judith (L26) Flashcards
How do you diagnose viral infections?
Clinical history and examination
Detection of the virus
Live virus, viral particles, viral antigens or nucleic acid
Detection of the body’s response to infection
Usually virus specific antibodies
Principle of immunofluorescence
Look for viral antigens expressed in infected cells.
Fix infected cells to slide.
Add virus-specific antibody eg mouse anti-HSV.
Incubate.
Wash.
Add ‘tagged’ anti-antibody eg rabbit anti- mouse with fluorescent label.
Incubate.
Wash.
Visualise under UV light.
Look for apple-green fluoresence.
diagnosis of virus infections
Antigen detection (by immunofluorescence)
Virus isolation (attempt to grow virus in cell culture, can be followed by antigen detection for typing and confirmation)
Direct visualisation of virus particles (electron microscopy)
Genome detection
Virus-specific antibodies
define genome detection
Usually involves genome amplification
eg polymerase chain reaction assay (PCR)
Highly sensitive assays
For HSV assays can be type-specific eg by using type-specific probes or melting curve analysis
Can be made quantitative ie how much virus is there?
eg monitoring of HIV viral load in response to therapy
examples of virus-specific antibodies
Virus specific antibodies ie serology
eg IgG or IgM antibodies to HSV
or type-specific antibodies to HSV-1 or HSV-2
types of HSV infection
Primary (first encounter with HSV) Initial or 1st episode (first encounter with ‘the other’ virus) Reactivation of either virus Endogenous reinfection (another site) Exogenous reinfection (another strain)
Recurrent oral-labial herpes simplex virus-1 infection
Neonatal HSV
Eczema herpeticum
HSV encephalitis
complications
VZV pneumonia
recurrent infection - herpes zoster or shingles
sight threats - Opthalmic zoster
( worse if immunocompromised )
VZV - therapy with aciclovir
Chicken-pox
- Adults, including pregnant women
- Complications eg pneumonia
- Immunocompromised child
Shingles
- Early treatment can reduce post herpetic neuralgia
- Ophthalmic
- Immunocompromised patient
causes of viral gastroenteritis
Rotaviruses (Reoviridae)
Enteric adenoviruses (group F Adenoviridae)
Noroviruses and Sapoviruses (Caliciviridae)
Astroviruses (Astroviridae)
diagnosis methods
Antigen detection
- ELISA for rotavirus and enteric adenoviruses.
Genome detection
- eg norovirus - most sensitive & specific
Electron microscopy
- now rarely used - slow, expensive, need 106 particles/ml.
Serology and virus isolation not used
MERS-CoV in what countries
Countries in or near the Arabian Peninsula with Cases
Saudi Arabia, United Arab Emirates (UAE), Qatar, Oman, Jordan, Kuwait, Yemen, Lebanon, Iran.
Countries with Travel-associated Cases United Kingdom (UK), France, Tunisia, Italy, Malaysia, Philippines, Greece, Egypt, United States of America (USA), Netherlands, Algeria, Austria, Turkey, Germany, Republic of Korea, China, Thailand.
MERS-CoV
First identified September 2012 in a Qatari man who had recently travelled to Saudi Arabia.
Once sequence known a diagnostic PCR could be developed.
The nearest relatives are bat coronaviruses.
Camels have a high prevalence of MERS-CoV infection – not just camels across the Arabian Peninsula.
All known viruses are closely related, belong to the same serotype and all may originally stem from Africa.
ways in which one may acquire a zoonotic MERS-CoV infection
from an actively infected camel
- Camel calves excrete the virus at higher concentrations than adult camels.
- Detectable levels of antibodies do not prevent reinfection of adult camels.
camels are infectious (by sneezing on you, drinking their milk, cleaning after them)
if it is unwell, it is taken somewhere to take care of it but could spread
diagnosis of viral respiratory tract infection
Rapid tests for viral antigen (RSV and Flu A) - less sensitive than PCR.
Immunfluoresence.
Virus isolation – slow, now rarely used outside reference laboratories.
PCR - increasingly used but expensive
Serology – complement fixation tests – retrospective diagnosis.
respiratory PCR panel
Influenza A Influenza B RSV A & B HMPV A & B Parainfluenza virus 1-4 Adenovirus Rhino/enteroviruses Bocavirus Coronaviruses 229E, NL63, OC43, HKU1 (not MERS-CoV)
influenza vaccine efficacy
Efficacy in adults last winter was extremely low, particularly in the elderly, due to a combination of factors:
- Poor response to H3N2 component of the vaccine
More flu B – not covered by trivalent vaccine
For this season:
- adjuvanted trivalent vaccince for ≥ 65 and quadrivalent vaccine for other at risk groups.
who is offered flu vaccine?
Health and social care workers – to protect themselves, their patients and colleagues
Chronic neurological, hepatic, renal, pulmonary and chronic cardiac disease
Diabetes mellitus
Severe immunosuppression because of disease or treatment
HIV infection – regardless of immune status
Age over 65 years
Residents of residential or nursing homes
Carers
Household contacts of immunosuppressed patients
Pregnant women
Young children – live vaccine programme
Morbid obesity (BMI ≥40) not on list despite being high risk for complicated influenza Outside this list vaccination available but not free
complications of EBV infection - acute infection and long term
Acute infection
- Respiratory obstruction
- Hepatitis – don’t drink alcohol
- Rupture of spleen – avoid contact sports
Long term - association with various malignancies because EBV can ‘transform’ cells
- Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Hodgkins disease
- Lymphomas in AIDS and transplant patients
viral hepatitis
Acute hepatitis
- Hepatitis A, B, E (rarely C or D)
- Herpes viruses - EBV and CMV
- Yellow Fever
hepatitis A virus
Faecal-oral route of transmission
- Entry via contaminated food or water
- Excreted in faeces
hepatitis E virus
Incubation period – range 15-60 days (average 40 days).
Symptomatic infections are rare, < 1% & the disease is usually mild. Uncertain whether infection confers lifelong immunity.
Infections during pregnancy are associated with 30% mortality rate in mothers & poor neonatal outcome. This is seen in hyperendemic areas where G1 viruses circulate.
Infection in patients with pre-existing chronic liver disease is associated with a 70% mortality rate. Alcohol consumption is an important risk factor.
epidemiology
HEV infection & the disease it causes, hepatitis E, are found worldwide.
HEV is a family of ≥ four closely related viruses referred to as genotypes 1 to 4 (G1-4) each with distinct host preferences & patterns of illness.
HEV is hyper-endemic through much of the developing world where sanitation & food hygiene may be poor.
Infections in the developing world are usually linked to G1 (South Asia, Middle East and Africa) and G2 viruses (Mexico).
In these countries HEV causes sporadic cases of hepatitis but also large water-borne outbreaks associated with faecal contamination of water.
HBV modes of transmission
Sexual
Vertical transmission - mother to child
Parenteral - unsafe injections and transfusion
NB Largely preventable by vaccination
natural history of HBV infection - adults
Acute infection
- subclinical infection
- acute hepatitis with jaundice
- fulminant hepatitis (1%) – may die or survive by Tx
- chronic infection (10%)
Chronic infection
- healthy carrier
- chronic hepatitis
- cirrhosis
- hepatocellular carcinoma