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VIRAL INFECTIONS
Dr. ALAA HUSSAIN A.AWN
 Viruses
are simple infectious agents
consisting of a portion of genetic
material, RNA or DNA, enclosed in a
protein coat which is antigenically
unique for that species.
 They
are essentially inert and cannot
exist in a free-living state, needing to
infect host cells to survive.
 Once
it is in the intracellular
environment, they utilise host
material for protein synthesis and
genetic reproduction.
 All
viral infections must therefore
originate from an infected source by
either direct or vector-mediated
spread.
CLASSIFICATION OF VIRAL
INFECTIONS
 The
classification of viral infections in
humans is shown in the fallowing box
(13.25) dav. Pg 299 20th ed.
VIRUSES INVOLVED IN HUMAN
DISEASE
Classification/viruses
involved
Clinical syndromes
DNA VIRUSES
Adenoviruses
Upper respiratory tract
infection/pharyngitis
Acute diarrhoea
Herpes viruses
Herpes simplex types 1 and 2
Acute/recurrent vesicular rash
Varicella zoster
Chickenpox/shingles
Cytomegalovirus
Acute/recurrent hepatorenal
infection
Human herpes virus 6 and 7
Roseola infantum
Epstein-Barr virus
Infectious mononucleosis
Burkitt's lymphoma
Human herpes virus 8
Nasopharyngeal carcinoma
Kaposi's sarcoma
Classification/viruses
involved
Clinical syndromes
DNA VIRUSES
Papovaviruses
Human papillomavirus
Common wart
Polyoma
Progressive multifocal
leucoencephalopathy
Poxviruses
Variola
Smallpox
Classification/viruses
involved
Clinical syndromes
RNA VIRUSES
Picornaviruses
Poliovirus
Coxsackie viruses
Echoviruses
Enteroviruses 68-72
Gut/neurological illness
Hepatitis A
Rhinoviruses
Upper respiratory tract infection
Rheoviruses
Rheovirus
Mild upper respiratory tract
infection/gut disease
Rotavirus
Gastroenteritis
Classification/viruses
involved
Clinical syndromes
RNA VIRUSES
Togaviruses
Rubella
German measles
Yellow fever
Yellow/haemorrhagic fever
Dengue
Other arboviruses
Haemorrhagic fevers
Hepatitis C
Chronic hepatitis
Calicivirus
Hepatitis E
Acute gastroenteritis
Classification/viruses
involved
Clinical syndromes
RNA VIRUSES
Orthomyxoviruses
Influenza A, B
Paramyxoviruses
Measles,Mumps,
Respiratory syncytial virus
Rhabdoviruses
Rabies
Retroviruses
HIV-1 and 2
Hepadnavirus, Hepatitis B
HIV infection syndrome/AIDS
CLASSIFICATION ACCORDING
TO THE HOST AND ORGANS
INVOLVED
 COMMON
VIRAL INFECTIONS AND
CHILDHOOD EXANTHEMS.
 VIRAL INFECTIONS OF THE SKIN.
 SYSTEMIC VIRAL INFECTIONS.
 GASTRO-INTESTINAL VIRAL
INFECTIONS.
 RESPIRATORY VIRAL INFECTIONS.
 VIRAL INFECTIONS WITH
NEUROLOGICAL INVOLVEMENT.
COMMON VIRAL INFECTONS
AND CHILDHOOD EXANTHEMS
 MEASELS
 RUBELLA
 MUMPS
(GERMAN MEASELS)
VIRAL INFECTIONS OF THE SKIN
 THE
HERPES VIRUS GROUP
13.29 HERPES VIRUS INFECTIONS
Virus
Infection
Herpesvirus hominis (herpes simplex,
HSV)
Type 1
Herpes labialis ('cold sores')
Keratoconjunctivitis
Finger infections ('whitlows')
Encephalitis
Primary stomatitis
Genital infections
Type 2
Genital infections
Neonatal infection (acquired during
vaginal delivery)
Varicella zoster virus
Chickenpox , Shingles (herpes zoster)
Cytomegalovirus (CMV)
Congenital infection
Disease in immunocompromised patients
Pneumonitis
Retinitis
Enteritis
Generalised infection
Epstein-Barr virus (EBV)
Infectious mononucleosis
Burkitt's lymphoma
Nasopharyngeal carcinoma
Oral hairy leucoplakia (AIDS patients)
Human herpes virus 8
Associated with Kaposi's sarcoma
HERPES SIMPLEX VIRUS (HSV)



Types 1 and 2 of this
common virus affect
humans.
Type 1 HSV produces
mucocutaneous
lesions, predominantly
of the head and neck
type 2 disease is a
sexually transmitted
anogenital infection

The source of infection is a case of
primary or active recurrent disease.
Primary infection
normally occurs as a gingivostomatitis in
infancy and may be subclinical or
mistaken for 'teething'.
 It may present as a keratitis (dendritic
ulcer), viral paronychia ('whitlow'),
 vulvovaginitis, cervicitis (often
unrecognised), balanitis
 or rarely as encephalitis.

('whitlow'),


Recurrent disease,
involving reactivation of
HSV from latency in the
dorsal root ganglion,
produces the classical
'cold sore' or 'herpes
labialis'.
Prodromal
hyperaesthesia is
followed by rapid
vesiculation, pustulation
and crusting.
Recurrences can be
precipitated by
disturbance of local skin
integrity by ultraviolet
light or systemic upset
from menstruation or
fever of any cause.
 Type
2 (genital) disease is a common
cause of recurrent painful genital
ulceration
Complications
Neonatal HSV disease,
contracted from the
birth canal, may be
disseminated and is
potentially fatal.
Active HSV in a preterm mother is an
indication for either
elective caesarean
section or antiviral
therapy.
*eczema herpeticum __
HSV infection in patients
with eczema can
result in a spreading
and potentially serious
infection (Fig. )



Dendritic ulcers may produce corneal
scarring and permanently damage
eyesight. These require aggressive
antiviral therapy.
Encephalitis, the most serious
complication of HSV disease, may occur
following either primary or secondary
disease. A haemorrhagic necrotising
temporal lobe cerebritis produces
temporal lobe epilepsy and decreasing
conscious level/coma. Without treatment,
mortality is 80%. Any suggestion of HSV
encephalitis is an indication for immediate
empirical systemic antiviral therapy.
DIAGNOSIS
PCR,
 Electron microscopy or culture from
vesicular fluid.
 CSF PCR is very useful in HSV
encephalitis.
 Serology is of limited value, only
confirming primary infection.

Management
The acyclic antivirals are the treatment of
choice for HSV infection.
 Therapy must commence in the first 48
hours of clinical disease (primary or
recurrent); thereafter it is unlikely to
influence clinical outcome or modify the
disease process.
 Severe manifestations should be treated
regardless of the time of presentation
(Box 13.30).

Rx.

Primary HSV
-Famciclovir 250 mg 8-hourly
-Valaciclovir 500 mg 12-hourly
-Aciclovir 200 mg 5 times daily
* Severe and preventing oral intake
Aciclovir 5 mg/kg 8-hourly i.v.
*Recurrent HSV-1 or 2
- Aciclovir ointment 3-5 times daily
-Oral aciclovir 200 mg 6-hourly
-Famciclovir 250 mg 12-hourly
-Valaciclovir 500 mg daily
* In immunocompromised
-Aciclovir 400 mg 6-hourly
-Famciclovir 500 mg 12-hourly
-Valaciclovir 1 g 12-hourly
 Severe
complications
- Aciclovir i.v. 10 mg/kg 8-hourly
(up to 20 mg/kg in severe
encephalitis)
CHICKENPOX



Varicella zoster virus (VZV) is dermo- and
neurotropic infection. Spread by the
aerosol route, it is highly infectious to
susceptible individuals.
Disease in children is usually well
tolerated. It is more severe in adults,
pregnant women and the
immunocompromised.
Pneumonitis can be fatal and is more
likely in smokers, pregnant women and
the immunocompromised.


The incubation period is 1421 days, after which a
vesicular eruption begins
(Fig.), often on mucosal
surfaces first, followed by
rapid dissemination in a
centripetal distribution
(most dense on trunk and
sparse on limbs).
New lesions occur every 2-4
days, each crop associated
with fever. The rash
progresses from small pink
macules to vesicles and
pustules within 24 hours.
These then crust. Infectivity
lasts until crusts separate.
complications



. Due to intense itch secondary bacterial
infection from scratching is the most
common complication of primary
chickenpox.
Self-limiting cerebellar ataxia may rarely
occur 7-10 days after recovery from the
rash.
Maternal infection in early pregnancy
carries a 3% risk of neonatal damage, and
disease within 5 days of delivery can lead
to severe neonatal varicella.
Diagnosis
Usually this is clinically obvious from the
classical appearance of the rash .
 Aspiration of vesicular fluid and PCR or tissue
culture will confirm the diagnosis.
 Electron microscopy cannot distinguish HSV
from VZV.
 Serological examination for rising titres of
antibody is only useful in primary infection.


Chickenpox can recur as a subclinical infection
following primary disease.
Management
Aciclovir, valaciclovir and famciclovir,
effective if commenced within 48 hours of rash
appearance.
 They are required in the management of the
immunocompromised or any case of
pneumonitis .
 Note
Aciclovir shortens symptoms in chickenpox by
an average of 1 day. In shingles aciclovir
reduces pain by 10 days and the risk of postherpetic neuralgia by 8%. Aciclovir is therefore
cost-effective in shingles but not chickenpox.

Human VZV immunoglobulin may be used to attenuate infection in
highly susceptible contacts of chickenpox such as:








bone marrow recipients
patients with debilitating disease
HIV-positive contacts without VZV immunity
pregnant women with no known VZV antibody (screen
for antibody if in doubt)
immunosuppressed contacts who have received highdose corticosteroids in the previous 3 months
neonates whose mothers develop chickenpox between
1 week before and 4 weeks after delivery
neonates in contact with chickenpox/shingles whose
mothers have no history of chickenpox or any
demonstrable antibody
premature infants of less than 30 weeks' gestation, or
weighing less than 1 kg at birth who contact
chickenpox or shingles.
SHINGLES (HERPES ZOSTER)
 This
is produced by reactivation of latent
VZV from the dorsal root ganglion of
sensory nerves.
 Commonly seen in the elderly,
 It
may present in younger patients with
immune deficiency or after intra-uterine
infection.


Although thoracic
dermatomes are most
commonly involved
(Fig.),
the ophthalmic
division of the
trigeminal nerve is
frequently implicated;
vesicles may appear
on the cornea and
lead to ulceration.
 Geniculate
ganglion involvement causes
the Ramsay Hunt syndrome of facial
palsy, ipsilateral loss of taste and
buccal ulceration, plus a rash in the
external auditory canal. This may be
mistaken for Bell's palsy.
 Bowel
and bladder dysfunction occurs
with sacral nerve root involvement.
 The
virus occasionally causes myelitis
or encephalitis.
Clinical features
 Burning
discomfort in the affected
dermatome progresses to frank
neuralgia. Discrete vesicles appear in
the dermatome 3-4 days later and often
coalesce.
 Severe
disease, multiple dermatomal
involvement or recurrence suggests
underlying immune deficiency.
Complications
 The
most common and troublesome
complication is post-herpetic neuralgia:
persistence of pain for 1-6 months or
more following healing of the rash.
Management

Early therapy with aciclovir 800 mg 5 times
daily or valaciclovir 1 g 8-hourly, or aciclovir 10
mg/kg i.v. 8-hourly in severe infection and in
the immunocompromised has been shown to
reduce both early- and late-onset pain,
especially in patients over 65 .
Post-herpetic neuralgia requires
 aggressive analgesia and
 the use of transcutaneous nerve stimulation (a
'TENS' machine), along with
 neurotransmitter modification with agents such
as amitriptyline 25-100 mg daily or gabapentin
(commencing at 300 mg daily and building
slowly to 300 mg 12-hourly or more.
Smallpox (variola)


This severe disease, with a 30% mortality in
the unvaccinated patient and no current
effective therapy, was eradicated world-wide
in 1980 by a successful international
vaccination campaign coordinated by the
WHO.
Interest in the disease has re-emerged due
to its potential as a bioterrorist weapon .In
view of this threat some developed countries
have reintroduced vaccination for key healthcare personnel and re-evaluated national
plans for the containment of disease.
Clinical features
 The
classical form is characterised by
a typical deep-seated centrifugal
vesicular/pustular rash, worst on the
face and extremities, with no
cropping (i.e. unlike chickenpox);
 the
rash is accompanied by fever,
severe myalgia.
SYSTEMIC VIRAL INFECTIONS
 INFLUENZA
EBV -Infectios mononucleosus
 CMV
 VIRAL HEMORAGIC FEVER
 HIV

INFECTIOUS MONONUCLEOSIS
(IM)

-
Virology and epidemiology
The disease is caused by the Epstein-Barr virus (EBV), a
gamma herpes virus. .
-
In developing countries and poorer societies in developed
nations subclinical infection in childhood is virtually universal. In
richer communities, particularly among upper socioeconomic
groups, primary infection may be delayed until adolescence or
early adult life.
-
About 50% of infections result in typical IM. The virus is usually
acquired from asymptomatic excreters. .
-
Saliva is the main means of spread, either by droplet infection
or environmental contamination in childhood, or by kissing
among adolescents and adults. .
-
IM is not highly contagious, isolation is unnecessary and
documented outbreaks seldom occur.
Clinical features (IM)
 lymphadenopathy,
especially posterior
cervical,
 pharyngeal inflammation or exudates,
 fever,
 splenomegaly,
 palatal petechiae,
 periorbital oedema,
 clinical or biochemical evidence of
hepatitis,
 And a non-specific rash.



20% or more of peripheral
lymphocytes must have an
atypical morphology (Fig.)
characteristic heterophile
antibody. (classical PaulBunnell titration or by slide
test 'Monospot‘)).
Specific EBV serology
(immunofluoresence)
COMPLICATIONS OF
INFECTIOUS MONONUCLEOSIS
Common
 Severe pharyngeal oedema
 Antibiotic-induced rash
 Chronic fatigue syndrome
(10%)
Uncommon
Neurological
 Cranial nerve palsies
 Polyneuritis
 Transverse myelitis
 Meningoencephalitis






Rare
Ruptured spleen
Respiratory obstruction
Arthritis
Agranulocytosis
Agammaglobulinaemia



Haematological
Haemolytic anaemia
Thrombocytopenia
Renal
Glomerulonephritis
Interstitial nephritis

Cardiac
Myocarditis
Pericarditis

Pulmonary
Interstitial pneumonitis

Management






Treatment is largely symptomatic:
aspirin gargles to relieve a sore throat.
If a throat culture yields a β-haemolytic streptococcus,
a course of erythromycin should be prescribed.
Amoxicillin and similar semi-synthetic penicillins should
be avoided .
When pharyngeal oedema is severe a short course of
corticosteroids, e.g. prednisolone 30 mg daily for 5
days, may help to relieve the swelling.
contact sports should be avoided until splenomegaly
has completely resolved because of the danger of
splenic rupture.
Unfortunately, about 10% of patients with IM suffer a
chronic relapsing syndrome.
ACQUIRED CYTOMEGALOVIRUS
INFECTION
Virology and epidemiology
- Cytomegalovirus (CMV) is a beta herpes
virus.

- It circulates readily among children,
especially in crowded communities.
- Although most primary infections are
asymptomatic, many children continue to
excrete virus for months or years.



A second peak in virus acquisition occurs
among teenagers and young adults. CMV
infection is persistent, and is characterised
by subclinical cycles of active virus
replication and by persistent low-level
virus shedding.
Sexual transmission and oral spread are
common among adults, but infection may
also be acquired by women caring for
children with asymptomatic infections.
The peak incidence occurs between the
ages of 25 and 35, rather later than with
EBV-related mononucleosis.
Clinical features



Most post-childhood CMV infections are
subclinical, although some young adults
develop a mononucleosis-like syndrome .
Some patients have a prolonged influenzalike illness lasting 2 weeks or more .
Physical signs such as a palpable liver and
spleen resemble those of IM, but in CMV
mononucleosis hepatomegaly is relatively
more common, while lymphadenopathy,
pharyngitis and tonsillitis are found less
often. Jaundice is uncommon and usually
mild.
complications
 neurological
involvement,
 autoimmune haemolytic anaemia,
 pericarditis,
 pneumonitis .
 arthropathy.
Investigations
 Atypical
lymphocytosis is not as
prominent as in IM
 heterophile


antibody tests are negative.
LFTs are often abnormal, with an
alkaline phosphatase level raised out of
proportion to transaminases.
Serological diagnosis depends on the
detection of CMV-specific IgM antibody.
 Only
Management
symptomatic treatment .
 Amoxicillin and similar antibiotics
should not be prescribed because of the
risk of a skin reaction.
 Since CMV infection in
immunocompetent subjects is selflimiting, the use of potentially toxic
antiviral agents is usually inappropriate
In immunosupp. Pt. ,
 Ganciclover injection
 valganciclover tab. (valcyte) 450mg
2 tab. 12 hourly for 4-6 weeks






VIRAL HAEMORRHAGIC
FEVERS
The viral haemorrhagic fevers are zoonoses caused by several
different viruses .They are endemic world-wide, examples.:
Yellow feverReservoir ; Monkeys
Transmission;Mosquitoes
Geography ;Tropical Africa, South and Central AmericaMortality rate ;10-60% death
Clinical features ;Hepatic failure
Blood oozing
:
* Dengue
 Reservoir ; Humans
 Transmission; Aedes aegypti Geography ; tropical and subtropical coasts
 Mortality rate ; Nil-10%
 Clinical features - Joint and bone pain
Petechiae
Pathogenesis
 These
viruses cause endothelial
dysfunction with the development of
leaky capillary syndrome.
 Bleeding
is due to this and associated
platelet dysfunction.

Hypovolaemic shock and acute
respiratory distress syndrome develop
Clinical features
 All
viral haemorrhagic fevers have similar
non-specific presentations with fever,
malaise, body pains, sore throat and
headache.

On examination conjunctivitis, throat
congestion, an erythematous or petechial
rash, haemorrhage, lymphadenopathy
and bradycardia may be noted.
Investigations
 There
is leucopenia,
 thrombocytopenia
 proteinuria.
 Prolong PT and PTT
Diagnosis
 The
clue to the viral aetiology will come
from the travel and exposure history, so
it is important to be aware of the
incubation periods for these illnesses .
 The causative virus may be isolated, or
antigen detected, in maximum security
laboratories from serum, pharynx, pleural
exudate and urine.
Management
It is important to exclude other causes of fever,
especially malaria, typhoid and respiratory tract
infections.
 Particular care must be taken with body fluids.
Patients returning from endemic area with a
fever should be managed in isolation until a
diagnosis is made.
 General supportive measures, preferably in a
special unit, are required.
 Ribavirin is given intravenously (100 mg/kg,
then 25 mg/kg daily for 3 days and 12.5 mg/kg
daily for 4 days).
 Once haemorrhagic fever is confirmed, full
pressure isolation is mandatory and good
infection control practices will prevent further
transmission.

GASTROINTESTINAL VIRAL
INFECTIONS
ROTAVIRUS




Rotaviruses are the major cause of diarrhoeal illness in
young children, accounting for 30-50% of cases
admitted to hospital in developed countries, and 1020% of deaths due to gastroenteritis in developing
countries.
Infection is endemic in developing countries and there
are winter epidemics in developed countries.
These viruses are easily transmitted and resist alcohol
denaturation; person-to-person spread, especially by
health-care workers in hospitals, is well documented.
The virus infects enterocytes, causing decreased
surface absorption and loss of enzymes on the brush
border.
Diagnosis
 The

incubation period is 48 hours .
patients present with watery diarrhoea,
vomiting, fever and abdominal pain.
 Diagnosis
is aided by commercially
available enzyme immunoassay kits
which simply require fresh or
refrigerated stool for effective
demonstration of the pathogens.
Treatment
 The
disease is self-limiting but
dehydration needs appropriate
management .
 Immunity
infection.
develops to natural
Other GIT viruses


HEPATITUS VIRUSES (A, B, C, D,E, F).
Adenoviruses
-Are frequently identified from stool culture
and implicated as a cause of diarrhoea.
-Two serotypes (40 and 41) appear to be
more frequently found in association with
diarrhoea rather than the more common
upper respiratory types 1-7.
RESPIRATORY VIRAL
INFECTIONS
 Adenoviruses,
rhinoviruses
 enteroviruses (Coxsackie viruses and
echoviruses)
often produce non-specific symptoms.
The individual infections each produce
lasting specific immunity.
** Influenza viruses

Human
immunodeficiency
virus infection (HIV) and the
acquired immunodeficiency
syndrome (AIDS)
EPIDEMIOLOGY AND BIOLOGY
OF HIV


The acquired immunodeficiency syndrome
(AIDS) was first recognized in 1981. It is
caused by the human immunodeficiency virus
(HIV-1). HIV-2 causes a similar illness to HIV-1
but is less aggressive and restricted mainly to
western Africa.
Since 1981 AIDS has grown to be the second
leading cause of disease burden world-wide and
the leading cause of death in Africa, where it
accounts for over 20% of deaths.
.
Immune deficiency is a
consequence of continuous high-level
HIV replication leading to immunemediated destruction of the key
immune effector cell, the CD4
lymphocyte.
MODES OF TRANSMISSION
HIV is present in blood, semen and other body
fluids such as breast milk and saliva.
 Exposure to infected fluid leads to a risk of
contacting infection, which is dependent on the
integrity of the exposed site, the type and
volume of body fluid, and the viral load.
 HIV can enter either as free virus or within
cells.
 The modes of spread are sexual (man to man,
heterosexual and oral), parenteral (blood or
blood product recipients, injection drug-users
and those experiencing occupational injury)
and vertical.

VIROLOGY AND IMMUNOLOGY
HIV is a single-stranded RNA retrovirus from
the Lentivirus family.
 After mucosal exposure, HIV is transported to
the lymph nodes via dendritic, CD4 or
Langerhans cells, where infection becomes
established.
 Free or cell-associated virus is then
disseminated widely through the blood with
seeding of 'sanctuary' sites (e.g. central
nervous system) and latent CD4 cell reservoirs.
 With time, there is gradual attrition of the CD4
cell population, resulting in increasing
impairment of cell-mediated immunity and
susceptibility to opportunistic infections.

As CD4 cells are pivotal in orchestrating the
immune response, any depletion in numbers
renders the body susceptible to opportunistic
infections and oncogenic virus-related tumours.
 The predominant opportunist infections seen in
HIV disease are intracellular parasites (e.g.
Mycobacterium tuberculosis) or pathogens
susceptible to cell-mediated rather than
antibody-mediated immune responses.
 The reduction in the number of CD4 cells
circulating in peripheral blood is tightly
correlated with the amount of plasma viral
load.
 Both are monitored closely in patients and are
used as measures of disease progression.

 Virus-specific
CD8 cytotoxic T-cell
lymphocytes develop rapidly after
infection and are the most important
element in recognising, binding and
lysing infected CD4 cells.

They play a crucial role in controlling HIV
replication after infection and determine
the viral 'set-point' and subsequent rate
of disease progression.
NATURAL HISTORY AND
CLASSIFICATION OF HIV
 Primary
infection
 Asymptomatic
 HIV
infection
SYMPTOMATIC DISEASES
 Mildly
symptomatic disease
 Acquired
immunodeficiency
syndrome (AIDS)
Primary infection
 Fever
with rash
 Pharyngitis with cervical
lymphadenopathy
 Myalgia/arthralgia
 Headache
 Mucosal ulceration






Primary infection is symptomatic in 70-80% of cases
and usually occurs 2-6 weeks after exposure.
Rarely, presentation may be neurological (aseptic
meningitis, encephalitis, myelitis, polyneuritis).
This coincides with a surge in plasma HIV-RNA levels to
> 1 million copies/ml (peak between 4 and 8 weeks),
and a fall in the CD4 count to 300-400 cells/mm3, but
occasionally to below 200 when opportunistic infections
(e.g. oropharyngeal candidiasis, Pneumocystis carinii
(jirovecii) pneumonia) may rarely occur .
Symptomatic recovery occurs after 1-2 weeks but
occasionally may take up to 10 weeks and parallels the
return of the CD4 count and fall in the viral load.
In many patients the illness is mild and only identified
by retrospective enquiry at later presentation.
However, the CD4 count rarely recovers to its previous
value.
Diagnosis is made by
 1- detecting HIV-RNA in the serum or
 2- immunoblot assay (which shows
antibodies developing to early proteins).
 The
appearance of specific anti-HIV
antibodies in serum (seroconversion)
takes place later at 3-12 weeks (median
8 weeks), although very rarely
seroconversion may take place after 3
months.
Factors likely to indicate a faster
progression of HIV are
 1-the presence and duration of
symptoms,
 2- evidence of candidiasis, and
 3- neurological involvement.
 4- The level of the viral load postseroconversion strongly correlates with
subsequent progression of disease.
The differential diagnosis of primary HIV
includes
 acute Epstein-Barr virus (EBV),
 cytomegalovirus (CMV),
 streptococcal pharyngitis,
 toxoplasmosis
 secondary syphilis.
Asymptomatic infection
category A disease in the Centers for Disease
Control (CDC) classification
 follows and lasts for a variable period, during
which the infected individual remains well with
no evidence of disease except for the possible
presence of persistent generalised
lymphadenopathy (PGL, defined as enlarged
glands at ≥ 2 extra-inguinal sites).
 At this stage the bulk of virus replication takes
place within lymphoid tissue (e.g. follicular
dendritic cells).
 There is sustained viraemia with a decline in
CD4 count dependent on the height of the viral
load but usually between 50 and 150
cells/cc/year

HIV SYMPTOMATIC DISEASES
Oral hairy leucoplakia
 Recurrent oropharyngeal candidiasis
 Recurrent vaginal candidiasis
 Severe pelvic inflammatory disease
 Bacillary angiomatosis
 Cervical dysplasia
 Idiopathic thrombocytopenic purpura
 Weight loss*
 Chronic diarrhoea*
 Herpes zoster
 Peripheral neuropathy
 Low-grade fever/night sweats*

Mildly symptomatic disease
 Centers
for Disease Control (CDC)
Classification category B disease .
 indicating some impairment of the
cellular immune system.
 These diseases correspond to AIDSrelated complex (ARC) conditions but by
definition are not AIDS-defining.
 The median interval from infection to the
development of symptoms is around 7-10
years, although subgroups of patients
exhibit 'fast' or 'slow' rates of
progression.
Acquired immunodeficiency
syndrome (AIDS)
 AIDS
(CDC Classification category C
disease)
 is defined by the development of
specified opportunistic infections,
tumours etc.
 There is correlation between CD4 count
and HIV-related diseases (type of the
disease). ( box 14.7)
AIDS-DEFINING DISEASE (box14.6 )
Oesophageal candidiasis
 Cryptococcal meningitis
 Chronic cryptosporidial diarrhoea
 CMV retinitis or colitis
 Chronic mucocutaneous herpes simplex
 Disseminated Mycobacterium avium
intracellulare
 Pulmonary or extrapulmonary tuberculosis
 Pneumocystis carinii (jirovecii) pneumonia
 Progressive multifocal leucoencephalopathy
 Recurrent non-typhi Salmonella septicaemia
 Cerebral toxoplasmosis

AIDS-DEFINING DISEASE
(box14.6 ) cont.
 Extrapulmonary
coccidioidomycosis
 Invasive cervical cancer
 Extrapulmonary histoplasmosis
 Kaposi's sarcoma
 Non-Hodgkin lymphoma
 Primary cerebral lymphoma
 HIV-associated wasting
 HIV-associated dementia
oseophageal candidiasis
DIFFERENTIAL DIAGNOSIS OF
HIV-RELATED SKIN DISEASE
















Early HIV
Infection
Herpes simplex
Varicella zoster
Human papillomavirus (HPV)
Impetigo
Dermatophytosis
Scabies
Syphilis
HIV seroconversion
Other
Xeroderma
Pruritus
Seborrhoeic dermatitis
Drug reaction (co-trimoxazole/nevirapine)
Itchy folliculitis
Psoriasis
Acne
Late HIV
Common
 Kaposi's sarcoma
 Molluscum contagiosum
 Chronic mucocutaneous herpes simplex
Rare
 Bacillary angiomatosis
 CMV
 Non-Hodgkin lymphoma
 Cryptococcus
 Histoplasmosis
 Mycobacterial (tuberculosis/atypical)
Figure 14.5 Presentation and differential diagnosis of HIVrelated gastrointestinal disorder
Figure 14.6 Cryptosporidial infection. Duodenal biopsy may be
necessary to confirm cryptosporidiosis or microsporidiosis.
Figure 14.7 Pneumocystis pneumonia. Typical chest Xray appearance. Note the sparing at the apex and base
of both lungs.
Figure 14.8 Chest X-ray of pulmonary tuberculosis in HIV
infection. Appearances are often atypical but in this case there is
a typical large cavity accompanied by a pleural effusion.
Figure 14.9 Presentation and differential diagnosis of
HIV-related neurological disorders
Figure 14.10 Cerebral toxoplasmosis. Multiple cortical ringenhancing lesions with surrounding oedema are characteristic.
Figure 14.11 Primary CNS lymphoma. A single enhancing
periventricular lesion with moderate oedema is typical.
Figure 14.12 Progressive multifocal leucoencephalopathy.
Non-enhancing white matter lesions without surrounding
oedema are seen.
Figure 14.13 Oral Kaposi's sarcoma. A full examination is
important to detect disease that may affect the palate, gums,
fauces or tongue.
MANAGEMENT OF HIV
Management of HIV involves both treatment of
the virus and prevention of opportunistic
infections. The aims of HIV treatment are to:
1- reduce the viral load to an undetectable
level (< 50 copies/ml) for as long as possible
 2- improve the CD4 count (above 200
cells/mm3 ,when the significant HIV-related
events rarely occur)
 3- increase the quantity and improve the
quality of life without unacceptable drugrelated side-effects or lifestyle alteration
 4- reduce transmission (mother-to-child and
person-to-person).

DRUGS
ANTIRETROVIRAL DRUGS
 Nucleoside reverse transcriptase
inhibitors (NRTIs)
 Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)
 Protease inhibitors (PIs)
 Others
The drugs that are currently used,
their side-effects and a glossary of
terms and abbreviations are given in
Boxes 14.22, 14.23 and 14.24.
Nucleoside reverse transcriptase
inhibitors (NRTIs)
 Zalcitabine
(ddC)
 Didanosine (ddI)
 Lamivudine (3TC)
 Zidovudine (ZDV)
 Stavudine (d4T)
 Abacavir
 Emitricitabine (FTC)
Non-nucleoside reverse
transcriptase inhibitors (NNRTIs)
 Nevirapine
 Efavirenz
 Delavirdine1
Protease inhibitors (PIs)
Indinavir2
 Ritonavir
 Nelfinavir
 Lopinavir3
 Atazanavir2
 Fosamprenavir2
 Saquinavir2
 Amprenavir1,2
 Tipranavir1,2

Others
 Tenofovir
 Enfuvirtide (T-20)
Notes about HIV drugs



The inclusion of two NRTIs, or one NRTI and tenofovir,
remains the cornerstone of HAART. (highly active antiretroviral therapy)=combination treatment
Resistance to all NRTIs will occur unless they are part
of a maximally suppressive HAART regimen .
. More recently, two PIs (atazanavir and osamprenavir)
have become available; they allow for once-daily
administration with fewer tablets. The subsequent fall
in morbidity and mortality can be directly linked to the
introduction of these drugs and their use in HAART.
When they are given with two NRTIs the combination
controls viral replication in plasma and tissues, and
allows reconstitution of the immune system.


Short- and long-term side-effects are not
infrequent. Fat redistribution occurred in 2030% of patients treated with HAART including a
PI after 2 years. The syndrome is characterised
by peripheral fat-wasting (cheeks, temples,
limbs and buttocks), localised collections
(buffalo hump, peripheral lipomatosis, and
breast enlargement in women) and central
adiposity.
Enfuvirtide (T-20) is a new class of
antiretroviral drug which prevents viral entry
into cells and preventing fusion. It is highly
active but has to be injected subcutaneously
12-hourly and therefore is reserved for patients
with more advanced disease and fewer options.
14.27 FACTORS TO CONSIDER
WHEN CHOOSING HAART
Ease of compliance
 Fit of the drug regimen around the patient's
lifestyle
 Wishes of the patient
 Stage of disease
 Coexisting/past medical history
 Possibility of additive side-effects (e.g. ddI and
neuropathy)
 Potential for drug interactions with non-HIV
medications
 Antagonistic NRTI combinations (ZDV/d4T and
ddC/3TC)
 CNS penetration
 Possibility of acquisition of resistant virus

POST-EXPOSURE PROPHYLAXIS

Combination therapy is now recommended for
occupational post-exposure prophylaxis (PEP)
where the risk is deemed to be significant,
although there is no evidence for this practice.
The first dose should be given as soon as
possible. However, protection is not absolute
and health-care workers have been reported to
seroconvert despite taking a full course of three
drugs started within hours of exposure.
Recommended PEP is ZDV, 3TC and indinavir
or nelfinavir for 28 days.
 Vaccine development is slow.
