viruses topics Flashcards
1
Q
III.11 Adenovirus characteristics
A
- dsDNA (L)
- Icosahedral capsid
- Non-enveloped
- Surface Fibers (toxic Ag’s): attachment to rec. & agglutination of RBCs
- 57 serotypes (# 14 most severe), differentiated by hemagglutinin inhibition
2
Q
III.11 Adenovirus Transmission
A
- Occurs worldwide
- Naked virus: resistant to drying, detergents, GI secretions
• Fecooral, Aerosol, fingers, close contact
(Crowded places: daycare, military camps, sports clubs)
• Mostly asymptomatic infections (enhanced spread)
3
Q
III.11 Adenovirus Pathogenesis
A
Pentons of the icosahedral capsid contains fibers that acts as hemagglutinin (toxic to cells)
- In permissive cells: replication –> production –> cell lysis
- In non-permissive cells: can be chronic or oncogenic (transformation occurs but not in humans)
4
Q
III.11 Adenovirus Clinical
A
a) Respiratory diseases:
-Tonsillitis: #1 cause
-Acute febrile pharyngitis: in infants and young children (Sore throat, fever, myalgia, cough)
-Pharyngoconjunctival fever (7-14y children)
-Pneumonia: possible complication of the above
-Pertussis-like synd.
-Acute respiratory disease: Fever, cough, myalgia, fatigue,
cervical lymphadenomegaly
b) Gastroenteric infection:
- Gastroenteritis: Watery diarrhea in infants and children
c) Eye infection:
- conjunctivitis: Mild, either following RTI or develops alone
- ->Watery, itchy, Painful, Photosensitivity, heals rapidly. (1 eye or both)
- ->highly contagious, spread by: coughing, sneezing, Swimming pools
- ->Irritation of the eye –> other infections
d) UTI:
- Acute hemorrhagic cystitis: with dysuria, hematuria
e) Immunosuppressed patients: Disseminated infections (Pneumonia, Hepatitis)
* Reactivation can occur in case of immunosuppressed patients
5
Q
III.11 Adenovirus Ddx
A
• mostly not identified
• In some cases it can be important to rule out other pathogens (to prevent unnecessary Abx)
• Immunoassays: IF, ELISA
• PCR
• Rapid test: for diarrhoea causing viruses
-Cultivation on HeLA, epithelial cell culture –> strong CPE
6
Q
III.11 Adenovirus treatment
A
-No approved treatment
(just Symptomatic therapy and fluid replacement)
- Riba.virin: for disseminated infections
- Live vaccine: pills for military
7
Q
III.12 Herepesvirus : HSV1 and HSV2 characteristics
A
- Alpha-Herpesvirinae (Ubiquitous viruses, frequent infections)
- Herpes Simplex Viruses
- dsDNA (L)
- Icosahedral capsid
- Enveloped: Sensitive to acid, detergents etc.
- Produce Virokins: cytokin-like proteins for pathogenesis –> suppress immun. resp.
- Infections can be: Lytic, latent-recurrent, persistent, immortalising
8
Q
III.12 Herepesvirus : HSV1 and HSV2 Transmission
A
- Close contact
- Saliva
- Vaginal secretions
9
Q
III.12 Herepesvirus : HSV1 and HSV2 Pathogenesis
A
• 80% HSV1 (+)
• 20% HSV2 (+)
- Primary (acute) infection of mucosus membranes: The virus targets Mucoepithelial cells
- Lifelong latent infection in DRG of innervating neurons
- Recurrent infection: by stress, trauma, sunlight, fever, immunosupp.
10
Q
III.12 Herepesvirus : HSV1 clinical
A
a) Primer Herpetic Gingivo-ostomatitis:
- Childhood disease (1st HSV1 exposure)
- Multiple painful oral lesions: prodrome -> macule -> vesicle -> ulcer -> scar -> healing
- Symp.: pharyngitis, fever, Local lymphadenopathy
b) Herpes Labialis (cold sores):
- Recurrent infc. of lips with HSV1
- Less severe & shorter than primer infc.
- Course: prodrome –> vesicles –> ulcer –> crust –> heals (without scar)
c) Herpetic keratitis:
- Recurrent Ulceration of cornea (possible blindness)
- UV light Detection: Eyedrops containg fluorescent labelled Ab’s vs. HSV
d) Herpetic Whitlow (gladiatorum):
- Infection of fingers and body (Former injury needed)
- at risk: Nurses, dentists, wrestlers
e) Herpes Encephalitis:
- HSV1
- Location: temporal lobe (high mortality)
- -> Haemorrhagia, seizures, other CNS complications
11
Q
III.12 Herepesvirus : HSV2 clinical
A
a) Genital herpes:
- Primer & recurrent infc. by HSV2 (rarely HSV1)
- Location: Glans, vulva, vagina, cervix, perianal, rectum
- Primer infc. accompanied by fever, myalgia, Lyphadenomegaly
* Meningitis may develop – not severe)
* Virus shed also possible in the asymp. periods
b) Neonatal herpes:
- From the mother’s genital herpes
- transmission: during vaginal delivery or ascending infc. (rarely) during pregnancy
- Lead to: Stillbirth, generalised infc. , skin vesicles, Encephalitis, internal organ affection, high mortality
- Prevention: cesarean section
12
Q
III.12 Herepesvirus : HSV1 and HSV2 ddx
A
- Clinical symp’s
- Direct examination of sample:
- micro for CPE (Cultivation: Scraping the base of lesions –> cultivation on HeLA –> CPE to find inclusion bodies, rounded cells, syncytia, Lysis)
- IF Ag’s detection
- PCR
- Virus isolation: from vesicles (not crusted lesions) –> Aspiration or swab sample onto cell cultures
- Serology: ONLY for primer infections & epidemiology
13
Q
III.12 Herepesvirus : HSV1 and HSV2 treatment
A
• Nucleoside analogues: A.cyclovir, vala.cyclovir, pen.cyclovir (inhibition of DNA synthesis)
–> local or systemic -depends on severity-
- Can’t eliminate the latent viruses
- Resistance may develop
- Prevention: avoid close contact
14
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus characteristics
A
- α-herpesvirus
- Human herpes virus 3
- dsDNA (L)
- Icosahedral capsid
- Enveloped
15
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus transmission
A
by inhalation of resp. droplets (or contact with vesicules)
16
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus Pathogenesis
A
- Virus replicates in the resp. tract –> spread via bloodstream to RES (no symp. yet) –> secondary viraemia after 2 w. skin symptoms –> Primer infection: chickenpox (dermal vesiculopapular rash)
- Establish latent infection in neurones of DRG or cranial nerve ganglia –> Reactivates in old or imunocompromissed –> herpes zoster Shingles (May disseminate)
- Life-long infection
- Cell-mediated immunity important in control
17
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus Clinical
A
- Highly contagious before and during symp.
- 90% get infected during life with VZV
- 10-20% experiences herpes zoster reactivation
Clinical picture:
• Primary infection: Chickenpox (Varicella)
- Classic childhood disease (2 w incubation)
- Fever, maculo-papular itchy rash all over the body (scalp, mucosa)
- Vesicles on erythematous base –> pustule –> crust –> healing
- Asynchronous rash: Any given time all stages present!
- Scratching –> secondary bacterial inf. –> scars
**Chikenpox is more severe in adults
**Interstitial pneumonia may develop, possibly lethal
• Secondary inf.: Zoster (Shingles)
- Recurrent infc.
- Belt-like distribution in a dermatome: trunk or face
- symp: Severe pain, vesicles, pos-herpetic neuralgia for months
- Disseminated infection in immunocompromissed
***Herpes Zoster ophthalmicus: Vision loss when CNV/I is affected
***Congenital varicella synd: Limb Hypoplesia, cutaneous dermal scarring, blindness
18
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus ddx
A
- CPE on cell culture: rarely used
- PCR
- Serology: ELISA for detection of antibodies
***Tzanck smear –> Will show multinucleated giant cells, Cowdry bodies
19
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus treatment
A
- Only for complications and immunocompromised
* A.cyclovir, fam.cyclovir, vala.cyclovir (large dose)
20
Q
III.13 Herpesvirus - VZV - Varicella Zoster Virus Vaccine
A
- Passive: Immunoglobulin (VZIg) for immunocompromised
* Active: Live attenuated vaccine: for children, 15 and 18 m (recommended)
21
Q
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) characteristics
A
- Human herpes virus 4
- gamma-herpesvirus
- large dsDNA (L)
- Icosahedral capsid
- Enveloped
22
Q
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) transmission
A
- Spread with and respiratory secretions (90% of population is seropositive)
23
Q
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) pathogenesis
A
- initially infects oral epithel cells –> spread to B cells, latent infection (Trophism to B-lymphocytes)
- Possible immortalisation of infected cells
- Binds CDRI and produce LMP1 (latent membrane protein 1) –>
a) NFKB activation and B-cell proliferation ( Heterophil antibody production –> IgM to Paul-Bunnell Ag)
b) Bcl2 ⊣ apoptosis - -> This causes production of atypical CD8+ T-cells – Downey cells against it
***Asymptomatic virus shedding possible throughout life
24
Q
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) clinical
A
a) Infectious mononucleosis: “Kissing disease”
• 70% of population get infected by age 30
• Milder or no symptoms in children
• Spread with saliva & contaminated items
• T cell response against infected B cells –> symp:
- Lymphadenomegaly
- HepatoSplenomegaly
- Exudative pharyngitis & tonsillitis: white plaques on tonsils (DD from S.pyogenes!)
- generalised: Fever, malaise, fatigue
- Complications (rarely): spleen rupture, meningo-encephalitis, Guillan-Barré…
- Lymphocytosis with atypical lymptocytes (Downey cells): Presence of atypical lymphocytes used to distinguish from CLL.
- Fatigue may last for months after infection
- Chronic infection: cyclic recurrent infection, chronic fatigue
• If patient with mononucleosis got ampicillin treatment (for „sore throat”) –> rash may develop (misdiagnosed often as penicillin allergy)
b) Burkitt’s lymphoma:
- Epidemic in children in malarial regions of Africa
- Sporadic/non-African type: affects ileocecal region
- Immunodeficient type: associated with AIDS
- Monoclonal B cell lymphoma of lymph nodes (maxilla and mandible)
- -> Due to translocation of c-myc oncogene which becomes active promotor (t(8;14)).
- EBV inf. → immortalisation (malaria could be cofactor)
c) Nasopharyngeal carcinoma:
- Epidemic in Asia (adults)
- Tumor contains EBV DNA
- Exact role of virus is unknown
d) Lymphoproliferative diseases:
- in immunocompromised
- In lack of T cell immunity (eg. after transplantation, AIDS)
- Polyclonal leukaemia-like B cell proliferation or lymphoma
e) Hairy oral leukoplakia:
- EBV infection of oral epithelial cells –> non-precancerous hyper-proliferation
- Opportunistic (AIDS patients)
f) Hodgkin’s (B-cell) lymphoma – Dx by presence of Reed-Sternberg cells
25
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) ddx
• Blood smear:
- Mononuclear lymphocytosis
- Atypical lymphocytes (Downey cells)
• Heterophil Ab's: (Heterophiles Ab's are produced due to B-cell induction by EBV)
– Paul-Bunnell reaction: Monospot test --> IgM agglutination of sheep RBC's (Paul-Bunnel Ag's)
– Monospot test, ELISA
* Other serological methods to detect Ab's
* PCR, DNA probes
26
III.14 - Herpesvirus - Epstein-Barr Virus (HHV-4) treatment
- No treatment or vaccine available
| - Lifelong immunity after infection
27
III.15 - Herpes - Cytomegalovirus (HHV-5) characteristics
- HHV-5
- beta-herpesvirus
- dsDNA (L)
- Icosahedral capsid
- Enveloped
- Latency in monocytes, macrophages, T-cells
28
III.15 - Herpes - Cytomegalovirus (HHV-5) Transmission
Spead: secretions
- orally
- sexually
- blood transfusion
- transplant
- in utero / at birth (TORCH)
29
III.15 - Herpes - Cytomegalovirus (HHV-5) Pathogenesis
* Common pathogen
* Immune status of host: determines the Severity & form of the disease
* Trophism to lymphocytes but can infect other cells (salivary glands by binding to the integrin rec.)
* Carries mRNA in the virion
* Lifelong latent infection: established in mononuclear leukocytes (B-cells, T-cells, macrophages)
* reactivation may develop by immunosuppression.
* Cellular immunity important for control
* May cause asymptomatic shedding
30
III.15 - Herpes - Cytomegalovirus (HHV-5) clinical
• In immunocompetent adults and children:
- Mainly asymp.
- Mononucleosis-like disease may develop (less severe than EBV)
- Pharyngitis, lymphadenopathy, hepatitis
- Heterophiles Ab's (--)
• Infection of immunocompromised patients:
- in Organ transplant, cytostatic therapy, AIDS...
- Reactivation of latent infection or new infection from blood transfusion or transplanted organ
- -> Pneumonia (possibly lethal)
- -> Retinitis, encephalitis,
- -> Colitis, oesophagitis – diarrhoea, weight loss, anorexia
- -> Failure of transplants
• Congenital infection:
- Most frequent viral congenital infection!
- 10% of infected babies will show symp.
- Cytomegalic inclusion disease:
- -> Small size
- -> Thrombocytopenia
- -> Microcephaly, Intra-cerebral calcification, Hearing loss, mental retardation
- -> HepatoSplenomegaly & Jaundice
• Perinatal infection:
- Neonates acquire CMV during birth from: cervix, vagina, or from maternal milk or blood transfusion
- No syms in healthy full-term babies
- Premature babies: pneumonia, hepatitis
31
III.15 - Herpes - Cytomegalovirus (HHV-5) ddx
• Histology: stain with Pap or H&E
- cytomegalic basophilic cell, owl's eye, inclusion bodies
* ELISA, PCR – detection of virus
* Cultivation: fibroblast culture (slow)
* Serologic detection of Ab's
* Congenital: detection of virus from urine during 1st w of life
32
III.15 - Herpes - Cytomegalovirus (HHV-5) treatment
* Gan.cyclovir, Valgan.cyclovir, Cido.fovir
| * No vaccine
33
III.16 Herpesvirus - HHV6 characteristics
- dsDNA
- Icosahedral capsid
- Enveloped
- beta-herpesvirus
34
III.16 Herpesvirus - HHV6 Transmission
- salvia
- Common (most people get infected during childhood)
- Asymptomatic, or mild febrile viral disease
35
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
36
III.16 Herpesvirus - HHV6 clinical
• Childhood disease: Exanthema subitum = Roseola infantum
- High fever, 39C, for 3-5 days
- maculopapular rash develops (After the fever subsizes) but spares the face
- Latent infection (possible reactivation)
- Role in degenerative neurologic diseases
* Mononucleosis-like disease in adults
* Immunocompromised: reactivation
- -> Encephalitis
- -> Pneumonitis
- -> Rejection of transplant
37
III.16 Herpesvirus - HHV6 ddx
Clinical picture
PRC, serology – Virus isolation from lymphocytes
38
III.16 Herpesvirus - HHV6 treatment
- Self-limited
- Gan.cyclovir
- no vaccine
39
III.16 Herpesvirus - HHV 7 clinical
- Common (most children get infected)
- Infect T cells
- May cause asymptomatic infection
- Cause some cases of exanthema subitum (less frequently than HHV6)
- Possible complications:
- -> meningitis, encephalitis, otitis...
- -> Latent, persistent infection may develop
- -> may have a Role in pityriasis Rosea
40
III.16 Herpesvirus - HHV8 characteristics
- gamma-herpesvirus
- dsDNA
- Icosahedral capsid
- Enveloped
41
III.16 Herpesvirus - HHV8 transmission
- Saliva
| - sexual contact
42
III.16 Herpesvirus - HHV8 pathogenesis
• Opportunistic infection in AIDS patients
→ Kaposi's sarcoma: Brownish skin tumor (rarely visceral manifestation) by activating VEGF
- Infects mainly B-cells (like EBV), but also epithelial cells, monocytes etc.
43
III.16 Herpesvirus - HHV8 clinical
a) Kaposi sarcoma
- Malignant tumor of the endothelial cells
- Most commonly affects the skin, lymph nodes, mucosa, and viscera
- Develops mostly in AIDS patients
b) Primary effusion (B-cell) lymphoma
- Large B-cell lymphoma located in body cavities
- Characterized by pleural, peritoneal, pericardial fluid lymphomatous effusions
44
III.16 Herpesvirus - HHV8 ddx
- Clinical
- Serology
- PCR
45
III.16 Herpesvirus - HHV8 treatment
- Treat HIV
| - chemotherapy
46
III. 17 Parvovirus characteristics
- ssDNA
- Icosahedral capsid (smallest virus)
- non-enveloped
- Parvovirus B19 ~ only one to cause human disease
• Dependoviruses: Adeno-associated viruses (AAV)
- Need other viruses for replication
- Don’t cause illness
- Potential use in gene replacement therapy
47
III. 17 Parvovirus transmission
- Respiratory droplets
- TORCH
• Pathogenesis:
- Replication in cells of erythroid line: bone marrow, fetal liver, RBCs
- 65% of population infected by 40y
- Generally in winter and spring
48
III. 17 Parvovirus clinical
a) Erythema Infectiosum: “fifth disease”
- childhood infection
- Biphasic course:
1. Starts with: mild, flu-like syms, fever, headache --> Infective stage: Blocks RBC production for few days (no complication in healthy)
2. Late phase: after 1-2 w (imm. resp.): Maculopapular rash on the cheeks ,,slapped face”
- -> Spread to arms and legs
• Infection of adults:
- Polyarthritis with/without rash (on Hands, wrists, knees, ankles)
- For weeks - months
• Aplastic crisis:
- Hosts with chronic anaemia (sickle)
- Life-threatening Reticulocytopenia
• Hydrops fetalis
- Infection of seronegative pregnant woman
- Transplacental inf. of the fetus --> anaemia, heart failure
49
III. 17 Parvovirus ddx
- Clinical
| - serology: Pregnants: Detection of specific IgM
50
III. 17 Parvovirus treatment
self-limiting
51
III. 18 Papilloma Virus characteristics
- dsDNA (C)
- Icosahedral capsid (small)
- non-enveloped
HPV:
- 100 serotypes
- Cutaneous and mucosal infections
- Spread to the skin basal layer through microscopic wounds
- Multiplication → koilocytes, wart / papilloma
- Spread with desqammation of the upper layer of the skin
52
III. 18 Papilloma Virus Transmission
*Spread with desqammation of the upper layer of the skin*
* Contact – directly or by objects
* Sexual – most frequent STD!
* During birth
(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)
53
III. 18 Polymoavirus characteristics
- dsDNA (C)
- Icosahedral capsid
- naked
**similar to papilloma*
54
III. 18 Papilloma Virus ddx
Clinical – for cutaneous warts
PCR – to distinguish serotype
***HPV don’t grow on cell cultures - difficult to study***
55
III. 18 Papilloma Virus prevention
Vaccine against to most important serotypes for girls before
| the begining of sexual life
56
III. 18 Polymoavirus Transmission
- Respiratory droplets, saliva
| - most people infected asymptomatically
57
III. 18 Polymoavirus Pathogenesis
Reactivation in immunocompromised – AIDS, transplantation:
- Infects tonsils & lymphocytes --> spreads by blood to kidney.
(secondary viremia occurs: become latent in immunocompetent or reactive in immunosuppressed)
1) BK virus (from first patient): latency in kidney
- Nephropathy (ureter 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 Leuko-encephalopathy (PML) --> oligodendrocytes --> CNS demyelination --> Multifocal brain lesions in white matter
- Speech, vision, mentation defects, paralysis, death in AIDS patients (DDX; Toxoplasma)
58
III. 18 Polymoavirus ddx
MRI/CT
| PCR of CSF
59
III. 18 Polymoavirus treatment
none
60
III. 18 Papilloma Virus clinical
• Skin warts: "verruca"
- Low risk serotypes (1-4)
- Very frequent
- benign skin disease (Hyperkeratosis)
- Self-limited, may resolve spontaneously
- Usually affect hand and feet
- Thrombosed vessels in the lesion: black dots
* **Th: surgical removal, cryotherapy, chemical solutions
• Benign head and neck tumors: (6,11)
a) Oral, conjunctival papillomas:
- Frequent, papillary, cauliflower-like
b) Laryngeal papilloma:
- May obstruct the airway
* **Th: surgical removal
• genital warts: "Condyloma Accuminatum"
- Low risk serotypes; 6-11
- Genital & perianal region
• Cervical dysplasia and neoplasia:
- High risk serotypes; 16, 18, 31, 33, 45 (associated with cervix cancer)
- Genital HPV infection (STD)
- Soft cervical warts
- Koilocytes: detected on Papanicolaou smear
• After years of infection wart may transform into dysplasia --> neoplasia (CIN) --> carcinoma!
E6 ⊣ p53
E7 ⊣ Retinoblastoma
***th: surgical removal
61
III.19 Poxvirus characteristics
- dsDNA (L)
- Complex structure (Biggest virus!)
- Enveloped
- replicates in cytoplasm
• Vaccinia and canary pox viruses can be used as gene delivery vectors in hybrid vaccines:
Infection with a recombinant apathogenic virus expressing antigens of other microbe
- Variola virus ~ Smallpox
- Cow pox virus ~ Share antigenic determinant with variola virus (Jenner)
- Vaccinia virus ~ Vaccination of smallpox
62
III.19 Poxvirus transmission
• Spread: resp.droplets, lymph nodes affected, viraemia
• Smallpox (Variola)
- Variola major and minor
- Once huge epidemics, now eradicated (since 1980)
• Importance: Possible bioterrorism agent
63
III.19 Poxvirus clinical
1) Smallpox (Variola – minor or major depending on immune status)
--> Virus enters the upper resp.T. --> 5-7 days of incubation --> lymphatics --> viremia --> second viremia --> infects all dermal tissues & internal organs “pocks":
• Fever, headache, vomiting, diarrhea, bleeding (2-4 days)
• Heamorrhage of small vessels, rash, vesicules (Stages of skin signs: macule, paule, vesicule, pustule). All vesicules at the same stage (DD from chickenpox!)
• Spleen, liver, bone marrow, other organs…
***Therapy: cidofovir
```
2) Molluscum contagiosum virus
• Nodular, wart-like skin lesion (Benign epithelial tumor)
• Spread by direct contact or objects
• Fingers, trunk, genitals
• Treated by liquid nitrogen
```
64
III.19 Poxvirus ddx
Smallpox Variola:
• Clinical signs
• Cultivation on cell cultures
• PCR
Molluscum contagiosum:
• clinical
• biopsy
65
III.19 Poxvirus vaccine
• Vaccine contained Live attenuated vaccinia (cowpox) virus (side effects)
• (From XVIII.century – Jenner)
• Eradicated by immunization, vaccination stoped in 1980:
- No animal reservoir
- single serotype
- no asymptomatic infection or carriage
- inexpensive vaccine
66
III.20 Arenavirus characteristics
- arena: sand in latin
- from BunyaVirales order (big family)
- ssRNA (Ambisense, has both positive and negative sense sections)
- Helical
- Enveloped with projections
- Natural host; rodents
67
III.20 Arenavirus transmission
Zoonotic, rodents
68
III.20 Arenavirus -Lymphocytic choriomeningitis virus (LCMV)
reservoir: mouse
spread: bite or bodily fluids
Infection:
- often asymptomatic
- symptomatic: Fever --> asymp. period --> aseptic meningitis (headache, fever, stiff neck)
- Rarely: encephalitis
D: Ig from serum or CSF
Treatment: not available
69
III.20 Arenavirus - Machupovirus
- Machupo virus: Bolivian hemorrhagic fever (BHF)
- Reservoir: mouse
- symp: Fever, headache, bleeding, CNS symp. (High mortality)
Diagnosis:
- Ig from serum or CSF
Treatment : not available
70
III.20 Arenavirus - Lassavirus
- Lassa: village in Nigeria
- Lassavirus: Lassa fever
- Reservoir: African rats
spread:
urine, contaminated food, human to human
Symp:
- High fever, myalgia, haemorrhages
- spleen and liver necrosis
- oedema of face, lung
- shock
- Mortality 15-20%
Diagnosis:
- PCR
- serology
Th: supportive
Prevention:
rodent control, safe storage of food
71
III.21 Bunyaviruses (Hanta-.. Crimean-Congo hemorrhagic fever virus) characteristics
- Name: Bunyamwera --> town in Uganda
- BunyaVirales order (big family)
- (-) ssRNA -circular-
- Helical capsid
- Enveloped with projections
- Bunyavirales contain:
- ->Hantaviridae: Hantaan virus
- -> Arenaviridae
- -> Nairoviridae: Crimean Congo hemorrhagic fever virus (CCHFV)
***mostly causing viral haemorrhagic fevers***
72
III.21 Bunyaviruses HANTAVIRUSES
transmission
Spread: zoonotic
| - robovirus: rodent borne. from rodents with bite or bodily fluids
73
III.21 Bunyaviruses- HantaVirus
clinical
Diseases:
1. Hantavirus pulmonary synd.:
- American continent
- by Sin Nombre virus (SNV)
- reservoir: deer mice
- flu-like symp --> sudden dyspnea, lung oedema, high mortality!
2. Hemorrhagic fever with renal synd.:
a) Nephropathia epidemica:
- -> Scandinavia
- -> by Puumala virus (PUUV)
- -> reservoir: bank vole, by inhalation of dried fees
b) Hemorrhagic fevers:
- -> Korean haemorrhagic fever Hantaan virus
- -> Seoul virus from rats
- ->Fever, vomiting, rash, headache, high mortality
prevention:
- vaccine: Hantavax
74
III.21 Bunyaviruses Crimean-Congo hemorrhagic fever virus
transmission
Spread:
- tick bite Hyalomma
- animals
- human to human
75
III.21 Bunyaviruses Crimean-Congo hemorrhagic fever virus
clinical
Symptoms:
- Fever
- vomiting
- stiff neck
- hepatomegaly
- bleeding: into skin , mucosa , viscera
- Shock
- high mortality (30-40%)
76
III.21 Bunyaviruses Crimean-Congo hemorrhagic fever virus
| diagnosis, treatment
Diagnosis:
- PCR
- serology
Th:
- supportive
77
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
78
III.22 Coronavirus characteristics
- (+) ssRNA -positive sense-
- Circular
- Helical Nucleocapsid (crownlike)
- Enveloped
- Infects mammals and birds
79
III.22 Coronavirus SARS coronavirus (SARS CoV)
- SARS: Severe Acute Respiratory Syndrome
- Pandemic: started in 2002 in China (10% case fatality rate)
- Symp: Fever, dry cough, headache, muscle pains, difficulty breathing
- Origin: bats → civets → humans
80
III. 22 Coronavirus - (MERS CoV)
* MERS coronavirus: Middle Eastern Respiratory Syndrome
* Started in 2012, in Saudi Arabia 37% fatality
* Origin: bats --> camels --> humans
81
III. Coronavirus - (SARS-Cov2)
• SARS CoV2: Severe acute respiratory syndrome coronavirus 2 --> official name of the virus
→ COVID-19: COronaVirus Disease 2019 --> name of the infection
* First detected in Wuhan, China, in December 2019 --> Became a Public Health Emergency of International Concern in Jan 2020 --> pandemic in March 2020
* Belongs to β coronaviruses SARS-CoV-2: 79.5 % genomic identity to SARS CoV
```
Origin: bats
--> 96.2% identity to a bat coronavirus
• Intermediate host: unknown
• Possible recombination of bat CoV with other CoV
• Under investigation
```
82
III. Coronavirus -CORONAVIRUSES SARS COV2-
| structure, replication, transmission, effect
Structure:
```
- 4 structural proteins:
• Spike (S): allows entry by attaching to the ACE2 rec. of the host cell
• Envelope (E)
• Membrane (M)
• Nucleocapsid (N)
```
- 16 nonstructural proteins (NSP): form the replicase-transcriptase complex (RTC)
Replication:
- -> Receptor: ACE2-rec., expressed in the surface epith. of the lungs, heart and others
- -> Increased concentrations of ACE2 in DM, cardiovascular disease, COPD, cigarette smoking
- -> Transmembrane protease, serine 2 (TMPRSS2) --> cleaves S protein --> fusion
Transmission:
• Mainly with resp. droplets, hand to face contact from fomites
• Incubation period : usually 5 days
Effects
• Direct cytopathic effects: mainly to alveolar epith. (also liver & heart)
• Dysregulated immune response
--> Activation of the immune system --> cytokine release --> acute inflam. resp.
--> cytokine storm: overshooting imm. resp. --> very high Lvls of cytokines --> organ failure & death
83
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.
84
III.22 Coronavirus clinical
Clinical course:
• Mild (80%)
- Uncomplicated course without dyspnea
- Lasts 1-2 w
• Severe 15%)
- 5-7 d after symptom onset
- dyspnea and hypoxia, pneumonia
- Lasts 3-6 w
• Critical (5%)
- Severe pneumonia (Resp. failure)
- ARDS
- coagulopathy
- shock
- multiple organ dysfunction syndrome (MODS)
- Lasts 3-6 w
***Mortality rate : 0.5 3%***
85
III.22 Coronavirus ddx
RT-qPCR (NAAT):
- detetction of SARS-CoV2 specific genes sequences
- Fast, most reliable method, specific and sensitive
• serology:
1. Ag's detection from resp. sample:
- Possibly as an point of care (POC) test
- less reliable, can be false negative
2. Detection of antibodies from blood:
- By rapid test or ELISA
- Not as reliable as PCR in identifying fresh infection
- Used for identify individuals who had a recent or past infection or immunisation
3. Virus isolation & culture:
- From sputum or other sample, on Vero cell line
- For research use
- CPE: is observed after 96h
- Virus viability is determined by determining the plaque forming unit (PFU)
86
III.22 Coronavirus treatment and prevention
TREATMENT:
Antiviral drugs: best effect in early phase
1. Neutralizing mAbs prevents rec. binding:
- -> Casiri.vimab , bamlani.vimab
2. Inhibition of RNA dependent RNA polymerase
- -> Remde.sivir
```
Immune resp. modulation:
1. Tocilizu.mab:
--> IL6 rec. inhibitor
--> mAb
2. Bari.citi.nib
inhibitor of janus kinase JAK 1 and 2
3. Corticosteroids:
--> Dexamethazon
```
VACCINATION:
• mRNA vaccines: Pfizer-BioNTech, Moderna
• Viral vector vaccines: Oxford AstraZeneca, Janssen, Sputnik
• Killed whole virus: Sinopharm, Sinovac, Co.vaxin, Covi.vac, CovIran
• Subunit : Epi.VAc.Corona
87
III.22 Filovirsues characteristics
- (-) ssRNA -negative sense-
- Helical caspid (Filamentous shape)
- Enveloped
* Causes viral hemorrhagic fever in humans and other primates
* BSL4 level, bioterrorist agents
* Ebola virus genus (EBOV)
* Marburg virus genus (MARV)
88
III.22 Filovirsues EBOV
| transmission and symps
Spread:
- Mainly in Sub Saharan Africa (Ebola: river in congo)
- Zoonosis: from bats and primates
- Human to human spread: all bodily fluids
(semen spreads the virus even after recovery)
Symptoms:
- 1-2 weeks incubation
- Fever, myalgia, headache
- Internal and external bleeding --> shock
- High mortality: 40 90%
89
III.22 Filovirsues EBOV
| Diagnosis, treatment, prevention
Diagnosis
- In BSL4 lab only
- Virus detection from bodily fluids
- Serology for antibodies
Treatment:
- Not available (supportive only)
Prevention:
- Approved vaccine : Ervebo , since 2019
- Live attenuated recombinant vaccine
(Genetically modified vesicular stomatitis virus expresses surface glycoproteins of EBOV)
90
III.22 Filovirsues MARV
| transmission and symps
Spread:
- first recognised in 1967, Marburg, Germany
(researchers got the infection from African green monkeys)
- Zoonotic: from bats & monkeys
- Human to human: with bodily fluids
Symptoms:
- Marburg virus disease (MVD) (viral hemorrhagic fever)
- Fever, headache, vomiting, maculopapular rash, petechiae , hematomas
- Encephalitis, confusion, visceral & mucosal bleeding, MOF, shock
- High mortality
91
III.22 Filovirsues MARV
| diagnosis, treatment, prevention
Diagnosis:
- PCR for viral RNA from serum
- Serology for Ab's
Treatment:
- Not available (supportive only)
Prevention:
- No vaccine yet
- Avoid contact
92
III. 23 Flavivirus - Yellow Fever, Dengue Fever characteristics
(Flavus= yellow blonde in latin refers to jaundice caused by some of these viruses)
- (+) ssRNA =mRNA
- Icosahedral capsid
- Enveloped
Common in Flavivirus genus:
- Spread by vectors
- Often asymp.n
- Biphasic course of symp:
1. Incubation period
2. Aspecific symp, fever
3. Asymptomatic phase
4. CNS symp.
Arboviruses: Arthopod-borne
Many causes
viral haemorrhagic fever
93
III. 23 Flavivirus - Yellow Fever vector
Aedes mosquitos, hosts are humans and monkeys
94
III. 23 Flavivirus - Yellow Fever clinical
```
Yellow fever:
Acute viral haemorhagic disease:
- 1 w incubation time
- Fever, headache
- In 15 20% more severe form develops: jaundice & liver, kidney damage, Haemorrhages, vomiting
(in this group mortality: 20 50%)
```
95
III. 23 Flavivirus - Yellow Fever
| diagnosis, treatment, prevention
Diagnosis:
difficult , as symptoms are similar to many other infections
DD: malaria , viral hepatitis, leptospirosis, dengue
-PCR: blood or urine
-Serology: Ab's
Treatment:
- not available , only supportive care
Prevention:
- Vaccination: for babies living in affected areas at 9-12 m
and for travellers: 10 days prior travel
- Attenuated virus: single dose
-Vector control
96
III. 23 Flavivirus - Dengue Fever vector
Spread: Aedes mosquito
97
III. 23 Flavivirus - Dengue Fever clinical
Symptoms
- 1-2 weeks incubation
- Fever , rash , muscle pain
- More severe form : dengue hemorrhagic fever
98
III. 23 Flavivirus - Dengue Fever
| diagnosis, treatment, prevention
Diagnosis:
- PCR from serum
- IgM, IgG (but cross reactivity with other flaviviruses)
Treatment:
- No specific treatment (Supportive care)
Prevention
- Insect repellents
- Vaccine: Deng.vaxia
--> only for those who live in affected areas and previously infected
(To prevent further, more severe infection)
99
III. 24 Flavivirus - West Nile, Tick Born Encephalitis, Zika Virus characteristics
(Flavus= yellow blonde in latin refers to jaundice caused by some of these viruses)
- (+) ssRNA =mRNA
- Icosahedral capsid
- Enveloped
Common in Flavivirus genus:
- Spread by vectors
- Often asymp.n
- Biphasic course of symp:
1. Incubation period
2. Aspecific symp, fever
3. Asymptomatic phase
4. CNS symp.
Arboviruses: Arthopod-borne
Many causes
viral haemorrhagic fever
100
III. 24 Flavivirus - Zika Virus vector
Spread:
- Aedes mosquito
- tropical/subtropical regions
- transplacental spread
101
III. 24 Flavivirus - Zika Virus
clinical
Symptoms:
In non-pregnant: -generally mild infection-
- fever, rash, myalgia,arthralgia, conjunctivitis
-Complication: CNS involvement, Guillan Barre
Transplacental:
- infection of foetus
- stillbirth, premature birth
- Congenital Zika syndrome: Microcephaly, CNS damage, congenital glaucoma
102
III. 24 Flavivirus - Zika Virus
| diagnosis, treatment, prevention
Diagnosis:
1. Adults:
- PCR: blood , urine
- Serology: cross reactivity with other Flaviviruses
2. Pregnant:
- Anamnesis travel or sex partner
- Ultrasound sign of foetal damage
- PCR: 3 times during pregnancy from mother’s serum
- PCR: from amniotic fluid
Treatment: not available
Prevention:
- Avoid travel while pregnant
- Safe sex during pregnancy, if partner travelled
- Mosquito control
103
III. 24 Flavivirus - West Nile
treansmission
Spread: Culex mosquito
- Traditionally tropical/subtropical regions
- now spreads North
104
III. 24 Flavivirus - West Nile
clinical
Symptoms:
- Often asymptomatic (8/10)
- 1-2 w incubation
- West Nile fever: fever, diffuse maculo-papular rash, headache, myalgia
- Rarely encephalitis, paralysis
105
III. 24 Flavivirus - West Nile
| diagnosis, treatment, prevention
Diagnosis:
- PCR
- Serology
Treatment: Not available
- Supportive care
- IVIG: intravenous polyclonal Ig's
Prevention:
- No specific prevention
- Insect repellents, mosquito nets
- Vaccine: under development
106
III. 24 Flavivirus - Tick Born Encephalitis
transmission
Spread:
- "Ixodes" tick bite
- unpasteurised milk of infected animal
107
III. 24 Flavivirus - Tick Born Encephalitis
clinical
Symptoms:
- 1-2 weeks incubation
- Fever, then 5-10 asymp. days
- Encephalitis: headache, dizziness, photophobia, paralysis, vomiting
- Usually full recovery
- Mortality: 0.5-2% for EU subtype, 20% Far East subtype
108
III. 24 Flavivirus - Tick borne Encephalitis
| diagnosis, treatment, prevention
Diagnosis:
- IgM and IgG from blood
- IgM from CSF
- PCR or virus isolation
Treatment:
- Not available
Prevention:
- Vaccine: inactivated virus (Encepur)
- 2-3 doses needed, and boosters every 5 y
- not to be given during tick season
- recommended for everybody
109
III. 25 Calicivirus
characteristics
- (+) ssRNA =mRNA
- Icosahedral capsid
- Naked
- cannot be cultivated
- Many strains have cup-shaped depression (calyx = cup)
- Two genera of human pathogenic viruses;
- -> Noro-virus & Sapo-virus
110
III. 25 Calicivirus transmission
Fecal oral route
contaminated water (Resistant: may remain alive in water supply system)
contaminated food
111
III. 25 Calicivirus clinical
Acute Gastroenteritis:
- abd. cramps
- vomiting
- watery diarrhea – self-limiting gastroenteritis
- resolves in 1-3 days
112
III. 25 Calicivirus ddx
- Clinical
- ELISA
- PCR
113
III. 25 Calicivirus treatment
- NOT available
| - rehydration
114
III. 25 Rotavirus characteristics
- from REOviridae family
- dsRNA, both positive & negative
- Icosahedral capsid
- Naked virus
115
III. 25 Rotavirus Transmission
Fecal-oral
116
III. 25 Rotavirus Clinical
GASTROENTERITIS:
- mainly in children < 5y
- fever, watery diarrhoea for 1 w (risk of dehydration)
- Nosocomial epidemics occur
117
III. 25 Rotavirus ddx
- Immunochromatography rapid test: faeces
| - PCR from faeces
118
III. 25 Rotavirus treatment
supportive therapy
119
III. 25 Rotavirus vaccine
Oral, live attenuated vaccine:
- Rota.teq, Rota.rix
- for infants 6-32 w old
- not part of vaccination schedule
120
III. 25 Astrovirus characteristics
- (+) ssRNA
- Icosahedral capsid
- Naked virus
- STAR shape
121
III. 25 Astrovirus transmission
Fecal-oral route
122
III. 25 Astrovirus clinical
Gastroenteritis:
- in children and older people
- Watery diarrhea, vomiting, abd pain
- resolves 2-3 days
- occur in winter
123
III. 25 Astrovirus ddx
- ELISA
| - Hybridisation
124
III. 25 Astrovirus treatment
Supportive
125
III. 26 Orthomyxoviruses characteristics
- (-)ssRNA -negative sense- segmented
- Helical
- Enveloped
- RNA synthesis in nucleus (only RNA virus)
- Possesses Hemagglutinin and Neuraminidase glycoproteins
126
III. 26 Orthomyxoviruses transmission
- Respiratory droplets & contaminated hand
| - Seasonal spread: in fall and winter
127
III. 26. Orthomyxoviruses Replication (of influenza)
1. Attachment: HaemmAglutinin (HA) binds to sialic acid on cell surface
- ->Target: resp. epith. cells
- ->HA: important Ag's , variable
2. Uncoating
3. Virus replication
4. Assembly
5. Release: mediated by NeurAminidase (NA) enzyme
- ->cleaving the budding virus off from the cell
- ->NA: important Ag's , variable
128
III. 26 Orthomyxoviruses - INFLUENZA "A" VIRUS
• Most virulent human influenza virus
• Subdivided into different serotypes based on surface Ag's HA and NA
(eg . H1N1 and H3N2)
• Causes epidemics & pandemics
• Infects birds and mammals (different variants)
Avian influenza bird flu:
- Aquatic birds are the natural reservoirs of influenza A virus (migration)
- Infection of poultry: economic importance
- Reassortment of bird and human strains: new variants --> potential for human pandemics
129
III. Orthomyxoviruses - INFLUENZA "B" VIRUS
* Exclusively infects humans
* Less common than influenza A
* Lower mutation rate, no Ag shift (lower diversity), lower risk for epidemics
* Generally infects younger population
130
III.26 Orthomyxovirus - INFLUENZA "C & D" VIRUSES
* Mostly infect animals pigs , cattle
| * C can cause human infections
131
III. 26 Orthomyxoviruses variation
NEW VARIANTS OF INFLUENZA VIRUSES RISE AS A RESULT OF:
* Antigenic shift:
- Accumulation of point mutations
- Gradual change
- Occurs in influenza A and B
* Antigenic drift:
- Reassortment: mixing of genes between two organisms to make a new genetic sequence when 2 types infect same cell
- Sudden change, explosive spread pandemics
- Occurs only in influenza A virus
132
III. 26 Orthomyxoviruses clinical
- Influenza A, B and C (also known as flu)
```
- Symptoms:
• May be asymp.
• Sudden onset
• Fever : 38 to 39 C , chills
• Dry cough
• Muscle pain , fatigue , headache
```
133
III.26. Orthomyxovirus - Influenza Complications?
* Pneumonia: viral or bacterial superinfection
* Sinus or ear infections
* Myocarditis
* Myositis
* Encephalitis
* Multiorgan failure , SIRS
* Possibly lethal
134
III. 26 Orthomyxoviruses ddx
* Mostly based on clinical symptoms
* RT PCR
* Rapid antigen test
* From respiratory sample usually nasopharynegal swab , in VTM
***More precise lab diagnosis for epidemiology (follow of epidemics):
• Virus isolation and cultivation on cell cultures or embryonated egg
• HA inhibition assay test for Ab's
135
III. 26 Orthomyxoviruses treatment
• Generally antivirals are not needed:
Bedrest , increased fluid intake , antipyretics
ANTIVIRALS:
1. Attachment is inhibited by Ab's in immune people.
(monoclonal Ab's in clinical trials for treatment)
2. Uncoating Inhibited by adamantanes:
- ->amanta.dine and rimanta.dine (resistance problem)
3. Virus replication inhibition:
- ->baloxa.vir
5. Release:
blocked by (NA) enzyme inhibitors
-->zana.mivir, pera.mivir (Tamiflu)
136
III. 26 Orthomyxoviruses vaccine
• Recommeded for everyone >6m , every season
• Especially important for risk groups & healthcare workers
•Tri/Tetravalent, inactivated or recombinant subunit:
--> Vaxi.grip , Fluarix , Influvac , Afluria
--> for 2 „A” types and 1-2 "B”s , intramuscular
• Nasal spray of live attenuated virus
137
III. 27 - Paramyxoviruses - Mumps, Morbillivirus (measles) characteristics
* Non-segmented (-) ssRNA genome
* Helical
* Enveloped
* HN: HaemAgglutinin-NeurAminidase on surface
* F-protein: glycoproteins for fusion
* RNA synthesis in cytoplasm
PaRaMyxoviruses: Parainfluenza
RSV
Mumps , Measles , Metapneumo
138
III. 27 - Paramyxoviruses - Morbilli (measles) clinical
Spread: resp. droplets
- Most infectious virus
- Occurs in regions with low vaccination rates (mostly in children)
Clinical features:
• Incubation period
• CATARRHAL STAGE: nonspecific symp:
- Rhinitis (Coryza ), Cough, Conjunctivitis , fever
- Koplik spot: Small white spots on oral mucosa
•EXANTHEM STAGE: MACULO-PAPULAR RASH
- Confluent
- starts behind ears , spreads towards feet
- High fever, generalised lymphadenopathy
- Heals with desquamation after 5-7 days
139
III. 27 - Paramyxoviruses - Morbilli (measles) complications
```
SHORT TERM:
• Bacterial superinfection:
- Measles --> temporary immunosuppression --> Lymphocyte count ↓↓ --> immune amnesia
- Otitis media
- Pneumonia (most common cause of death)
• Gastroenteritis , viral pneumonia
• Acute encephalitis Frequency: 1:1000
```
LONG TERM:
• Subacute sclerotizing pan-encephalitis - SSPE
- 10 yrs after measles infection
- Generalised demyelinating inflammation of the brain
- 100% lethal in a few years , no cure
- Sy: dementia , personality change , epilepsy, vegetative state
- Cause: persistence of measles in brain as slow virus
- Frequency: 1-2:10,000 measles cases
140
III. 27 - Paramyxoviruses - Morbilli ddx
* Based on clinical symptoms
* Serology : Measles specific IgM
* RT PCR
141
III. 27 - Paramyxoviruses - Morbilli treatment and prevention
TREATMENT:
• Not available
- vitamin A reduces morbidity and mortality
PREVENTION ! :
• MMR (mumps-morbilli-rubella) vaccine for every child at 15 m & 6,11 yrs of age
• Post-exposure prophylaxis (PEP ): active immunisation of healthy , passive for immunosupressed
142
III. 27 - Paramyxoviruses - Mumps clinical
* Spread:
resp. droplets (unvaccinated) , in children mainly
- -> Highly infectious
*Pathomechanism:
Initial replication in Nasopharyngeal mucosa → viraemia → parotid gland → dissemination possible to testes, ovaries , pancreas , CNS
Clinical course:
- Prodrome: fever
- Inflamm. of the salivary glands PAROTITIS (Swelling of parotid, salivary, lymph nodes, pain
Earache -earlobe turned upwards-)
143
III.27 Paramyxoviruses - Mumps complications
* Orchitis: inflam of the testicles (Mostly post-pubertal age)
* Meningitis
* Encephalitis
* Pancreatitis: link to later diabetes mellitus 1
144
III. 27 - Paramyxoviruses - Mumps ddx
- RT-PCR
| - serology: mumps virus specific IgM
145
III. 27 - Paramyxoviruses - Mumps treatment and prevention
```
- Treatment:
only supportive (antipyretics, bedrest)
```
- PREVENTION:
MMR (mumps-morbilli-rubella) for every child at 15m and 6, 11 yrs
146
III. 28 - Paramyxoviruses - RSV, Parainfluenzavirus characteristics
- RSV: Resp. Syncytial Virus
- (-) ssRNA -negative sense-
- non-segmented
- Helical
- Enveloped: HA, NA, F glycoproteins RNA synthesis in cytoplasm
147
III. 28 - Paramyxoviruses - RSV clinical
Spread:
- resp. droplets
- Common infection
- nosocomial spread also possible
Clinical forms:
• Common cold , rhinitis
• Acute exacerbation of COPD and old people
• Bronchiolitis:
- in infants
- URTI followed by tacwypnoe , cyanosis , wheezing
148
III. 28 - Paramyxoviruses - RSV Diagnosis, Treatment, Prevention
Diagnosis:
- clinical
- RSV PCR from nasal sample if necessary
Treatment:
- Bronchodilators, epinephrine, corticosteroids
Prevention:
Palivizumab for premature babies
(mRNA vaccine in trial)
149
III. 28 - Paramyxoviruses - Parainfluenzavirus 1-4 clinical
Spread:
- resp. droplets
- common infections Infects epith. cells of resp. tract
* Common cold URTI: not severe
* Bronchiolitis, pneumonia: more severe
• Croup: Acute Laryngo-Tracheo-Bronchitis: children age 0,5-6y
--> Acute obstructive laryngitis --> tracheal swelling Hoarseness, barky cough, tachypnoea, Dyspnoea (Usually at night, in autumn, winter)
150
III. 28 Paramyxoviruses - Parainfluenza virus 1-4 DDX and treatment
D:
- Clinical sign
- X ray: steeple signs
Tx:
- cold humid air
- steroid inhalation or suppository Rectodelt
- salbutamol inhalation for bronchodilatation
- intubation
151
III. 29 Picornavirus - Poliovirus characteristics
- (+) ssRNA -positive sense- =mRNA
- icosahedral
- Naked
- Member of Enterovirus genus (of the Picornaviridae family)
- Polio has 3 serotypes – 1, 2, and 3
152
III. 29 Picornavirus - Poliovirus transmission
- because member of Enteroviruses:
- -> very resistant (pH, heat, detergents) --> enhances spread
- -> fecoral spread (but rarely causes enteric disease)
153
III. 29 Picornavirus - Poliovirus pathogenesis and clinical
--> Replicates in lymphoid.T. & tonsils (Peyer’s patches)
--> viremia to Ant. Horn of spinal cord & brain stem.
--> Replicates in motor neurons
--> causing cell lysis (leading to asymmetrical flaccid paralysis)
(severity and location depends on the infected neurons)
====> can affect: Limbs, Cranial n., Resp. muscles
* Asymptomatic infection is possible
* Symptomatic: Febrile illness, Aseptic meningitis
* Severe: 1%
===> possible outcome:
- Recovery
- residual paralysis
- death
154
III. 29 Picornavirus - Poliovirus
| Ddx, Th, Prevention
DDx:
- cultivation
- Serology
Th:
- not available (supportive only)
Prevention:
- vaccine: since 1995
1. IPV: inactivated PV. (Salk v.)
- -> 2,3,4, 15m then 3,6 yrs
2. OPV: oral live PV (Sabine v.)
- ->risk for vaccine related poliomyelitis
- -> not used in Hungary
155
III. 30 Picornavirus - Coxasckie A Virus
| transmission, Clinical
Transmission:
- Fecal-oral route
```
Clinical:
1. Herpangina:
- Fever
- Sore throat
- Vomiting
- soft palate vesicular ulcerations
(self limited, only supportive th)
```
2. Hand-Foot-Mouth disease:
- vesicular exanthem
- fever
3. Hemorrhagic conjunctivitis
156
III. 30 Picornavirus - Coxasckie B Virus
| clinical
1. Pleurodynia
- Fever
- Unilateral severe plueritic hest pain
- abd pain
- vomiting
2. Myocarditis, pericarditis
- fever
- heart failure
- high mortality
3. infection of langrhans cells
- maybe associated with insulin dependant DM
157
III. 30 Picornavirus - Echovirus transmission
Fecal-oral route --> can infect any tissue (broad tropism)
158
III. 30 Picornavirus - Coxasckie Virus characteristics
- (+)ssRNA -positive sense- =mRNA
- Icosahedral capsid
- Naked
- 30 serotypes
- we focus on A and B
159
III. 30 Picornavirus - Echovirus characteristics
ssRNA, positive sense
Icosahedral capsid
Naked
160
III. 30 Picornavirus -Rhinovirus characteristics
- ssRNA, positive sense
- Icosahedral capsid
- Naked
- 100 serotypes
- sensitive to pH, Temp
- Can survive on objects
161
III. 30 Picornavirus - Echovirus clinical
1. aseptic meningitis (~ nr.1 cause)
- headache and meningeal irritation
2. Acute febrile URTI with RASH
- viral exanthem, non-specific rash
3. Necrotizing hepatitis
- in newborns
(no treatment or prevention available)
162
III. 30 Picornavirus -Rhinovirus transmission
- Respiratory droplets and by hands --> URTI (multiply in Nose)
- Unable to replicate in GI tract as enteroviruses
- Rhinoviruses have Ag drift, as seen in influenza
163
III. 30 Picornavirus -Rhinovirus clinical
- URTI
- common cold
--> sneezing, Rhinorrhea, Sore throat, Headache
RARELY fever !!!
164
III. 30 Picornavirus - Enterovirus
clinical
- very resistant to environmental factors (pH, heat, detergents)
- Fecoral spread (rarely causes enteric disease)
- initial multiplication: mucosa of pharynx and tonsils --> viraemia
- 70 serotypes
- most infectious: Asymp
- Humoral immunity is important here
- Exclusively human pathogen
165
III. 30 Picornavirus - Enterovirus characteristics
- (+) ssRNA =mRNA
- Icosahedral capsid
- Naked
- 5 genera:
- -> Entero (coxsackie, polio, Echo)
- -> Rhino
- -> Hepato (hepatitis A)
- -> cardio
166
III. 31 Rhabdoviruses characteristics
- (-) ssRNA -negative sense-
- Bullet shaped (rhabdo=ROD)
- Enveloped
Includes:
- Lyssa virus genus (Rabies)
- Vesiculovirus genus (vesicular stomatitis virus (VSV))
167
III. 31 Rhabdoviruses
transmission
Spread: zoonosis
- worldwide
- by Bite or bodily fluids of animals or human: dog, cat, fox, wolf, bat
- Aerosol: from bat dropings
168
III. 31 Rhabdoviruses
pathogenesis
1. At entry: virus infects muscle, nerves --> replicates (long incubation)
2. Ascending spread: DRG & brain
(speed depends on the proximity of entry to brain)
3. Demyelinisation & Negri bodies formation in CNS
4. Descending infection: to salivary gland & other organs
169
III. 31 Rhabdoviruses clinical
Symptoms:
- incubation: 20-90 days
- Prodromal stage: fever, headache
1. Encephalitic rabies:
- -> fever
- -> Hydrophobia
- -> pharyngeal spasms
- -> hyperactivity subsiding to paralysis
- -> coma and death
2. Paralytic rabies : descending flaccid paralyis
170
III. 31 Rhabdoviruses diagnosis
Diagnosis:
- anamnesis
- PCR: from saliva or CSF
- Ab's: from serum or CSF
- Post mortem: Negri bodies
171
III. 31 Rhabdoviruses treatment
Treatment:
- No treatment after onset of symp! (100% mortality)
- POSTEXPOSURE ACTIVE IMMUNISATION: if risk of rabies suspected (before symp)
- Inactivated virus vaccine: series of injections (Pasteur)
172
III. 31 Rhabdoviruses Prevention
Prevention:
- Vaccination of dogs yearly! (live attenuated)
- Immunisation of wild reservoir animals with vaccine containing food (ORV oral rabies vaccine)
- Pre-exposure prophylaxis for people at high risk eg. hunters
- Avoid animal contact especially at risk countries
173
III. 33 Togavirus characteristics
ssRNA, positive sense
Icosahedral capsid
Enveloped
Includes Alpha- and Rubiviruses
174
III. 33 Togavirus Alphavirus transmission
Via mosquitos (vectors – where replication occurs) – Humans are dead-end hosts
175
III. 33 Togavirus Alphavirus ddx
Serology
| RT-PRC
176
III. 33 Togavirus Alphavirus prevention
Killed vaccine for EEE and WEE
| vaccination of horses
177
III. 33 Togavirus Rubiviruses characteristics
- Rubi-virus genus (Rubella name: little red)
- Used to belong to Togavirus family (toga : coat in Latin)
- (+) ssRNA
- icosahedral
- enveloped
178
III. 33 Togavirus Rubiviruses transmission
Spread:
- Aerosol
- Respiratory droplets (unvaccinated), mostly in children
179
III. 33 Togavirus Rubiviruses Clinical
Symptoms:
• 2 w incubation (most contagious)
• Low grade fever, lymphadenomegaly, headache, pink eye
• Maculopapular rash: starts on face, spreads down
--> In children it is milder (maybe asymp)
--> In adults more systemic signs: arthritis, arthralgia
(Self-limiting illness in non pregnant)
CONGENITAL RUBELLA SYNDROME CRS
- reason for vaccination
- Transplacental spread of virus to foetus:
--> Risk of congenital malformation in first 20 w of pregnancy → In utero death, premature birth or congenital defects:
•Ear: Hearing impairment
•Heart: congenital heart defects
•Eye: cataracts/congenital glaucoma, pigmentary retinopathy
•Late onset manifestations:
--> CNS: intellectual disability, Diabetes mellitus, Thyroid dysfunction
180
III. 33 Togavirus Rubiviruses treatment and diagnosis and prevention
```
Th:
Not available (just supportive)
```
DDx:
-Lab diagnosis: if pregnant, or to DD from other conditions-
• Serology: IgM from mother (may be false positive in pregancy) or newborn
--> Confirmation: Low avidity IgG / 4 fold increase in IgG titere
--> Vaccinated: has Ab's
• Screening of pregnant
• PCR: from pharynx or urine of newborn or placenta
Prevention:
-MMR: live attenuated rubella virus, at age 15 m, booster at 11 yrs (in hungary)
181
III. 34 Hepatitis A characteristics
- (+) ssRNA =mRNA
- Icosahedral capsid
- Naked
- Hepatovirus genus (from Enterovirus from Picornaviruses)
- Only 1 serotype
- Resistant to environmental factors
182
III. 34 Hepatitis A
| transmission and clinical
Spread: fecooral food, water, bad hygiene, undercooked shellfish
- ->intestine --> liver (via circulation) --> Infects hepatocytes --> Kupffer cells
- -> immune response against infected hepatocytes --> Liver damage
Clinical:
- Long incubation
- Acute hepatitis (never chronic)
- -> Fatigue, faver, nausea, jaundice
- Sometimes subclinical (rarely fulminant)
- lifelong immunity develops
183
III. 34 Hepatitis A
| diagnosis, treatment, prevention
Diagnosis:
- serology : Anti-HAV (IgM +)
Therapy: not available
Prevention:
- active immunisation for travellers to endemic areas
- passive : anti-HAV human Ig's
184
III. 34 Hepatitis E characteristics
ssRNA positive sense
| resistance to heat and acid
185
III. 34 Hepatitis E clinical
severe in pregnancy
186
III. 34 Hepatitis E treatment
none
187
III. 34 Hepatitis E prevention
vaccination in China
188
III. 34 Hepatitis E ddx
Anti-HEV IgM
189
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)
190
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)
191
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
192
III. 35 Hepatitis B transmission
Blood contamination (e.g. parenteral, needles etc.)
Sexual contact
Vertical infection (perinatal) – TORCHES
193
III. 35 Hepatitis D characteristics
envelope
| ssRNA negative - circular
194
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
195
III. 35 Hepatitis B prevention
Recombinant vaccine made of HBsAg given by 3 injections (at birth, 1 month and 6 months)
196
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.
197
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
198
III. 35 Hepatitis C transmission
Blood transfusions
Needle sharing (I.V drug users, accidental pricks from carrier, tattooing etc.)
sexual contact
199
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
200
III. 35 Hepatitis C treatment
- Ribavirin (nucleoside inhibitor, guanosine analogue)
- Interferon a
- Protease inhibitors (Broceprevir or Telaprevir)
201
III. 35 Hepatitis D transmission
parental
202
III. 35 Hepatitis D clinical
acute hepatitis
203
III. 35 Hepatitis D ddx
anti-HDV ELISA
