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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 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!