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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.

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infectious diseases part ii

INFECTIOUS DISEASESPART II

BERNADETTE R. ESPIRITU, M.D. FPSP AP-CP

infectious diseases of the cns
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
CNS INFECTIOUS DISEASES
  • CSF PROVIDES BOTH:
    • Culture Medium for the infecting organism
    • Rapid means of disseminating infection throughout the system once the outer defenses have been breached
meningitis
MENINGITIS
  • Inflammatory state of the:

leptomeninges

subarachnoid space

  • It is usually the result of infection
meningitis5
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
meningitis6
MENINGITIS
  • CARCINOMATOUS MENINGITIS

- Infiltration of the subarachnoid

space by tumor cells and eventually

spread to the entire neuraxis

- no inflammatory response

infectious meningitis classification
INFECTIOUS MENINGITIS CLASSIFICATION
  • ACUTE PYOGENIC - Usually Bacterial
  • ACUTE LYMPHOCYTIC - Usually Viral
  • CHRONIC MENINGITIS - Bacterial or Fungal
acute pyogenic meningitis
ACUTE PYOGENIC MENINGITIS

CAUSATIVE ORGANISM

  • E. coli:Neonate w/ neural tube defect
  • H. influenza: Infants & Children
  • Neisseria meningitides
    • 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 meningitis9
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 meningitis10
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 meningitis11
ACUTE PYOGENIC MENINGITIS
  • CLINICAL MANIFESTATIONS:
    • General signs of infection
    • Signs of meningeal irritation
    • headache
    • photophobia
    • irritability
    • clouding of consciousness
    • neck stiffness
acute pyogenic meningitis12
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 meningitis13
ACUTE PYOGENIC MENINGITIS
  • LAB DIAGNOSIS
    • CSF SMEAR – Increase number of WBC (smear)
    • CSF CULTURE – ID causative org
acute pyogenic meningitis14
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 meningitis15
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 meningitis16
ACUTE PYOGENIC MENINGITIS
  • MENINGITIS IN IMMUNOSUPPRESSED
    • Klebsiella or anaerobic organism
acute lymphocytic meningitis
ACUTE LYMPHOCYTIC MENINGITIS
  • CAUSATIVE AGENTS (viruses)
    • Mumps
    • ECHO viruses
    • Coxsackie virus
    • Epstein-Barr virus
    • Herpes simplex II
acute lymphocytic meningitis25
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 meningitis26
ACUTE LYMPHOCYTIC MENINGITIS
  • LABORATORY DIAGNOSIS
    • Lymphocytic Pleocytosis
    • CHON elevation is moderate
    • Sugar content is nearly always normal
viral meningitis31
VIRAL MENINGITIS

Typical owl-eye intranuclear inclusions are seen in

cytomegalovirus encephalitis together with distention of the

Cytoplasm by viral particles

chronic meningitis
CHRONIC MENINGITIS
  • CAUSATIVE AGENTS
    • Mycobacterium TB
    • Treponema pallidum (Syphilis)
    • Brucella spp
    • Fungi
      • Coccidioisis
      • Candida
      • Cryptococcus neoformans
tb meningitis
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 meningitis34
TB MENINGITIS

MICRO:

  • Exudate consists of lymphocytes, plasma cells, macrophages & fibroblasts
tb meningitis35
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 meningitis36
TB MENINGITIS
  • CLINICAL MANIFESTATION
      • headache
      • malaise
      • mental confusion
      • vomiting
tb meningitis37
TB MENINGITIS
  • COMPLICATIONS
    • Hydrocephalus
    • Obliterative endarteritis causing arterial occlusion & infarction of the underlying brain
    • Cranial nerves may be affected
tb meningitis38
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
cryptococcal 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 meningitis44
CRYPTOCOCCAL MENINGITIS
  • CLINICAL MANIFESTATION
    • Course is fulminant & fatal in 2 weeks
    • indolent over months or years
cryptococcal meningitis45
CRYPTOCOCCAL MENINGITIS
  • LABORATORY DIAGNOSISMucoid encapsulated yeasts can be visualized in the CSF by: india ink
  • INDOLENT CASES:
  • Few cells
  • Very high CHON - > 500 mg/dl
  • Pathognomonic cryptococcal antigen
viral heart disease
VIRAL HEART DISEASE
  • CAUSATIVE AGENTS
    • Coxsackie A & B viruses
    • Echoviruses
    • Poliovirus
    • Influenza A & B viruses
    • HIV
myocarditis
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
myocarditis50
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
myocarditis51
MYOCARDITIS
  • HISTOPATHOLOGY: Viral Myocarditis
    • isolated fiber necrosis
    • Mononuclear infiltrates
    • interstitial edema separating the individual myofibers
myocarditis52
MYOCARDITIS
  • HISTOPATHOLOGY:BACTERIAL MYOCARDITIS
    • Patchy focal suppurative reaction
    • Microabscesses with less prominence of diffuse interstitial component
myocarditis53
MYOCARDITIS
  • LABORATORY DIAGNOSIS:
    • Serologic tests to determine the rising antibody titer in the serum
    • Antibodies demonstrated by immunofluorescent along sarcolemmal sheaths of myofibers
myocarditis54
MYOCARDITIS
  • 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
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
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
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
slide58
IDENTIFICATION OF Chlamydial sp.
  • Direct examination:
  • Detection of inclusion bodies
    • Cytologic examination of the conjunctiva of newborns : Giemsa stain
  • Detection of Chlamydia elementary bodies
    • Smears using monoclonal antibodies: highly specific
    • Flourescein conjugated antibodies or iodinestain for C. trachomatis inclusion bodies in cell culture
3 chlamydia species associated with human diseases
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
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 psittacosisLess Useful for LGV, Trachoma, Genital infections, inclusion conjuctivitisVery useful in Neonatal infection – Complement Fixation – Most frequently used serologic test: Useful in the diagnosis of C. psittacosisLess useful in C. trachoma
chlamydia61
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
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 afterdelivery
lymphogranuloma venereum63
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
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

lymphogranuloma65
LYMPHOGRANULOMA
  • PATHOLOGY

- Reactive atypia with nuclear enlargement,

hyperchromasia and prominent nucleoli seen in native squamous, metaplastic columnar cells

- Stromal fibrosis

lymphogranuloma venereum66
LYMPHOGRANULOMA VENEREUM

Pseudoepitheliomatous hyperplasia

lymphogranuloma venereum67
Lymphogranuloma Venereum

Deep fissure type ulcer

lymphogranuloma venereum68
Lymphogranuloma venereum

Part of the ulcer

fungal infections
FUNGAL INFECTIONS
  • CANDIDIASIS
    • CAUSATIVE ORGANISM: Candida albicans
        • opportunistic organism
        • D.M.
        • Pregnancy
        • on antibiotic & chemotherapy & corticosteroids
candidiasis or moniliasis
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
CANDIDIASIS
  • CLINICAL MANIFESTATIONS
      • Pruritus
      • Edema
      • Dysuria
      • Dyspareunia
      • Leukorrhea
candidiasis72
CANDIDIASIS
  • CLINICAL FINDINGS:
    • Involvement of labia & vestibule
    • Erythema
    • Thrush Patches: white or yellow
    • Pseudomembrane covers the vaginal mucosa
candidiasis73
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