Herpesvirus (dsDNA, enveloped icosahedral capsid)

Virus & Disease Characteristics Epidemiology Pathogenesis Dx, Rx, Px

Alphaherpesviridae Reproductive cycle: HSV-1 and HSV-2 HSV-1: associated with infection above the Cell culture; look
HSV-1 Short share many waist for
HSV-2 Primary target cell: properties HSV-2: below the waist, and has greater cytopathogenic
Mucoepithelial cells Human are the only potential to cause viremia effect (CPE)
o Vesicular lesions of the skin; Site of latency: neuron natural hosts Formation of
fluid contain infectious virions, Cause lytic (Asymptomatic/ Local infection of the oral/mucoepithelial multi-nucleate
heals without scar. infection of most recurrent ds is cells syncytia

o Oral Herpes Simplex/ herpes cells and latent source of Contact with the cutaneous r/c of local
Serology for
labialis/cold sore infection of contagion) sensory nerves epidemiology
Most often occurs in neurons Risk group of 1ry Vesicular rash
infancy/childhood infection: newborn, Virus transported retrogradely along the culture (fluid,
Gingivostomatitis young children, microtubules of the axons scraping, swab
most common young adults CPE, PCR, IxFx
presentation in Virus attaches to and penetrates the CNS (CSF)
young children trigeminal ganglia
Transmission: PCR, virus

(painful) Contact Establishes latency isolation
Pharyngitis more Sexual *
common Prenatal Reactivation of virus Rx: Acyclovir/ other
presentation in nucleoside analogues
adolescent HSV-1: >90% positively Virus returns to initial site of infection
DDx: HFMD, seroconvert by year 2
chancre. Recurrent HSV infection
HSV-2: Seroconversion
o Genital Herpes (usually HSV- occur later in life
2) *UV, stress, pregnancy, trauma/surgery,
o HSV Infections of the Skin syst. ds, cancer
Herpes simplex
dermatitis
Herpetic Whitlows
(fingers; dentists)
Herpes Gladiatorum
(wrestlers and rugby
players)
Eczema Herpeticum
Erythema Multiforme
CPE Ballooning of cells
Other clinical findings:
Keratoconjunctivitis
Severe encephalitis (temporal
lobe)
Neonatal herpes (HSV-2, in-utero)
Alphaherpesviridae Varicella (Chicken pox) Unlike HSV, VZV is Day 0 Day 3-6 Rx: High dose acyclovir,
HSV-3 (VZV) Acute, mild, transmitted predominantly by Airborne route Mucosa of oral (prevent 2ry infection)
highly respiratory route. URT/conjunctiva replicate in
Varicella contagious Viremia Form skin lesions regional lymph node 1ry Dx:
o Incubation period: 14d disease, mostly all over the body viremia replicate in liver & Ab detection
o Fever, malaise, anorexia affecting spleen DNA detection
o Skin maculopapular rash, children Epidemiology Day 7 Day 14 Virus isolation
itch Generalized Worldwide Virus continues to replicate in the Histology smears
Trunk head vesicular Varicella; highly liver & spleen 2ry viremia (start
(scalp) limbs eruptions of the communicable, of sx), transported to skin
Macule papule skin and mostly children <10 (vesiculopustular rash), lungs
clear filled vesicle mucous Zoster; adult-elderly (major source of contagion), gut
cloudy vesicle membrane and sometimes brain
maculopapular Zoster (Shingles) Virus remain cell associated and
eruption scabbing Reactivation of transmitted by cell to cell
(heal) VZV present in interaction
o Cx; 2ry bact infection, latent form in Gain access to trigeminal and
pneumonia, CNS involvement neurons in dorsal root ganglia latency
Varicella in Pregancy sensory ganglia
o Virus cross placenta Localization of Reactivation
o 2 types of intrauterine sd one or few Virus replicates and released
Congenital Varicella dermatomes along the entire neuronal
Syndrome (1st gest) pathway to infect skin causing
Neonatal Varicella vesicular rash (Shingles)
(final phase);
unilateral, first 4wks
of life, pneumonitis,
encephalitis, damage
to msk system

Zoster
o Rash limited to skin
innervated by a single sensory
ganglion
o Intense inflammation and pain
precedes skin lesion
o Cx; Ophthalmic zoster,
Postherpetic neuralgia
o Trunk, head, neck (T3-L3),
unilateral
Ophthalmic Zoster
o Trigeminal nerve, ocular cx
o Followed by Postherpetic N
Betaherpesviridae Reproductive cycle: Endemic in all parts of the Normal Host Dx:
HSV-5 (CMV) long world. Incubation period: 4-8wks PCR (detect
Primary target cells: Systemic dissemination replicating virus)
Clinical Features Monocytes and Transmission May readily establish lifelong Isolation of virus;
Normal Host granulocytes Sexually: semen, latent infections throat washing
o Spontaneous Infectious Latency: T cells cervical secretions, Virus shed intermittently from and urine.
Mononucleosis syndrome saliva, even urine pharynx and in urine for months Serology (IgM,
(less severe pharyngitis and Inapparent Vertically: in-utero, to years after primary infection IgG)
lymphadenopathy) infection is breast milk Reactivation of latent infection
o Cx: hepatitis (jaundice) common during Organ transplant occurs by immunosuppression
childhood and and blood borne (eg: corticosteroids)
Immunocompromised adolescent (WBC)
o Pneumonia is a freq cx The most
o Disease of transplantation common Risk group
Bone marrow congenital Individuals who
transplant recipient; infection lead to attend/work at a
interstitial severe daycare centre CPE (Owls eye) on
pneumonitis congenital Pts who undergo fibroblast cell culture
Solid organ anomalies blood transfusion
transplant recipient; Frequently Person with multiple Rx: Ganciclovir (DOC),
leukopenia found in adults sex partners Acyclovir, Valacyclovir
Heart transplant; who are Tissue
graft atherosclerosis immunocompro transplantation Px:
Renal allograft; CMV mised Isolation of
related rejection newborns
o Untreated AIDS pt; Screening of
disseminated disease transplant donors
and recipients
Congenital & Perinatal
No vaccine
o Small size, microcephaly,
jaundice,
hepatosplenomegaly, rash.
o Virus detected in
Infants urine (1st wk)
Maternal breastmilk
Ab in breast milk
does not prevent
transmission
Betaherpesviridae Replication >90% of children
HHV-6 mainly in CD4 T over age 1 and
HHV-7 lymphocytes adults are virus
Virus present in positive
saliva Typically occur in
Clinical findings Latency site not early childhood
o 1ry infection Exanthem known Mode of
Subitum (Roseola transmission
infantum/Sixth Disease) presumed to be via
o Infection persists for life oral secretions
Gammaherpesviridae Major target cell: B cells - Worldwide (>90% Reactivation from latency Dx:
HSV-4 (EBV) Latent site: B cells seropositive) Clinically silent Isolation &
Replicates in: Epithelial - >50% symptomatic Evidenced by increased levels of identification of
Clinical findings cells of oropharynx, in adolescent virus in salica and of DNA in virus (NA
o Lymphoid & epithelial tumours parotid gland, uterine - No EBV vaccine blood cells hybridization,
o Infectious mononucleosis cervix Immunosuppression is known to viral Ag marker,
o Cancers reactivate infection, sometimes viral isolation)
Burkitt lymphoma; with serious consequences Serology
fever, night sweats, (ELISA, IxFx)
swollen lymph
nodes, weight loss Rx: Acyclovir reduces
NPC EBV shedding but doesnt
affect immortalized B cells
Gammaherpesviridae A new herpesvirus Transmission: orally, Dx:
HHV-8 (KSHV) discovered in 1994. sexually, vertically, blood No readily test
Replicate in: borne, organ transplant available
Clinical findings: Lymphocytes Blood test
o A blood cancer called Outstanding feature: - Frequently occur in
Kaposis sarcoma molecular AIDS patients Rx: Ganciclovir (effective
o Lymphoma piracy/molecular mimicry - Africa >50% in preventing KS, but
o Castlemans disease (some (Rather than dev its own - Italy, Greece, Israel, unsure on tumors that
forms of severe lymph node oncoprotein, it steals Saudi Arabia >10% already exist)
enlargement) many genes from host - North America
cell) <10%
Hepatitis Viruses
Virus Characteristics
Hepatitis A Nucleic acid: ssRNA, +ve Routes of transmission
Classification: Picornaviridae
Non enveloped, acid
and heat stable.
One serotype, multiple
genotypes.
In vivo replication:
cytoplasm of
hepatocytes (humans
and higher primates
Hepatitis E Nucleic acid: ssRNA, +ve
Classification: Unclassified,
hepevirus
Non enveloped, acid - Mainly young adults
stable
One serotype with
genetic heterogeneity
In vivo replication:
cytoplasm of
hepatocytes (humans &
higher primates)
Hepatitis C Nucleic acid: ssRNA, +ve Prevalence
Classification: Flaviviridae
Enveloped
Epidemiology Clinical Features Dx, Px, Rx
No chronic infection. Dx test:
- Fecal oral/ Acute Infection
Contamination of Sporadic IgM anti-HAV
food or water Transmission Chronic Infection
- Close personal o Oral (common) not applicable
contact o Percutaneous (rare)
- Blood borne (rare) o No sexual/perinatal Immunity: IgG anti-HAV
Average incubation period: 30d - Pre-exposure
Jaundice: Adult (30%), Children (travellers to high
(<5%) risk regions)
Fulminant <1% - Post-exposure
Onset of symptoms (within 14 days)
o Fatigue
o Abdominal pain Case fatality rate: 0.1-2.7%
o Loss of appetite
o Nausea & vomiting
o Dark urine
o Jaundice
- Fecal oral Similar to HAV; more severe in preg. Dx test:
transmission Can cause severe acute hepatitis. Acute Infection
(Contaminated No chronic infection. IgM anti-HEV
water supplies) Chronic Infection
Transmission not applicable
- Can infect primates, o Oral (common)
swine, sheep, rats o No sexual Immunity: not applicable
- Maternal-infant o Yes perinatal Case fatality rate:
transmission occurs Incubation period: 15-16d 0.5-4% in non-pregnant
(last trimester) and Clinical illness at presentation: 70- 1.5-21% in pregnant
is often fatal 80% in adults
Jaundice (common)
Fulminant <1%, in pregnancy 30%
Transmission Dx test:
- Worldwide (3%) o No oral Acute Infection
- Africa (5.3%) o Percutaneous (common; HCV RNA, Anti-
- Eastern IVDU) HCV
Mediterranean o Yes sexual (rare) Chronic Infection
(4.6%) o Yes perinatal (low freq) HCV RNA, Anti-
- SEA (2.15%) Incubation period: 14-160d HCV >6mnths
- Americas (1.7%) Clinical illness at presentation: ALT (>x10)
 - Europe (1%) jaundice (5-10%) Chronic pt may
Fulminant: rare have normal ALT
With/ without
jaundice

Immunity: no vaccine
available
Rx: Ribavirin & IFN therapy
Case fatality rate: 1-2%
Hepatitis B Nucleic acid: dsDNA Risk factors Transmission Dx test:
Classification: Hepadnaviridae - Perinatal o Oral (not likely) Acute Infection
- Sexual o Percutaneous (common) HbsAg, IgM anti-
Enveloped - IVDU o Sexual (common) HBC
Multiple serotypes and - Organ transplant o Perinatal (common) Chronic infection
genotypes A-F - Hemophiliac Incubation period: 60-180d HbsAg, IgG anti-
- Pt with chronic renal Jaundice: 5-20% HBC
failure/ Fulminant <1% HBeAg (high
hemodialysis Chronic infection infectivity)
- Healthcare workers o >90% infants Anti-HBc IgM
- Tatooing/ body o <5% adults (Acute Infection)
piercing Anti-HBe (Low
HBV Gene Products infectivity)
Risk of chronic infection: - Core gene; HBcAg, HBeAg Anti-HBs
Neonates - Surface; HBsAg (Immunity)
- Polymerase HBV DNA
Terminal protein (priming) (Viremia/Active
Reverse transcriptase replication)
Rnase H
Immunity: HBIg, HBV
Vaccine (IgG anti-HBc, anti-
HBs)
Rx: IFN-, Pegylated IFN-,
Lamivudine, Adefovir,
Entecavir, Telbivudine,
Tenofovir
Hepatitis D Nucleic acid: ssRNA - HDV requires HBV to replicate and Dx test:
Classification: Unclassified, delta frequently assoc with severe Serological test for
virus acute/chronic hepatitis delta Ag or HDV
- Co-infection or superinfection IgM and IgG
HBV Envelope
One serotype, 3 Immunity: no vaccine
genotypes
Respiratory Viruses

Virus Characteristics Epidemiology Pathogenesis & Clinical Features Dx, Px, Rx

Orthomyxoviruses Virion: spherical, Epidemiologic pattern differ: Surface Ag of influenza undergo antigenic Dx:
Influenza A pleiomorphic, helical Influenza A can variation Usually based on
Influenza B nucleocapsid sweep across - Antigenic drift: Minor changes (point characteristics of
Influenza C Genome: ssRNA, -ve, continents mutation) amino acid changes symptoms
segmented (pandemic) escape from immune system local Specimen (nasal
Envelope: Contain HA Influenza B cause outbreaks washing, gargles,
(hemagglutinin) and NA epidemics - Antigenic shift: Major changes in HA throat swab)
(neuraminidase) (exclusive human & NA (Only Influenza A) new RT-PCR
Replication: Nuclear virus) subtypes pandemic Isolation and
transcription, particle Influenza C cause identification of virus
mature by budding sporadic respiratory Gene reassortment: (CPE)
from plasma disease Infection of two/more members of the Serology
membrane influenza virus of the same genus, mixtures of
Outstanding 3-5 million cases, parental gene segments may be assembled Rx:
characteristics: 2.5-5mil deaths into progeny virions Acetaminophen
Influenza A undergo worldwide Antihistamines
Airborne droplet/contracted with contaminated
genetic reassortment; Epidemic outbreak: Zanamivir and
hands/surface
cause worldwide seasonal Oseltamivir (target
epidemics Escape Ab neutralization NA)
Subtypes: based on People at risk Amantadine and
HA and NA (Only Seronegative Infect and kill epithelium Rimantadine
Influenza A has people (uncoating step)
subtypes) Adults: classic flu Progeny virus kill adjacent cells
Vaccine
syndrome
Viral NA lower the viscosity of the mucus
Children:

asymptomatic to Spread virus-containing fluid to lower portion of
severe RTI the respiratory tract
High risk groups:
elderly and Many cells are killed
immunocompromis
ed, people in Pathology
nursing homes or Incubation period: 1-4d
with underlying IFN and cytokines detected in
cardiac/ respiratory respiratory secretion
problems Cellular destruction is repaired may
be exposed to 2ry bacterial infection
(staph, strep, H.influenzae)

Clinical findings
 Acute influenza (Adults): Rapid onset
fever, chills, headache, dry cough,
myalgia, malaise, anorexia
Acute influenza (Children): Higher
fever, GI manifestation, febrile
convulsion, otitis media, croup
Cx: pneumonia (1ry viral, 2ry
bacterial), neurologic sd (Reyes sd,
GBS, encephalitis)
Paramyxoviruses Morphology: spherical Measles (Rubeola) Replication: Lab Dx RSV:
Respiratory Genome: ssRNA, -ve, linear, Acute, highly - Attach to host cells - Antigen detection
Syncytial Virus non-segmented infectious disease - Virion envelope fuses with the cell (IxFx, ELISA)
(RSV) Envelope: contain viral HN charac by fever, membrane by F protein - Isolation and
Measles Virus (hemagglutinin that sometime resp sx, and a - Transcription, translation, RNA identification of virus
Mumps Virus carries neuraminidase activity) & maculopapular rash replication takes place in the - Nucleic acid
fusion (F) glycoprotein fusion, Cx are common cytoplasm (-ve sense use +ve detection
hemolysis and viral entry (pneumonia, sense as template) - Serology
Replication: cytoplasm; particle diarrhea, - Maturation
buds out from plasma encephalitis) budding of cell surface
membrane Leading cause of - Assembly & release;
Outstanding characteristics: death in young M protein important
antigenically stable, particle are children NA activity prevent self-
labile yet highly infectious In pregnancy aggregation of virus
abortion, stillbirth, Exit without killing cell
Classification based on specific premature birth
features Airborne/droplet RSV CPE (Syncytial
Pneumovirus cause Encephalitis caused by
Escape Ab production
formation)
pneumonia (eg:RSV) measles:

Henipavirus cause 0.5% occurrence, Infect respiratory epithelia Dx Mumps:
zoonotic infection (eg: 1.5% mortality - Usually clinical
Nipah virus) 2 ways: Common cold, croup [Type 1,2,3 RSV] - Sx of mumps are
Classification based on HN & F: postinfectious non-specific
Respirovirus & encephalitis Viremia [Measles, Mumps]/Spread to lower - Classic finding of
Rubulavirus possess (immune mediated), trachea & bronchi Pneumonia/bronchitis parotid gland
direct infection of [RSV, type 3]
HA and NA activities tenderness and
Measles has HA but neurons swelling (day 3)
Subacute RSV:
lacks NA activity, has - Lab Ix: Isolated viral
F. sclerosing Inapparent infection or the common culture from saliva,
cold pneumonia in infants to
F of RSV possess panencephalitis urine and CSF
(SSPE) very rare bronchiolitis in very young babies - Serology
fusion property but not
hemolysin. RSV lacks and late sequelae Wheezing
HA and no NA of measles Reinfection is common in both adults Rx Mumps:
and children
 Mumps cx:
Measles (Rubeola)
Structure differs from
other paramyxoviruses
Spikes carry HA but not
NA function
F protein is also a
haemolysin
Only one serotype
Mumps
Highly contagious viral
infection
Self-limited disease but
presence of
complications might be
severe
Envelope: HN
(agglutinate RBC and
attachment), F (fusion,
hemolysin, antigenic)
No cross immunity with
parainfluenza virus
Replication: Nasal or
URT epithelial cells
Viremia to salivary
glands & other major
organ systems
In elderly may cause symptoms To provide comfort;
- Aseptic meningitis similar to influenza virus disease. Analgesics
(50%) Pneumonia may develop (acetaminophen,
- Meningoence- RSV is an important cause of otitis ibuprofen), warm or
phalitis after media cold packs.
inflammation of MMR Vaccine (80%
salivary glands Measles: effective)
- Meningitis > Regional lymph nodes
encephalitis
- Usually resolve Viremia/monocytes & lymphocytes
without sequelae
Lytic infection of cells of conjunctiva, RT, UT,
- Others; arthralgia in
lymph, blood vessels and persistant infection of
young male, CNS
myocarditis,
abortion in pregnant Rash caused by T cell response
women
Prodromal illness; high fever, cough,
coryza, conjunctivitis, photophobia
Koplik spots (red spots with white
centre on buccal mucosa) appear
after 2d
Within 24hr exanthema start below
ears and spread over
Mumps:
Prodromal period: malaise & anorexia
Classic parotitis; tender, earache
Propensity to replicate in various
visceral organs; kidney, CNS, testes
and ovaries
Virus entrance into URT
Local lymph nodes/1ry viremia
Salivary glands/Testes, ovaries, CNS, pancreas
2ry viremia
Kidneys
Viruria
Enterovirus & Poliovirus

Virus Epidemiology Pathogenesis Dx, Rx, Px

Picornaviridae Enterovirus Enterovirus pathogenesis Dx polio:
Enteroviruses - Resist pH3 to pH9, detergent, mild 1. Entry into the body Virus usually
o Polio sewage treatment, heat a. Cell surface receptors mediate tissue present in the
o Coxsackie A - Transmitted fecal-oral route or tropism throat and in the
o Coxsackie B respiratory route (aerosol droplet) b. Poliovirus receptor (restricted) stools before onset
o Echovirus - Asymptomatic shedding can occur up c. Coxsackie and Echovirus receptors are Virus may be found
Rhinoviruses to months more widespread on tissues (broader in the blood of pt
Hepatoviruses - Schools and day care settings disease spectrum) with aseptic
Parechoviruses 2. Viral replication and disease progression meningitis
Kobuviruses Poliovirus a. Primary infection Ab to virus appear
- Vaccine era i. Mucosa and lymphoid tissues of early in the disease
Virion: Icosahedral Wild type poliovirus has tonsils and pharynx Specimen: throat
Genome: ssRNA, +ve, linear been eliminated from ii. Lymphoid cells of Payers swabs, rectal
Replication: Cytoplasm developed countries patches and underlying intestinal swabs, stool
Non enveloped Paralytic polio is still mucosa Cell culture
prevalent in Nigeria, b. Primary viremia Genome and
Genera of diseases Afghanistan, Pakistan c. Secondary viremia and sx serology: RT-PCR,
Enteroviruses Mutation in live vaccine virus i. Disseminated to target organ IF, ELISA, IgM
disease of GIT and re-establishes ii. Potential target organ: CNS and (four fold)
able to cause CNS neurovirulence skin
disease Salk (killed virus) IPV 3. Immunity: protection via Ab Symptomatic Rx:
Rhinovirus Sabin (live attenuated virus) 4. Release of virus back to environment by fecal - Acetaminophen
Nasopharyngeal ds trivalent OPV shedding (fever)
- Children are more susceptible than
Hepatovirus HAV - Mouthwashes and
adults, causing infantial paralysis, but Poliomyelitis; acute infectious ds that affects the CNS in its
Parechovirus GIT sprays (oral
infection in adults would produce serious form. The destruction of motor neurons in the spinal discomfort)
and RT
more severe sx cord results in flaccid paralysis.
Kobuvirus Viral GE - Fluids
- Levels of hygiene Only a fraction develop paralytic disease (dehydration)
Asymptomatic infection (90%) - Cold milk
Enterovirus serotypes
Polio (1-3) Abortive/minor illness (5%) (neutralize acid
Coxsackie A (1-22, Non-paralytic progression to CNS or aseptic juices that irritate
24) meningitis (1-2%) mouth ulcers)
Coxsackie B (1-6) Paralytic polio (0.1-2%) - Topical
Echovirus (1-9, 11- o Spinal polio destruction of motor neuron diphenhydramine
27, 29-34) o Bulbar (cranial) polio destruction of (hand and foot
Other enteroviruses cranial nerve discomfort)
(68-71) - IVIg treatment
Paralytic poliomyelitis
- Spinal polio
Viremia virus infect skeletal ms and
 travel up innervating nerves spread
along axons of peripheral nerves to CNS
destruction of motor neuron of anterior
horn of spinal cord and motor cortex of
brainstem
Nerve damage extend of paralysis
Asymmetric flaccid paralysis with no
sensory loss
- Bulbar polio
Involve the brainstem where the cranial
nerves are located
Involve muscles of the pharynx, vocal
cords and respiration
75% death inability to swallow, breath

Postpoliomyelitis; years after infection

Coxsackie viruses
Group A
o Herpangina (vesicular pharyngitis),
HFMD, acute hemorrhagic conjunctivitis,
diarrhea, pneumonitis
Group B
o Pleurodynia (pleuritic chest pain),
myocarditis, pericarditis, severe infantile
generalized disease
A number of group A and B serotypes can give rise
to meningoencephalitis and paralysis

Enterovirus 68-71
Nonspecific fever, aseptic meningitis, paralysis,
myocarditis, sepsis
Enterovirus 70 hemorrhagic conjunctivitis
Enterovirus 71 HFMD, polio-like syndrome
Arboviruses

Virus Epidemiology Pathogenesis Dx, Rx, Px

Family: Togaviridae
Genera: Alphavirus
- Chikungunya
Family: Flaviviridae
Genera: Flavivirus
- Dengue
- Japanese Encephalitis
- West Nile Fever
- Yellow Fever
- St. Louis Encephalitis
Transmission pattern of Arboviruses:
Human-arthropod cycle (Eg: Urban
yellow fever, dengue, chikungunya)
Lower vertebrate-arthropod
Human accidental host (Eg: Jungle
yellow fever, St. Louis encephalitis)
Arthropod-arthropod cycle,
occasionally humans and lower
vertebrate (Eg: Colorado tick fever)
General clinical manifestations:
Four types of reactions to Arboviruses
A mild fever: sometimes with a rash
A long term fever: persistent arthritic
symptoms, often with a rash
Hemorrhagic fever: serious
Encephalitis: serious, often fatal

Family: Bunyaviridae
Genera: Bunyavirus, Plebovirus,
Nairovirus, Hantavirus
Dengue Fever (DF)
4 main serotypes DENV
1,2,3,4
Vector; female Aedes
o Aedes aegyptii
(day)
o Aedes albopticus
(day and night)
Tropic areas Viral pathogenesis Dx:
o Poorly planned Bite: Skin inoculation by vector Clinical finding
urbanization Travel history
Virus infects immature dendritic cells/macrophage
o Global population growth
FBC
o Increased air travel Migration of virus to lymph nodes Hematocrit (Correlate
50-100mil infections per year well with plasma
worldwide Activation of cellular and humoral immune response volume loss and
>2.5 billion people at risk of disease severity)
infection Viral replicates in macrophage for 3-6 days (incubation Serology;
period to viremic state)
Fatality rate <1% with appropriate o Hemagglutinin
therapy Inhibition (HAI)
Clinical criteria of dengue infection
Warm and wet conditions are test detect
Asymptomatic (50-90%)
favoured by the mosquitoes early but cross
Classic DF rapid onset high fever, HA,
Transmission react with
retro-orbital pain, myalgia, vomiting, sore
o Epidemic introduced as other
throat, maculopapular rash flaviviruses in
an isolated event, involves
single viral strain Dengue hemorrhagic fever/Dengue shock late infection
o Hyperendemic syndrome bleeding and endothelial leak Direct detection
continuous circulation of o RT-PCR
multiple viral serotypes Clinical Manifestations and Pathophysiology o NS-1 Ag
o Persons with DENV in their 1. Incubation period detection by
blood can transmit the 2. Febrile phase ELISA (IgM Ab
viruses to the mosquito 1 a. High grade fever (2-7d) capture
day before onset of febrile b. Usually: facial flushing, skin ELISA)
erythema, generalised body ache,
 period and remain
infectious for the next 6-7d
o A. aegypti bites
interruptedly during blood
meals
o Mosquito remains
infectious for its 1-month
life
Japanese Encephalitis (JE) 50,000 cases annually, with
Vector; Culex mosquitoes permanent neurological or
4 distinct genotypes psychological handicap, 25% died
Birds pigs/cattle/dogs
Humans are dead-end host
Cannot be spread from human to
hman and eating pork
Rural areas
All genotypes: Malaysia, Indonesia
Zika Virus Transmission: Mosquito bites, mother to
Vector; Aedes child (transplacental), sexual contact, blood
transfusion
myalgia, arthralgia, HA
c. Sometimes: sore throat, injected IgG ELISA
pharynx, conjunctival infection - Paired samples
d. Common: anorexia, nausea and - Differentiate between
vomiting 1ry and 2ry infections
e. DHF: petechiae, bruising - Confirmatory test
3. Critical phase (Day 3-7)
a. Progression of leukopenia Lab confirmation: Plague
(neutropenia) reduction and neutralization test
b. Mod-severe thrombocytopenia (PRNT)
c. Plasma leakage; hemoconc. And
hypoproteinemia Prognosis:
d. Sweat, cool extremity, restless, DHF; treated 2.5% mortality,
skin and mucosal bleeding untreated 50% mortality
e. Shock
4. Recovery phase Management
a. Resorption of leaked plasma - Acetaminophen for
b. Stable hemodynamic status pain/fever
c. Profound fatigue for several - Monitor development of
weeks plasma leakage
(haematocrit)
DHF/DSS - Monitor hydration status
Ab-dependent enchancement - Blood transfusion if
Pre-existing non neutralizing Ab (IgG) bing significant bleeding
to DENV [AgAbCx] - Careful volume
Viral entry through monocytes and other repletion
FcR-presenting target cells
Suppression of innate immune response; Control; No vaccine, surveillance
release of inf cytokines and chemokines, control, vector control
enhanced disease
- Target cell: T lymphocytes and periph. - Antigen relatively
Mononuclear cells neurons homogenous &
- More severe in young and elderly recovery results in solid
individual protection
- Early: Fever, GI symptoms, HA - Cut trans of disease,
- After 3-14d: rapid LOC, stupor coma education and
- Survivor: brain damage vaccination
- Seizures in children - No effective drug avail,
ribavirin can be given
Sx: fever, rash, joint pain, conjunctivitis
In pregnancy: microcephaly, other fetal brain
defects
Retroviridae
Virus
Lentiviruses
Human Immunodeficiency
Viruses
o HIV-1
o HIV-2
All retroviruses have 3 essential
genes which encode polyprotein
precursors for viral replication Transmission
Gag (group specific - Blood
antigen) gene encodes
o Viral matrix (MA)
p17
o Capsid (CA)
p24
o Nucleo-protein
(NC)
Pol gene encodes
o RT including
RNase H
o Intergrase (IN)
provirus
integration
o Protease (PR) HIV and STDs
encodes prod
that cleaves gag
Env(elope) gene
o Surface
glycoprotein (SU)
o Transmembrane
(TM) polyprotein
Morphology: Type C Lack of
morphologically recognizable
intracytoplasmic form.
Genome: ssRNA, +ve, 2 copies of
RNA genome
Replication: Depends on RT
Enveloped
Epidemiology
In 2010, WHO estimated that 34 mil
people were living with HIV, of whom
>30 mil were living in low-middle income
countries
2014 36.9 mil people living with AIDS
worldwide, more than half do not know
they are infected, 1.2 mil died
Open cuts
Breaks in the skin
Mucous membranes
Direct injection
Occupational exposure
- Sexual contact
MSM, FSF, MSF
Semen
Vaginal secretion
- Perinatal
Breast milk
- Not transmitted by casual contact
STDs increase infectivity to HIV
o Increase in HIV viral shedding
o More WBC carrying HIV in
mucosa of genital area
STDs increase susceptibility to HIV
o Ulcerative and inf. STDs
compromise the
mucosal/cutaneous surfaces of
genital tract that normally acts
as barrier against HIV
o Ulcerative STDs: syphilis,
chancroid, genital herpes
o Inf. STDs: chlamydia,
gonorrhoea, trichomoniasis
Effect of HIV on immune system
increases risk of STDs
Pathogenesis Dx, Rx, Px
HIV primarily infects CD4 T cells and cells Lab Dx:
of macrophage lineage Screening tests
o Requires blood
Virus causes lytic infection of CD4 T cells
and persistent low level productive sample
infection of macrophage lineage cells o Detect the bodys Ab
response to HIV
Virus causes syncytia formation, with response
cells expressing large amounts of CD4 o Test does not detect
antigen (T cells); subsequent lysis occurs HIV
o 4th generation Ab/Ag
Virus alters T cell and macrophage cell
tests p24 (detected
function
during window period)
Virus reduces CD4 T cell number and o Assay for viral Ag and
helper cell maintainence of CD8 T cell and viral genome can also
macrophage function detect very early/very
late infections
CD8 T cell number and macrophage o Exposed should be
function decrease
retested at least 6
months after last
Three Phases of HIV exposure
o EIA/ELISA
Confirmatory tests
o IFA
o Western Blot; show
atleast 2 of p24, gp41
and gp120/160
Viral load tests
EIA/ELISA
+ve
Phase I: Primary infection/Acute Repeat EIA/ELISA
infection +ve
IFA/Western blot
- Lasts 3-8wks
+ve
- Virus replicates to high titer
Positive for HIV
(usually of RS type which is M
tropic MO tropic)
HIV Testing
- When CTL develop,
- Requires informed consent
seroconversion occurs and viral
- Premarital testing
load diminished in blood
recommended
- Prenatal testing not required
 o Supressed IR due to HIV can: Phase II: Asymptomatic/latent/ but recommended
Classification of HIV-1 Genital ulcer chronic phase
Major group M reactivation - Lasts for months to >15y, HIV Risk Reduction
Outlier group O Rate of abnormal average 10 y - Avoid drug and alcohol use
New group N cell growth - Continuation of virus replication - Dont share needles used by
- More than 90% of HIV-1 Difficulty in curing mainly in lymph node others for; drugs, tattoos, body
infections belong to HIV-1 reactivated/newly - Active IR and antigenic escape piercings
group M acquired genital ulcer - Concluded by development of - Avoid exposure to blood
Risk of becoming opportunistic infection (CD4 T products
infected with cell <200/mm3) - Practice safe sex; use
additional STDs condoms
Phase III: AIDS
HIV Post Exposure Prophylaxis - Host immune response HIV vaccines
HIV Occupational Exposure collapses - Preventive vaccines
Medical follow up Constitutional sx - Therapeutic vaccines
Baseline and follow-up HIV testing Opportunistic
4wk course of medication initiated one infections
to two hours after exposure Neoplasm
LFT to monitor medication tolerance - Clinical progression to AIDS
Exposure precautions practiced - Syncytium inducing T tropic T
lymphocyte tropic (x4 viruses)
are detected in most if not all
cases