Download INFECTIOUS DISEASES PART II

INFECTIOUS DISEASES
PART II
BERNADETTE R. ESPIRITU, M.D. FPSP AP-CP
INFECTIOUS DISEASES OF THE CNS

Important ANATOMIC FEATURE of the CNS that
affects the pathophysiology of INFECTIONS is
that:
The BRAIN is surrounded by
MENINGES & bathed in CSF
CNS INFECTIOUS DISEASES

CSF PROVIDES BOTH:
1. Culture Medium for the infecting organism
2. Rapid means of disseminating infection
throughout the system once the outer defenses
have been breached
MENINGITIS

Inflammatory state of the:
leptomeninges
subarachnoid space

It is usually the result of infection
MENINGITIS
CHEMICAL MENINGITIS
 caused by release or insertion of
irritative substance into the CSF
 Pleocytosis (Increase # of PMNs)
 Increased CHON
 Normal sugar content
 Organism can neither be seen nor
cultured
MENINGITIS
CARCINOMATOUS MENINGITIS
- Infiltration of the subarachnoid
space by tumor cells and eventually
spread to the entire neuraxis

- no inflammatory response
INFECTIOUS MENINGITIS
CLASSIFICATION
ACUTE PYOGENIC - Usually Bacterial
 ACUTE LYMPHOCYTIC - Usually Viral
 CHRONIC MENINGITIS - Bacterial or Fungal

ACUTE PYOGENIC MENINGITIS
CAUSATIVE ORGANISM
1. E. coli: Neonate w/ neural tube defect
2. H. influenza: Infants & Children
3. Neisseria meningitides
–
–
–
4.
adolescents & young adults
most common cause: epidemic meningitis
Oral commensal & transmitted through the air
Pneumococcus:
–
very young or the very old and following trauma
ACUTE PYOGENIC MENINGITIS
GROSS:
 cloudy or frankly purulent CSF
 Location of the exudate varies:
– H. influenza – basal
– Pneumococcal – over the cerebral convexities
near the sagittal sinus
– Fulminant meningitis – extend into the ventricles
ACUTE PYOGENIC MENINGITIS
MICRO:
 PMNs fill the entire subarachnoid space & around
the leptomeningeal blood vessels (less severe
cases)

Fulminant – inflammatory cells infiltrate the walls
of the leptomeningeal veins that can lead to
venous occlusion – hemorrhagic infarction of the
underlying brain

Arteritis – uncommon unless meningitis is
prolonged
ACUTE PYOGENIC MENINGITIS

CLINICAL MANIFESTATIONS:
1. General signs of infection
2. Signs of meningeal irritation
– headache
– photophobia
– irritability
– clouding of consciousness
– neck stiffness
ACUTE PYOGENIC MENINGITIS
LABORATORY DIAGNOSIS:
 SPINAL TAP
– Cloudy or purulent CSF
– Increased pressure
– 90,000 / mm3 PMNs
– Increased CHON level
– Markedly reduced sugar content

ACUTE PYOGENIC MENINGITIS

LAB DIAGNOSIS
– CSF SMEAR – Increase number of
WBC (smear)
– CSF CULTURE – ID causative org
ACUTE PYOGENIC MENINGITIS
 FATAL
 RECOVERY: Fibroblastic proliferation in
the meninges that produced adhesive
arachnoiditis
 If obliteration sufficiently impede CSF
flow
– HYDROCEPHALUS
– Pneumococcal meningitis
ACUTE PYOGENIC MENINGITIS

HYDOCEPHALUS due to Pneumococcal
Meningitis:
Large quantities of the capsular
polysaccharide of the organism produce
glutinous exudate that encourages
arachnoid fibrosis  obliteration 
impede CSF circulation
ACUTE PYOGENIC MENINGITIS

MENINGITIS IN IMMUNOSUPPRESSED
– Klebsiella or anaerobic organism
ACUTE PYOGENIC MENINGITIS
ACUTE PYOGENIC MENINGITIS
ACUTE PYOGENIC MENINGITIS
BACTERIAL MENINGITIS
BACTERIAL MENINGITIS
BACTERIAL MENINGITIS
BACTERIAL MENINGITIS
ACUTE LYMPHOCYTIC MENINGITIS

CAUSATIVE AGENTS (viruses)
1. Mumps
2. ECHO viruses
3. Coxsackie virus
4. Epstein-Barr virus
5. Herpes simplex II
ACUTE LYMPHOCYTIC MENINGITIS
CLINICAL MANIFESTATION
- Same as bacterial meningitis with meningeal
irritation but is LESS FUMINANT & the CSF
findings are markedly different
 Self-limiting
 No life-threatening complications

ACUTE LYMPHOCYTIC MENINGITIS

LABORATORY DIAGNOSIS
1. Lymphocytic Pleocytosis
2. CHON elevation is moderate
3. Sugar content is nearly always
normal
ACUTE LYMPHOCYTIC MENINGITIS
(VIRAL MENINGITIS)
ACUTE LYMPHOCYTIC MENINGITIS
ACUTE LYMPHOCYTIC MENINGITIS
VIRAL MENINGITIS
VIRAL MENINGITIS
Typical owl-eye intranuclear inclusions are seen in
cytomegalovirus encephalitis together with distention of the
Cytoplasm by viral particles
CHRONIC MENINGITIS

CAUSATIVE AGENTS
– Mycobacterium TB
– Treponema pallidum (Syphilis)
– Brucella spp
– Fungi
 Coccidioisis
 Candida
 Cryptococcus neoformans
TB MENINGITIS
GROSS:
 Subarachnoid space contains gelatinous or
fibrinous exudate that is most obvious
around the base of the brain extending to the
lateral sulci
 Focal densities visible along the course of
the cerebral vessels
TB MENINGITIS
MICRO:
 Exudate consists of lymphocytes, plasma
cells, macrophages & fibroblasts
TB MENINGITIS
MICRO:
 Focal densities are tubercles with giant
cells & caseation necrosis
 Arteries in the subarachnoid space may
show obliterative endarteritis with
inflammatory cells in their walls and
marked intimal thickening
 Fibrous adhesive arachnoiditis around the
base of the brain
TB MENINGITIS

CLINICAL MANIFESTATION
 headache
 malaise
 mental confusion
 vomiting
TB MENINGITIS

COMPLICATIONS
– Hydrocephalus
– Obliterative endarteritis causing arterial
occlusion & infarction of the underlying brain
– Cranial nerves may be affected
TB MENINGITIS

LABORATORY DIAGNOSIS
– Moderate CSF either entire mononuclear
pleocytosis or mixture of PMNs and
mononuclears = 1000 cells per mm3
– CHON level is elevated
– sugar is moderately reduced / normal
TB MENINGITIS
TB MENINGITIS
TB MENINGITIS
TB MENINGITIS
CRYPTOCOCCAL MENINGITIS

Frequent in debilitated or immunocompromised
hosts
Trivial inflammatory response despite the large
number of organism
GROSS:
 Found in the subarachnoid space
 Distends the Virchow-Robin spaces producing
characteristic “soap bubbles”

CRYPTOCOCCAL MENINGITIS

CLINICAL MANIFESTATION
– Course is fulminant & fatal in 2 weeks
– indolent over months or years
CRYPTOCOCCAL MENINGITIS

LABORATORY DIAGNOSIS
Mucoid encapsulated yeasts can be
visualized in the CSF by: india ink

INDOLENT CASES:
Few cells
Very high CHON - > 500 mg/dl
Pathognomonic cryptococcal antigen
-
-
CRYPTOCOCCAL MENINGITIS
CRYPTOCOCCAL MENINGITIS
VIRAL HEART DISEASE

CAUSATIVE AGENTS
– Coxsackie A & B viruses
– Echoviruses
– Poliovirus
– Influenza A & B viruses
– HIV
MYOCARDITIS

Inflammatory involvement of the heart muscle
– leukocytic infiltrate
– necrosis or degeneration of myocytes
Occurs at any age
 May induce cardiac failure & sudden death by
arrythmia

MYOCARDITIS
 DIAGNOSIS
– Fever
– Sudden appearance of ECG changes
indicative of diffuse myocardial lesion
– Autopsies – 1-4%
– Infants & pregnants are vulnerable
– Follows some days to few weeks after the
primary viral infection somewhere
MYOCARDITIS

HISTOPATHOLOGY:
Viral Myocarditis
– isolated fiber necrosis
– Mononuclear infiltrates
– interstitial edema separating the individual
myofibers
MYOCARDITIS

HISTOPATHOLOGY:
BACTERIAL MYOCARDITIS
– Patchy focal suppurative reaction
– Microabscesses with less prominence of
diffuse interstitial component
MYOCARDITIS

LABORATORY DIAGNOSIS:
– Serologic tests to determine the
rising antibody titer in the serum
– Antibodies demonstrated by
immunofluorescent along
sarcolemmal sheaths of myofibers
MYOCARDITIS

1.
2.
MECHANISM OF MYOCARDIAL DAMAGE
Direct viral cytotoxicity
The specific agent may evoke a cell-mediated
immune reaction
 damages the cardiac myofibers harboring
virus or virus dictated antigens
VIRAL MYOCARDITIS
Diffuse inflammatory reaction in the interstitial tissues. Lymphocytes, plasma cells &
macrophages are present. Few eosinophils are seen. Muscle fibers are separated by cellular
infiltrate & inflammatory Edema. Destroyed & necrotic muscle fibers
CHLAMYDIAL DISEASES

CAUSATIVE AGENTS
– Chlamydia are obligate intracellular parasite
– gram negative, non-motile that form intracellular
inclusion bodies on replication within the host cell
cytoplasm.
– larger than virus w/ DNA & RNA
– form their own cell wall
– not respond to PCN
– classified as bacteria, properties shared by both
viruses & bacteria
Chlamydia trachomatis Infection

Infection begins with entry of 300 nm elementary
bodies into the cell by endocytosis. (within the
cytoplasm)

Each inclusion, containing 100-1000 elementary
bodies ruptures by lysis or exocytosis
IDENTIFICATION OF Chlamydial sp.

Direct examination:
A.
Detection of inclusion bodies
–
B.
Cytologic examination of the conjunctiva of newborns : Giemsa
stain
Detection of Chlamydia elementary bodies
–
–
Smears using monoclonal antibodies: highly specific
Flourescein conjugated antibodies or iodine stain for C.
trachomatis inclusion bodies in cell culture
3 CHLAMYDIA SPECIES ASSOCIATED WITH
HUMAN DISEASES

C. trachomatis – leading bacterial pathogen responsible
for STDs including NGU in males & PID in females,
infertility & ectopic pregnancy
– Trachoma – chronic disease of conjunctiva & cornea –
blindness
– Inclusion Conjunctivitis
– Lymphogranuloma Venereum (LGV)
C. psittaci – psittacosis, disease transmitted by birds
that lead to atypical pneumonia
 C. pneumoniae – pneumonia & bronchitis

CHLAMYDIA
DIAGNOSIS
 Tissue Culture (Cycloheximide treated McCoy cells)
 Giemsa stain (Direct examination)
 Serologic tests
– Immunofluorescent technique –
90% sensitivity rate
99.6% specificity rate:
Useful for psittacosis
Less Useful for LGV, Trachoma, Genital infections, inclusion
conjuctivitis
Very useful in Neonatal infection
– Complement Fixation – Most frequently used serologic test:
Useful in the diagnosis of C. psittacosis
Less useful in C. trachoma
CHLAMYDIA
Cervical biopsy: with + culture for Chlamydia trachomatis.
Metaplastic squamous cells lining the endocervical glands
Nuclear enlargement, irregularity, hyperchromasia &
binucleation. Numerous PMNs,& plasma cells
LYMPHOGRANULOMA VENEREUM

CLINICAL FINDINGS
– 50% of reported cases of urethritis
– 50% of acute epididymitis
– Women, asymptomatic but may
 cause mucopurulent cervicitis, acute
 PID or infections of mother & baby during
pregnancy or after delivery
LYMPHOGRANULOMA VENEREUM
CERVIX:
- edematous & congested and is
covered with mucopurulent material
 Femoral & Inguinal lymph nodes lesions – lead to
fistulas and perianal abscess
 PATHOLOGY:
- Org. preferentially affect the columnar cells

LYMPHOGRANULOMA

PATHOLOGY
- Severe inflammatory response of the
stroma
- Inflammatory infiltrates are typically
mixed consisting of lymphocytes, plasma
cells, histiocytes & neutrophils
- Lymphoid hyperplasia prominent
- epithelium ulcerated
LYMPHOGRANULOMA

PATHOLOGY
- Reactive atypia with nuclear enlargement,
hyperchromasia and prominent nucleoli seen
in native squamous, metaplastic columnar
cells
- Stromal fibrosis
LYMPHOGRANULOMA VENEREUM
Pseudoepitheliomatous hyperplasia
Lymphogranuloma Venereum
Deep fissure type ulcer
Lymphogranuloma venereum
Part of the ulcer
FUNGAL INFECTIONS
 CANDIDIASIS
– CAUSATIVE ORGANISM: Candida albicans
– opportunistic organism
– D.M.
– Pregnancy
– on antibiotic & chemotherapy & corticosteroids
CANDIDIASIS or MONILIASIS

Pregnancy
– Increased glycogen content of the epithelium,
glycosuria in pregnancy & reduced glucose tolerance
leading to increase sugar level
Menstruation
 Oral contraceptives

CANDIDIASIS

CLINICAL MANIFESTATIONS
 Pruritus
 Edema
 Dysuria
 Dyspareunia
 Leukorrhea
CANDIDIASIS

CLINICAL FINDINGS:
– Involvement of labia & vestibule
– Erythema
– Thrush Patches: white or yellow
– Pseudomembrane covers the vaginal
mucosa

CANDIDIASIS
DIAGNOSIS
– Papsmear: Spores & hyphae identified
– Culture w/ sugar fermentation
– Biopsy: Acanthosis, spongiosis, hyperemia of
the
 lamina propia
 Lymphocytes, plasma cells & few neutrophils
– 10-20% potassium hydroxide admixed with
vaginal discharge
CANDIDIASIS
HYPHAE
HAVE A NICE DAY!