VIRAL INFECTIONS

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VIRAL INFECTIONS

• Dr. ALAA HUSSAIN A.AWN

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• 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.

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• 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.

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CLASSIFICATION OF VIRAL INFECTIONS

• The classification of viral infections in humans
  is shown in the fallowing box
• (13.25) dav. Pg 299 20th ed.

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VIRUSES INVOLVED IN HUMAN DISEASE
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Clinical syndromes Classification/viruses involved
DNA VIRUSES
Upper respiratory tract infection/pharyngitisAcute diarrhoea Adenoviruses
Herpes viruses
Acute/recurrent vesicular rash Herpes simplex types 1 and 2
Chickenpox/shingles Varicella zoster
Acute/recurrent hepatorenal infection Cytomegalovirus
Roseola infantum Human herpes virus 6 and 7
Infectious mononucleosisBurkitt's lymphoma Epstein-Barr virus
Nasopharyngeal carcinomaKaposi's sarcoma Human herpes virus 8
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Clinical syndromes Classification/viruses involved
DNA VIRUSES
Papovaviruses
Common wart Human papillomavirus
Progressive multifocalleucoencephalopathy Polyoma

Poxviruses
Smallpox Variola


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Clinical syndromes Classification/viruses involved
RNA VIRUSES
Picornaviruses
Gut/neurological illness PoliovirusCoxsackie virusesEchovirusesEnteroviruses 68-72
Hepatitis A
Upper respiratory tract infection Rhinoviruses
Rheoviruses
Mild upper respiratory tract infection/gut disease Rheovirus
Gastroenteritis Rotavirus

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Clinical syndromes Classification/viruses involved
RNA VIRUSES
Togaviruses
German measles Rubella
Yellow/haemorrhagic fever Yellow fever
Haemorrhagic fevers Dengue  Other arboviruses
Chronic hepatitis Hepatitis C
Calicivirus
Acute gastroenteritis Hepatitis E

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Clinical syndromes Classification/viruses involved
RNA VIRUSES
Orthomyxoviruses
Influenza A, B
Paramyxoviruses
Measles,Mumps, Respiratory syncytial virus
Rabies Rhabdoviruses
Retroviruses
HIV infection syndrome/AIDS HIV-1 and 2
Hepadnavirus, Hepatitis B
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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.

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COMMON VIRAL INFECTONS AND CHILDHOOD EXANTHEMS

• MEASELS
• RUBELLA (GERMAN MEASELS)
• MUMPS

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VIRAL INFECTIONS OF THE SKIN

• THE HERPES VIRUS GROUP

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13.29 HERPES VIRUS INFECTIONS
Infection Virus
Herpesvirus hominis (herpes simplex, HSV)
Herpes labialis ('cold sores')KeratoconjunctivitisFinger infections ('whitlows')EncephalitisPrimary stomatitisGenital infections Type 1
Genital infectionsNeonatal infection (acquired duringvaginal delivery) Type 2
Chickenpox , Shingles (herpes zoster) Varicella zoster virus
Congenital infection Disease in immunocompromised patientsPneumonitisRetinitisEnteritisGeneralised infection Cytomegalovirus (CMV)
Infectious mononucleosisBurkitt's lymphomaNasopharyngeal carcinomaOral hairy leucoplakia (AIDS patients) Epstein-Barr virus (EBV)
Associated with Kaposi's sarcoma Human herpes virus 8


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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

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• 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.

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('whitlow'),
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• 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.

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• Type 2 (genital) disease is a common cause of
  recurrent painful genital ulceration

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Complications

• 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.
• eczema herpeticum __
• HSV infection in patients with eczema can result
  in a spreading and potentially serious infection
  (Fig. )

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• 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.

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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.

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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).

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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

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

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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.

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• 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.

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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.

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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.

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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.

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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.

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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.

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• 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.

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• 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.

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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.

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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.
  

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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.

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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.

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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.

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SYSTEMIC VIRAL INFECTIONS

• INFLUENZA
• EBV -Infectios mononucleosus
• CMV
• VIRAL HEMORAGIC FEVER
• HIV

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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.

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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.

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• 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)

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COMPLICATIONS OF INFECTIOUS MONONUCLEOSIS

• Uncommon
• Neurological
• Cranial nerve palsies
• Polyneuritis
• Transverse myelitis
• Meningoencephalitis
• Haematological
• Haemolytic anaemia
• Thrombocytopenia
• Renal
• Glomerulonephritis
• Interstitial nephritis
• Cardiac
• Myocarditis
• Pericarditis

• Common
• Severe pharyngeal oedema
• Antibiotic-induced rash
• Chronic fatigue syndrome (10)
• Rare
• Ruptured spleen
• Respiratory obstruction
• Arthritis
• Agranulocytosis
• Agammaglobulinaemia

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Management

• Treatment is largely symptomatic
• aspirin gargles to relieve a sore throat.
• If a throat culture yields a ß-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.

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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.

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• 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.

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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.

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complications

• neurological involvement,
• autoimmune haemolytic anaemia,
• pericarditis,
• pneumonitis .
• arthropathy.

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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.

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Management

• 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

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VIRAL HAEMORRHAGIC FEVERS

• The viral haemorrhagic fevers are zoonoses caused
  by several different viruses .They are endemic
  world-wide, examples.
• Yellow fever-
• Reservoir Monkeys
• TransmissionMosquitoes
• Geography Tropical Africa, South and Central
  America-
• Mortality rate 10-60 death
• Clinical features Hepatic failureBlood oozing
• Dengue
• Reservoir Humans
• Transmission Aedes aegypti-
• Geography tropical and subtropical coasts
• Mortality rate Nil-10
• Clinical features - Joint and bone pain Petechiae

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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

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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.

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Investigations

• There is leucopenia,
• thrombocytopenia
• proteinuria.
• Prolong PT and PTT

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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.

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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.

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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 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.

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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.

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Treatment

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

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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.

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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

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• Human immunodeficiency virus infection (HIV) and
  the acquired immunodeficiency syndrome (AIDS)

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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.

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• . 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.

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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.

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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.

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• 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.

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• 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.

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NATURAL HISTORY AND CLASSIFICATION OF HIV

• Primary infection
• Asymptomatic infection
• HIV SYMPTOMATIC DISEASES
• Mildly symptomatic disease
• Acquired immunodeficiency syndrome (AIDS)

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Primary infection

• Fever with rash
• Pharyngitis with cervical lymphadenopathy
• Myalgia/arthralgia
• Headache
• Mucosal ulceration

75

• 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 gt 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.

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• 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.

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• 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 post-seroconversion
  strongly correlates with subsequent progression
  of disease.

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

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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

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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

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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.

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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)

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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

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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

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oseophageal candidiasis
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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

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

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Figure 14.5 Presentation and differential
diagnosis of HIV-related gastrointestinal disorder
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Figure 14.6 Cryptosporidial infection. Duodenal
biopsy may be necessary to confirm
cryptosporidiosis or microsporidiosis.
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Figure 14.7 Pneumocystis pneumonia. Typical chest
X-ray appearance. Note the sparing at the apex
and base of both lungs.
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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.
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Figure 14.9 Presentation and differential
diagnosis of HIV-related neurological disorders
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Figure 14.10 Cerebral toxoplasmosis. Multiple
cortical ring-enhancing lesions with surrounding
oedema are characteristic.
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Figure 14.11 Primary CNS lymphoma. A single
enhancing periventricular lesion with moderate
oedema is typical.
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Figure 14.12 Progressive multifocal
leucoencephalopathy. Non-enhancing white matter
lesions without surrounding oedema are seen.
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Figure 14.13 Oral Kaposi's sarcoma. A full
examination is important to detect disease that
may affect the palate, gums, fauces or tongue.
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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
  (lt 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).

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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.

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Nucleoside reverse transcriptase inhibitors
(NRTIs)

• Zalcitabine (ddC)
• Didanosine (ddI)
• Lamivudine (3TC)
• Zidovudine (ZDV)
• Stavudine (d4T)
• Abacavir
• Emitricitabine (FTC)

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Non-nucleoside reverse transcriptase inhibitors
(NNRTIs)

• Nevirapine
• Efavirenz
• Delavirdine1

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• Protease inhibitors (PIs)
• Indinavir2
• Ritonavir
• Nelfinavir
• Lopinavir3
• Atazanavir2
• Fosamprenavir2
• Saquinavir2
• Amprenavir1,2
• Tipranavir1,2
• Others
• Tenofovir
• Enfuvirtide (T-20)

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Notes about HIV drugs

• The inclusion of two NRTIs, or one NRTI and
  tenofovir, remains the cornerstone of HAART.
  (highly active anti-retroviral therapy)combinatio
  n 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.

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• Short- and long-term side-effects are not
  infrequent. Fat redistribution occurred in 20-30
  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.

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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

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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.

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good luck