescents/ young adults= close human contact ( kissing) thru saliva
 Epstein-Barr Virus (EBV)

MORPHOLOGY:
 peripheral blood - absolute lymphocytosis
 > 60% of white blood cells
 5%- 80% -large, atypical lymphocytes, most of which express CD8
 BACTERIAL
INFECTIONS
GRAM(+) BACTERIAL INFECTIONS

 Staphylococcal infection
 Streptococcal infections
 Diphtheria
 Listeriosis
 Anthrax
 Norcardia
STAPHYLOCOCCAL INFECTIONS
 Staphylococcus aureus

 Pyogenic G(+) cocci in clusters (bunches of grapes)

 Diseases:
skin lesions(Furuncle, Carbuncle and Hydradenitis) , abscesses, sepsis,
osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock
syndrome (TSS)

 Virulence factors
 surface receptors for fibrinogen, fibronectin, and vitronectin
 Surface protein A and Lipase
 Hemolytic toxins (α-toxin, β-toxin and δ-toxin, γ-toxin and leukocidin)
 Exfoliative A and B toxins
 Superantigens - food poisoning and TSS
 Staphylococcus
Staphylococcal scalded-skin syndrome (Ritter disease)
 sunburn-like rash over the entire body and evolves into fragile bullae that
lead to partial or total skin loss
 desquamation of the epidermis: Granulosa layer
 Streptococcal and
Enterococcal Infections
 STREPTOCOCCI
 Gram(+) cocci in pairs or chains
 Classified by the pattern of hemolysis on blood agar
 β (complete or clear hemolysis)
 Α (partial or green hemolysis)
 γ (no hemolysis)

 ENTEROCOCCI
 gram(+) cocci in chains
 Streptococcus

 Virulence factors and toxins:

 S. pyogenes
M protein – prevents bacterial phagocytosis
 Secrete phage-encoded pyrogenic exotoxin – fever and rash in scarlet fever
 antistreptococcal M protein abs and T cells cross react to cardial proteins -
leading to Poststreptococcal acute rheumatic fever

 S. pneumoniae
Pneumolysin – tissue damage

 S. mutans - metabolizing sucrose to lactic acid and secreting high-molecular-

weight glucans – bacterial aggregation and plaque formation
 STREPTOCOCCAL INFECTIONS:

1. ERYSIPELAS
 Middle-aged persons in warm climates
 Exotoxins from infection with S. pyogenes
 Rapidly spreading erythematous cutaneous
swelling begins on the face to
body or extremities
2. STREPTOCOCCAL PHARYNGITIS
 major antecedent of poststreptococcal glomerulonephritis
 edema, epiglottic swelling, and punctate abscesses of the tonsillar crypts

3. Scarlet fever
 associated with pharyngitis - S. pyogenes
 3 and 15 years old
 punctate erythematous rash
 most prominent over the trunk and inner aspects of the arms and legs, face is also
involved

 inflammation of the skin - leads to hyperkeratosis and scaling

 CORYNEBACTERIUM
DIPHTHERIAE
 slender gram(+) rod with clubbed ends
 aerosols or skin exudate
 asymptomatically or cause illnesses ranging from
skin lesions to life-threatening syndrome
 produces phage-encoded A-B toxin
 blocks host cell protein synthesis
Corynebacterium diphtheriae

• fibrinosuppurative exudate – coagulate and creates a tough, dirty

gray to black, superficial membrane, pseudo-membrane – not formed
by viable tissue
 Listeria monocytogenes

 Facultative (+) intracellular bacillus

 severe food-borne infections
 Mini-epidemics - dairy products, chicken, and hot dogs
 Pregnant women - AMNIONITIS -result in abortion,
stillbirth, or neonatal sepsis

 NEONATES - disseminated disease (granulomatosis

infantiseptica) and an exudative meningitis
 Listeria monocytogenes

MORPHOLOGY
 Infants with L. monocytogenes sepsis
 papular red rash over the extremities
 listerial abscesses can be seen in the placenta
 BACILLUS anthracis

 large, spore-forming gram(+) rod-shaped bacterium

 common pathogens in farm and wild animals that have
contact with soil contaminated with spores
 spores can be ground to a fine powder - potent biologic
weapon
 Bacillus anthracis
MORPHOLOGY
 large, boxcar-shaped gram-positive extracellular bacteria in chains
 BACILLUS anthracis
1. GASTROINTESTINAL ANTHRAX
 uncommon form
 contracted by eating undercooked meat
 INHALATIONAL ANTHRAX
 spores - inhaled
 Hemorrhagic mediastinitis
 Perihilar interstitial pneumonia
 CUTANEOUS ANTHRAX
-painless, pruritic papule that develops into a vesicle within 2 days

ulcer ruptures

BLACK ESCHAR