VIROLOGY

I. General Characteristics:
> Viruses are not considered true living organisms, bec, they lack the metabolic properties that enable the simpler forms of life
to live and replicate autonomously.
> INTRACELLULAR parasites
A. Size : vary ultrafilterable agents.
> 20 x 20 nm 250 x 300nm
(Parvovirus & Picornavirus) ; Poxvirus
> cannot be visualized by conventional microscope
B. Replication:
> can only multiply in living cells (B. Lab. Animals, embryonated eggs , and various cell lines )
C. Host specificity:
1. most viruses have a narrow range of host specificity.
* bacteriophages ( virus that infects bacterial cells
* virus that infects plants ( tobacco mosaic virus)
* infect specific species of animals
2. viruses with wide range of host specificity;
a. arthropod-borne viruses (arboviruses) -birds herbivores, mosquitoes & occ. Humans
b. rabies virus can infect several mammalian species
c. influenza viruses can infect both humans & ducks

II.Viral structure:
Virion= nucleocapsids ( nucleic acid core + capsid)
> Envelope/ naked
a. NA = viral genome either DNA or RNA
1. single strand ( most RNA virus, except reovirus), or
= double strand ( most DNA virus, except parvovirus)
2. single segment or polysegmented genome
3. most have linear genomes, except papovaviruses (supercoiled circular genome)
4. NA could be infective or noninfective
*Infective DNA genomes are translated by cell polymerases into mRNA
*Infective RNA genomes are translated directly into protein by cellular ribosomes
b. Viral capsid
>. Functions: a) Protects the nucleic acid core
b) mediates viral adsorption & penetration
>. Resistance ; naked viruses are R to denaturation
c. Viral envelope:
> derived from cellular membrane ( lipid bilayer)
d. Viral proteins:
a. structural proteins = formation of infective viral particles
b. enzymes = viral polymerases
= proteases
= endonucleases & ligases.
Viral polymerases = essential for NA replication
Proteases = used by some viruses to process large transcript into small, functional proteins
Endo & ligases = used by some for replication

III. Nomenclature and Classification :

A.
> usually from the disease they cause; ( herpes)
> locality first isolated ( Norwalk )
> scientists responsible for isolating the virus ( Epstein-Barr)
> epidemiological characteristics ( arbovirus)
B. Taxonomic Classification
1. Homology of nucleic acid
2. Morphology, shape and size
3. Presence or absence of envelope
4. Nucleoplasmid symmetry
5. Nucleic acid characteristics
Viral replication:
> Cell receptors for attachment/ penetration
> adequate cell environment for viral replication
> cell survival while infected until viral replication is completed
Stages of viral replication :
A. Adsorption = adheres to specific receptors ( glycoproteins)
B. Penetration
a). Membrane fusion
b). Receptor-mediated endocytosis ( viropexis)
C. Uncoating of the viral nucleic acid
D. Synthesis (NA replication & synthesis of viral proteins)
E. Assembly
F. Release

Viral Infections:
I.
Epidemiology
A. Transmission of viral diseases;
1. Horizontal : person to person
a). Respiratory route = most common ( close contact)
b). Fecal-oral route =
c). Venereal route

d). Cutaneous
e). Inoculatiion

2. Vertical transmission :
a). Transplacental = congenital ( HIV, rubella. Herpes, CMV HbV)
b). Perinatal
c). During lactation ( HIV)

3. Zoonotic transmission:
a). Rabies virus
b). Hantavirus

B. Viral infections from the community perspective

1. Public health
a). Inapparent infections
b). Latent infections
2. Role of resistance
a. Ways of acquiring resistance
1. Previous infection ( viruses are excellent Ags & induce strong humoral immune responses)
2. Mass immunization
b. Herd immunity : ( 60-70%) of population is immune, chain of transmission will be broken.
> explains the self-limiting nature of an epidemic.
3. Periodicity of epidemics :
Factors that contributes to periodic occurrence of viral epidemics
a. Herd immunity may disappear with time
b. Nonimmume babies continue to be born
c. some viruses undergo continual antigenic variation.
C. Seasonal fluctuation:
1. Summer : diseases transmitted by mosquitoes
2. Cold months : Rhinoviruses
II. Pathogenesis :
1. Virus factors that influence the outcome of infection
a. Cell tropism; cell specificity
b. Mutation
2. Host factors: age, nutrition, genetic factors
Clinical Virology

Herpesviruses pathogenic to humans:

1. HSV1 & 2
2. Varicella zoster virus
3. Epstein- Barr virus
4. Cytomegalovirus (CMV)
5. Human herpesvirus-6 ( HHV-6)
General Characteristics of Herpesviruses :
> double- stranded DNA
> Nucleocapsid with icosahedral or cubic symmetry
> Enveloped
> Latency
Herpesviruses *(HSV)
1. HSV-1 ; HSV-2
A. Pathogenesis & Clinical disease:
IP: 5-6 days
a. Primary infection : virus replicates actively in skin or mucosal vesicular lesions;
b. Latent infection :virus localized in sensory ganglia ( trigeminal-HSV1, sacral- HSV2)
c. Recurrences ( trigger mechanisms) fever, colds, sunlight, menses, certain foods & stress.
*HSV1; HSV2 = virus invades cutaneous vascular endothelium, causing epithelial cell necrosis & leading to formation of vesicles.
2. Clinical disease :
a. HSV-1 ; causes perioral lesions (Herpetic gingivostomatitis) fever blister
b. HSV-2 ; causes genital lesions
c. Complications;
> encephalitis; meningitis; keratitis; eczema herpeticum( Kaposis varicelliform eruption)
B. Transmission :
1. Direct contact with vesicular discharge
2. sexual transmission
3. perinatal transmission
4. congenital transmission = rarely transmitted across placenta
C. Diagnosis :
1. Clinical ( typical vesicular lesions
2. Lab. Dx : Tzanck cells ( giant multinucleated cells with IN inclusions that push the chromatin to the margin.
3. Serology : > direct immunoflourescense (biopsied tissue)
> Det. IgM antibody
D. Treatment :
> uncomplicated fever blisters and genital lesions are
self-limiting
1. Acyclovir = indicated for all serious HSV infections
oral/ parenteral/topical
> initiate Tx w/n 72 hours
2. Famciclovir = oral, with less frequency than Acyclovir
Varicella-zoster virus
Clinical disease :
A. Chicken pox : IP 10-21 days ( 13days)
> vesicular rash / lesions at different stages of devt.starts as papular lesions- vesicular crust heal w/o scarring.
Cx; a). Reyes syndrome = may occur in children ff. VZV
b). Large cell pneumonia = immunocompromised pts
c). Post-infection encephalitis or meningitis

B. Shingles :
> vesicular rash appear in dermatomal distribution (chest)
> rash is very painful
Transmission :
> VZV spreads via respiratory route;
> vesicle are infectious
Diagnosis :
> Tzanck cells from lesions
Treatment:
> acyclovir
Immunoprophylaxis:
> Live, attenuated vaccine, recommended for all children
( 1 year up)
Epstein-barr virus
Pathogenesis :
> E-B virus targets the B lymphocytes, which carry the CR2 molecules, a specific receptor for the virus.
Clinical Diseases :
A. Infectious mononucleosis
(1). Acute mononucleosis : acute exudative pharyngitis with lymphadenopathy (submandibular), fever, rash
(2). Chronic E-BV = chronic fatigue syndrome
B. Butkitts lymphoma = lymphoma in soft tissue (jaw)
C. Nasopharyngeal carcinoma = prevalent among Asian men
*Chronic fatigue syndrome = unexplained fatigue & depression over a 6 month period
EBV Transmission;
> spread via respiratory secretions through oral contact;
> blood transfusion & venereal transmission
Diagnosis:
1. CBC = shows atypical lymphocytes (lymphoblasts)
2. Serology = (a). Monospot test based on detection of heterophile antibodies that agglutinate horse RBC
(b). EBV- specific antibody test ; detect capsid Ag, early Ag, EBV nuclear Ag
Treatment :
> supportive
Cytomegalovirus
> minimal or asymptomatic in healthy adults; severedisease in immunocompromised .
Clinical disease :
a. Mononucleosis-like syndrome ff. transplantation or transfusion
> Fever, pneumonia, esophagitis, enteritis, hepatitis,retinitis, uveitis
Transmission :
> Respiratory route; venereal; Perinatal &;
> Congenital ( 1st trimester) : newborn may show chorioretinitis ; hydrocephalus
CMV Diagnosis :
1. Optical microscopic examination : stained smears of urinary sediment and stained kidney biopsy;
owl-eye inclusion= typical of CMV
2. Culture & isolation
3. Serology : TORCH panel = titer in mother &child
( Toxoplasmosis, Other (SY) , Rubella, Cytomegalovirus, HSV)
Treatment :
1. Ganciclovir = DOC
2. Foscarnet = DOC

Human herpes virus-6(HHV-6, HBLV)

Clinical Disease :
1. B- cell lymphoma
2. Roseola infantum (exanthema subitum)
3. Chronic fatigue syndrome
Transmission : Unknown
*HBLV= first isolated from patients with B-cell lymphoma ( human B cell lymphotrophic virus)
II.
Papovaviruses
> naked DNA viruses
I Papillomaviruses :
> special tropism for skin & mucosae
a. Transmission = direct contact ; sexually ; perinatal
b. Clinical Disease :
1. Skin Warts
2. Genital warts ( condyloma acuminatum)
3. Cervical carcinoma
4. Laryngeal warts
5. Epidermoplasia verruciformis
c. Diagnosis : Clinical
d. Treatment: Chemicals , cauterization ; laser therapy, freezing, IF-,
salicylic acid, podophylin, surgery
*Epidermoplasia *== lifelong disease, multiple,polymorphic wart-like lesions distributed through out the body.
II. POLYOMAVIRUSES :
a. BK virus : infect children early in life.
50% of children have antibodies to BK virus (3-4 y.o.)
100% children seroconverted by age 10
> virus tend to infect renal epithelial cells
b. JC virus = Progressive multifocal leukoencephalopathy (PML), rare, slow degenerative neurologic dis.
C. Simian virus 40 ( SV40)
iii. Adenoviruses, poxviruses , parvoviruses
A. Adenoviruses;
> first isolated in 1953 from adenoidal & tonsillar tissues
> naked, icosahedral, ds-DNA
> over 40 antigenically distinct serotypes
IP: 4-5 days
Clinical disease : mild to subclinical
a. Common colds
b. LRT infections (bronchiolitis, pneumonia)
c. conjunctivitis ( pharyngoconjunctival fever)
d. Hemorrhagic cystitis
*e. Diarrhea ; meningoencephalitis ; intussusception ; epidemic keratoconjunctivitis ( welders )
B. POXVIRUSES
>Largest animal virus, brick-shaped; non-enveloped.
> ds-DNA, replicates in cytoplasm
> resistant to disinfectants and antiseptics
1. Variola virus = small pox
2. Vaccinia virus =
3. Cowpox virus
4. monkeypox virus

1. Smallpox:
> 1st human disease for which effective immunoprophylaxis was
developed
> WHO declared smallpox -free world. *1977= last known case reported in Somalia.
1.1 Variola major
1.2 Variola minor ( alastrim)
Diagnosis :
> Guarnieri bodies = cytoplasmic inclusions bodies of infected epithelial cells
2. Vaccinia virus = used for vaccination vs. smallpox
3. Molluscum contagiosum = venereally transmitted. Papules that resolve sponraneously.
C. PARVOVIRUSES:
> smallest DNA viruses; naked with single-strand negative DNA
> Parvovirus-like agent (PVLA) strain B19
Clinical Disease :
1. Aplastic crisis =infection of the precursor cells of the erythroid lineage in the bone marrow by PVLA -B19, can
trigger an aplastic crisis in children who have homozygous sickle cell disease.
2. Erythema infectiosum (fifth disease) = affects infants, slapped cheeks appearance. Faint reticular rash- limbs.
3. Hydrops fetalis
Rna viruses

1. Picornaviruses:
> small, single strand, naked with+ RNA genome
> icosahedral,
> replicate in the cytoplasm
A. Enteroviruses
1. Poliovirus ( types 1,2,and 3)
2. Coxsackievirus A ( 24 serotypes ); Coxsackie B ( 6serotypes )
3, Echovirus (34 serotypes )
4. New enteroviruses ( strains 68-72 )
B. Rhinoviruses

Enteroviruses
Poliovirus
= 3 serologic types:
Type 1 Brumhilde - most paralytogenic
Type 2 Lansing
Type 3 Leon - least paralytogenic

Disease: Poliomyelitis / Infantile Paralysis / HeinMedlin Disease

>acute infectious disease that in serious form affect CNS
> found worldwide
> spread rapidly among densely populated area with poor sanitary hygiene
>almost extinct, due to success in mass immunization

Polio

> children (5 years & above) more susceptible than adults

> human-only known reservoir of infection
> Mode of Transmission: fecal-oral route
> incubation period 1-2 weeks (7-14 days)
Five Clinical types of infection:
1. Inapparent / Asymptomatic
2. Abortive
3. Non-Paralytic (aseptic meningitis)
4. Paralytic Poliomyelitis
5. Bulbar poliomyelitis
1. Inapparent infection :
> most polio infection
2. Abortive infections :
> assoc. with non-sp.
symptoms
3. Aseptic meningitis:
> approx. 1% develop a self-limiting meningitis; usually w/o sequellae
4. Paralytic Poliomyelitis :
> approx. 0.1%
(A). Spinal = char. by flaccid
paralysis ( motor neurons)
> assymetrical paralysis;
> lower extremeties
> muscle atrophic
(B). Bulbar = more common in adults.; involves cranial nerves; resp. & circ. centers in medulla
(C). Bulbospinal = very poor prognosis
Postpolio syndrome :
> 20-30% of individual with paralytic episode of polio (youth);
> fatigue, muscle pain, weakness, & atrophy 25- 35 years later. ( further denervation)
> affected muscle are usually those affected in the original episode.
> progression of symptoms slow & does not cause significant disability.

Prevention:
> Vaccination (using killed or attenuated polio virus)
1. Salk vaccine
= inactivated/killed polio virus contains all 3 serotypes
= parenterally given
= induce IgG in the blood
= does not induce secretory IgA
= refrigeration not needed
2. Sabin vaccine
(Trivalent oral polio vaccine - TOPV)
= live attenuated polio virus contains all 3 serotypes
= given orally
= induce IgG and secretory IgA
= prepared vaccine and routinely administered to children U.S.
*Sabin vaccine : widely used ; 100% protection; must be refrigerated
Oral vaccine is preferred in most countries incl. US
Immunity:
> lifetime immunity
> passive immunity transferred from motherneonate
> maternal antibodies disappear during 6 month of life
Coxsackie viruses
> Classification based on pathogenicity (lesion produce in suckling mice)
1. Coxsackie A
= grows well in suckling mice following intracerebral and or intraperitoneal inoculation producing widespread necrosis of
skeletal muscle (myositis) leading to flaccid paralysis and death
Disease produced:
1. Aseptic meningitis
= may be caused by either Coxsackie A & B
= usually mild & may last 5-14 days
2. Herpangina
= mild self-limiting disease characterize by fever & sore throat with vesicular nodule in oropharynx
Coxsackie B

> causes generalized less severe lesion of the heart, liver, pancreas and CNS
> 6 serotypes
> leading cause of viral myocarditis and pericarditis
Disease produced:
1. Pleurodynia (Bornholm Disease/ Epidemic Myalgia/Devils Grip)
> characterized by fever with severe chest pain especially during inspiration
2. Aseptic meningitis
3. Hands Foot and Mouth disease
= characterize by vesicular rashes in the hands and feet with ulceration in the mouth
= common in children
4. Primary Pericarditis/Myocarditis
> infection and inflammation of the heart muscle and pericardial membrane
> characterize by fever, chest pain and sign of congestive heart failure

> fatal in neonates

> infection in pregnant women can cause congenital heart defects in the fetus
5. Common Cold
Disease

Coxsackie A

Coxsackie B

1. Herpangina

Serotypes 2-6, 8, 10

----------

2. Infantile diarrhea

Serotypes 18, 20-22, 24

-----------

3. Hand-foot-and mouth disease

Many serotypes

----------

4. Multisystemic disease in neonates

--------

Serotypes 2-5

5. Pleurodynia

---------

All serotypes

6. Pericarditis, myocarditis

----------

All serotypes

Laboratory Diagnosis:
1. Isolation virus - Intracerebral inoculationsuckling mice
Cell culture Monkey Kidney cell/Hela cell + CPE
2. Serological Observe a rise of neutralizing antibody titer during convalescent period
Treatment :
- No specific antiviral drug
- No vaccine available
ECHOvirus : (Enteric Cytophatogenic Human Orphan Virus)
> called orphan virus not associated with any disease
> worldwide in distribution
> 30 serotypes (not all can cause human disease)
> different from Coxsackie virus by their failure toproduce pathological changes in suckling mice (not pathogenic to mice)
> one of the leading cause of aseptic meningitis
> acquired by fecal oral route
Disease produced:
1. Aseptic Meningitis
2. Infantile Diarrhea
3. Febrile illness with or without rash (Boston Exanthem Disease)
4. Common Cold
5. Acute Hemorrhagic Conjunctivitis
Laboratory Diagnosis:
Isolation of virus - (throat washing/rectal swab) MKC / Hela cell / Human Ammion cell + CPE
Treatment: Symptomatic = no antiviral drug
Prevention: - No vaccine available = avoid contact with the virus
Hepatitis A virus
(Enterovirus 72)
> only 1 serotype
Disease: Acute Hepatitis
= occurs after short incubation period of 3-4 weeks
= acquired by fecal-oral-route and virus appears in the feces 2 weeks before appearance of the symptoms

Pathogenesis: (HAV)
= virus replicate in the gastrointestinal mucosa spread liver via the bloodstream
= characterize by fever, loss appetite, nausea, vomiting, and jaundice (typical)
= mild undiagnosed cases common
= younger patients fewer symptoms
= most cases resolved spontaneously with no chronic infection or carrier state
= mortality rate very low (<0.5%)
Laboratory Diagnosis :
> detection of IgM antibody to HAV (most important test)
Treatment:
= Symptomatic
= no antiviral drug
Prevention:
Active immunization
> vaccine containing inactivated hepatitis A virus (virus grown in human cell culture inactivated) with formalin
> vaccine recommended to people traveling to endemic areas
> immunity lifelong
Enterovirus 70
= main cause of Acute Hemorrhagic Conjunctivitis
= characterized by pain, swelling and petechial hemorrhages in the bulbar conjunctiva
= very contagious disease
= also seen with coxsackie A and B infection
Enterovirus 71
= one of the leading cause of CNS disease including meningitis, encephalitis and paralysis
= also causes Hand Foot and Mouth Disease characterize by the presence of herpetiform lesions in the hands, foot
and mouth
Rhinovirus
> over 100 antigenically distinct
> Common Cold
IP: 2-5 days
> Coryza = most common symptoms
Complications:
1. chronic bronchitis
2. Sinusitis
3. Otitis media

Rna viruses II : arboviruses & rubella

Arboviruses :
> transmitted by blood-sucking arthropod vectors
> over 200 identified arboviruses; ( 80) shown to cause disease in humans.
a. Alphaviruses = members of Togaviridae family
b. Flaviviruses = Flaviviridae family
c. Bunyaviruses = Bunyaviridae
d. Reoviruses = Reoviridae
> most arboviruses are named acc. To where they were discovered. ( California encephalitis virus)

Major Families & Genera of Arbovirus :

Family

Structural Characteristics

Genus

Examples

1. Togaviridae

+ RNA, enveloped

Alphaviruses

Eastern equine encephalitis

Western equine encephalitis
California equine; Venezuelan
equine

2. Flaviviridae

+ RNA, enveloped

Flaviviruses

Yellow fever virus;

Dengue virus;
St. Louis encephalitis
Japanese B encephalitis
Central European encephalitis
virus

3. Bunyaviridae

-RNA, enveloped

Bunyaviruses

California encephalitis virus;

LaCross encephalitis virus

Phleboviruses
Nairoviruses

Sandfly fever virus

Crimean-Congo hggc fever

4. Reoviridae

A.

Segmented DS,RNA
naked

Orbiviruses

Colorado tick fever virus

Pathogenesis :
IP: approx. 1 WEEK
> viral replication take place in the vascular endothelium viremia.
> morbilliform rash
hemorrhagic (mucous membrane & GI mucosa, skin. DIC and thrombocytopenia
> Circulating virus reach organ for which it has special tropism. Liver (yellow fever virus), brain (encephalitis virus).

B. Clinical Disease : ( 3 clinical syndromes)

1. Arthralgia syndrome ; (exemplified by Dengue fever)
a. Flu-like syndrome with chills, saddle-back fever, headache, retroocular pain, & conjunctivitis.
b. Severe muscular & joint pain breakbone fever
c. a measles-like morbilliform rash lasting 2-3 days
2. Hemorrhagic syndrome : (yellow fever)
a. Mild cases= flu-like
*b. severe cases =extensive hemorrhage in mm of nose, GIT and bladder.

*Melanemesis = vomiting of digested blood ( typical SX)

Decrease in BP accom by paradoxical decrease in pulse rate

3. Encephalitis syndrome :
> alphavirus, flavivirus and bunyaviruses
> severe flu-like syndrome, drowsiness, nuchal rigidity and focal neurologic symptoms
> full recovery with life-long immunity.
C. Epidemiology:
1. Dengue fever =humans are the natural reservoir; transmitted by mosquito-man-mosquito cycle
2. Yellow fever = prevalent in south & central America
a. Urban yellow fever : mosquito-man-mosquito cycle
- can be controlled by immunization & mosquito extermination program
b. Sylvatic yellow fever : jungle or wild-type
3. Encephalitis :
a. Transmission = Birds are natural reservoirs, but mosquitoes can transmit the disease to horses & humans.
b. Distribution = Common in the US

Eastern, Western, California equine encephalitis,

St. Louis, and Venezuelan equine encephalitis virus

D. Diagnosis:
1. Serology = detection of antiviral antibody by ;
> hemeagglutination-inhibition or
> complement-fixation
E. Control and Prevention :
1. Mosquito abatement program
2. Exposure avoidance
Prevention :
Immunoprophylaxis for yellow fever and
Japanese B encephalitis

Rubella virus
> the only member of the Rubiviridae, also a member of the Togaviridae family.
> person- person transmission
> not an arbovirus
A. Clinical Disease : a. German measles
IP; 12-23 days ( ave. 18days)
> mild maculopapular rash ( face & thorax), accom. by retroauricular lymphadenopathy, mild fever & joint pain.
b. Congenital rubella
> Fetal defects ( infection during the 1st trimester)
*(LBW, thrombocytopenic purpura ( blueberry muffin baby)
** ( cataract, cardiac lesions-PDA, pulmonic stenosis, microcephaly w/ mental retardation ,& deafness.)

Transient abnormalities
** permanent abnormalities

B. Epidemiology :
Transmission = person to person inhalation of infected aerosolized respiratory secretions
> viral shedding is highest while the rash is present
C, Diagnosis :
a. Infant : TORCH titers
b. Pregnant women:
> specific antirubella IgM detection
D. Prevention:
a. vaccination
b. Booster shots: Lifelong immunity ff natural infection

RNA III : Orthomyxoviruses

> Influenza viruses ( types A, B, and C )

A. Structure :
Genome : (-)RNA segmented (8); enveloped
Enveloped ( lipid bilayer):
a. Hemeagglutinin (H) spikes (H1,H2,H3)
b. neuraminidase (N) spikes (N1, N2)
> both H & N spikes are immunogenic
B. Classification :
> all strains of influenza virus are designated & differentiated by the combinations of H & N Ags
II. Epidemiology :
A. Incidence: Influenza types A & B =epidemics that recur
years.
I.

q 1-3

Pandemics: 1918 (21M) deaths

1. Antigenic shift = minor antigenic changes resulting from point mutations in H & N glycoproteins
2. Antigenic drift = major antigenic changes, that results from reassortment of the 8 nucleic acid segments.
1957 = Asian influenza (H2N2)
1967 = HK influenza (H3N2)
1977 = Russian influenza (H1N1)
3. Seasonal variation : peaks in late December or January
B. Transmission :
> person-person via respiratory secretions.
III. Pathogenesis & Clinical Disease:
a. Portal of Entry = URT
b. IP. 1-3 days
c. sudden onset of fever, chills, & myalgia. Dry cough
d. Convalescence period = 1-2 weeks ( 10 days to 2 weeks for Abs to viral hemagglutinin to peak.
IV. Diagnosis :
a. Isolation
b. Serologic Dx
V. Treatment :
a. Amantadine = prevents viral penetration of the target cell or uncoating; given as prophylaxis or early in
the infection.
Side effects = insomnia, dizziness & difficulty in concentrating
b. Rimantadine = newer drug with fewer side effects than amantadine
VI. Complications:
a. Cx related to the spread of viral infection
> croup, myositis, myocarditis & pericarditis
b. Cx related to secondary infection
> secondary bacterial pneumonia; & exacerbation of COPD
c. Cx related to hypersensitivity Rxn.
1. Reyes syndrome= acute metabolic encephalopathy assoc. with fatty degeneration of the liver & other viscera.
> link to aspirin administration
2. Guillain- Barre syndrome ( ascending paralysis)=
acute inflammatory demyelinating polyradiculoneuropathy
Prevention:
a. Prophylactic amantadine = for elderly & COPD
b. Vaccination = elderly; health care workers
Important Properties of Paramyxovirus

 All members of the Paramyxoviridae family initiate infection via the respiratory tract.
Replication of the respiratory pathogens is limited to the respiratory epithelia
-Measles and mumps become disseminated throughout the body and produce generalized disease.
Classification :
> 3 genera in Paramyxoviridae family:
a. Paramyxovirus = have both H & N on their envelopes.
> Parainfluenza and Mumps
b. Morbillivirus = express hemagglutinin only.(H only)
> measles (rubeola)
c. Pneumovirus = do not express H or N
> Respiratory syncytial virus (RSV)
Paramyxoviruses include the most important agents of respiratory infections of infants and young children
Respiratory syncytial virus [RSV]
Parainfluenza viruses
Causative agents of two of the most common contagious diseases of childhood (mumps and measles).
Parainfluenza virus : 4 serotypes
a. Types 1 & 2 = usually infect children
b. Type 3
= infects infants younger than 2 years old
> tend to cause more severe disease
c. Type 4
= causes mild disease
Clinical Disease :
1. common cold
2. Laryngotracheobronchitis = assoc. with type1 & 2
3. Bronchiolitis & pneumonia = assoc. with type3

Parainfluen
za virus
(PIV)
Parainfluenza virus 4
rarely causes disease, except
for the common cold

Parainfluenza virus 3 - most

common PV isolated from
children with lower respiratory
tract infection in US

Parainfluenza
virus 1 & 2 major causes of
croup

PIV transmitted through

inhalation of respiratory
droplets from the infected
person

It enters into the human

body and reside in the
bronchioles, causes croup
(laryngotracheobronchitis)

Pathogenesis & Immunity

cause upper & lower
respiratory tract disease
without viremia
large proportion of infections
are subclinicals

Parainfluenza
Transmission= inhalation of infectious aerosolized secretions
Treatment = no specific therapy, adequate supportive therapy
MUMPS virus
> acute, generalized viral infection primarily affects the parotid glands. Usually a mild disease.
> Immunity is life-long
1. Subclinical disease = 1/3 of infections
2. Clinical disease = IP.=2-3 weeks ; non-suppurative swelling of salivary glands ( parotid). Uni or bilateral
Mumps Complications:
A. CNS
1). Encephalitis
2). Meningitis
3). Deafness = transient (4%)
B. Glandular
1). Epididymoorchitis = adolescents, rarely bilateral; infertility (rare)
2). Oophoritis = may occur
3). Pancreatitis & Hepatitis = extremely rare
Prevention:
> IMMUNIZATION
-live, attenuated vaccine
-effective & long lasting (10 years)
-given subcutaneously to children 15mos, in combination w/ measles & rubella vaccines (MMR)
-shouldnt be given to immunocompromised or pregnant women
Immune globulin isnt useful for preventing or mitigating mumps orchitis

MEASLES (Rubeola)
Transmission: inhalation respitory droplets - URT - blood, cells -skin
Clinical Disease :
1. Measles ( rubeola) :
a. IP= 10-20 days
b. Prodromal phase : lasts several days
> coryza, conjunctivitis, cough,photophobia
c. Kopliks spots = tiny, punctate, whitish rash with an erythematous base-- buccal mucosa just above the lower
molars. Occurs bilaterally 24-36 hours before rash appears.
d. Exanthematic stage = typical morbilliform rash, starts facethorax , & spreads peripherally. Rash last x 5 days.
Measles complication :
a. Respiratory tract
1. Measles pneumonia ( giant cell pneumonia)
2. Reactivation of tuberculosis =due to temporary anergy
b. CNS
1. Postinfectious encephalitis
2. Subacute sclerosing panencephalitis (SSPE) = a chronic degenerative neurologic disease with high mortality
rate occurs several years after infection with measles virus.
Treatment: none.
PREVENTION & CONTROL
Live, attenuated vaccine (1963)
Subcutaneous to children 9mos. of age

BOOSTER DOSE recommended

Pregnant women & immunocompromised persons should not be given

*Measles virus is serologically monotypic and antigenically stable qualities that facilitated the devt of a vaccine.
Respiratory Syncytial Virus (RSV)
Clinical Features
Incubation Period: 4 to 6 days after exposure (range: 2 to 8 days)
In Infants: Lower Respiratory Infections Bronchiolitis and Pneumonia
Tachypnea
Wheezing
Rales
Hypoxemia
In Young Children: Otitis Media
Older Children and Adults: URTI resembling Common Colds
productive cough
mild to moderate nasal congestion
clear rhinorrhea
increase in oral secretions with "drooling
low-grade fever
Diagnosis :

> based on clinical and epidemiologic basis

1. viral isolation from nasal swab
2. Serology
> Enzyme immunoassay (EIA) = detection of viral Ag from nasal swab.

Treatment
Supportive care (eg. Removal of secretions and Oxygen administration)
Ribavirin aerosol 3-6 days
Prevention
Vaccine still being developed
Contact Isolation
Handwashing
Use of Gloves
V: other Rna Viruses
1. Filoviruses
2. Coronaviruses
3. Rhabdoviruses
4. Reoviruses
5. Arenaviruses
6. Bunyaviruses
7. Hepatitis viruses
8. HIV and AIDS
Filovirus
Pleomorphic particles, appearing as long filamentous threads or as odd-shaped forms 80 nm in diameter.
Unit-length particles are from 665 nm (Marburg) to 805 nm (Ebola).
Filoviruses are highly virulent and require maximum containment facilities.
Types OF fILOVIRUS:
1. EBOLA VIRUS
cylindrical/tubular and contain viral envelope, matrix and nucleocapsid
is a zoonotic pathogen

envelope glycoprotein is encoded in two reading frames

Sudan & Zaire ebola virus are highly pathogenic

2. MARBURG VIRUS
>this virus was the reason the filovirus family was created
>like Ebola it is extremely rare and potentially deadly

>the disease was named after the City of Marburg Germany were the virus was first discovered in 1996

Virus

Disease

Marburg virus
(MARV)

Marburg
Hemorrhagic Fever

Ebola virus
(EBOV)

Ebola
Hemorrhagic
Fever

Suspected Natural
Host

Signs/ Symptoms

Bats

Sudden onset of fever, malaise, muscle pain,

headache, inflammation of the pharynx,
vomiting, bloody diarrhea

Bats

Sudden onset of fever, malaise, muscle pain,

headache, inflammation of the pharynx, vomiting,
bloody diarrhea

Genome structure
Non-segmented
Linear, negative-sense, single stranded RNA
Contain 7 structural and regulatory genes
(4 virion structural protein : VP30, VP35, NP, polymerase L protein 3 membrane associated protein: VP40, GP, VP24)
Virion Structure
Pleomorphic
Enveloped
Consists:
Nucleocapsid
Polymerase complex
Matrix protein
80nm in diameter and 130-1400 nm long
U or 6 shaped
Epidemiology
The reservoir of filoviruses remains a mystery.
No non-human vertebrate hosts or arthropod vectors have been identified.
Serological studies suggest filoviruses are endemic in many countries of the central African region.
It might also be endemic in other countries (Germany, United States, Philippines).
Marburg and subtypes Sudan and Zaire of Ebola are common in African continent.
The Ebola Reston outbreak documented for the first time the presence of a filovirus in Asia.
Mode of transmission
> Person-to-person transmission
> Blood (through broken skin or mucous membrane)
> Sexual contact
>Needles
> Bodily fluids from infected animals
*Not spread through the air or by water, or food.
Incubation Period:
>ranges from 2-21 days after exposure, (Ave.) 8-10 days.

Early signs and symptoms:

> Fever with chills
> Severe headache
> Joint and muscle aches
> Weakness

Over time, symptoms may include:

.Diarrhea (may be bloody)
.Red eyes
.Raised rash
.Chest pain and cough
.Stomach pain
.Severe weight loss
. Bleeding, usually from the eyes, and bruising (people near death may bleed from other orifices, such as ears, nose and
rectum)
Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.
*People recover from ebola infection develop antibodies that last for at least 10 years.
LABORATORY
Test

Target

Source

Remarks

Indirect immunofluorescence
assay (IFA)

Antiviral antibodies

Serum

Simple to perform, but prone to

non-positives and subjective
interpretation

Enzyme-linked immunosorbent
assay (ELISA)

Antiviral Antibodies

serum

Specific and sensitive, but initial

response slower than IFA

Polymerase chain reaction (PCR)

Viral Nucleic acid

(RNA)

Blood, serum,
tissues

Rapid and sensitive, but requires

expensive and specific equipment

Electron Microscopy

Viral particle

Blood, tissues

Unique morphology
(immunostaining possible), but
insensitive and requires expensive
equipment

Virus Isolation

Viral particle

Blood, tissues

Virus available for studies, but

requires time

Immune blot

Antiviral Antibodies

Serum

Protein specific, but interpretation

sometimes difficult

Antigen ELISA

Viral Antigen

Blood, serum,
tissue

Rapid and sensitive, but requires

specific equipment

Immunohistochemistry

Viral Antigen

Tissues (skin,
liver)

Inactivated material, but requires

time

Fluorescence Assay (FA)

Viral Antigen

Tissues (liver)

Rapid and easy, but subjective

interpretation

Prevention
Treatment:
Palliative care
Fluids and electrolytes
Oxygen
Blood transfusions
Treatment for other infections
CORONAVIRUSES
The genome
- SS linear non segmented +ve sense RNA
- the largest among RNA viruses.
First isolated in chicken in 1937
First human corona virus was isolated in 1965
They cause prevalent disease in humans and domestic animals (cats, dogs, birds)
Coronaviruses are large enveloped virions 120 to 160 nm,
Helical nucleocapsids.
On the surface of the envelop are club shaped projections that resemble
a solar corona
The three major antigenic groups of CoV
Group I : contains canine, feline, porcine coronaviruses and a human corona virus HCoV 229E the prototype of the group
Group II: contains bovine, porcine, rat and mouse CoV and the other human strain which is OC43
Group III :no human strains only Turkey and Avian CoV
Evolution of SARS 2003
A novel human corona virus named SARS associated corona virus represents a new fourth antigenic group intermediate
between groups I & III
Major antigenic proteins in coronavirus
1. Nucleocapsid (N) protein - phospholipid
- Binds to the viral genome to form the helical nucleocapsid that protects it from environmental conditions.
- Plays an important role in regulation of RNA synthesis transcription and virus budding
2. Spike (S) protein- Glycoprotein
- The structural proteins which forms petal shape projections of viral envelope.

- Possesses several biological function including: a. binding to specific cell receptor (viral attachment); b. Induction of
cell fusion (virus penetration, cell to cell spread and syncytia formation) c. haemagglutination and haemadsorption; d)
induction of humural and cellular responses

3.

Haemagglutinin esterase (HE) protein Glycoprotein

- Envelope protein found in group 2
corona virus which also contain shorter fringe of projection
- Responsible for virus attachment, haemagglutination and receptor destruction (virus release)

4. Integral (M) protein Glycoprotein

- A short transmembrane responsible for virus assembly and budding.
5. Small membrane (E) protein-Glycoprotein
- A small protein linked to virus envelope and plays role in virus assembly.
Epidemiology
Distributed worldwide
> Major cause of respiratory illness in adults during some winter
months
> cause 1530% of all colds
> Antibodies to respiratory coronaviruses appear in childhood, increase in prevalence with age, and are found in more than
90% of adults.
colds, usually afebrile, in adults,
symptoms are similar to those produced by rhinoviruses, by nasal
discharge and malaise.
> IP : 2 -5 days, and symptoms usually last about 1 week
SEVERE ACUTE RESPIRATORY SYNDROME (SARS)
> Animal strain from a cat like mammal in Southern China;
Pneumonia, late 2002
> Person to person spread by close contact through respiratory droplets
> Resulting in progressive respiratory failure
> First coronavirus that causes severe LRT disease in humans
Laboratory Diagnosis
1. Antigen and Nucleic Acid Detection
ELISA test
Eclectron microscopy
Polymerase chain reaction (PCR) assays
2. Isolation and Identification of Virus
> Isolation of human coronaviruses in cell culture has been difficult.
However, the SARS virus was recovered from oropharyngeal specimens using Vero monkey kidney cells.
3. Serology
ELISA
Indirect immunifluorescent antibody assays
Hemagglutination tests
4. TReament
> no specific treatments for illnesses caused by human coronaviruses
> no vaccines.
> Most people with common human coronavirus illness will recover on their own.
> Supportive and symptomatic management of symptoms
Prevention and Control
1. Administrative controls
> provide the infrastructure of policies and procedures to prevent, detect, and control infections during health care.

> To be effective, IPC measures must anticipate the flow of patients from the first point of encounter until discharge from the
facility.
2. Personal Protective Equipment
3. Standard Precautions
4. Additional infection prevention and control
Wear a medical mask when in close contact (i.e. within approximately 1 m) and upon entering the room or cubicle of
the patient;
> Perform hand hygiene before and after contact with the patient and his or her surroundings and immediately after removal
of a medical mask.

Retroviridae

Retroviridae is a family of enveloped viruses that replicate in a host cell through the process of reverse transcription.
Positive sense
Single-stranded
Linear RNA
Nucleic Acid in mRNA
3 polyadenylated tail 5 cap
Gene Groups

GAG genes
o Capsid proteins
o Core and Structural CHONS
POL genes
o Enzymes
Reverse Transcriptase
Integrase
Protease
ENV
o Envelope (Coat) Glycoproteins

VIRION STRUCTURE
General Components
Envelope
Nucleocapsid
Nucleoid
Shape
Spherical Enveloped
Pleomorphic Enveloped
Size: 80nm 100nm

Capsid (Protein Capsid)

Helical
Icosahedral
Envelope
Outer coat
Bi-lipid Layer
Spiked appearance
o Gp120
Attachment
o Gp41
Cell Fusion
Human Immunodeficiency Virus (HIV)
a.k.a.
Lymphadenopathy Associated Virus
Human T-Lymphotropic Virus
Causative agent of Acquired Immune Deficiency Syndrome
a.k.a.
Gay Compromise Syndrome
Gay-Related Immune Deficiency (GRID)
ANTIGENICITY :
> HIV infects CD4 positive cells
> Binding to CD4 by gp120
> Entry by fusion
> DNA made from RNA via reverse transcriptase
> Co-infections stimulate further HIV production
CD4 T Cell Functions include:
Macrophage Activation
Maturation of B-Cells
Induction of specific immune cell
Secretion of solubles affecting hematopoietic cells.
Cardinal Features:
T lymphocyte depletion
Death of uninfected T cells by indirect mechanisms
Monocytes are relatively refractory to the cytopathic effects of HIV
Virus survival and transport
EPIDEMIOLOGY:
Global
Since it began
75 million people have been infected
36 million people have died of HIV.
Sub-Saharan Africa (nearly 1 in every 20 adults)
71% of the people living with HIV worldwide.
119 countries; 95 million people tested in 2010.
Mortality: 1.6 million AIDS-related death in 2012.
35.3 million living with HIV at the end of 2012
National
> Most at risk: IV drug users and Unprotected sexual practice (with multiple sex partners)
> Unprotected sex: leading MOT with MSMs (increased number of new cases).
> In some areas, one in three persons most at-risk are in the 15-17 age group

> Initiation to sex and drug use is between 14 and 19 years on average.
> Only five per cent of HIV-positive pregnant women have received antiretroviral medicines
CLINICAL FEATURES OF THE DISEASE
Stages :
1. Primary infection
2. Dissemination of virus to lymphoid organs
3. Clinical latency
4. Elevated HIV expression
5. Clinical disease
6. Death
Signs and Symptoms
1. Acute Infection
2. Clinical Latency
3. Progression to Acquired Immune Deficiency Sydrome
Acute Infection:
2 4 weeks post infection (variable)
> Acute Retroviral Syndrome
Worst Flu Ever!!!
Rash
Fatigue
Muscle and joint aches and pains
Flu-like illness
Clinical Latency
Post Acute Infection up to 8 9 years (variable)
Asymptomatic HIV Infection
Chronic HIV Infection
> May be asymptomatic or with mild infections
> Chronic symptoms
> Swollen lymph nodes
> Diarrhea, Weight loss, Fever
> Cough and shortness of breath
Progression to Acquired Immune Deficiency Sydrome
Defining Criterion: CD4 T-Cell < 200 cells/mm3
Chronic Intractable Diarrhea
Pneumonia
Rapid weight loss
Recurring fever or profuse night sweats
Prolonged swelling of the lymph glands in the armpits, groin, or neck
Red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids
Opportunistic Infections
HIV infection predisposes the patient into developing certain cancers, especially Kaposi's sarcoma, cervical cancer and
lymphoma.

DIAGNOSIS
1. Antibody Tests
Enzyme Linked Immuno-Sorbent Assay (ELISA)
Rapid HIV Antibody Test
2. Antigen Tests p24 protein
3. Nucleic Acid-Based Tests (NAT)
HIV-I GAG, HIV-II GAG, HIV-env, or the HIV-pol
Confirmatory Tests :
> Western Blot for antibodies specific to HIV
> Immunoelectrofluorescence
> PCR
Other Tests
> CD4/T-cell count
> CD4 Percentage:
> Viral Load
> Complete Blood Count
> Serum Chemistry Panel
> Sexually Transmitted Disease (STD) Screening
TREATMENT
HIV-AIDS is NOT CURABLE but it can be MANAGED
The cocktail
ART (AntiRetroviral Therapy)
HAART (Highly Active AntiRetroviral Therapy)

Classes of Drugs Used Against HIV

1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3. Protease Inhibitors (PIs)
4. Entry/Fusion Inhibitors
5. Integrase Inhibitors
*Fixed-dose combinations: combo of the above classes

Indications for Treatment

HIV positivity plus either one of the following:
severe symptoms of HIV disease
opportunistic infection
CD4 count = 350 cells/mm3 or less
Pregnancy
HIV-related kidney disease
PREVENTION AND CONTROL

Rhabdoviruses
A. General Properties :
> (-) RNA, enveloped , helical
EPIDEMIOLOGY :
1. Sylvatic rabies = rabies occurring in wild animals, (skunks, raccoons, foxes, wolves coyotes mongoose, weasels, bats )
2. Urban rabies = rabies in domestic animals ( dogs, cats, horses, cattles)
Transmission :
> via animal bite ( majority of cases)
> scratch or inhalation of contaminated aerosolized animal materials ( rare)
a). Virus is found in the saliva of infected animals few days before clinical signs become recognizable.
>Virus in saliva at time of bite :30-40% transmission
> Virus in brain : 10- 15% risk of transmission
b). Bat infection maybe latent
Pathogenesis:
a. Replication and dissemination

Hepatitis viruses
Heterogeneous group of viruses with a tropism for the liver
major cause of viral hepatitis
Viruses

Classification

Nucleic acid

Enveloped

Hepatitis A

Picornavirus

SS + RNA

No

Hepatitis B

Hepadbavirus

Incomplete circular ds DNA

Yes

Hepatitis C

Flavivirus

SS + RNA

Yes

Hepatitis D

Unclassified

Circular SS - RNA

Yes

Hepatitis E

Calicivirus

SS + RNA

No

HEPATITIS VIRUSES
HAV

HBV

HCV

HDV

HEV

Transmission

Enteral

Parenteral

Parenteral

Parenteral

Enteral

Classification

Picornavirus

Orthohepadnavirus

Hepacivirus

Deltavirus

Hepevirus

Genome

+ssRNA

dsDNA-RT

+ssRNA

ssRNA

+ssRNA

HBsAg,HBeAg

Core antigen

Delta antigen

45160 days

15150 days

3060 days

Antigens
Incubation period

2040 days

1560 days

normal
exacerbates
patients, mild;
symptoms of
pregnant
HBV; chronic
women,
w/ HBV
severe; acute

Severity/Chronicity[2]

mild; acute

occasionally severe; subclinical;

510% chronic
70% chronic

Vaccine

10year
protection

Investigational
3injections, lifetime
None available None available (approved
in
protection
China)

Hepatitis B virus ( HBV )

> more serious than HAV
General Properties :
1. Structure : DANE particle
a. lipid-containing outer envelope = contains HBsAg
b. inner protein core, that sorroubds the viral nucleic acid HBcAg
c. circular ds DNA
d. DNA polymerase , which also function as reverse transcriptase
2. Associated Antigens
a. HBs Ag ( envelope): strongly immunogenic ( 70% protein
b. HBe Ag = is not part of the virus particle; but is translated from RNA that contains the pre-core and core (HBcAg)
regions
= modulates the host immune response to HBV and is an important indicator of transmissibility.

B. Classification :
>* 4 antigenic strains of HBV = same clinical disease

Significance of serologic typing of HBV ::

a). Epidemiologic
b). Medico-legal

C. Epidemiology :
1. Transmission > HBV is found in blood & blood by-products, tears, saliva, semen, urine, feces, breast milk, synovial fluid, &
CSF ( acute ill & carriers).
2. Prevalence
> 3-5% adults have been infected ( US )
> 7-10% infected becomes chronic carriers
3. Incidence :
> peaks in 15-19 year-old age group
> rarely diagnosed in children younger than 14 y.o
* Parenteral transmission ( venereal transmission )
4. Susceptibility :
Population at risks includes the ff:
a. Health care workers
b. Institutionalized individuals
c. Intravenous drug users
d. hemophiliacs
e. Renal dialysis patients
f. Infants born to HBsAg positive mothers
g. Sexual partners of HBV carriers
h. Individuals with multiple sexual partners( hetero/homo
Key facts
Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.
The virus is transmitted through contact with the blood or other body fluids of an infected person.
An estimated 240 million people are chronically infected with hepatitis B (defined as hepatitis B surface antigen
positive for at least 6 months).
More than 780 000 people die every year due to complications of hepatitis B, including cirrhosis and liver cancer 1.
Hepatitis B is an important occupational hazard for health workers.
However, it can be prevented by currently available safe and effective vaccine.
D. Pathogenesis and Clinical disease :
1. IP = 40 to 180 days
2. Clinical Disease
a. Acute (1). Subclinical
(2). Clinical infections
> Anicteric infection
> Icteric infection
Symptoms
> Most people do not experience any symptoms during the acute infection phase.
However, some people have acute illness with symptoms that last several weeks, including yellowing of the skin and eyes
(jaundice), dark urine, extreme fatigue, nausea, vomiting and abdominal pain.
> A small subset of persons with acute hepatitis can develop acute liver failure which can lead to death.
> In some people, the hepatitis B virus can also cause a chronic liver infection that can later develop into cirrhosis of
the liver or liver cancer.

> More than 90% of healthy adults who are infected with the hepatitis B virus will recover naturally from the virus
within the first year.
In infants and children:
8090% of infants infected during the first year of life develop chronic infections;
3050% of children infected before the age of 6 years develop chronic infections.
In adults:
<5% of otherwise healthy persons who are infected as adults will develop chronic infection;
2030% of adults who are chronically infected will develop cirrhosis and/or liver cancer.
Laboratory diagnosis of hepatitis B infection
Acute HBV infection :

HBsAg and immunoglobulin M (IgM) antibody to the core antigen, HBcAg.

During the initial phase of infection, patients are also seropositive for hepatitis B e antigen (HBeAg).

HBeAg is usually a marker of high levels of replication of the virus. The presence of HBeAg indicates that the
blood and body fluids of the infected individual are highly contagious.
Chronic infection is : characterized

persistence of HBsAg for at least 6 months (with or without concurrent HBeAg).

Persistence of HBsAg is the principal marker of risk for developing chronic liver disease and liver cancer
(hepatocellular carcinoma) later in life.
Treatment
WHO recommends the use of oral treatments
tenofovir or entecavir, because these are the most potent drugs to suppress hepatitis B virus. (1x/day)
> interferon injections
Prevention
> Hepatitis B vaccine is the mainstay of hepatitis B prevention.
The first virus capable of causing hepatitis was the yellow fever virus hepatitis a mosquito borne flavivirus. Other viruses than can cause
include:
Adenoviruses
[12]
Arenaviruses: Guanarito virus, Junn virus, Lassa fever virus, Machupo virus and Sabi virus ; Bunyaviruses: CrimeanCongo hemorrhagic fever virus, Dobrava virus, Hantaan virus, Puumala virus, Rift Valley fever virus and Seoul virus
[13]
Coronavirus: Severe acute respiratory syndrome virus
[14]
Erythrovirus: Parvovirus B19
Filoviruses: Ebola virus and Marburg virus
Flaviviruses: Dengue, Lujo virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus and Yellow fever virus
[15]
[16]
[17]
Herpesviruses: Cytomegalovirus, EpsteinBarr virus, Varicella-zoster virus, Human herpesvirus 6, Human
[18]
herpesvirus 7 and Human herpesvirus 8
[19]
Orthomyxoviruses: Influenza
Picornaviruses: Echovirus
Reovirus: Colorado tick fever virus, Reovirus 3
KIs-V is a virus isolated in 2011 from four patients with raised serum alanine transferases without other known cause. A causal role is
[20]
suspected.

Viral Hemorrhagic Fevers (VHFs)

Virus Families
Arenaviruses
Bunyaviruses
Filoviruses
Flaviviruses
Paramyxoviruses

VHFs are caused by viruses of five distinct families:

Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.
Each of these families share a number of features:
They are all RNA viruses, and are all enveloped, in a fatty (lipid) coating.
Their survival is dependent on an animal or insect host, called the natural reservoir.
The viruses are geographically restricted to the areas where their host species live.
Humans are not the natural reservoir for any of these viruses
Humans are infected when they come into contact with infected hosts. However, with some viruses, after the
accidental transmission from the host, humans can transmit the virus to one another.
Human cases or outbreaks of hemorrhagic fevers caused by these viruses occur sporadically and irregularly. The
occurrence of outbreaks cannot be easily predicted.
With a few noteworthy exceptions, there is no cure or established drug treatment for VHFs.

Virus

Disease

Vector

Distribution

Flexal virus

Influenza-like illness

Rice rat (Oryzomys)

Brazil

Guanarito virus

Venezuelan hemorrhagic fever

Short-tailed Cane Mouse (Zygodontomys

brevicauda)

Venezuela

Junin virus

Argentine hemorrhagic fever

Drylands Vesper Mouse (Calomys musculinus)

Argentina

Lassa virus

Lassa fever

Natal Multimammate Mouse (Mastomys

natalensis)

West Africa

Lymphocytic
choriomeningitis virus

Lymphocytic choriomeningitis

House mouse (Mus musculus)

Worldwide

Machupo virus

Bolivian hemorrhagic fever

Large Vesper Mouse (Calomys callosus)

Bolivia

Sabi virus

Brazilian hemorrhagic fever

Unknown

Brazil

Bat (Artibeus)

Trinidad

Woodrat (Neotoma)

Southwestern USA

Tacaribe virus
Whitewater Arroyo
virus

Hemorrhagic fever

BUNYAVIRIDAE
The Bunyaviridae are a very large family of single-strand, enveloped RNA viruses and consists of five genera of viruses.
Bunyaviruses that cause disease in humans include:

California encephalitis virus

Hantavirus
Crimean-Congo hemorrhagic fever
Rift Valley fever
Bwamba Fever
severe fever with thrombocytopenia syndrome

FLAVIVIRIDAE
The Flaviviridae are a family of single-stranded, enveloped RNA viruses. They are found in arthropods, and can occasionally
infect humans.
PARAMYXOVIRIDAE
The Paramyxoviridae are a large family of single-strand, enveloped RNA viruses which causes a number of human and animal
diseases.

End