MICROBIOLOGY Dra. Bunyi 3rd shifting Dec.

5, 2007

Herpesviruses shar, cams, joy Class no.:

 Mean number of episodes per year: 16

PROPERTIES OF HERPESVIRUSES
 enveloped double stranded DNA viruses PATHOGENESIS:
 genome: long and short fragments oriented in either  Primary infection, HSV spreads locally and a short-
direction, giving a total of 4 isomers lived viremia occurs, whereby the virus is
 set up latent or persistent infection following primary disseminated in the body. Spread to the
infection craniospinal ganglia occurs.
 Reactivation – more likely during periods of  The virus then establishes latency in the
immunosuppression craniospinal ganglia.
 Both primary infection and reactivation are likely to be  The exact mechanism of latency is not known. It
more serious in immunocompromised patients may be true latency where there is no viral
 3 subfamilies: replication or viral persistence where there is a
1. Alphaherpesviruses – HSV-1, HSV-2, VZV; rapid low level of viral replication.
growth, latency in sensory ganglia  Reactivation – triggers can provoke a recurrence.
2. Betaherpesviruses – CMV, HHV-6, HHV-7; slow These include:
growth; restricted host range o Physical or psychological stress
3. Gammaherpesviruses – EBV, HHV-8; growth in o Infection, especially pneumococcal and
lymphoblastoid cells meningococcal
o Fever
HERPESVIRUS PARTICLE o Irradiation, including sunlight
ALL herpesviruses have identical morphology and cannot o Menstruation
be distinguished from each other under electron
microscopy. CLINICAL MANIFESTATIONS:
HSV is involved in a variety of clinical manifestations
HERPES SIMPLEX VIRUS which includes:
PROPERTIES:  Acute gingivostomatitis
 Belong to the α-herpesvirus subfamily of  Herpes labialis (cold sore)
herpesviruses  Ocular herpes
 Double stranded DNA enveloped virus with a  Herpes genitalis
genome of around 150 kb  Other forms of cutaneous herpes
 The genome of HSV-1 and HSV-2  Meningitis
o Share 50-70% homology  Encephalitis
o Share several cross-reactive epitopes with  Neonatal herpes
each other
o Also antigenic cross-reaction with VZV ACUTE GINGIVOSTOMATITIS
 Man is the only natural host for HSV  Commonest manifestation of primary herpetic
infection
EPIDEMIOLOGY:  Manifestations: pain and bleeding of the gums
 HSV – spread by contact (shed in saliva, tears, o 1-8 mm ulcers with necrotic bases are present
genital and other secretions) o Neck glands are commonly enlarged
 most common form of infection result from a KISS accompanied by fever
given to a child or adult from a person shedding  Usually a self-limiting disease which lasts around
the virus 13 days
 primary infection:
o usually trivial or subclinical in most individuals HERPES LABIALIS (COLD SORE)
o disease mainly of very young children (<5  Following primary infection, 45% of orally infected
years) individuals will experience reactivation
 two peaks of incidence:  Herpes labialis is a recurrence of oral HSV
o 0-5 years  A prodrome of tingling, warmth or itching at the
o Late teens (sexual activity commences) site usually heralds the recurrence. About 12
 10% of the population acquires HSV infection hours later, redness appears followed by papules
through the genital route and the risk is and then vesicles.
concentrated in young adulthood
 Generally: OCULAR HERPES
o HSV-1 causes infection above the belt HSV causes a broad spectrum of ocular disease, ranging
o HSV-2 below the belt from mild superficial lesions involving the external eye to
 Clinical isolates: severe sight-threatening diseases of the inner eye.
o 40% from genital sores are HSV-1 Diseases caused include the following:
o 5% of strains isolated from the facial area are  Primary HSV keratitis – dendritic ulcers
HSV-2 (data is complicated by oral sexual  Recurrent HSV keratitis
practices)  HSV conjunctivitis
 Following the primary infection, 45% of orally  Iridocyclitis, chorioretinitis, and cataract
infected individuals and 60% of patients with
genital herpes will experience recurrences GENITAL HERPES
 Actual frequency of recurrences varies widely  Genital lesions may be primary, recurrent, or
between individuals initial

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  Sites: penis, vagina, cervix, anus, vulva, bladder,
sacral nerve routes, spine and meninges
o Lesions of genital herpes prone to secondary
bacterial infection
o E.g., S. aureus, Streptococcus, Trichomonas,
C. albicans
 Dysuria: common complaint; in severe cases,
there may be urinary retention
 Local sensory nerves may be involved leads to
radiculitis
 A mild meningitis may be present
 60% of patients with genital herpes will
experience recurrences. Recurrent lesions in the
perianal areas tend to be more numerous and
persists longer than their oral HSV-1 counterpart.
HERPES SIMPLEX ENCEPHALITIS
 One of the most serious complications of HSV
disease
 2 forms:
o Neonatal: global involvement; brain is almost
liquefied; mortality rate approaches 100%
o Focal disease: temporal lobe most commonly
affected; appears in children and adults; arise
from reactivation of virus; mortality rate is
high (70%) without treatment
 Utmost importance: make a diagnosis of HSE early
o IV acyclovir: given in all cases of suspected of
HSE before laboratory results are available
NEONATAL HERPES SIMPLEX
 Incidence varies from country to country
o US: 1 in 4000 live births
o UK: 1 in 10000 live births
 Baby is usually infected perinatally during
passage through the birth canal
 Premature rupturing of the membranes is a well
recognized risk factor
 Risk of perinatal transmission: greatest when
there is a florid primary infection in the mother
 Smaller risk from recurrent lesions in the mother:
lower viral load and the presence of specific
antibodies
 Other sources: oral lesions from the mother or a
herpetic whitlow in a nurse
 Spectrum: mild disease; localized to the skin 
ftal disseminated infection
 Infection: particularly dangerous in premature
infants
 Organs involved in disseminated disease:
o Liver, adrenals and the brain
o Brain involvement: prognosis is severe
 Encephalitis is global; brain may be
liquefied
 Survivors: residual disabilities
 Acyclovir should be promptly given in all
suspected cases of neonatal HSV infection
 Only means of prevention: offer C-section to
mothers with florid genital HSV lesions
OTHER MANIFESTATIONS:
 Disseminated herpes simplex: more likely to occur
in immunocompromised individuals
o Vesicular lesions resembles that of chicken pox
o Involved organs other than skin: liver, spleen,
lungs, CNS
 Other cutaneous manifestations include:
o Eczema herpeticum: potentially a serious
disease that occurs in patients with eczema
o Herpetic whitlow: arise from implantation of
the virus into the skin and typically affect the
fingers
o Zosteriform herpes simplex: rare presentation
of herpes simplex where HSV lesions appear is
a dermatomal distribution similar to herpes
zoster
LABORATORY DIAGNOSIS:
 Direct detection:
o EM of vesicle fluid: rapid result but cannot
distinguish between HSV and VZV
o IF of skin scrapings: can distinguish between
HSV and VZV
o PCR: diagnosis of herpes simplex encephalitis
 Virus isolation:
o HSV-1 and HSV-2 are among the easiest
viruses to cultivate; takes only 1-5 days
 Serology:
o Not that useful in the acute phase because it
takes 1-2 weeks for before antibodies appear
after infection. Used to document to recent
infection.
MANAGEMENT:
General indications for antiviral chemotherapy:
 Where the primary infection is especially severe
 Where there is dissemination
 Where sight is threatened
 Herpes simplex encephalitis
Acyclovir – DOC for most situations at present. Available
formulations:
 IV (HSV infection in normal and
immunocompromised patients)
 Oral (treatment and long term suppression of
mucocutaneous herpes and prophylaxis of HSV in
immunocompromised patients)
 Cream )HSV infection of the skin and mucus
membranes)
 Ophthalmic ointment
Famiciclovir and Valacyclovir – oral only, more expensive
than acyclovir
Other older agents – e.g., idoxuridine, trifluorothymidine,
vidarabine (ara-A)
 These agents are highly toxic and is suitable for
topical use for ophthalmic infection only.
VARICELLA-ZOSTER VIRUS
PROPERTIES:
 Belong to the herpesvirus subfamily of
herpesviruses
 Double stranded DNA enveloped virus
 Genome size is 125 kbp, long and short fragments
with a total of 4 isometric forms
 One antigenic serotype only, although there is
some cross reaction with HSV
EPIDEMIOLOGY:
 Primary varicella is an endemic disease; classic
diseases of childhood
o Highest prevalence: 4-10 y/o age group
 Varicella is highly communicable, attack rate of
90% in close contacts
 Most people become infected before adulthood
but 10% of young adults remain susceptible
 Herpes zoster: occurs sporadically and evenly
throughout the year

PATHOGENESIS:
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  Entry via the respiratory tract and spreads to the
lymphoid system
 After an IP of 14 days, the virus arrives at its main
target organ, the skin
 Following the primary infection, the virus remains
latent in the cerebral or posterior root ganglia
o In 10-20% of individuals, a single recurrent
infection occurs after several decades
 Virus reactivates in the ganglion and tracks down
the sensory nerve to the area of the skin
innervated by the nerve, producing a varicella
form rash in the distribution of the dermatome
VARICELLA
 Primary infection results in varicella (chickenpox)
 IP of 14-21 days
 Manifestations:
o Fever, lymphadenopathy, a widespread
vesicular spread
 Clinical features are characteristic
o Diagnosis made on clinical grounds alone
 Complications are rare
o Occurs more frequently and with greater
severity in adults and immunocompromised
patients
 Most common complication: secondary bacterial
infection
 Severe complications: life threatening – viral
pneumonia, encephalitis, and hemorrhagic
chickenpox
HERPES ZOSTER (SHINGLES)
 Herpes zoster mainly affect a single dermatome of
the skin
 May occur at any age; majority of patients are
>50 y/o
 Latent virus reactivates in a sensory ganglion and
tracks down the sensory nerve to the appropriate
segment
 Eruption of vesicles in the dermatome is often
accompanied by intense pain which may last for
months (postherpetic neuralgia)
 Herpes zoster affecting the eye and face may
pose great problems
 As with varicella, herpes zoster is a far greater
problem in immunocompromised patients in whom
the reactivation occurs earlier in life and multiple
attacks occur as well as complications
 Complications: rare and include encephalitis and
disseminated herpes zoster
CONGENITAL VZV INFECTION:
 90% of pregnant women already immune,
therefore, primary infection is rare during
pregnancy
 Primary infection during pregnancy carries a
greater risk of severe disease, in particular,
pneumonia
 First 20 weeks of pregnancy:
o 3% chance of transmission to the fetus
o Recognized congenital varicella syndrome:
 Scarring of skin
 Hypoplasia of limbs
 CNS and eye defects
 Death in infancy normal
NEONATAL VARICELLA
 VZV can cross the placenta in the late stages of
pregnancy to infect the fetus congenitally
 Neonatal varicella: vary from a mild disease to a
fatal disseminated infection
 If rash in mother occurs > 1 week before delivery,
sufficient immunity transferred to the fetus
 VZIg should be given to susceptible pregnant
women who had contact wit suspected cases of
varicella
 VZIg should also be given to infants whose
mothers develop varicella during the last 7 days
of pregnancy or the first 14 days after delivery
LABORATORY DIAGNOSIS:
 Clinical presentation: characteristic
 Laboratory diagnosis: required only for atypical
presentations, particularly in the
immunocompromised
o Virus isolation: rarely carried out; results
available after 2-3 weeks
o Direct detection – EM may be used for vesicle
fluids but cannot distinguish between HSV and
VZV
o IF on skin scrapings can distinguish between
the two
o Serology: (+) VZV IgG – past infection and
immunity
(+) IgM – recent primary infection
 Culture: cytopathic effect on cells
MANAGEMENT:
 Uncomplicated varicella: self-limited; no specific
treatment
o Acyclovir: accelerate the resolution of the
disease
o Indications:
 Immunocompromised individuals
 Individuals with serious complicationsL
pneumonia and encephalitis
 Herpes zoster in a healthy individual: not a cause
for concern
o Management of the postherpetic neuralgia can
be problematic
o The International Herpes Management Forum
recommends that antiviral therapy should be
offered routinely to all patients over 50 y/o
presenting with herpes zoster
o 3 drugs for the treatment of herpes zoster:
acyclovir, valacyclovir, and famciclovir. There
appears to be little difference in efficacy
between them
PREVENTION:
 Preventive measures: considered at risk of
contracting severe varicella infection e.g.
leukemic children, neonates, and pregnant women
 Where urgent protection is needed, passive
immunization should be given
o Varicella zoster immunoglobulin (VZIG) is the
preparation of choice but is very expensive
o A live attenuated vaccine is available
 Safe, even in children with leukemia
provided that they are in remission
CYTOMEGALOVIRUS
PROPERTIES:
 Belong to the betaherpesvirus subfamily of
herpesviruses
 Double stranded DNA enveloped virus
 Nucleocapsid 150 nm in diameter, 162 capsomers
 Genomic structure of CMV is similar to other
herpesviruses, consisting of long and short
segments which may be oriented in either
direction, giving a total of 4 isomers
 A large number of proteins are encoded for, the
precise number is unknown
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EPIDEMIOLOGY:  No evidence of teratogenicity, damage to the
 CMV: one of the most successful human fetus results from destruction of target cells once
pathogens they are formed
o Can be transmitted vertically or horizontally
usually with little effect on the host CYTOMEGALIC INCLUSION DISEASE
 Transmission may occur in utero, perinatally or  CNS abnormalities:
postnatally o Microcephaly, mental retardation, spasticity,
 Once infected, the person carries the virus for life epilepsy, periventricular calcification
which may be activated from time to time, during  Eye: chorioretinitis and optic atrophy
which infectious virions appear in the urine and  Ear: sensorineural deafness
the saliva  Liver: hepatosplenomegaly and jaundice due to
 Reactivation can also lead to vertical transmission hepatitis
 It is also possible for people who have  Lung: pneumonitis
experienced primary infection to be reinfected  Heart: myocarditis
with another or the same strain of CMV, this  Thrombocytopenic purpura, hemolytic anemia
reinfection does not differ clinically from  Late sequelae in individuals asymptomatic at
reactivation birth: hearing defects and reduced intelligence
 In developed countries with a high standard of
hygiene, 40% of adolescents are infected and INCIDENCE OF CYTOMEGALIC DISEASE:
ultimately 70% of the population is infected USA UK
 In developing countries, over 90% of people are No. of live
ultimately infected 3,000,000 700,000
births p.a.
Rate of
PATHOGENESIS: 1% 0.3%
Congenital CMV
 Once infected, the virus remains in the person for No. of Infected
life 30,000 2,100
Infants
o May be reactivated from time to time, Symptomatic at
especially in immunocompromised individuals 1,500 – 3,000 105
Birth (5-10%)
 Transmission: in utero, perinatally, or postnatally. Fatal Disease
Perinatal transmission occurs 300-600 22
(≈20%)
 Perinatal infection: acquired mainly through No. With
infected genital secretions, or breast milk Sequelae (90% 1080-2160 83
o 2-10% of infants infected by the age of 6 of survivors)
months Asymptomatic
o Perinatal infection: 10x more common than 27,000 1,995
(90-95%)
congenital infection No. with Late
 Postnatal infection mainly occurs through saliva. 1,350-4,550 315
Sequelae
Sexual transmission may occur as well as through
blood and blood products and transplanted organ. LABORATORY DIAGNOSIS:
 Direct detection:
CLINICAL MANIFESTATIONS: o Biopsy specimens: histologic examination for
 Congenital infection: result in cytomegalic CMV inclusion antibodies or for the presence of
inclusion disease CMV antigens
 Perinatal infection: usually asymptomatic  Sensitivity may be low
 Postnatal infection: usually asymptomatic o The pp65 CMV antigenaemia test: routinely
o Minority of cases: a syndrome of infectious used for rapid diagnosis of CMV infection in
mononucleosis may develop – fever, immunocompromised patients
lymphadenopathy, and splenomegaly. The o PCR for CMV-DNA: used in some centers but
heterophil antibody test (-); atypical there may be problems with interpretation
lymphocytes may be found in the blood  Virus isolation
 Immunocompromised patients: transplant o Conventional cell culture: gold standard
recipients and AIDS patients are prone to severe  Requires up to 4 weeks for result
CMV disease such as pneumonitis, retinitis, colitis, o More useful: rapid culture methods such as the
and encephalopathy DEAFF test – provide a result within 24-48
 Reactivation or reinfection with CMV is usually hours
asymptomatic EXCEPT in immunocompromised  Serology:
patients o (+) CMV IgG antibody: past infection
o (+) CMV IgM antibody: primary infection; also
CONGENITAL INFECTION:
found in immunocompromised patients with
 Definition: isolation of CMV from the saliva or
reactivation
urine within 3 weeks of birth
 Most common congenital viral infection; affects SPECIMENS FOR LABORATORY DIAGNOSIS:
0.3-1% of all live births Serolog
 2 nd most common cause of mental handicap after Site for Virus Culture
y
Down’s syndrome; responsible for more cases of Tissue
congenital damage than rubella Urin Sali Bloo Ig Ig
Affecte
 Transmission to the fetus may occur following e va d G M
d
primary or recurrent CMV infection Neonates + + - - - +
o 40% chance of transmission to the fetus Adults + - + - + +
following a primary infection Pregnant
 May be transmitted to the fetus during all stages - - - - + +
Women
of pregnancy
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Immunocompro
+ + + + + -
mised
TREATMENT:
 Congenital infections: not usually possible to
detect congenital infection unless the mother has
symptoms of primary infection. ? chances of her
baby having CID
o ? offer the choice of an abortion
 Perinatal and postnatal infection: not necessary to
treat such patients
 Immunocompromised patients: early diagnosis of
CMV infection and give prompt antiviral therapy
o Anti-CMV agents in current use are ganciclovir,
foscarnet, and cidofovir
PREVENTION:
 No licensed vaccine available:
o Concern: administering a live vaccine which
can become latent and reactivates
 Prevention in transplant recipients: very
complicated and varies from center to center. It
may include the following measures:
o Screening and matching the CMV status of the
donor and recipient
o Use of CMV negative blood for transfusions
o Administration of CMV immunoglobulin to
seronegative recipients prior to transplant
o Give antiviral agents such as acyclovir and
ganociclovir prophylatically
EPSTEIN BARR VIRUS
PROPERTIES:
 Belong to the gammaherpesvirus subfamily
 Nucleocapsid: 100 nm in diameter, 162 capsomers
 Membrane is derived by budding of immature
particles through cell membrane and is required
for infectivity
 Genome: linear double stranded DNA; 172 kbp
 Viral genome does not normally integrate into the
cellular DNA but forms circular epitomes which
reside in the nucleus
 The genome is large enough to code for 100-200
proteins but only a few have been identified
EPIDEMIOLOGY:
 Two epidemiological patterns seen with EBV
 Developed countries: 2 peaks of infection
o Preschool children aged 1-6
o Adolescents and young adults aged 14-20
o Eventually 80-90% of adults are infected
 Developing countries: much earlier age so that by
the age of 2, 90% of children are seropositive
 Transmitted by contact with saliva (kissing)
PATHOGENESIS:
 Lifelong carrier stage develops once infected,
whereby a low grade infection is kept in check by
the immune defenses
 Low grade virus replication and shedding:
demonstrated in the epithelial cells of the pharynx
of all seropositive individuals
 EBV: able to immortalize B-lymphocytes in vitro
and in vivo
 Few EBV-immortalized B-cells can be
demonstrated in the circulation which are
continually cleared by the immune surveillance
mechanisms
 EBV is associated with several very different
diseases where it may act directly or one of
several co-factors
DISEASE ASSOCIATION:
1. Infectious Mononucleosis
2. Burkitt’s Lymphoma
3. Nasopharyngeal Carcinoma
4. Lymphoproliferative Disease and Lymphoma
in the Immunosuppressed
5. X-linked Lymphoproliferative Syndrome
6. Chronic Infectious Mononucleosis
7. Oral Leukoplakia in AIDS Patients
8. Chronic Interstitial Pneumonitis in AIDS
Patients
INFECTIOUS MONONUCLEOSIS:
 Primary EBV infection:
o Usually subclinical in childhood
o Adolescents and adults: 50% chance that the
syndrome of IM will develop
 IM: self-limiting disease – fever, lymphadenopathy
and splenomegaly
o In some: jaundice (due to hepatitis); (+)
atypical lymphocytes in the blood
 Complications: rare but may be serious
o E.g. splenic rupture, meningoencephalitis,
pharyngeal obstruction
 Chronic IM may occur where eventually the
patient dies of lymphoproliferative disease or
lymphoma
 Diagnosis of IM: heterophil antibody test and/or
detection of EBV IgM
 NO specific treatment
BURKITT”S LYMPHOMA:
 Burkitt’s lymphoma: occurs endemically in parts
of Africa (most common childhood tumor) and
Papua New Guinea
o Usually seen in children age 3-14 years
o Responds favorably to chemotherapy
 Restricted to areas with holoendemic malaria.
Therefore it appears that malaria infection is a
cofactor.
 Multiple copies of EBV genome and some EBV
antigens can be found in BL cells and patients
with BL have high titres of antibodies against
various EBV antigens.
 BL cells show a reciprocal translocation between
the long arm of chromosome 8 and chromosomes
14, 2 or 22
 This translocation result in the c-myc oncogene
being transferred to the immunoglobulin gene
regions  results in the deregulation of the c-myc
gene. It is thought that this translocation is
probably already present by the time of EBV
infection and is not caused by EBV.
 Sporadic cases of BL occur, especially in AIDS
patients which may or may not be associated with
EBV.
 In theory, BL can be controlled by the eradication
of malaria (as has happened in Papua New
Guinea) or vaccination against EBV
NASOPHARYNGEAL CARCINOMA (NPC):
 Malignant tumor of the squamous epithelium of
the nasopharync
 Prevalent in South China: most common tumor in
men and second common in women
 Rare in most parts of the world, though pockets
occur in North and Central Africa, Malaysia,
Alaska, and Iceland
 Multiple copies of EBV genome and EBV EBNA-1
antigen can be found in cells of undifferentiated
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 NPC. Patients with NPC have high titres of
antibodies against various EBV antigens
 Environmental and genetic cofactors in NPC
 NPC usally presents late and thus the prognosis is
poor
 In theory, NPC can be prevented by vaccination
IMMUNOCOMPROMISED PATIENTS:
 After primary infection, EBV maintains a steady
low grade latent infection in the body. Should the
person become Immunocompromised, the virus
will reactivate.
o In some, lymphoproliferative lesions and
lymphoma may develop. These lesions tend to
be extranodal and in unusual sites such as the
GI tract or the CNS
 Transplant recipients: EBV is associated with the
development of lymphoproliferative disease and
lymphoma
 AIDS patients: EBV is associated with oral
leukoplakia and with various non-Hodgkin’s
lymphoma
 Ducan X-linked lymphoproliferative syndrome:
occurs exclusively in males who had inherited a
defective gene in the X chromosome. This
condition accounts for half of the datal cases of
IM.
DIAGNOSIS:
 Acute EBV Infection: heterophil antibody test
and/or detection of anti-EBV VCA IgM
 Burkitt’s lymphoma histolohy: tumor can be
stained with antibodies to lambda light chains
which reveal a monoclonal tumor of B-cell origin.
In over 90% of cases, the cells express IgM at the
cell surface
 NPC: histology
 The determination of the titre of anti-EBV VCA IgA
in screening for earl lesions of NPC and also for
monitoring treatment.
 A patient with non-specific ENT symptoms who
have elevated titres of EBV IgA should be given a
thorough examination.
VACCINATION:
 A vaccine against EBV which prevents primary
EBV infection should be able to control both BL
and NPC
 Must be given early in life; also useful in
seronegative organ transplant recipients and
those developing severe IM, such as the male
offspring of X-linked proliferative syndrome
carriers
 The antigen chosen for vaccine development is
the MA antigen gp 340/220 as antibodies against
this antigen are virus neutralizing
 This vaccine is being tried in Africa
OTHER HUMAN HERPES VIRUSES
PROPERTIES OF HHV-6 AND 7:
 Belong to the betaherpesvirus subfamily of
herpesviruses
 Double stranded DNA genome of 170 kbp
 Main target cell: T-lymphocyte, although B-
lymphocytes may also be infected
 HHV-6 and HHV-7 share limited nucleotide
homology and antigenic cross-reactivity
 It is thought that HHV-6 and HHV-7 are related to
each other in a similar manner to HSV-1 and HSV-
2
EPIDEMIOLOGY AND PATHOGENESIS:
 HHV-6 and HHV-7: ubiquitous, found worldwide
 Transmitted mainly through contact with saliva
and through breast feeding
 HHV-6 and HHV-7 infections are acquired rapidly
after the age of 4 months when the effect of
maternal antibody wears off
 Adulthood, 90-99% of the population had been
infected by both viruses
 HHv-6 and HHV-7 remains latent in the body after
primary infection and reactivates from time to
time
CLINICAL MANIFESTATIONS:
 Primary HHV-6 infection: associated with Roseola
infantum
 Infants: 4 months and 2 years
 A spiking fever develops over a period of 2 days
followed by a mild rash. The fever is high enough
to cause febrile convulsions.
 May be complicated by encephalitis
 If primary infection is delayed until adulthood,
there is a small chance that an IM-like disease
may develop in a similar manner to EBV and CMV
 NO firm evidence linking HHV-6 to lymphomas or
lymphoproliferative diseases
 NO firm disease association with HHV-7 at present
 Although both viruses may be reactivated in
Immunocompromised patients, it is yet uncertain
whether they cause significant disease since CMV
is almost invariably present
DIAGNOSIS AND MANAGEMENT:
 Roseola infantum: clinical
 Very few virology laboratories offer a diagnostic
service for HHV-6 or HHV-7 infection
 Virus isolation: complicated
 Serology: mainstay of diagnosis – specific IgM and
IgG are detected
 NO specific antiviral treatment
HUMAN HERPES VIRUS 8
 Belong to the gammaherpesvirus subfamily
 Originally isolated from cells of Kaposi’s sarcoma
(KS)
 Associated wit KS as well as some lesser known
malignancies such as Castleman’s disease and
primary effusion lymphomas
 HHV-8 DNA is found in almost 100% of cases of
Kaposi’s sarcoma
 Most patients with KS have antibodies against
HHV-8
 Seroprevalence of HHV-8: low among general
population but is high in groups of individuals
susceptible to KS, such as homosexual
 Does not have a ubiquitous distribution
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