Micro Topics Flashcards
III.11 Adenovirus characteristics
- dsDNA
- Icosahedral capsid
- Naked
- Fiber antigens for attachment to receptor and agglutination of RBCs
- Human adenovirus has 57 serotypes (number 14 most severe), differentiated by hemagglutinin inhibition
III.11 Adenovirus Transmission
Contact, respiratory droplets, feces and aerosol
III.11 Adenovirus Pathogenesis
Pentons of the icosahedral capsid contains fibers that acts as hemagglutinin (toxic to cells)
- In permissive cells: virus is lytic – production occurs/replication
- In non-permissive cells: can be chronic of oncogenic (transformation occurs)
III.11 Adenovirus Clinical
a) Respiratory diseases: Tonsillitis (#1 cause), pharyngitis, pharyngoconjunctival fever, pneumonia, pertussis-like symptoms
b) Enteric infection: Watery diarrhea
c) Eye infection: Epidemic keratoconjunctivitis, follicular conjunctivitis
d) UTI: Acute hemorrhagic cystitis
e) Immune suppressed patients: Pneumonia, hepatitis, encephalitis
* Reactivation can occur in case of immunosuppressed patients
III.11 Adenovirus Ddx
Serology, cultivation on HeLA, epithelial cell culture –> strong CPE (cytopathic effect), rapid test for diarrhea
III.11 Adenovirus treatment
none - supportive
III.11 Adenovirus vaccine
Live attenuated (serotype 4 and 7) –> only for military recruits
III.12 Herepesvirus : HSV1 and HSV2 characteristics
- dsDNA – linear
- Icosahedral capsid – Encode glycoproteins for attachment, fusion, immune escape
- Enveloped – Sensitive to acid, detergents etc.
- α-herpesvirus
III.12 Herepesvirus : HSV1 and HSV2 Transmission
Saliva, vaginal secretions, transcervical (perinatal), TORCH
III.12 Herepesvirus : HSV1 and HSV2 Pathogenesis
The virus targets Mucoepithelial cells:
Viral replication in site of infection –> local nerve ending invasion –> retrograde axonal transport to dorsal root ganglia –> latency
*Generally: acute infection (early proteins) –> latency (viral genome present, but no viral proteins produced – periodic reactivation i.e. due to UV, stress etc.
III.12 Herepesvirus : HSV1 clinical
- Herpes labialis (cold sores) and gingivostomatitis Keratoconjuntivitis
- Herpetic Whitlow – rash on fingers
- Erythema multiforme – back of hands/feet
- Encephalitis – due to necrosis and hemorrhage of neurons
III.12 Herepesvirus : HSV2 clinical
- Genital herpes – inguinal lymphadenopathy and painful genital lesion
- Neonatal herpes – transcervical or transplacental (liver involvement/encephalitis)
- Aseptic meningitis
III.12 Herepesvirus : HSV1 and HSV2 ddx
Scrapings of the base of lesions – cultivation on HeLA
PCR of CSF – for encephalitis
Serology to distinguish HSV-1 and HSV-2
Genital infections – virus isolation from vesicles –> Tzanck smear
*Tzanck smear - Cytology that will show multinucleated giant cells, intranuclear eosinophilic Cowdry type A inclusion bodies are also seen
III.12 Herepesvirus : HSV1 and HSV2 treatment
Acyclovir (inhibition of DNA synthesis) – does not prevent latent infection
III.13 Herpesvirus - VZV - Varicella Zoster Virus characteristics
- dsDNA
- Icosahedral capsid ~ 150nm
- Enveloped
- α-herpesvirus
III.13 Herpesvirus - VZV - Varicella Zoster Virus transmission
Respiratory droplets, contact(rare), TORCH
III.13 Herpesvirus - VZV - Varicella Zoster Virus Pathogenesis
Primary infection in mucosa of respiratory tract –>blood and lymphatics –> dissemination to skin –> dermal vesiculopapular rash –> chicken pox –> latency in sensory ganglia –> reactivation –> migrates along neural pathways to skin –> Shingles
III.13 Herpesvirus - VZV - Varicella Zoster Virus Clinical
Primary infection: Varicella (chicken pox)
- Asynchronous rash forms small, itchy blisters all over the body (different stages; Macula, vesicles, scabs).
- Presents with fever, headache, pharyngitis, malaise (general discomfort), rhinitis.
- Adults present with pneumonia, encephalitis. Highly contagious!
Secondary infection (recurrence): Zoster (Shingles)
- Pain in a given dermatome with rash limited to said dermatome.
- Develops in immunocompromised patients
- Can cause post-herpetic neuralgia (chronic pain that lasts for years due to damage of nerves addected by virus) *
Herpes Zoster ophthalmicus – Vision loss when CNV/I is affected
Congenital varicella syndrome –> Limb hypoplasia, cutaneous dermal scarring, blindness
III.13 Herpesvirus - VZV - Varicella Zoster Virus ddx
Serology –> Examine skin lesion scraping
Tzanck smear –> Will show multinucleated giant cells, Cowdry bodies
III.13 Herpesvirus - VZV - Varicella Zoster Virus treatment
Acyclovir
III.13 Herpesvirus - VZV - Varicella Zoster Virus Vaccine
Passive (VZ-Ig) – immunosuppressed patient, ineffective in active cases
Active; live, attenuated – cell mediated immunity
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) characteristics
- large linear dsDNA
- Icosahedral capsid
- Enveloped
- gamma-herpesvirus
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) transmission
Saliva and respiratory secretions (90% of population is seropositive)
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) pathogenesis
Infects permissive nasopharyngeal epithelial cells, salivary and lymphoid tissues.
Latent infection in B-cells;
Binds CDRI and produce LMP1 (latent membrane protein 1) –>
a) NFKB activation and B-cell proliferation
b) Bcl2 ⊣ apoptosis
This causes production of atypical CD8+ T-cells – Downey cells against it
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) clinical
a) Infectious mononucleosis – “Kissing disease” (transmitted by saliva)
Exudative tonsillitis, lymphadenopathy, splenomegaly.
Presence of atypical lymphocytes used to distinguish from CLL.
Paul-Bunnel reaction positive – it has heterophile antibody
b) Hairy oral leukoplakia – non-precancerous hyperproliferation of lingual epithelial cells
oral thrush
c) Burkitt lymphoma – Tumor growth in lymph nodes; maxilla and mandible (joint).
Due to translocation of c-myc oncogene which becomes active promotor (t(8;14)).
Endemic type – Associated with endemic areas of malaria
Sporadic/non-African type – commonly affects the ileocecal region
Immunodeficient type – associated with AIDS
d) Nasopharyngeal carcinoma – commonly in Asians. Tumor cell of epithelial origin
e) Hodgkin’s (B-cell) lymphoma – Dx by presence of Reed-Sternberg cells
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) ddx
Blood smear –> Downey cells
Monospot test – a form of heterophile Ab-test –> heterophile Abs positive – IgM agglutination to Paul-Bunnel antigens on sheep RBCs.
Heterophile Abs are produced due to B-cell induction by EBV
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) treatment
symptomatic treatment for mono
III.15 - Herpes - Cytomegalovirus (HHV-5) characteristics
- dsDNA
- Icosahedral capsid ~ 150nm
- Enveloped
- beta-herpesvirus
- Latency in monocytes, macrophages, T-cells
III.15 - Herpes - Cytomegalovirus (HHV-5) Transmission
Direct and sexual contact by bodily fluids
transplantation
TORCH
III.15 - Herpes - Cytomegalovirus (HHV-5) Pathogenesis
Infects salivary glands epithelial cells by binding to the integrin receptors.
Established persistent in fibroblasts, epithelial cells, macrophages, etc.
Latency is established in mononuclear leukocytes (B-cells, T-cells, macrophages).
Reactivation occurs by immunosuppression.
III.15 - Herpes - Cytomegalovirus (HHV-5) clinical
a) Congenital CMV infection – CNS damage causes sensorineural deafness.
Periventricular calcifications lead to seizures. Thrombocytic purpura w/ “blueberry Muffin” rash, jaundice, hepatosplenomegaly, pneumonitis, fetal hydrops
b) Mononucleosis – negative heterophile
c) Esophagitis – with linear ulcerations
d) CMV colitis – with ulcerated walls
e) Interstitial pneumonitis – leads to severe systemic infection due to reactivation in transplant patients or AIDS
f) CMV Retinitis – common in AIDS patients with a CD4+ count under 50 cells/&L. Blind spots, vision loss, retinal
necrosis and pizza pie retinopathy on fundoscopic exam
g) Hepatitis – in pregnancy
III.15 - Herpes - Cytomegalovirus (HHV-5) ddx
Histology –> intranuclear basophilic Owl’s eyes inclusions. Take sample from buffy coat (the layer of WBC from a centrifuged blood) and stain with Pap or H&E
PCR –> DNA detection and amplification
Cell culture –> fibroblast culture
Serology –> ELISA, Paul-Bunnel antigen detection
III.15 - Herpes - Cytomegalovirus (HHV-5) treatment
Immunocompetent people which are asymptomatic do not require treatment
Severe infection in immunocopromised people, Gancyclovir, Cidofovir and Foscarnet (for resistance, UL97 mut) can be given.
III.16 Herpesvirus - HHV6 characteristics
dsDNA
Icosahedral capsid ~ 150 nm
Enveloped
beta-herpesvirus
III.16 Herpesvirus - HHV6 Transmission
salvia
III.16 Herpesvirus - HHV6 Pathogenesis
Replicate in salivary glands, shed and transmitted through saliva.
Can also infect lymphocytes (mainly CD4+ T-cells) in peripheral blood
Can lead to immunosuppression by decreasing the CD4+ T-cells
III.16 Herpesvirus - HHV6 clinical
in immunocompromised (HHV6a)
- Encephalitis
- Pneumonitis
- Chorioretinitis
Neonatal HHV-6B ~ Roseda infantum (exanthema subitum)
- Primarily in children 3-6 months old
- Fever that could lead to febrile seizures
- Maculopapular rash that spares the face
III.16 Herpesvirus - HHV6 ddx
Clinical picture
PRC, serology – Virus isolation from lymphocytes
III.16 Herpesvirus - HHV6 treatment
Self-limited
Gancyclovir, symptomatic, no vaccine
III.16 Herpesvirus - HHV 7 clinical
Also causes Exanthema subitum, but less frequently than HHV-6. Same symptoms
Others: - Pytiriasis rosea (Herald patches), “gloves and socks syndrome” Severe cases: - encephalitis - flaccid paralysis - hepatitis, gastritis - lowered lymphocyte count - LAD - diarrhea
III.16 Herpesvirus - HHV8 characteristics
dsDNA
Icosahedral capsid
Enveloped
gamma-herpesvirus
III.16 Herpesvirus - HHV8 transmission
Saliva, sexual contact – higher prevalence in Russian men, Sub-Saharan Africa and Mediterranean
III.16 Herpesvirus - HHV8 pathogenesis
Infects mainly B-cells (like EBV), but also epithelial cells, monocytes etc.
HHV-8 activates VEGF
III.16 Herpesvirus - HHV8 clinical
a) Kaposi sarcoma
Opportunistic infection associated with AIDS
Lesions on nose, extremities, mucus membrane
Lesions may be plaque, patches, macule or nodule – arise from mesenchymal cells Angiogenesis within lesion causes violet color
Commonly affects hard palate, and also seen in GI
b) Primary effusion (B-cell) lymphoma
Large B-cell lymphoma located in body cavities
Characterized by pleural, peritoneal, pericardial fluid lymphomatous effusions
III.16 Herpesvirus - HHV8 ddx
Clinical, antibody detection, viral DNA by PCR
Differential diagnosis from bacillary angiomatosis (B. henslae) by microscopic exam (will show neutrophil infiltrate, instead of lymphocytes as with HHV-8)
III.16 Herpesvirus - HHV8 treatment
Liquid nitrogen
interferon-alpha
III. 17 Parvovirus characteristics
ssDNA
Icosahedral capsid ~20-25 nm (smallest virus)
No envelope
Erythrovirus –> Parvovirus B19 ~ only one to cause human disease
III. 17 Parvovirus transmission
Respiratory droplets, fomites, TORCH
III. 17 Parvovirus clinical
a) Erythema Infectiosum ~ “fifth disease”
Slapped cheek syndrome – starts as fever, then rash
Teenagers may develop papular purpuric gloves and socks syndrome Adults may develop arthralgia, arthritis and edema
b) Fetal hydrops
Can cross-placenta; occurs in the first 2 trimesters of pregnancy
This is due to CHF (congestive heart failure) leading to severe anemia and edema
c) Aplastic anemia
Infection can lead to lower erythropoiesis
This may cause anemia which is only significant in patients with blood disorders (i.e. sickle cell, Thalassemia, Hereditary spherocytosis)
Bone marrow depletion – severe situation if chronic anemia is present
III. 17 Parvovirus ddx
Clinical, serology
III. 17 Parvovirus treatment
self-limiting
III. 17 Parvovirus pathogenesis
Parvovirus B19
Target cells: Normoblasts –> failure of RBC production
III. 18 Papilloma Virus characteristics
cdsDNA
Icosahedral capsid
naked
III. 18 Papilloma Virus Transmission
Direct and sexual contact (can also infect children during delivery)
Infects the basal cell layer of the skin (stem cells) and mature as the cell matures up to the surface
The virus persists in basal layer and stays hidden from immune system
III. 18 Papilloma Virus ddx
Clinical – for cutaneous warts
PCR – to distinguish serotype
III. 18 Papilloma Virus treatment
Cryotherapy
Cidofovir
III. 18 Papilloma Virus prevention
Guardisol – using capsid proteins (recombinant)
III. 18 Polymoavirus characteristics
cdsDNA
Icosahedral capsid
naked
III. 18 Polymoavirus Transmission
Respiratory droplets, saliva
III. 18 Polymoavirus Pathogenesis
Infects tonsils and lymphocytes, then spreads by viremia to kidney.
secondary viremia occurs and become latent in immunocompetent or reactive in immunosuppressed.
1) BK virus (from first patient) ~ latency in kidney
Nephropathy (nephritis and urethral stenosis) and hemorrhagic cystitis (hematuria) in bone marrow transplanted patients (DDX; Adenovirus)
2) JC (John Cumingham) virus ~ latency in kidney, B-cells, monocytes ++
Progressive multifocal leukoencephalopathy (PML) ~ infection of oligodendrocytes causing demyelination of CNS.
Multifocal brain lesions in white matter (DDX; Toxoplasma)
Symptoms are deranged speech, vision and coordination loss, paralysis of limbs, death
Usually occurs in AIDS patients
III. 18 Polymoavirus ddx
MRI/CT
ELISA
PCR of CSF
III. 18 Polymoavirus treatment
none
III. 18 Papilloma Virus clinical
1) Mucosotropic genotypes
a) Low risk serotypes; 6-11 Condyloma Accuminata (anogenital warts) Laryngeal papilloma
b) High risk serotypes; 16-18, 31, 33
Pre-neoplastic condition (associated with dysplasia) CIN/VIN/VAIN, penis, anus, mouth, throat
E6 ⊣ p53
E7 ⊣ Retinoblastoma
2) Cutaneous genotypes; 1-4
Low risk serotypes
Hyperkeratosis (growth of basal and spinosum) leads to formation of warts
Common warts (2-4): Found on hands/fingers
Plantar warts (1): Found on soles – deeper and more painful
III.19 Poxvirus characteristics
dsDNA ~ replicates in cytoplasm
Complex structure ~ 300 nm (Biggest virus!)
Enveloped
2 lateral bodies
Variola virus ~ Smallpox
Vaccinia virus ~ Vaccination of smallpox
Cow pox virus ~ Share antigenic determinant with variola virus (Jenner)
III.19 Poxvirus transmission
Respiratory droplets, contact
III.19 Poxvirus clinical
1) Smallpox (Variola – minor or major depending on immune status)
Virus enters the upper respiratory tract and disseminates via lymphatics causing viremia After second viremia, it infects all dermal tissues and internal organs – “pocks”
5-7 day of incubation;
Flu-like symptoms for 2-4 days followed by a rash (macule – papule – vesicle – pustule –>
synchronous). The vesicles are deep and hemorrhagic.
2) Molluscum contagiosum virus Benign epithelial tumor (wart-like). Acquired by direct contact Common on trunk and genitalia. Treated by liquid nitrogen
III.19 Poxvirus ddx
Isolation from vesicles – intra-cytoplasmic eosinophilic
Guarnieri inclusion bodies (site of viral replication)
Embryonated egg – chorioallantoic membrane inoculation
Serology
III.19 Poxvirus vaccine
Live attenuated- Cowpox vaccine is efficient against cowpox and smallpox
III.20 Arenavirus characteristics
ssRNA ~ Ambisense, has both positive and negative sense sections
Helical ~ 50-300 nm
Enveloped with projections
Natural host; rodents
“Sandy” – ribosome granules of host cell origin
III.20 Arenavirus transmission
Zoonotic, rodents shedding virus via saliva, urine and feces
III.20 Arenavirus pathogenesis
Arenaviruses usually cause persistent infections. They infiltrate macrophages leading to release of IFN and cytokines that causes cell and vascular damage. T-cell induced effects will cause further tissue destruction. Incubation time is 10-14 days.
III.20 Arenavirus ddx
Grainy appearance on EM, serology, RT-PCR
III.20 Arenavirus treatment
Ribavirin for Lassa fever, supportive therapy for LCM
- Virus could be inactivated by heating, low pH, irradiation and detergents
III.20 Arenavirus -Lymphocytic choriomeningitis virus (LCM)
Ranges from asymptomatic (in immune competent) to aseptic meningitis
Biphasic disease; 10 phase with fever, flu-like symptoms and myalgia to the 20 phase with meningitis, encephalitis, lymphocytic infiltration of choroid plexus
III.20 Arenavirus - Lassavirus
Hemorrhagic fever with 50% mortality due to hypovolemic shock. May present with coagulopathy, petechia, no vasculitis
III.20 Arenavirus - Machupovirus
Similar symptoms to Lassavirus, but less severe * Different endemic areas
Lassa- Hemorrhagic fever with 50% mortality due to hypovolemic shock. May present with coagulopathy, petechia, no vasculitis
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) characteristics
ssRNA ~ 3 segments. Circular, negative
Helical capsid
Enveloped with projections
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) transmission
Arboviruses (arthropod-borne), except Hantavirus (rodent-borne)
III.21 Bunyaviruses- HantaVirus clinical
Hantavirus (aka Sin Nombre)
Transmission via rodent feces or urine
- Hemorrhagic fever with Renal syndrome (HFRS)
Hemorrhagic fever (leakage of RBC and plasma through endothelium)
Pre-renal azotemia - Pulmonary syndrome
Pulmonary edema due to capillary leak
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) ddx
PCR – Hantavirus
RVFP + CEO – ELISA
Crimean-Congo – ELISA
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) treatment
none
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) prevention
Inactivated Henta in Asia
III.21 Bunyaviruses Crimean-Congo hemorrhagic fever virus clinical
Crimean-Congo virus
Transmission via tick: Arbovirus/arthropod-borne - Crimean-Congo hemorrhagic fever (CCHF)
10 lesion involves leakage of RBCs and plasma through endothelium
Presents with fever, myalgia, headache, vomiting, diarrhea and bleeding into skin
Complications; liver failure, kidney damage, DIC, shock and death
III.22 Coronavirus characteristics
ssRNA, positive sense
Helical capsid
Enveloped ~ glycoproteins give a halo.
Three proteins (open reading frame, nucleocapsid protein, enveloped protein) Cell receptors – SARS-CoV, SARS-CoV-2: ACE2
III.22 Coronavirus transmission
Respiratory droplets
III.22 Coronavirus pathogenesis
Most coronaviruses infect and replicate the upper respiratory tract mucosa which leads to symptoms of a common cold
SARS strains replicate in respiratory tract –> viremia –> RES –> systemic infection
Extrapulmonary replication happens in GI, CNS and UT.
III.22 Coronavirus clinical
- Common cold: URT infection Mild symptoms, no fever
- SARS-CoV: LRT infection
Acute bronchitis that leads to ARDS
Flu-like illness with fever, dry cough, dyspnea, progressive hypoxia
CT shows ground glass opacities, multifocal consolidation lesions
(Pneumonia, ARDS, cytokine storm, MOF) - MERS: endemic version of SARS
III.22 Coronavirus ddx
PCR
serology
III.22 Coronavirus treatment
Supportive therapy
Antiviral treatment (i.e. HIV protease inhibitor – ritonavir) can reduce incidence of severe/critical cases
III.22 Filovirsues characteristics
ssRNA
negative sense
Helical capsid
Enveloped
III.22 Filovirsues transmission
From monkeys to human, and then human-to-human (bodily fluids)
III.22 Filovirsues clinical
- Marburg virus
- Ebola virus
Severe form of hemorrhagic fever, could lead to hypovolemic shock and multiple organ failure
III.22 Filovirsues ddx
Careful to avoid accidental infection
– level 4 isolation required
Marburg virus in tissue culture, Ebola virus in animal inoculation
Serology
RT-PCR
III.22 Filovirsues treatment
No treatment - Remdesivir
III. 23 Flavivirus - Yellow Fever, Dengue Fever characteristics
ssRNA, positive sense
Icosahedral capsid
Enveloped
III. 23 Flavivirus - Yellow Fever vector
Aedes mosquitos, hosts are humans and monkeys
III. 23 Flavivirus - Yellow Fever clinical
Yellow fever
Jaundice, backache, bloody diarrhea, nausea, vomiting, headache
III. 23 Flavivirus - Dengue Fever vector
Aedes mosquitos, hosts are humans and monkeys
III. 23 Flavivirus - Dengue Fever clinical
Dengue fever/breakbone fever:
Infects bone marrow; presents with fever, headache, vomiting, muscle/joint pain and measles-like rash that blanches when compressed
In severe dengue we can see thrombocytopenia, hemorrhagic fever, renal failure
III. 23 Flavivirus - Yellow Fever, Dengue Fever ddx
ELISA
HAI (hemagglutinin inhibition)
Latex particle agglutination
III. 23 Flavivirus - Yellow Fever, Dengue Fever treatment
supportive
III. 23 Flavivirus - Yellow Fever, Dengue Fever vaccine
yellow fever - live attenuated
III. 24 Flavivirus - West Nile, Tick Born Encephalitis, Zika Virus characteristics
ssRNA, positive sense
Icosahedral capsid
Enveloped
III. 24 Flavivirus - West Nile, Tick Born Encephalitis, Zika Virus ddx
ELISA
HAI (hemagglutinin inhibition)
Latex particle agglutination
III. 24 Flavivirus - West Nile, Tick Born Encephalitis, Zika Virus treatment
supportive
III. 24 Flavivirus - West Nile, Tick Born Encephalitis, Zika Virus prevention
inactivated vaccine - tick-borne encephalitis
III. 24 Flavivirus - Zika Virus vector
Aedes mosquitos
III. 24 Flavivirus - Zika Virus clinical
Fever, rash, myalgia, arthralgia
Congenital Zika syndrome – microcephaly, CNS damage
III. 24 Flavivirus - West Nile vector
Culex mosquitos, hosts are birds (killed by virus)
III. 24 Flavivirus - West Nile clinical
Complications; encephalitis, meningitis, flaccid paralysis, seizures, coma
III. 24 Flavivirus - tick borne encephalitis (Fruehsommer-meningo-encephalitis virus) vector
Ixodes tick, hosts are animals, tick-transovarian infection, can spread by goat milk
III. 24 Flavivirus - tick borne encephalitis (Fruehsommer-meningo-encephalitis virus) clinical
Biphasic; influenza-like symptoms, febrile illness
Aseptic meningitis/meningoencephalitis
III. 25 Calicivirus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked virus
Many strains have cup-shaped depression (calyx = cup)
Divided into two genera of human pathogenic viruses; Norovirus (aka. Norwalk virus) and Sapovirus
III. 25 Calicivirus transmission
Fecal oral route
contaminated water
aerosol
III. 25 Calicivirus clinical
Nausea
vomiting
watery diarrhea – self-limiting gastroenteritis
III. 25 Calicivirus ddx
Serology
RT-PCR
radioimmunoassay
III. 25 Calicivirus treatment
rehydration
III. 25 Rotavirus characteristics
dsRNA, both positive and negative
Icosahedral capsid
Naked virus
All viruses have between 10-12 segments
All viruses have unique, double protein shell (coat) made of inner/outer capsid (resembles couch wheel)
III. 25 Rotavirus Transmission
Fecal-oral
III. 25 Rotavirus Clinical
NSP4 viral enterotoxin increases Cl- permeability which prevents absorption of water leading to - watery diarrhea - vomiting - dehydration
III. 25 Rotavirus ddx
ELISA – from stool (virion)
Blood – Ab titer
III. 25 Rotavirus treatment
supportive therpay
III. 25 Rotavirus vaccine
Live attenuated – needs to be given before 3 months or else there’s an increased risk for intussusception
III. 25 Astrovirus characteristics
ssRNA
positive sense
Icosahedral capsid
Naked virus
III. 25 Astrovirus transmission
Fecal-oral route
III. 25 Astrovirus clinical
Watery diarrhea for 2-3 days
III. 25 Astrovirus ddx
Serology
RT-PCR
III. 25 Astrovirus treatment
Supportive
III. 26 Orthomyxoviruses characteristics
ssRNA, negative sense
Helical
Enveloped
RNA synthesis in nucleus (only RNA virus)
Possesses Hemagglutinin and Neuraminidase glycoproteins
III. 26 Orthomyxoviruses transmission
Respiratory droplets, bodily fluids
III. 26 Orthomyxoviruses variation
- Antigenic drift: small, slow change of Antigen – change by point mutation.
Neutral Antibody against HA block binding to cells. Mutations in HA epitopes prevents neutral Aantibody from binding.
Influenza A, B – causes epidemic/seasonal flu
- Antigenic shift: great, fast change of Ag – co-infection of 2 different strains causes gene reassortment
Gives new subtypes due to genetic recombination of H and N segments of human and non-human species.
No cross-protective immunity against virus with new HA i.e. H1N1 - Spanish flu H2N2 - Asian flu H3N1 - Hong Kong Flu H5N1 Hong Kong avian flu
III. 26 Orthomyxoviruses pathogenesis
HA binds sialic acid on cell membrane of epithelial cells in lung/throat. Many different HA antigens (H1, H2, H3) are seen in influenza. These antigens detect cell tropism (which cell the virus can infect). Anti-HA antibodies protects the person from infection with the same stain in the future. M2 protein (a H+ channel which adjusts the pH for the virus need) gets the virus ready for viral encoding. After replication in nucleus, the virus binds host cell via the same residues as HA. NA cleaves Sialic acid from membrane to rely new virion from cell.
III. 26 Orthomyxoviruses clinical
Influenza A, B and C (also known as flu)
Upper respiratory tract infection with headache, high fever, malaise, chills, myalgia and coughing (GI symptoms in kids)
Complications include pneumonia and bronchitis
Associated with Guillan Barré syndrome: ascending paralysis, albuminocytological dissociation, elevation in CSF proteins with normal WBC count.
III. 26 Orthomyxoviruses ddx
Clinical or HA serotyping to detect virus type
III. 26 Orthomyxoviruses treatment
Amantadine (only for influenza A) and Rimantadine ~ M2 ion channel modifier
Osettamavir ~ Neuraminidase inhibition (Tamiflu)
- Aspirin is contraindicated in children after infection (Reye’s syndrome) – Fatty liver, LF, encephalitis, rash etc
III. 26 Orthomyxoviruses vaccine
Trivalent type consists of 2 A strains and 1 B strain/or tetravalent with 2A2B
- Inactivated (killed): given intramuscular
- Live attenuated: given intranasally (as spray)
III. 27 - Paramyxoviruses - Mumps, Morbillivirus characteristics
ssRNA, negative sense, non-segmented
Helical
Enveloped – HA, NA, F glycoproteins RNA synthesis in cytoplasm
III. 27 - Paramyxoviruses - Mumps clinical
Mumps virus (Rubulavirus). Enters upper respiratory tract --> spread to lymph node --> viremia.
Painful edematous enlargement of parotid and other glands ~ inflammation salivary glands, parotitis, pancreatitis, orchitis, adrenal gland etc.
Symptoms includes fever, headache and malaise. If CNS is also affected it could lead to meningoencephalitis which can eventually leads to deafness.
III. 27 - Paramyxoviruses - Mumps ddx
ELISA
HAI
III. 27 - Paramyxoviruses - Mumps prevention
live attenuated vaccine, MMR vaccine
III. 27 - Paramyxoviruses - Morbilli clinical
4 C’s; cough, coryza (runny, stuffy nose), conjunctivitis, koplik.
Symptoms include
- Koplik spots (vesicles on buccal mucosa)
- maculopapular rash (confluent, DDX from Rubella)
- acute rhinitis and conjunctivitis.
Complications are otitis media, bronchitis, giant cell pneumonia (with Warthrin-Finkeldy cells), subacute sclerosing panencephalitis (SSPE) which leads to CNS degeneration.
III. 27 - Paramyxoviruses - Morbilli ddx
ELISA
HAI
III. 27 - Paramyxoviruses - Morbilli prevention
live attenuated vaccine, MMR vaccine
III. 28 - Paramyxoviruses - RSV, Parainfluenzavirus characteristics
ssRNA, negative sense, non-segmented
Helical
Enveloped – HA, NA, F glycoproteins RNA synthesis in cytoplasm
III. 28 - Paramyxoviruses - RSV clinical
Atypical pneumonia in first year, bronchitis, bronchiole necrosis can occur
III. 28 - Paramyxoviruses - RSV characteristics
Respiratory syncitial virus (RSV)
F glycoprotein
i.e. pneumovirus
III. 28 - Paramyxoviruses - Parainfluenzavirus 1,2 clinical
Croup (laryngotracheobronchitis) in first 5 years
III. 28 - Paramyxoviruses - Parainfluenzavirus 3 clinical
Pneumonia in first year
III. 28 - Paramyxoviruses - Parainfluenzavirus 4 clinical
Upper RTI, mild catarrhal symptoms
III. 29 Picornavirus - Poliovirus characteristics
ssRNA, positive sense
Naked
Member of Enterovirus genus of the Picornaviridae family
Polio has 3 serotypes – 1, 2, and 3
III. 29 Picornavirus - Poliovirus transmission
Fecal-oral route
III. 29 Picornavirus - Poliovirus pathogenesis
Replicates in lymphoid tissue and tonsils (Peyer’s patches). Spreads (viremia) from lymphoid tissue to anterior horn of spinal cord and brain stem. Replicates in motor neurons, causing cell lysis (leading to paralysis)
III. 29 Picornavirus - Poliovirus clinical
- Asymptomatic illness – 75% of cases
- Absortive Poliomyelitis – 20% of cases (presents with URT infection and GI disturbances)
- Non-paralytic poliomyelitis – 0,1-0,5% of cases
Causes acute flaccid paralysis in which muscles become weak, floppy and paralyzed. Most commonly in lower limb (vary from 1 to 4 limbs – tetraplegia).
Depending on the site paralysis, can be classified as spinal, bulbospinal, bulbar. Bulbar polio is the most severe since it paralyzes respiratory muscles. - Post-polio syndrome – occurs 15-30 years after
Loss of muscle function (due to late harm of neurons)
III. 29 Picornavirus - Poliovirus ddx
Specimen from throat (few days) or from feces (for 30 days)
Serology
RT-PCR, virus is absent from CSF despite meningitis
III. 29 Picornavirus - Poliovirus treatment
Supportive. Iron-lung earlier (negative pressure respirator)
III. 29 Picornavirus - Poliovirus prevention
- Inactivated (killed) trivalent poliovirus vaccine (IPV) – Salk vaccine (given IM) ~ Does not form IgA
- Live attenuated bivalent poliovirus vaccine (OPV) – Sabin vaccine (given orally) ~ Forms IgA and IgG
Can infect immunocompromised, no longer used in USA/Hungary because of its potential to shed in feces.
Polio is found in three different countries today; Afghanistan, Pakistan, Nigeria
III. 30 Picornavirus - Coxasckie Virus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked
III. 30 Picornavirus - Coxasckie Virus transmission
Fecal-oral route
III. 30 Picornavirus - Coxasckie Virus pathogenesis
Replicates in enterocytes and lymphocytes of intestines.
Primary viremia –> target tissue (i.e. cardiac myocyte) –> 2nd viral replication –> secondary viremia
III. 30 Picornavirus - Coxasckie Virus A clinical
- Hand, foot, mouth disease ~ usually A16 serotype
Red vesicular rash and mild fever. Appear on hands, feet and in the mouth - Herpengina
Sore throat, fever and vomiting
Vesicular ulcerated lesions around posterior part of soft palate and uvula - Acute hemorrhagic cystitis ~ usually A24 serotype
Extremely contagious, subconjunctival hemorrhages and conjunctivitis
Aseptic meningitis
III. 30 Picornavirus - Coxasckie Virus B clinical
- Pleurodynia (Bornholm disease) aka Devil’s grip
Sudden onset of fever with lower chest and pleuritic pain – unilateral - Myocarditis and pericarditis
Sudden fever, cyanosis, cardiomegaly® heart failure
Dilative cardiomyopathy
Aseptic meningitis ~ both Cox A and B
III. 30 Picornavirus - Coxasckie Virus ddx
Virus isolation – throat, stool, CSF
Inoculation in mice –> Cox A (fast, flaccid paralysis)
–> Cox B (slow, spastic paralysis)
III. 30 Picornavirus - Coxasckie Virus treatment
supportive
III. 30 Picornavirus -Rhinovirus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked
III. 30 Picornavirus -Rhinovirus transmission
Respiratory droplets –> Upper respiratory tract infection
Unable to replicate in GI tract as enteroviruses
Rhinoviruses have Ag drift, as seen in influenza
III. 30 Picornavirus -Rhinovirus clinical
Upper respiratory tract infection ~ common cold
III. 30 Picornavirus - Echovirus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked
III. 30 Picornavirus - Echovirus transmission
Fecal-oral route –> can infect any tissue (broad tropism)
III. 30 Picornavirus - Echovirus clinical
Gastroenteritis Boston-exanthema (fever, sore throat, exanthemas) maculopapular rash aseptic meningitis (~ nr.1 cause) necrotizing hepatitis in neonates
III. 30 Picornavirus - Enterovirus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked
III. 30 Picornavirus - Enterovirus D68 clinical
EV-D68, infants, children and teens. Mild to severe respiratory illness, however, the full spectrum of EV-D68 is not well defined. Most start with common cold symptoms of runny nose and cough. Some, but not all, may also have fever. For more severe cases, difficulty breathing, wheezing or problems catching your breath may occur.
III. 30 Picornavirus - Enterovirus A71 clinical
One of the major causative agents for hand, foot and mouth disease, and is sometimes associated with severe central nervous system diseases. Increases in the level of mRNAs encoding chemokines, proteins involved in protein degradation, complement proteins, and pro-apoptosis proteins have been implicated.
III. 31 Rhabdoviruses characteristics
ssRNA, negative sense
Helical
Enveloped
Includes:
- Vesiculovirus genus (vesicular stomatitis virus (VSV))
- Lyssa virus genus (Rabies virus, Rabies-like virus)
Described as bullet-shaped on EM
III. 31 Rhabdoviruses clinical
Caused by Rabies virus, typical zoonotic infection from animals to humans
- Urban rabies: domestic animals i.e. dogs
- Sylvan rabies: wild animals i.e. bats, foxes
III. 31 Rhabdoviruses pathogenesis
The virus envelope is covered with glycoproteins for attachment and neutralizing Abs.
GPs bind to nAch receptors at the neuromuscular junction, then replicate inside the muscle (at wound). After replication period of days/weeks, the virus travels retrograde from peripheral nerve to dorsal root ganglion and spinal cord until it rapidly infects the brain.
Disseminate via afferent neurons to innervation sites in head (salivary gland, retina etc.)
Length of incubation depends on the proximality of the wound to CNS – the closer, the shorter
III. 31 Rhabdoviruses phases
- Prodromal phase
Fever, nausea, pain at site of bite - Neurological phase
Muscle: spasm of throat causing dysphagia and foaming of mouth
CNS: Increased saliva production, encephalitis and sweating, hydrophobia, seizures, disorientation, hallucinations, coma.
* Ab detectable in serum and in CNS
- Death
III. 31 Rhabdoviruses ddx
Clinical symptoms, RT-PCR from saliva, serum, CSF
Negri inclusion bodies (intracytoplasmic eosinophilic bodies) in pyramidal cells and purkinje cells of hippocampus
III. 31 Rhabdoviruses treatment
Fatal if not treated
Post-exposure vaccination – passive immunization via Abs
Pre-exposure vaccination – inactivated (killed), given to people exposed to animals
III. 32 Retrovirus and AIDS characteristics
ssRNA, positive sense, diploid
Conical capsid
Enveloped
III. 32 Retrovirus types
Oncornaviruses: HTLV 1, 2, 5 (Human T-cell lymphotrophic viruses)
Lentivirinae: HIV1 (AIDS), HIV2 (AIDS related syndrome)
Simple retroviruses have 3 major groups
- Gag (p24 = capsid protein, p17 = matrix protein, p7 = core nucleocapsid proteins)
- Pol (reverse transcriptase, integrase, protease)
- Env (gp120, gp41)
Complex retroviruses (i.e. HTLV, HIV) which have several regulatory proteins (regulate splicing). Reverse transcriptase converts RNA to DNA which can be installed into host cell genome
Oncornaviruses (HTLV) –> Leukemias, sarcomas, carcinomas.
Lentiviruses attack T-cells –> diminishing the hosts cell immune response (AIDS)
III. 32 Retrovirus and AIDS - HIV transmission
Bodily fluids
TORCH
III. 32 Retrovirus and AIDS - HIV Pathogenesis
Gp41 promotes cell-cell fusion, gp120 binds to CD4 receptors (and CCR5 and CXCR4) on T-cells. Following infection, HIV can remain latent for many years. Eventually infected T-cells lose their ability to function ® loss of humoral (CD4+ count <200) and cell mediated immunity.
III. 32 AIDS - clinical
Severe diseases related to AIDS
- Lymphadenopathy and fever
- Opportunistic infection i.e. M. tuberculosis, oral candidiasis
- Malignancies i.e. Kaposi sarcoma (HHV8), Burkitt’s lymphoma, and DLBL (Diffuse large B-cell lymphoma)
- AIDS related dementia
III. 32 Retrovirus and AIDS ddx
Clinical symptoms, patient history
HIV Ab measurement ~ using
ELISA Positive result confirmed using WB
III. 32 Retrovirus and AIDS treatment
Nucleoside RT inhibitor (Retrovir), non-nucleoside RT inhibitor (Rescriptovir), protease inhibitor (Crixivan), integrase inhibitor Given in combination to tackle virus in different ways.
III. 32 Retrovirus and AIDS - HTLV transmission
Bodily fluids and TORCH, sex, blood, breast-feeding
III. 32 Retrovirus and AIDS - HTLV pathogenesis
Spreads in CD4+ T-cells after transmission.
Neurons also express HTLV-1 receptor.
There is a long latency period before leukemia onset:
- Tropical spastic paraparesis – progressive weakness in lower extremities
- Adult T-cell leukemia – develops after a long latency period (~30-50 years)
Initial form = leukocytosis, abnormal lymphocytes
Mature form = Pleomorphic neoplastic cells with T-cell markers
Chronic form = Skin lesions (like Sezary syndrome), leukopenia, and no visceral involvement
III. 32 Retrovirus and AIDS - HTLV ddx
ELISA – presence of HTLV-specific Ab
PCR – Viral genome
Labs, bone marrow
III. 32 Retrovirus and AIDS - HTLV treatment
Glucocorticoids – tropical spastic paralysis
Chemotherapy – Leukemia
Zidovudine and INF-alpha - Virus
III. 33 Togavirus characteristics
ssRNA, positive sense
Icosahedral capsid
Enveloped
Includes Alpha- and Rubiviruses
III. 33 Togavirus Alphavirus transmission
Via mosquitos (vectors – where replication occurs) – Humans are dead-end hosts
III. 33 Togavirus Alphavirus ddx
Serology
RT-PRC
III. 33 Togavirus Alphavirus prevention
Killed vaccine for EEE and WEE
vaccination of horses
III. 33 Togavirus Rubiviruses characteristics
One species; Rubella virus – humans are only host for Rubella
Rubella ~ German measles One of the five classic childhood exanthema 1. Measles (Morbilli/Robeola) 2. Scarlet fever (S. pyogenes) 3. Rubella (German measles) 4. Erythema infectiosum (Parvovirus B19) 5. Roseola infantum (HHV6)
Child rubella – lymphadenopathy, maculopapular rash (pink, pinpoints, moves faster –> DDX from measles)
Adult rubella – lymphadenopathy, bone and joint pain, thrombocytopenia
Congenital rubella – developmental abnormalities (cataracts, deafness, patent ductus arteriosus, pulmonic stenosis, microcephaly, jaundice, purpuric rash), abortion
III. 33 Togavirus Rubiviruses transmission
Respiratory droplets
III. 33 Togavirus Rubiviruses ddx
Serology
RT-PCR
III. 33 Togavirus Rubiviruses treatment
Supportive, prevention with live attenuated vaccine
III. 34 Hepatitis A characteristics
Resistance to heat and acid
ssRNA positive sense
naked
III. 34 Hepatitis A epidemiology
Infectious hepatitis (HAV) is endemic throughout the world – low mortality ~ no carrier state
III. 34 Hepatitis A transmission
fecal-oral
III. 34 Hepatitis A ddx
Anti-HAV IgM
III. 34 Hepatitis A treatment
none
III. 34 Hepatitis A treatment
vaccine
III. 34 Hepatitis A pathogenesis
Ingestion of virus –> spread to bloodstream by penetrating epithelium of the oropharynx or intestine –> reaches the parenchyma of the liver –> replicates in hepatocytes and Kupffer cells (without lysis) –> release of new virions into bile –> shed in large quantities in the stool
III. 34 Hepatitis A clinical
Acute hepatitis
- Children: mild disease, often asymptomatic (10% jaundice)
- Adults: fever, fatigue, nausea, dark urine, pale stool, itchy skin and jaundice
- Smokers that develop hepatitis A tend to develop aversion to smoking (tobacco)
III. 34 Hepatitis E characteristics
ssRNA positive sense
resistance to heat and acid
III. 34 Hepatitis E treatment
none
III. 34 Hepatitis E prevention
vaccination in China
III. 34 Hepatitis E clinical
severe in pregnancy
III. 34 Hepatitis E ddx
Anti-HEV IgM
III. 35 Hepatitis B characteristics
dsDNA, circular
Icosahedral capsid
Enveloped
Replicates in and outside the nucleus
Uses reverse transcriptase (but does not integrate into the host chromosome)
III. 35 Hepatitis B transmission
Blood contamination (e.g. parenteral, needles etc.)
Sexual contact
Vertical infection (perinatal) – TORCHES
III. 35 Hepatitis B pathogenesis
Infects the liver, but can also infect kidney and pancreas
Symptoms and disease due to type 3 HSR (immune complexes of HBsAg+Anti-HBs Ag)
III. 35 Hepatitis B clinical
Acute hepatitis
- Prodromal serum sickness (fever, malaise) with rash and arthralgia
- Polyarthritis nodosa – systemic vasculitis affecting medium to small arteries
- Glomerular nephritis ~ 2 forms
Membranous nephropathy – more common Membranoproliferative glomerulonephritis
Chronic hepatitis ~ 5-10% chance to develop chronic hepatitis; newborns have ~90% chance
- Can progress to cirrhosis and to hepatocellular carcinoma
III. 35 Hepatitis B ddx
ALT (Alanine aminotransferase) rises during acute infection and then falls close to normal after symptomatic phase.
Neonates often have a normal ALT level.
III. 35 Hepatitis B treatment
- Lamivudine – cytidine analogue (inhibit viral DNA synthesis)
- Nucleoside Reverse Transcriptase Inhibitor (NRTI)
- Interferon a
- For kids at risk – Anti-HepB Immunoglobulins
III. 35 Hepatitis B prevention
Recombinant vaccine made of HBsAg given by 3 injections (at birth, 1 month and 6 months)
III. 35 Hepatitis C characteristics
ssRNA, positive sense
Icosahedral capsid
Enveloped
Member of the Flaciciridae family
Virus-encoded RNA polymerase lacks proofreading exonuclease activity in the 3’-5’ direction. This makes the virus prone to mutation, causing antigenic variability (of envelope proteins). The virus mutates so quickly there is no protection from it ~ no vaccination
III. 35 Hepatitis C transmission
Blood transfusions
Needle sharing (I.V drug users, accidental pricks from carrier, tattooing etc.)
sexual contact
III. 35 Hepatitis C clinical
Acute hepatitis
- fever, malaise, headache, anorexia, vomiting, dark urine and jaundice
Chronic hepatitis ~ 60-80% of hepatitis C infections will become chronic
- Same symptoms, but also chronic fatigue
- Extrahepatic manifestations include
Membranous nephropathy and membranoproliferative glomerulonephritis - Can progress to cirrhosis (used also to grade the disease severity)
- Can progress to hepatocellular carcinoma – primary cause
III. 35 Hepatitis C ddx
- Acute infection ~ ALT will rise and eventually fall after 6 months – Viral RNA persist in serum after 6 months
- ELISA of anti-HCV antibodies or PCR of RNA genome for diagnosis – Western-blot for confirmation (like HIV)
- Associated with cryoglobulins – precipitating Ig (mostly IgM) in cooler temperatures
- Liver biopsy – shows lymphocytes in the portal triad
III. 35 Hepatitis C treatment
- Ribavirin (nucleoside inhibitor, guanosine analogue)
- Interferon a
- Protease inhibitors (Broceprevir or Telaprevir)
III. 35 Hepatitis C pathogenesis
HCB binds to CD81 (tetraspanin) surface receptors (of hepatocytes and B-cells). It can also coat itself in LDL and use the LDL receptor to enter the hepatocytes. Cell-mediated immune response (CD8+) will cause resolution of infection and tissue damage. Chronic infection leads to exhaustion of CD8+ T-cells.
III. 35 Hepatitis D characteristics
envelope
ssRNA negative - circular
III. 35 Hepatitis D transmission
parental
III. 35 Hepatitis D clinical
acute hepatitis
III. 35 Hepatitis D ddx
anti-HDV ELISA
IV. 7 Coccidioides immitis characteristics
Dimorphic – molds in the cold, yeast in the heat
Coccidioides yeast cells > RBC
IV. 7 Coccidioides immitis clinical
Disease is caused by inhalation of infectious arthroconidia Endemic regions: Southwestern USA, Mexico
Immunocompetent:
~ asymptomatic, pneumonia, fever, arthralgia, erythema nodosum
Immunocompromised:
~ Progressive pulmonary infection, “the great imitator”, wide variety of lesions; skin, bone, lung, meninges (coccoidal granuloma)
Tissue form:
~ Spherule – thick walled structure with endospores.
Disruption of wall leads to spore release which can form new spherules in neighboring tissues
IV. 7 Coccidioides immitis ddx
~ Microscopic exam of sample from i.e. sputum
~ Serology – Ab titers
~ Skin test – coccidioidin or spherulin
IV. 7 Coccidioides immitis treatment
Surgery + Amphotericin B/Azoles
IV. 7 Histoplasma capsulatum characteristics clinical
Grows in soil, especially in soil contaminated with excretions of bat/birds
Endemic regions: Caves; USA, Latin-America
Histoplasma yeast cells < RBC Systemic fungi
IV. 7 Histoplasma capsulatum ddx
~ Direct exam of specimen – Blastosphores inside macrophages
~ Latex agglutination
~ Rapid serum and urine antigen test
~ Skin test: Histoplasmin
IV. 7 Histoplasma capsulatum treatment
~ Surgery + Amphotericin B/Azoles
IV. 7 Histoplasma capsulatum clinical
Acute histoplasmosis:
~ After inhalation, the microconidia are phagocytosed by pulmonary macrophages. Conversion to parasitic yeast form, occurs intracellular
Disseminated histoplasmosis:
~ Occurs in immunocompromised patients, AIDS: Calcified, destructive lesions on lung, hepatosplenomegaly with calcifications, erythema nodosum
IV. 8 Blastomyces dermatitidis characteristics
systemic infection
Endemic regions: North America Dimorphic fungi found in decaying organic material (i.e. woods)
In tissue: broad-based budding yeast Mold form: Mycella with/typical piriform mycroconidia
IV. 8 Blastomyces dermatitidis clinical
Blastomycosis – by inhalation of conidia spores (RBC size)
- Pulmonary disease
- Extrapulmonary: skin, bone, GU, CNS - Disseminated disease in immunocomp
IV. 8 Blastomyces dermatitidis ddx
Direct exam of specimen (spherules)
IV. 8 Blastomyces dermatitidis treatment
Amphotericin B or Azoles
IV. 8 Paracoccidiodes brasiliensis characteristics
Endemic regions:
Similar to Blastomycosis, but located in south and central America
Dimorphic fungi, likely soil associated
In tissue:
Thin to thick walled, multiplying, captain’s wheel
Paracoccidiodes brasiliensis clinical
Brazilian Blastomycosis - Respiratory droplet
~ Self-limiting pulmonary disease
~ Extrapulmonary: skin, mucosa, bones, LN, viscera, meninges
~ Disseminated disease in immunocompromised patients and children
Paracoccidiodes brasiliensis ddx
When yeast buds look like “captain’s wheel”
Paracoccidiodes brasiliensis treatment
Amphotericin B
IV. 9 Cryptococcus neoformans characteristics
Ubiquitous saphrophyte, found worldwide especially in pigeon excretions.
Only yeast form
IV. 9 Cryptococcus neoformans virulence factors
Think capsule, melanin
Opportunistic fungal infection causing pneumonia and meningitis with soap bubble lesions and cysts in grey matter. Typical in immunodeficient patient.
IV. 9 Cryptococcus neoformans ddx
~ CSF specimen – India ink for capsule detection (black background, transparent fungi), latex agglutination for
polysaccharide capsule
~ Lung tissue – stain capsule with Mucicarmine (red), culture with Saboraud with cycloheximide (sample from BPL), urease positive
IV. 9 Cryptococcus neoformans treatment
Amphotericin B, Flucytosine
IV. 9 Pneumocystis jirovecii characteristics
Thought to be a protozoa until recently. Now, based on its RNA it is a fungus related to ascomycetes (obligate extracellular)
Pneumocystis is present in lung of many animals, i.e. rats and rabbits
Causes diffuse interstitial pneumonia in immunodeficient patients (ground-glass appearance on X-ray)
Frequency of infection is rising due to i.e. HIV, transplantations, AIDS
IV. 9 Pneumocystis jirovecii ddx
~ Microscopical exam with Giemsa stain
~ Methamine-silver (BAL) – disc shaped yeast
~ Lung biopsy
IV. 9 Pneumocystis jirovecii treatment
Sulphonamide, Trimetroprim (=Bactrim)
IV. 10 Aspergillus species characteristics
opportunistic fungi
Allergic bronchopulmonary Aspergillosis
- Asthmatic attacks, hypersensitivity pneumonitis, Aspergilloma which may progress to fibrotic lung disease
Invasive Aspergillosis
- Most frequently involves lungs and paranasal sinuses. Fungus may disseminate from lungs, via blood to i.e. brain, liver, kidney, heart. Main portal of entry is the respiratory tract. Predisposing factors are; neutropenia due to i.e. chemotherapy
IV. 10 Aspergillus species transmission
Inhaled conidiospores from peanuts, rice, grains etc.
IV. 10 Aspergillus species ddx
~ Histopathology – Grocott stain
~ Isolation from specimen, culture and ID – septate hyphae branch at acute angle (~45°)
~ Ag (galactomannan test) from serum
~ Imaging – ring enhancing lesions in brain (DDX: lymphoma, toxoplasmosis)
IV. 10 Aspergillus species treatment
Amphotericin B
surgery for Aspergilloma
IV. 10 Penicillium genus characteristics
P. marneffei is a pathogenic dimorphic fungus
Present in soil, prominent infection in immunodeficient patients
Infection reminds of cryptococcus and histoplasmosis and other diseases – prominent in immunodeficient patients
IV. 10 Penicillium genus ddx
Microscopic detection of eliprical fission yeast inside macrophages
IV. 10 Penicillium genus treatment
Amphotericin B
IV. 10 Zygomycoses characteristics
Caused by Rhizopus, Rhizomucor, Absidia, Mucor ssp and other members of zygomycetes – Invasive sinopulm infection (Mucormycosis)
Especially severe form of zygomycosis is known as Rhinocerebral syndrome (black eschar, necrosis in nasal cavity) which occurs in DM with ketoacidosis.
Causative molds are:
~ Conidiobolus – facial area of adults
~ Basidiobolus – limbs of children
Risk factors are DMKA, neutropenia, corticosteroids
Both Aspergillus ssp, and zygomyceses tend to invade blood vessels
IV. 10 Zygomycoses ddx
Non-separate hyphae branching at 90°
IV. 10 Zygomycoses treatment
Itraconazole, oral KI, facial surgery
IV. 11 Candida genus characteristics
Opportunistic fungi
Candida species includes; C. krusei, C. glabrata, C. tropicalis, C. parapsilosis C. albicans is the most important
WHEN CULTIVATED: MOLD IN HEAT, YEAST IN COLD!
Candidiasis may be superficial or deep
~ Superficial candidiasis may involve epidermal and mucosal surfaces (endogenous transmission, normal flora). i.e. oral
soar, diaper rash, candida vulvovaginitis
~ Deep candidiasis involves the liver, kidney and spleen mainly. GI tract and IV catheters are major portals of entry.
IV. 11 Candida genus clinical
Immunocompetent:
~ Soor, vaginal flour, intertrigo (skin)
Immunocompromised:
~ General oral candidiasis, candida esophagitis (CD4 count under 100), candidemia (sepsis, infective endocarditis)
IV. 11 Candida genus risk factors
~ Broad spectrum antibiotics
~ Chemotherapy
~ Corticosteroids
~ IV catheters
IV. 11 Candida genus ddx
~ Microscopic exam
~ Cultivation: Saburaud, chrom agar
~ Identification: old methods – rice meal agar (chlamydospores), new methods – biochemical test (on glucose containing
serum is forms pseduhyphae), molecular methods, MALDI-TOF
~ Catalase positive
IV. 11 Candida genus treatment
~ Mild/local: Azoles
~ Oral: Nystatin
~ Disseminated: Amphotericin B
Prophylaxis for transplant patients: oral fluconazole
IV. 13 Entamoeba histolytica characteristics
Amoebic dysentery: Abdominal pain, blood and pus in stool (small volume, blood and mucus)
Source of infection: carriers, cyst-shedding humans
Fecal-oral transmission: contaminated water, anal transmission is rare
IV. 13 Entamoeba histolytica virulence factors
- Adhesion molecule (Gal/GalNac Lectin)
- Amoeboporin
- Pseudopodia (locomotion)
- Histolytic enzymes: protease, cysteine kinase, phospholipase A, hyaluronidase, collagenase, elastase, RNAase
IV. 13 Entamoeba histolytica pathogenesis
Ingestion of cysts → Reach stomach → Formation of trophozoite → Replication → Attachment to host cells by GalNAC → Local necrosis via cytokines → Invasion of intestinal wall and RBC (to feed) → Dissemination to other organs → Secondary organ involvement (lymphatic spread)
Extra-intestinal Amebiasis, when amoeba invades intestinal wall
~ Flask shaped ulcers in colon with extension to peritoneum and other organs
~ Abscess formation (i.e. brain, lung, liver)
IV. 13 Entamoeba histolytica ddx
Fecal antigen test: trophozoite and cyst seen
Serology: ELISA for confirmation/differentiation from commensal
Histology: Flask-shaped ulcers
IV. 13 Entamoeba histolytica treatment
Active disease – Metronidazole (10 days), Tinidazole (5 days)
Cyst carriers – Paromomycin
IV. 13 Entamoeba histolytica prophylaxis
Boil water, chlorination does not work
IV. 13 Entamoeba coli characteristics
Part of normal flora
When found in stool it’s often confused with E. histolytica
IV. 13 Entamoeba coli ddx
~ Cyst contains 1-8 nuclei (E. histolytica: 1-4)
~ Does not ingest RBC
~ Differentiated by antigen detection
IV. 14 Acanthamoeba characteristics
Acanthamoeba spp → A. castellani, A. keratitis = Trophozoite (infective term) and cyst → Found in soil and lakes (free living)
IV. 14 Acanthamoeba pathogenesis
Trophozoits travel via cribriform plate → into CNS Trophozoits/cysts may also be inhaled into respiratory tract
IV. 14 Acanthamoeba clinical
Granulomatous amebic encephalitis (GAE)
- Infects immunocompromised patients causing brain abscesses, edema of brain tissue, dissemination causing
granulomatous disease - Slower course of disease (DDX Naegleria)
Amoebic keratitis
- Source: eye trauma, contact lens contamination
- Results in corneal ulceration and pain
IV. 14 Acanthamoeba ddx
NICE N – Nasal discharge I – Iodine stained smear C – Corneal scraping E – Examination of CSF
- Both trophozoites and cysts are seen in tissues (ddx from naegleria)
IV. 14 Acanthamoeba treatment
Pentamidine
IV. 14 Naegleria genus characteristics
same as acanthamoeba
IV. 14 Naegleria genus clincial
Primary Amebic Meningoencephalitis (PAM)
~ Destruction of brain tissue, leads to death (rapid: 4-5 days)
~ Symptoms: prefrontal headache, nausea, high fever, stiff neck, altered olfaction
~ CSF is purulent: contain motile amoeba and blood
~ Diagnosis: NICE, but only trophozoites seen in tissues
~ Treatment. Amphotericin B, Rifampin
IV.15 Giardia lamblia characteristics
Flagellate
Trophozoite is kite-shaped, bi-nucleated with 4 flagella
Cyst is drug, chlorine and filtration resistant, with 4 nuclei
Both cyst and trophozoite from are detected in fecal samples.
Found mainly in non-hygienic water sources
IV.15 Giardia lamblia clinical
Giardiasis – Beaver fever, backpackers’ diarrhea
Can be asymptomatic and symptomatic.
Symptoms are ranging from mild diarrhea to severe malabsorption syndrome (steatorrhea).
Rarely blood/pus in stool since no tissue destruction (ddx: entamoeba)
IV.15 Giardia lamblia ddx
~ Fecal antigen test – Trophozoites and cysts seen
~ Duodenal aspiration – since it resides in duodenum
~ Enterotest – gelatin on a string (capsule)
IV.15 Giardia lamblia treatment
Metronidazole
IV. 15 Balantidium coli characteristics
Ciliate
Trophozoite is ciliated (motile), 2 nuclei (one micro and one macronucleus)
Cysts are smaller, surrounded by wall, 1 macronucleus
IV. 15 Balantidium coli clinical
Balantidiasis
Bloody diarrhea, abdominal cramps (tenesmus) → Fatal, but rare
IV. 15 Balantidium coli ddx
Stool examination
IV. 15 Balantidium coli treatment
Tetracycline (first choice)
Metronidazole
IV.15 Giardia lamblia pathogenesis
Fecal-oral transmission
Infection is initiated by ingestion of cysts, which reach duodenum and form trophozoites.
The trophozoites multiply by binary fission and attach to intestinal wall via ventral sucking disc (does not invade intestinal wall, ddx from Entamoeba)
IV. 15 Balantidium coli pathogenesis
Found in pigs and monkeys
Fecal-oral transmission
Ingestion of cysts, trophozoite invasion into mucosa of large intestine, cecum, terminal ileum
IV. 16 Cryptosporodium spp characteristics
Sporozoa
Sexual cycle: sporogony
Asexual cycle: schizogony
IV. 16 Cryptosporodium spp pathogenesis
affects SI mucosa via fecal-oral contamination of water
I) Ingestion of cyst with 4 motile sporozites (infective stage)
II) Sporozites attach to the intestinal epithelium and mature (schizogony)
III) Sexual form develops (gametogony) and produces fertilized oocysts with zygote inside
IV) Oocyst matures in intestine or is excreted to the environment via stool
IV. 16 Cryptosporodium spp clinical
Cryptosporidiosis - Severe watery diarrhea and dehydration (around 2 weeks)
IV. 16 Cryptosporodium spp ddx
Fecal antigen test
Acid-fast stain of stool – contains oocyst
IV. 16 Cryptosporodium spp treatment
Rehydration, probiotics
Spiramycin in immunocompromised
IV. 16 Blastocystis hominis characteristics
Amoeba
One of the most common parasitic infections in the world – number 1 in the US Reservoir:
Animal intestine
Transmission: Animal feces in cyst form
IV. 16 Blastocystis hominis pathogenesis
I) Ingested feces from environment
II) Cyst change to vacular form in GI and replicate, or change further to other forms i.e. amoeba or granular form
III) Release of new cysts via stool
IV. 16 Blastocystis hominis clinical
Symptoms range from asymptomatic to diarrhea, nausea, abdominal cramps
IV. 16 Blastocystis hominis ddx
Wet mount
Trichrome from stool
IV. 16 Blastocystis hominis treatment
Metronidazole
IV. 17 Trichomonas vaginalis characteristics
Flagellates, only trophozoite from (4 flagella, 1 nucleus)
Genital pathogen (in urethra, vagina/prostate), transmission by sexual contact, thermal baths, WC, birth canal
IV. 17 Trichomonas vaginalis pathogenesis
During intercourse, trophozoites in vaginal/prostatic secretions are passed and placed in vagina or urethra. Here the trophozoites multiply by longitudinal binary fission. Trophozoites are both the infective and diagnostic form
IV. 17 Trichomonas vaginalis clinical
Trichomoniasis
Yellow/green discharge with fish-like odor
Burning, itching, preterm delivery
Vaginitis, prostatitis, cervicitis (strawberry)
IV. 17 Trichomonas vaginalis ddx
Wet mount with blue-methylene stain: trophozoites with corkscrew motility
Grows on elevated pH
Giemsa stain
IV. 17 Trichomonas vaginalis treatment
Metronidazole (also for sex partners)
IV. 18 Plasmodia characteristics
Sporozoa
4 species that infect humans:
P. ovale and P. vivax (tertian paroxysm, 48h asexual reproduction), P. malariae (quatrain paroxysm, 72h asexual reproduction), P. falciparum (most malignant)
Plasmodium ssp are sporozoan parasites of blood
2 hosts are needed:
- (Anopheles) Mosquitos for sexual reproduction (sporogony)
- Human/animals for asexual reproduction (schizogony)
IV. 18 Plasmodia life cycle
~ Infection initiated by mosquito bite, releases sporozoites into blood
~ Sporozoites are carried to the liver for asexual reproduction (schizogony). Hepatocytes (liver stage schizonts) containing
2-40’000 merozoites (5-21 days)
~ Merozoite attach to RBC (1/RBC), developing into immature ring-shaped trophozoites, and later to blood stage schizonts
containing 8-36 merozoites.
~ Rupture of RBC – symptomatic
~ Gametocytes will then be sucked back up of the same mosquito and the life cycle is complete
* Sexual reproduction in mosquitos is known as sporogonic cycle
IV. 18 Plasmodia clinical
Malaria
Headache, fever, fatigue, coughing, sweating, nausea. Cerebral malaria, pulmonary edema, shock, coma, renal failure, hepatosplenomegaly, anemia. (Black urine)
IV. 18 Plasmodia ddx
Smear, PCR
Blood films
- Thick film: hemolyzed by distilled H2O – used for detection of Plasmodium
- Thin film: methanol fixed, non-hemolyzed – for detection of species
IV. 18 Plasmodia prophylaxis
P. falciparum vaccine (2018), made from fusion protein Doxycycline, chloroquine, mefloquine
IV. 19 Trypansoma brucei characteristics
Flagellates
T. brucei gambiense – human reservoir, tse-tse fly vector, sleeping sickness, West Africa
T. brucei rhodesiense – antelope, tse-tse fly vector, sleeping sickness, East Africa
IV. 19 Trypansoma brucei pathogenesis
Blood: Trypomastigote
Tissue: Amastigote (IC)
Undergo antigenic variation, evade immunity,
chronic infection
Trypomastigote enter by the wound of the tsetse fly bite. Travel in blood/lymph/CNS and reproduce at target site by binary fission. Ingested back from blood by fly, then multiply in fly1s midgut. Migrate and mature to epimastigote in salivary glands. Develop to trypomastigote in salivary glands (ready to infect)
IV. 19 Trypansoma brucei clinical
Sleeping sickness/African trypanosomiasis
~ Ulcer at the site of bite
~ Fever, chills, anorexia
~ Lymphadenopathy – cervical (Winterbottom’s sign) and axillary
~ CNS – lethargy (lack of energy), somnolence (sleepiness), dementia, meningoencephalitis
~ Coma, eventually death
- Differentiation between species → T. b. rhodesiense has shorter incubation time, rapidly progressing, more virulent. It is easier to detect in blood
IV. 19 Trypansoma brucei ddx
Blood films (thick and thin) → Showing trypomastigotes (ALWAYS extracellular)
Serology from CSF → High Ig levels
IV. 19 Trypansoma brucei treatment
Suramin – for acute infections
Melarsoprol – chronic/CNS infections
IV. 20 Trypanosoma cruzi characteristics
Flagellates
Armadillo/cat/dog reservoir, kissing bug (Recluviid bug) vector, Latin-America, Chagas disease
IV. 20 Trypanosoma cruzi pathogenesis
Trypomastigotes are passed in the feces of bug and enters the wound (aided by scratching). Migrate to different tissues forming small, oval amastigote, then multiply by binary fission. Rupture and destroy the host cells. Trypomastigotes can be ingested back by the kissing bug where they form epimastigotes in bugs midgut, then develop into trypomastigotes
IV. 20 Trypanosoma cruzi clinical
Chagas disease/American trypanosomiasis
Acute form ~ most severe in children under 5 years ~ Chagoma at bug bite site ~ Romana sign: periorbital edema ~ Fever, malaise, myalgia, fatigue
Chronic form
~ Dilated cardiomyopathy, megacolon, mega esophagus
~ Granulomas in brain
IV. 20 Trypanosoma cruzi ddx
Blood films in acute phase ~ showing trypomastigotes (difficult to find)
Biopsy of infected tissues, then serology
Xenodiagnosis
IV. 20 Trypanosoma cruzi treatment
Nifurtimox
Benznidazole
IV. 21 Leishmaniae characteristics
Hemoflagellates – infects blood and tissues
Obligate intracellular parasites of reticuloendothelial system, bone marrow, spleen, lymph nodes
Organism is not seen in peripheral blood
IV. 21 Leishmaniae pathogenesis
Fly bites and injects promastigotes into skin → invade macrophages and form amastigotes which replicate → cell rupture and release of the amastigotes → invades other cells and replicate again → Ingestion from blood back to fly → promastigote development → move to proboscis (nose of fly) and is ready to infect again.
IV. 21 Leishmaniae - L. tropica
Reservoir: rodents, dogs
Vector: phlebotomus fly
Disease: Cutaneous leishmaniosis ~ tropical sore/ulcer (secondary bacterial infections)
Location: Asia, Africa
IV. 21 Leishmaniae - L. braziliensis
Reservoir: rodents, dogs
Vector: phlebotomus fly
Disease: Mucocutaneous Leishmaniosis
~ Espundia (disfiguring of the face) → secondary bacterial infections with mucous membrane involvement
Location: South America
IV. 21 Leishmaniae - L. donoconi
Reservoir: dogs, cats, foxes
Vector: Phlebotomus fly
Disease: Visceral Leishmaniosis (~ Kala azar, black fever, dumdum fever) with
~ Fever, chills, sweating – like malaria
~ Deep tissue involvement – Hepatosplenomegaly, anemia, pancytopenia
~ Granulomatous lesions of the skin
Location: Southeast Asia i.e. Bangladesh, Nepal
IV. 21 Leishmaniae ddx
Aspirate from lymph node – Giemsa staining of biopsied tissues
Montenegro skin test – T4 HSR
IV. 21 Leishmaniae treatment
Sodium stibogluconate (and IFN gamma)
IV. 21 Leishmaniae prophylaxis
Protection from phlebotomus fly bite
IV. 22 Toxoplasma gondii characteristics
Obligate intracellular sporozoan
Definite host: cats where gametocysts and oocyst develop
Secondary host: i.e. humans where tachyzoites and bradyzoites develop
IV. 22 Toxoplasma gondii transmission
Route of human transmission
1) Cat stool
2) Undercooked meat
3) Contaminated vegetables
4) Transplacental (TORCH)
T. gondii develops and has it’s sexual cycle in cat intestine → Oocyst released in feces → 3-4 days of incubation in environment → ingested by human → sporozoites infect cells → develop into tachyzoites which replicate fast in macrophages (blood) and delivery into tissues where cyst develop → Bradyzoite reproduction in cyst (responsible for chronic infection)
IV. 22 Toxoplasma gondii clinical
Toxoplasmosis
In immunocompetent:
Asymptomatic, lymphadenopathy with fever. DDX; mono, but heterophile is negative
In pregnant women: Flu-like symptoms and heterophile negative
I) Early placental crossing
- Intracranial calcifications
- Hydro-/microcephaly, convulsions - Chorioretinitis and deafness
II) Late placental crossing
- Unapparent, but may lead to blindness in adolescence
In immunocompromised patients: Meningoencephalitis
Number 1 leading cause of focal DNA disease in AIDS patients.
If CD4+ count is <100, and seropositive for IgG, prophylactic TMP-SMX should be given
IV. 22 Toxoplasma gondii ddx
Serology: specific markers is IgM (after two weeks no IgG, then IgM is false positive)
Avidity test: To distinguish if recent or past infection (look for IgG)
PCR: from CSF, in HIV patients
IV. 22 Toxoplasma gondii treatment
Self-limiting in immunocompetent patients
Sulfadiazine and pyrimethamine
Spiramycin for pregnant women
IV. 24 Taenia saginata characteristics
Aka. Beef tapeworm
Cestode (tapeworm)
Intermediate host: cattle
Definite host: human
Transmitted via undercooked beef – cysterici are ingested 12m, 1-2mm in diameter with 4 suckers
IV. 24 Taenia saginata life cycle
Mature proglottidis give off eggs → cyst formation (cysticercosis) in intermediate host (i.e. cows) → Humans infected by eating meat → SI maturation → enteral taeniasis
IV. 24 Taenia saginata ddx
Proglottis or eggs in stool – eggs (thick double wall) only detect taenia genus, proglottis can differentiate spp
IV. 24 Taenia saginata treatment
Niclosamide and mebendazole
IV. 25 Taenia solium characteristics
Aka. Pork tapeworm
Intermediate host: Pigs
Definite host: Humans
Accidental intermediate host: Human (cysticercosis) ONLY SOLIUM
Transmitted via undercooked pork – cysticerci are ingested (eggs are transmitted via contaminated water) 6m, has rostellum with hooklets
IV. 25 Taenia solium life cycle
Mature proglottids give off eggs → cyst formation (cysticercosis) in intermediate host (i.e. cows) → Humans infected by eating meat → SI maturation → enteral taeniasis
IV. 25 Taenia solium clinical
~ Subcutaneous cysticerosis
~ Cerebral cysticerosis
~ Enteral taeniasis
IV. 25 Taenia solium ddx
Proglottids in stool
Cysts in tissue on CT scan
Serology – Ag detection of CSF by ELISA
IV. 25 Taenia solium treatment
Praziquantel
Niclosamide
+ corticosteroids and surgery
IV. 26 Diphyllobothrium latum characteristics
Aka. Fish tapeworm → largest tapeworm Definite host: humans
Reservoir: bears, other mammals Intermediate host: Fish
IV. 26 Diphyllobothrium latum pathogenesis
Humans infected by eating fish containing larvae, small intestinal maturation
IV. 26 Diphyllobothrium latum clinical
Abdominal pain with nausea and diarrhea, pernicious anemia due to B12 requirement of the parasite
IV. 26 Diphyllobothrium latum ddx
Finding eggs in stool
IV. 26 Diphyllobothrium latum treatment
Praziquantel
Niclosamide
IV. 26 Hymenolepis nana charcteristics
Dwarf tapeworm, 1-3 cm
Most prevalent in conditions of poor sanitation, and is endemic in tropical regions = hymenolepiasis
IV. 26 Hymenolepis nana pathogenesis
Swallowed eggs → SI maturation → developing helminths * some eggs pass out with feces
Asymptomatic infection – diagnosis based on finding eggs in stool
IV. 26 Hymenolepis nana treatment
Praziquantel
Niclosamide
IV. 27 Echinococcus species characteristics
E. granulosus: Carnivores, domestic animals ~ dog tapeworm
E. multilocularis: Wolf, fox ~ small fox tapeworm I
ntermediate host: Herbivores (sheep, cattle)
Definite host: Dogs
Accidental, dead-end host: humans
IV. 27 Echinococcus granulosus life cycle
After ingestion of eggs, the onchospheres penetrate the intestinal wall and reach host organs ~ liver/lung
They form cyst within a week, consisting of an external acellular part, and an internal/germinal.
The larvae develop from the germinal layer
IV. 27 Echinococcus granulosus hydatidosis
Hydatid cysts in lung, liver, brain
Fluid inside cyst is toxic → anaphylactic shock, death
IV. 27 Echinococcus granulosus ddx
Presence of isolated hooklets
CT or echography
ELISA, western blot
IV. 27 Echinococcus granulosus treatment
Sugery
Albendazole
IV. 27 Echinococcus multilocularis life cycle
Adult worm in small intestine of animal (reservoir), embryonated eggs in feces of that animal → orally into human OR from cyts in intermediate host until it reaches human → The activated onchosphere penetrates the small intestine, enters blood vessels and reaches liver via portal vein.
IV. 27 Echinococcus multilocularis pathogenesis
Alveolar echinococcosis (AE) The liver is the organ primarily affected, but could metastasize to any organ (brain, lungs etc). Causes infiltatrive growth – hepatomegaly, jaundice, abdominal pain
IV. 27 Echinococcus multilocularis ddx
CT/MRI
ELISA
IV. 27 Echinococcus multilocularis treatment
Surgery, chemotherapy
Benzimidazole
IV. 28 Fasciola Hepatica characteristics
Sheep liver fluke, high prevalence in Europe and south America
Definitive host: sheep, cattle, humans
Intermediate host: snails
IV. 28 Fasciola Hepatica organs affected
Biliary ducts
liver
IV. 28 Fasciola Hepatica pathogenesis
Consumption of larvae → Encystation in duodenum → Liver (maturation, necrosis of liver) → egg in bile duct → pass out with feces
IV. 28 Fasciola Hepatica clinical
Fever, severe eosinophilia, hepatosplenomegaly, bile duct obstruction
IV. 28 Fasciola Hepatica ddx
Eggs in feces
IV. 28 Fasciola Hepatica treatment
Triclabendazole
Bithionol
IV. 29 Paragonimus westermani characteristics
Lung fluke, high prevalence in Asia
Source of infection: eating undercooked freshwater crabs or crayfish (larvae)
IV. 29 Paragonimus westermani pathogenesis
Fluke develops in stomach → migration via intestinal wall → through diaphragm → pleural cavity where the adults lay eggs in lungs
IV. 29 Paragonimus westermani clincal
Pneumonia – can be fatal due to penetration of brain, heart, spinal cord
Fever, eosinophilia, chest pain, bloody sputum, lung tissue fibrosis (night sweats, pleuritis, bronchopneumonia)
IV. 29 Paragonimus westermani ddx
Eggs in feces/sputum
IV. 29 Paragonimus westermani treatment
Praziquantel + bithionol
IV. 30 Schistosomes characteristics
Only fluke with separate sexes
S. hematobium → IM hosts are snails (Bulinus) – urinary tract
S. mansoni → IM hosts are snails (biomphalaria) – GI
S. japonicum → IM hosts are snails (onchomelania) – GI
IV. 30 Schistosomes life cycle
1) Eggs hatch in water, releasing miracidia
2) Miracidia penetrate snail tissue and form sporocysts
3) Cercariae (infective form larvae) released
by snails, these are free-swimming
4) Cercariae penetrate human skin, loose tails and becomes schistosomulae
5) Blood stream → Liver: maturation
6) Migration to large intestine or venous plexus of urinary bladder
IV. 30 Schistosomes clinical
Hepatosplenic schistosomiasis
~ Results from eggs embolization in hepatic venules
~ Formation of granulomas and portal fibrosis
~ Hepatosplenomegaly and hepatic insufficiency
IV. 30 Schistosomes ddx
serology
IV. 30 Schistosomes treatment
Praziquantel
IV. 30 Schistosomes manosoni
S. mansoni → female lays eggs ~ 300 eggs/day → Africa
Adult Schistosomes live in pairs in the portal system and in the mesenteric venules
IV. 30 Schistosomes japonicum
S. japonicum → Female lays eggs ~ 2000 eggs/day → Southeast Asia
S. mansoni → female lays eggs ~ 300 eggs/day → Africa
IV. 30 Schistosomes hematobium characteristics
Female lays ~ 150 eggs/day
Adult schistosomes lives in pairs in pelvic veins (especially in venous plexus around urinary bladder)
IV. 30 Schistosomes hematobium clinical
Urinary schistosomiasis
~ Eggs induce granuloma formation, bladder wall enlargement, hematuria
~ Hyperplasia of mucosa, fibrosis and calcification with polyp formation in urinary bladder and urethral stenosis
~ Hydronephrosis and cancer are late complications
~ Damage to seminal vesicles
IV. 30 Schistosomes hematobium ddx
Eggs in urinary sediment ~ motility
Eggs in feces
ELISA, IF, RIA
IV. 30 Schistosomes hematobium treatment
Praziquantel
IV. 31 Ancylostoma dudenale and Necator americanus charcteristics
Intestinal nematodes
Hookworm
A. duodenale ~ old world hookworm
A. braziliense
N. americanus ~ new world hookworm
IV. 31 Ancylostoma dudenale and Necator americanus pathogenesis
Bare foot in environment → larvae infect through skin → enter blood stream → infection of lung, pharynx, SI (cough/swallow) → sucking blood (0,3-0,9 ml/day) (A. duodenale → 0,15 ml, N. americanus → 0,03 ml)
IV. 31 Ancylostoma dudenale and Necator americanus clinical
Hookworm infection
~ Live attached to mucosa of small intestine, where they feed on villous tissue
~ Hypochromic microcytic anemia (IDA)
~ Epigastric pain, hypoproteinemia, eosinophilia
Cutaneous larva migrans
~ A. braziliense
~ Intense skin scratching from dog/cat hookworm
IV. 31 Ancylostoma dudenale and Necator americanus ddx
Larvae in feces
IV. 31 Ancylostoma dudenale and Necator americanus treatment
Mebendazole/albendazole
Iron supplement
IV. 32 Toxocara canis Toxocara cait characteristics
Geohelminths = Toxocara (cati, canis) ~ nematode
IV. 32 Toxocara canis Toxocara cait pathogenesis
- Entry through mouth (eggs excreted by dog or cat)
- Larvae hatch in small intestine and penetrate mucosa
- Larvae enter portal system (some are trapped in liver)
- Larvae enter systemic circulation → dissemination (dead-end infection)
- Diseases depends on number of larvae ingested and the degree of the allergic response
IV. 32 Toxocara canis Toxocara cait ddx
Larvae in tissue (~10cm)
ELISA – serology
No adult worms in human
IV. 32 Toxocara canis Toxocara cait treatment
Albendazole
IV. 32 Toxocara canis Toxocara cait clinical
Visceral larva migrans:
fever, cough, malaise, leukocytosis with hypereosinophilia, hepatomegaly, high titers of isohemagglutinins * myocarditis, encephalitis, pneumonia
Ocular larva migrans:
retinal granulomas and uveitis → blindness
IV. 33 Trichinella spiralis characteristics
Nematode
Adult form lives in SI of flesh-eating mammals, i.e. pigs
Viable, encysted larvae is found in the meat (muscles of animals)
IV. 33 Trichinella spiralis pathogenesis
Cycle
1) Entry by ingestion of cyst: contaminated meat
2) Excystation and maturation in SI
3) Larvae enter systemic circulation → dissemination ~ dead-end infection
IV. 33 Trichinella spiralis clinical
Trichinellosis
Larvae encyst in striated muscle, causing inflammation, pain, myalgia, acute enteritis, fever, periorbital edema
IV. 33 Trichinella spiralis ddx
Larvae in muscle biopsy
Serology – ELISA
IV. 33 Trichinella spiralis treatment
Mebendazole
albendazole
IV. 34 Enterobius vermicularis characteristics
Nematode
Pinworm – male: 2-5mm, female: 10-13mm
IV. 34 Enterobius vermicularis pathogenesis
1) Entry through mouth – eggs (form environment) contain larvae
2) Eggs hatch in small intestine – migrate to large intestine and mature
3) Migrate to perianal area → lay eggs (1000/day) → perianal itch → scratch → autoinfection
IV. 34 Enterobius vermicularis clinical
Perianal prurutis
IV. 34 Enterobius vermicularis ddx
Eggs in perianal region – scotch tape smear used to see larva in eggs. *made in the morning before defecation/bathing
IV. 34 Enterobius vermicularis treatment
Mebendazole
IV. 35 Acaris lumbricoides characteristics
nematodes
Geohelminth
Most common and largest roundworm: males: 15-20 cm, female: 20-35cm
IV. 35 Acaris lumbricoides pathogenesis
1) Entry through mouth, eggs containing infective larvae from soil
2) Hatch in small intestine, enter blood stream
3) Infection of lung, trachea, esophagus, small intestine
IV. 35 Acaris lumbricoides clinical
Ascariasis
Larvae migrates through lung → pneumonitis
Migration into bile duct, gall bladder and liver → tissue damage
Peritonitis, abdominal pain, intestinal obstruction
* Protein deficiency (Kwashiorkor syndrome)
IV. 35 Acaris lumbricoides ddx
Eggs in feces
IV. 35 Acaris lumbricoides treatment
Mebendazole
IV. 35 Trichuris trichuria characteristics
Geohelminth
Whipworm: males: 30-45mm, female: 35-50mm
IV. 35 Trichuris trichuria pathogenesis
1) Entry through mouth: eggs contain larvae
2) Hatch in small intestine, migrate and mature in cecum, appendix, colon
IV. 35 Trichuris trichuria clinical
Mucosal damage, abdominal pain, bloody stool (anemia), appendicitis, rectal prolapse
IV. 35 Trichuris trichuria ddx
Eggs in feces (lemon-shaped)
IV. 35 Trichuris trichuria treatment
Mebendazole
IV 36. Strongyloides stercoralis characteristics
Geohelminth
Rhabditiform larvae = non-infective
Filariform larvae = infective
IV 36. Strongyloides stercoralis clinical
Abdominal pain, nausea, vomiting, diarrhea, paralytic ileus, hepatitis
IV 36. Strongyloides stercoralis ddx
Rhabditiform larvae in stool Hypereosinophilia
Antibody detection
Immunologic diagnosis by IF
IV 36. Strongyloides stercoralis treatment
Thiabendazole and ivermectine
IV. 36 Dirofilaria repens characteristics
Intermediate host: mosquito
Final host: Dogs, humans (rarely)
Larvae migrate to
~ Subcutaneous tissue → painless nodule
~ Very rarely to lungs lungs (coin-like lesion on X-ray)
~ Sometimes tissue under conjunctiva
- Adults die before fully matured – cannot spread further
IV. 37 Worms causing filariasis - Lymphatic filariasis characteristics
Wucheria bancrofti: mosquitos of genus culex, anopheles, aedes
Brugia malayi: mosquitos of genus mansonia, anopheles, aedes
IV. 37 Worms causing filariasis - Lymphatic filariasis pathogenesis
1) Larvae enter via mosquito bite
2) Larvae mature to filaria (adult) in lymphatics and produce microfilariae which enter blood and spread
3) Disease → Adenolymphangitis, eosinophilia, Elephantiasis (LL, scrotum) *Brufia never genitals
4) Microfilariae ingested back into mosquitos
IV. 37 Worms causing filariasis - Lymphatic filariasis ddx
Detection of microfilaria in blood smear (at night) ~ mosquito activity
IV. 37 Worms causing filariasis - Lymphatic filariasis treatment
Diethylcarbamazine (DEC) and Ivermectin
Spraying for mosquitos, nets etc.
IV. 37 Worms causing filariasis - Loaisis - Loa Loa characteristics
Transmitted by chrysops fly/Mango fly
After bite, the larvae travel subcutaneously where it produces microfilaria which travels through blood (most frequently to conjunctiva)
IV. 37 Worms causing filariasis - Loaisis - Loa Loa ddx
Detection of microfilaria in blood smear ~ 3-7cm
IV. 37 Worms causing filariasis - Loaisis - Loa Loa treatment
Diethylcarbamazine ~ for 10 years
Corticosteroids for allergic reaction
Surgery of the eye
IV. 37 Worms causing filariasis - Onchocera volvulus pathogenesis
Transmitted by black fly/simulium
- Larvae enter via bite
- Larvae mature to filaria in subcutaneous nodules and produce microfilaria
- Microfliaria cause
- Microfilaria ingested back by black fly
IV. 37 Worms causing filariasis - Onchocera volvulus ddx
Examination of blood free skin nips
IV. 37 Worms causing filariasis - Onchocera volvulus treatment
Ivermectin, surgical removal of skin nodule
IV. 37 Worms causing filariasis - Onchocera volvulus clinical
River blindness: due to hyperpigmentation and scarring of cornea
Skin lesions: pruritic dermatitis (elephant skin), depigmentation, loss of elasticity, subcutaneous nodules
IV. 37 Worms causing filariasis - Dracunculus medinensis pathogenesis
Transmitted through water (copepods with larvae; intermediate host)
Copepods ingested and die in stomach
They release the larvae which penetrates the abdominal wall and mature.
Once the female matured in the abdominal cavity, it migrates to the surface of the skin (usually in lower limb) and making painful ulcers
IV. 37 Worms causing filariasis - Dracunculus medinensis ddx
Female emerges from ulcer
IV. 37 Worms causing filariasis - Dracunculus medinensis treatment
Slowly wrapping the worm on a stick
V. 35 Protozoa and Helminths causing Ophthalmic Infections and their ddx
protozoa
- Acanthamobea - keratitis
ddx: specimen CSF, culture with Gram negative bacilli on agar - Taxoplasma gondii - chorioretinitis
ddx: serology, retinal exam, ELISA
helminth
- loa loa - chorioretinitis
ddx: serology - contains microfilana - onchocera volvulis - chorioretinitis
ddx: biopsy, serology - Toxocara ssp - ocular larva migrans
ddx: serology - Dirofilaria - occular infection
ddx: serology
