Viruses are infectious agents that contain genetic material enclosed in a protein coat. They cannot replicate without infecting a host cell. There are two main classifications of viral infections - by the type of genetic material (DNA or RNA viruses) and by the organ or host infected. Common viral infections in humans include those caused by herpes viruses like HSV-1 and VZV, influenza viruses, adenoviruses, enteroviruses and hepatitis viruses.

1. VIRAL INFECTIONS
Dr. ALAA HUSSAIN A.AWN

2.  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.

3.  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.

5. CLASSIFICATION OF VIRAL
INFECTIONS
 The classification of viral infections in
humans is shown in the fallowing box
(13.25) dav. Pg 299 20th ed.

6. VIRUSES INVOLVED IN HUMAN
DISEASE

7. Clinical syndromesClassification/viruses
involved
DNA VIRUSES
Upper respiratory tract
infection/pharyngitis
Acute diarrhoea
Adenoviruses
Herpes viruses
Acute/recurrent vesicular rashHerpes simplex types 1 and 2
Chickenpox/shinglesVaricella zoster
Acute/recurrent hepatorenal
infection
Cytomegalovirus
Roseola infantumHuman herpes virus 6 and 7
Infectious mononucleosis
Burkitt's lymphoma
Epstein-Barr virus
Nasopharyngeal carcinoma
Kaposi's sarcoma
Human herpes virus 8

8. Clinical syndromesClassification/viruses
involved
DNA VIRUSES
Papovaviruses
Common wartHuman papillomavirus
Progressive multifocal
leucoencephalopathy
Polyoma
Poxviruses
SmallpoxVariola

9. Clinical syndromesClassification/viruses
involved
RNA VIRUSES
Picornaviruses
Gut/neurological illnessPoliovirus
Coxsackie viruses
Echoviruses
Enteroviruses 68-72
Hepatitis A
Upper respiratory tract infectionRhinoviruses
Rheoviruses
Mild upper respiratory tract
infection/gut disease
Rheovirus
GastroenteritisRotavirus

10. Clinical syndromesClassification/viruses
involved
RNA VIRUSES
Togaviruses
German measlesRubella
Yellow/haemorrhagic feverYellow fever
Haemorrhagic feversDengue
Other arboviruses
Chronic hepatitisHepatitis C
Calicivirus
Acute gastroenteritisHepatitis E

11. Clinical syndromesClassification/viruses
involved
RNA VIRUSES
Orthomyxoviruses
Influenza A, B
Paramyxoviruses
Measles,Mumps,
Respiratory syncytial virus
RabiesRhabdoviruses
Retroviruses
HIV infection syndrome/AIDSHIV-1 and 2
Hepadnavirus, Hepatitis B

12. 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.

13. COMMON VIRAL INFECTONS
AND CHILDHOOD EXANTHEMS
 MEASELS
 RUBELLA (GERMAN MEASELS)
 MUMPS

14. VIRAL INFECTIONS OF THE SKIN
 THE HERPES VIRUS GROUP

15. 13.29 HERPES VIRUS INFECTIONS
InfectionVirus
Herpesvirus hominis (herpes simplex,
HSV)
Herpes labialis ('cold sores')
Keratoconjunctivitis
Finger infections ('whitlows')
Encephalitis
Primary stomatitis
Genital infections
Type 1
Genital infections
Neonatal infection (acquired during
vaginal delivery)
Type 2
Chickenpox , Shingles (herpes zoster)Varicella zoster virus
Congenital infection
Disease in immunocompromised patients
Pneumonitis
Retinitis
Enteritis
Generalised infection
Cytomegalovirus (CMV)
Infectious mononucleosis
Burkitt's lymphoma
Nasopharyngeal carcinoma
Oral hairy leucoplakia (AIDS patients)
Epstein-Barr virus (EBV)
Associated with Kaposi's sarcomaHuman herpes virus 8

16. 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

17.  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.

18. ('whitlow'),

19.  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.

20.  Type 2 (genital) disease is a common
cause of recurrent painful genital
ulceration

21. Complications
1.Neonatal HSV disease,
contracted from the birth
canal, may be
disseminated and is
potentially fatal.
Active HSV in a pre-term
mother is an indication for
either elective caesarean
section or antiviral
therapy.
2.eczema herpeticum __
HSV infection in patients with
eczema can result in a
spreading and potentially
serious infection (Fig. )

22. 3. Dendritic ulcers
may produce corneal scarring and permanently
damage eyesight. These require aggressive
antiviral therapy.
4. 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.

23. DIAGNOSIS
 PCR,(for HSV)
 Electron microscopy or culture from
vesicular fluid.
 CSF PCR is very useful in HSV
encephalitis.
 Serology is of limited value, only
confirming primary infection.

24. 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).

25. 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

26.  Severe complications
- Aciclovir i.v. 10 mg/kg 8-hourly
(up to 20 mg/kg in severe
encephalitis)

27. 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.

28.  The incubation period is 14-21
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.

29. 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.

30. 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.

31. 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 post-
herpetic neuralgia by 8%. Aciclovir is therefore
cost-effective in shingles but not chickenpox.

32. 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 high-
dose 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.

33. 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.

34.  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.

35.  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.

36. 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.

37. 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.

38. 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.

39. 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 health-
care personnel and re-evaluated national
plans for the containment of disease.

40. 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.

41. 13.29 HERPES VIRUS INFECTIONS
InfectionVirus
Herpesvirus hominis (herpes simplex,
HSV)
Herpes labialis ('cold sores')
Keratoconjunctivitis
Finger infections ('whitlows')
Encephalitis
Primary stomatitis
Genital infections
Type 1
Genital infections
Neonatal infection (acquired during
vaginal delivery)
Type 2
Chickenpox , Shingles (herpes zoster)Varicella zoster virus
Congenital infection
Disease in immunocompromised patients
Pneumonitis
Retinitis
Enteritis
Generalised infection
Cytomegalovirus (CMV)
Infectious mononucleosis
Burkitt's lymphoma
Nasopharyngeal carcinoma
Oral hairy leucoplakia (AIDS patients)
Epstein-Barr virus (EBV)
Associated with Kaposi's sarcomaHuman herpes virus 8

42. SYSTEMIC VIRAL INFECTIONS
 INFLUENZA
 EBV -Infectios mononucleosus
 CMV
 VIRAL HEMORAGIC FEVER
 HIV

43. 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.

44. Clinical features (IM)
 lymphadenopathy, especially posterior
cervical,
 pharyngeal inflammation or exudates,
 palatal petechiae,
 fever,
 splenomegaly,
 periorbital oedema,
 clinical or biochemical evidence of hepatitis,
 And a non-specific rash.

45. Ix.
 20% or more of peripheral
lymphocytes must have an
atypical morphology (Fig.)
 characteristic heterophile
antibody. (classical Paul-
Bunnell titration or by slide
test 'Monospot‘)).
 Specific EBV serology
(immunofluoresence) =Anti
EBV IgM Ab.

46. COMPLICATIONS OF
INFECTIOUS MONONUCLEOSIS
Common
 Severe pharyngeal oedema
 Antibiotic-induced rash
 Chronic fatigue syndrome
(10%)
Rare
 Ruptured spleen
 Respiratory obstruction
 Arthritis
 Agranulocytosis
 Agammaglobulinaemia
Uncommon
Neurological
 Cranial nerve palsies
 Polyneuritis
 Transverse myelitis
 Meningoencephalitis
Haematological
 Haemolytic anaemia
 Thrombocytopenia
Renal
 Glomerulonephritis
 Interstitial nephritis
Cardiac
 Myocarditis
 Pericarditis
Pulmonary
 Interstitial pneumonitis

47. Rx.
 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.

48. 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.

49.  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.

50. Clinical features
 Most post-childhood CMV infections are
subclinical, although some young adults
develop a mononucleosis-like syndrome .
 Some patients have a prolonged influenza-
like 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.

51. complications
 neurological involvement,
 autoimmune haemolytic anaemia,
 pericarditis,
 pneumonitis .
 arthropathy.

52. 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.

53. Rx.
 Only 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 self-
limiting, 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

54. VIRAL HAEMORRHAGIC
FEVERS The viral haemorrhagic fevers are zoonoses caused by several
different viruses .They are endemic world-wide, examples.:
Yellow fever-
 Reservoir ; Monkeys
 Transmission;Mosquitoes
 Geography ;Tropical Africa, South and Central America-
 Mortality 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

55. 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

56. 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.

57. Investigations
 There is leucopenia,
 thrombocytopenia
 proteinuria.
 Prolong PT and PTT

58. 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.

59. 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.

60. GASTROINTESTINAL VIRAL
INFECTIONSROTAVIRUS
 Rotaviruses are the major cause of diarrhoeal illness in
young children, accounting for 30-50% of cases
admitted to hospital in developed countries, and 10-
20% 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.

61. 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.

62. Treatment
 The disease is self-limiting but
dehydration needs appropriate
management .
 Immunity develops to natural
infection.

63. 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.

64. 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

65. Human immunodeficiency
virus infection (HIV) and the
acquired immunodeficiency
syndrome (AIDS)

66. 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.

67.  . Immune deficiency is a
consequence of continuous high-level
HIV replication leading to immune-
mediated destruction of the key
immune effector cell, the CD4
lymphocyte.

68. 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.

69. 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.

71.  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.

73.  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.

74. NATURAL HISTORY AND
CLASSIFICATION OF HIV
 Primary infection
 Asymptomatic infection
 Mildly symptomatic disease
 HIV SYMPTOMATIC DISEASES=AIDS
related complex (ARC).
 Acquired immunodeficiency syndrome
(AIDS)

75. Primary infection
 Fever with rash
 Pharyngitis with cervical
lymphadenopathy
 Myalgia/arthralgia
 Headache
 Mucosal ulceration

76.  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.

77. Diagnosis is made by
 1- detecting HIV-RNA in the serum (PCR).
 2- immunoblot assay (which shows antibodies
developing to early proteins)= Anti HIV
antibody.
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.

78. Factors likely to indicate a faster
progression of HIV are
 1-the presence and duration of symptoms,
 2- evidence of candidiasis,
 3- neurological involvement.
 4- The level of the viral load post-
seroconversion strongly correlates with
subsequent progression of disease.

79. The differential diagnosis of primary HIV
includes
 acute Epstein-Barr virus (EBV),
 cytomegalovirus (CMV),
 streptococcal pharyngitis,
 toxoplasmosis
 secondary syphilis.

80. 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

83. Mildly symptomatic disease
 Centers for Disease Control (CDC) Classification
category B disease .
 indicating some impairment of the cellular
immune system.
 These diseases correspond to AIDS-related
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.

84. 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*

85. 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)

86. 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

87. 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

88. oseophageal candidiasis

89. 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

90. Late HIV
Common
 Kaposi's sarcoma
 Molluscum contagiosum
 Chronic mucocutaneous herpes simplex
Rare
 Bacillary angiomatosis
 CMV
 Non-Hodgkin lymphoma
 Cryptococcus
 Histoplasmosis
 Mycobacterial (tuberculosis/atypical)

91. Figure 14.5 Presentation and differential diagnosis of HIV-
related gastrointestinal disorder

92. Figure 14.6 Cryptosporidial infection. Duodenal biopsy may be
necessary to confirm cryptosporidiosis or microsporidiosis.

93. Figure 14.7 Pneumocystis pneumonia. Typical chest X-
ray appearance. Note the sparing at the apex and base
of both lungs.

94. 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.

95. Figure 14.9 Presentation and differential diagnosis of
HIV-related neurological disorders

96. Figure 14.10 Cerebral toxoplasmosis. Multiple cortical ring-
enhancing lesions with surrounding oedema are characteristic.

97. Figure 14.11 Primary CNS lymphoma. A single enhancing
periventricular lesion with moderate oedema is typical.

98. Figure 14.12 Progressive multifocal leucoencephalopathy.
Non-enhancing white matter lesions without surrounding
oedema are seen.

99. Figure 14.13 Oral Kaposi's sarcoma. A full examination is
important to detect disease that may affect the palate, gums,
fauces or tongue.

100. MANAGEMENT OF HIV
Management of HIV involves (two arms), 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 drug-related side-effects or
lifestyle alteration.
 4- reduce transmission (mother-to-child and person-to-
person).

101. 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.

103. Nucleoside reverse transcriptase
inhibitors (NRTIs)
 Zalcitabine (ddC)
 Didanosine (ddI)
 Lamivudine (3TC)
 Zidovudine (ZDV)
 Stavudine (d4T)
 Abacavir
 Emitricitabine (FTC)

104. Non-nucleoside reverse
transcriptase inhibitors (NNRTIs)
 Nevirapine
 Efavirenz
 Delavirdine1

105. Protease inhibitors (PIs)
 Indinavir2
 Ritonavir
 Nelfinavir
 Lopinavir3
 Atazanavir2
 Fosamprenavir2
 Saquinavir2
 Amprenavir1,2
 Tipranavir1,2
 osamprenavir
Others
 Tenofovir
 Enfuvirtide (T-20)=(preventing fusion).

106. Notes about HIV drugs
 The inclusion of two NRTIs, or one NRTI and tenofovir,
remains the cornerstone of HAART. (highly active anti-
retroviral 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.

107.  Short- and long-term side-effects are not infrequent.
 Fat redistribution syndrome, occurred in 20-30% of
patients treated with HAART including a PI after 2
years.
The syndrome is characterised by:
1. peripheral fat-wasting (cheeks, temples, limbs and
buttocks),
2. localised collections of fat (buffalo hump, peripheral
lipomatosis, and breast enlargement in women)
3. central adiposity.

108.  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.

109. 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

110. POST-EXPOSURE PROPHYLAXIS (PEP)
 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.