B4 Flashcards
Describe about the anthrax
Causative agents : Bacillus anthracis
- Mainly affect animals
- Humans acquire the infection through contact with an infected animal or by inhaling spores.
-Importance : potential biological weapon , agent of bioterrorism
Explain the transmission of human anthrax
- Cutaneous mode : by spores entering through abraded skin ; seen in people with occupational exposure to animals ( most common mode )
- Inhalation of spores
- Ingestion of carcasses of animal dying of anthrax containing spores .
Explain the virulence factors of human anthrax
1) Anthrax toxin - consisting of 3 fragment. They produce local edema & generalised shock
- Edema factor : It is active fragment ; acts as adenylyl cyclase & increase host cell cAMP ( cyclic adenosine monophosphate. ) It is responsible for edema and other manifestation seen in anthrax.
- Protective factor : It is binding fragment that binds to the host cell receptors and facilitate the entry of other fragment into the host cell.
- Lethal factor : It causes death ; acts cleaving host cell MAPK ( mitogen- activated protein kinase )
2) Anthrax capsule
- plasmid ( pX02)coded
- inhibits complement mediated phagocytosis
Outline the clinical types of anthrax with manifestation.
Clinical types : Cutaneous anthrax , pulmonary anthrax , intestinal anthrax
Cutaneous anthrax ( Hide porter’s disease )
- Cutaneous exposure to spores
- Malignant pustule ( lesions begins as a papule that evolves into a painless vesicle followed by the development of coal- black , necrotic eschar surrounded by non pitting indurated edema.
Pulmonary anthrax
-Wool sorter’s disease
- Inhalation of spores
- Hemorrhagic pneumonia :
Bacilli spread by lymphatics or blood leading to
- Bacteremia , Hemorrhagic mediastinitis , Hemorrhagic meningitis.
Intestinal anthrax
- Rare
- Ingestion of spores contaminated with meat of animals
- highly fatal , manifests as bloody diarrhea
Describe the laboratory diagnosis of human anthrax
Specimen : Pus , sputum , blood , CSF
- Direct demonstration :
a) Gram staining : Gram positive , large rectangular bacilli
b) McFadyean’s reaction : Shows amorphous purple capsule surrounding blue bacilli ( polychrome methylene blue stain )
c) Direct IF : Detects capsular antigens
d) Ascoli’s thermal precipitate test - Culture
a) Nutrient agar : Medusa head appearance colonies
b) Blood agar : Dry wrinkled , nonhaemolytic colonies
c) Gelatin stab agar : Inverted fir tree appearance growth. - Culture smear : Gram positive rods with bamboo stick appearance
- Antibodies detection by ELISA
- Molecular diagnosis : PCR using BA pX01/02 primers
Explain about Brucellosis and state some of examples of Brucellosis
- Brucella is an obligate aerobic , small Gram-negative coccobacillus , responsible for highly contagious febrile illness
Brucella Melitensis ( Most pathogenic ) , B. abortus , B. suits , B.canis
Explain the features of Leptospirosis
- Spirochetes
- Gram negative bacteria : cell wall differs from other gram negative bacilli by presence of endoflagella **
- Antigenically complex : comprises of 2 species ( L.interrogates & L. biflexa )
Explain the Pathogenesis of leptospirosis
First phase ( septicemic phase ) : After entering through the mucosa ( oral / conjunctiva ) or abraded skin , Leptospira interrogates spill over to the bloodstream and then disseminate hematogenously to various organ ( brain , liver , lung )
: Vascular damage : Spirochetes can be found in the walls of capillaries, medium & large vessels .
: Penetration and invasion of tissue is due to active motility & release of hyaluronidase
Second phase ( immune phase ) : As antibodies develop , Spirochetes disappear from the blood . Antigen- antibody complexes are deposited in various organs. : Renal colonization : Bacilli become adherent to the proximal renal tubular brush border and are excreted in urine.
State the clinical manifestations of Leptospirosis
A) Mild anicteric febrile illness - 90% : biphasic ; a septicemic phase occurs first followed by immune phase , present as flu like illness.
B) Weil’s disease ( Hepto- renal - Hemorrhagic syndrome) 10%
Describe the lab diagnosis of Leptospirosis **
Specimens : CSF , Blood & urine
Microscopy :
- Dark ground or phase contact microscopy or silver impregnating staining
- Reveals spirally coiled bacilli ( tightly & regularly coiled ) with characteristic hooked ends like umbrella handle
Isolation :
- Culture condition : 30C for 4-6 weeks
- Medium : EMJH medium , Korthofs medium or Fletchers medium
Animal inoculation : Sample are inoculated into hamster and young Guinea pigs.
Serology for antibody detection :
- Genus specific tests : Macroscopic slide agglutination test , latex agglutination test , ELISA
- Serovar specific test : Gold standard & references test for leptospirosis.
- Microscopic agglutination test - detects antibodies against specific serovars of L . Interrogans
Molecular methods : PCR
Non specific findings : altered renal & liver function test
The vector of dengue virus is mosquitoes ( ……….. )
The vector of dengue virus is mosquitoes ( Aedes aegypti & aedes albopticus )
Describe the transmission of dengue
Humans, monkey are reservoirs for the virus —> infect mosquitoes ( A. aegypti , A . albopticus ) during blood feeding —> go on to infect others.
May be transmitted via vertical transmission, blood transfusions.
Describe the Pathogenesis of dengue fever & dengue haemorrhagic fever / dengue shock syndrome
1) Human bites by Aedes aegypti / albopticus initiates a dengue infections which leads to production of antibodies specific to that serotypes (1,2,3 or 4 ) & also cytokines to manifestation of clinical symptoms
2) Upon reinfection with a different serotypes , the antibodies bind to the virus but do not neutralise it , instead facilitating its entry into monocytes
3) Dengue virus replicates in the monocytes , causing increased release of cytokines into bloodstream.
4) Leads to vascular damage , increased plasma leakage , hypovolemia & shock ( dengue shock syndrome ) ; may also leads to DIC & severe bleeding ( dengue haemorrhagic fever )
Describe the clinical symptoms of dengue fever
1) May be asymptomatic
2) Dengue fever
- Acute febrile illness
- Myalgia , arthragia , bone pain , headache , retro-orbital pain , maculopapular rash
3) Dengue Hemorrhagic fever
- thrombocytopenia
- haemorrhage , especially in GIT ,mucosa , injection sites
- rising hematocrit
- plasma protein leakage to edema , pleural effusion
4) Dengue shock syndrome
- same as DHF but including hypotension , organ failure & death
Describe the pathogenic of Epstein - Barr virus
- transmitted via salivary secretion
- EBV infects the epithelial cells of oropharynx & also local B-cells esp in tonsil
- Infected B cells disseminate to organs ( liver , spleen , lymph nodes ) via lymphatics and blood stream where they are attacked by cytotoxic ( CD8 ) T - cells which release cytokines & cause clinical manifestations
- EBV can undergo latency in lymphoblastic cells & get reactivates during periods of immunocompromisation
Describe the clinical symptoms & complications of EBV
- Usually asymptomatic
- Infectious mononucleosis I) Pharyngotonsilitis II) Fever III) Cervical lymphadenopathy , hepatomegaly , splenomegaly IV) Hairy leukoplakia
Complications
- Hodgkin’s , Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Splenic rupture
- Post- transplant lymphoproliferative disorder ( PTLD)
Describe the lab diagnosis of EBV
1) Absolute lymphocytosis
- Presence of atypical lymphocytes in peripheral blood smear
- Atypical lymphocytes are enlarged , have expanded nucleus & vacuolated cytoplasm
2) Production of heterophil antibodies
3) IgM , Ig G VCA antibodies
4) antibodies to EA and EBNA
State the etio- Pathogenesis of the Syphilis
Causative agent : Treponema palladium
Pathogenesis : Transmission - Venereal , blood , congenital , non venereal Mode of entry - Intact mucus membrane / abraded skin - Congenital , blood tranfusions - Accidental finger picks
- Low infective dose
- Disseminates to blood stream - adheres to surface proteins of endothelial cells.
- End arteries : scarring , tissue necrosis , and replacement fibrosis
- Incubation period : 2-10weeks
Explain the Pathogenesis of syphilis in detail
A) Initial contact ( 2-10 weeks ) - Multiplication at infection site ; associated host response
: Primary chancre at the site of infectionB) Primary syphilis (1-3 months ) - Proliferation of treponema’s in regional lymph nodes
: Enlarged inguinal nodes , spontaneous healing
C)Secondary syphilis ( 2-6 weeks j
- Multiplication & production of lesions in LN , liver , joints , muscle , skin & MM
: Flu like illness : myalgia , headache. , fever , mucocutaneous rashes
D) Latent syphilis ( 3-30 years )
- Treponemes dormant in ? liver / spleen
- Re-awekening & multiplication
E)Tertiary syphilis - Futher dissemination & invasion , Host response (CMI) , Gummas in skin , bones , testis
: Neurosyphilis : general paralysis of the insane , tabes dorsalis
Explain the clinical manifestation of syphilis
Primary Syphilis
- Chancre ( hard chancre ) : painless , circumscribed , indurated , no tender , relatively avascular ( genital )
- Glairy exudate
- LN swollen , discrete , rubbery , non tender
- Heals by 1-3 months
Secondary Syphilis ( Most infectious stage)
- 1-3 months after healing
- Flu- like illness , myalgia , headache , macular / popular rashes ( 2-6 weeks )
- Moist lesions on genitalia ( condylomata lata)
- Organ involvement - meningitis , nephritis , hepatitis
Latent Syphilis (quite stage)
- ?. Dormancy in liver or spleen
- Several years
- Early / late Syphilis
Tertiary syphilis
- Gummatas ( Chronic granulomata ) - internal organs
- Neurosyphilis m meningeal syphilis , meningovascular - stroke
- Feneral paralysis of the insane / Tabes dorsalis ( demyelination of posterior columns)
- Cardio vascular : Aortic aneurysms , heart failure
Explain the structure of Human Papilloma Virus
- Double stranded DNA virus —> epitheliotropic
- Non-envelop , icosahedral
- Circular genome
- Infects squamous epithelial include the mucosal of the upper respiratory & anogenital tracts
- Genital infection by HPV is associated with genital warts & anogenital cancers in both men & women
- HPV is the leading cause of cervical cancer
- asymptomatic
Describe the types of Human papilloma virus
DNA genome encodes approximately eight open-reading frames ( ORFs)
ORF is divided 3 functional parts :
- Early (E) region that encodes proteins ( E1-E7) necessary for viral replication
- Late (L ) region that encodes the structural proteins (L1-L2) required for virion assembly
- Long control region ( LCR) : Non-coding part , which contain cis element that are necessary for the replication and transcription of viral DNA.
Explain the Pathogenesis of HPV
- Papillomaviruses are highly epitheliotropic
- productive infections only within straitified epithelial of the skin , the anogenital tract and the oral cavity.
1) Infection by penetrating through micro trauma of epithelium ( direct contact )
2) Basal cells are the target of infection
3) DNA from the virus enters the cells
4) The life cycle is initiated by the infection of basal epithelial cell , at sites of injury
5) HPV genome integrates with cell genome then persists for years -> stimulate the different of basal cells
6) Most infection clear within 1-2 years
7 ) Long term persistence leads pre cancerous lesion
State the transmission of of HPV
1) Horizontal transmission
- Sexual activity through contact with infected cervical , vaginal
- Self - inoculation
- Circumcision of male partner
2) Vertical transmission h rare)
