Viruses Involved In Eye Infections(1).pdf

Viruses involved in eye infections SYPM3704 Division of Virology (UFS) Objectives/Outcomes At the end of this lecture, students should be able to: 1. Describe the properties of a virus 2. Describe viral structure 3. Have an overview of laboratory diagnosis & methods used to detect viruses 4. Provide...

Viruses involved in eye infections SYPM3704 Division of Virology (UFS) Objectives/Outcomes At the end of this lecture, students should be able to: 1. Describe the properties of a virus 2. Describe viral structure 3. Have an overview of laboratory diagnosis & methods used to detect viruses 4. Provide a differential diagnosis for different eye conditions caused by viruses 5. Understand & explain how different viruses are transmitted 6. List specimens to send to the laboratory for confirming viral infections 7. Describe the epidemiology, transmission, clinical features, laboratory diagnosis and brief management of: adenovirus the herpes family of viruses picornaviruses 8. Describe the epidemiology, transmission, clinical picture of Molluscum contagiosum Properties of a virus 1. Viruses are obligate intracellular parasites Depend on the host cell for replication Viruses cannot make energy or proteins independently 2. Viruses are either enveloped or naked (unenveloped) 1. Viral genomes: RNA or DNA, but not both 1. Viral components are assembled and do not replicate by "division" 1. Viruses are filterable agents Very small: can pass through filters that retain bacteria Size of a virus Very small - measured in nanometres Range from 20nm – 300nm Too small to be seen under light microscope Can be visualised with electron microscope Structure of a virus 4 MAIN COMPONENTS ▪ Genome ▪ Capsid ▪ Envelope ▪ glycoproteins ▪ Non-structural proteins Quiz: True or False Viruses can be seen under a light microscope Quiz: True or False Viral genomes consist of both RNA and DNA Transmission of viruses Classification of viruses 1. Structure: size, morphology, and nucleic acid 1. Biochemical characteristics: structure & mode of replication 1. Disease: encephalitis, retinitis and hepatitis viruses 1. Means of transmission: e.g. arbovirus spread by insects 1. Host cell (host range): animal (human, mouse, bird), plant, bacteria 1. Tissue or organ (tropism): e.g. adenovirus and enterovirus Laboratory diagnosis of viral infections GENERAL PRINCIPLES 1. Specimen – to be taken at the appropriate time ▪ Understand pathogenesis & natural history of disease 1. Presence of virus vs disease e.g. latent viruses 1. Limitations of laboratory tests ▪ ▪ No single approach optimal for all viruses in all situations No “perfect” laboratory test 2. Interpretation of test result very important Laboratory methods Direct demonstration of virus/part of virus ▪ Virus via electron microscopy (EM) ▪ Viral antigen e.g. Immunofluorescence (IF), ELISA ▪ Viral nucleic acid e.g. polymerase chain reaction (PCR) Laboratory methods Demonstration of effect of virus ▪ Virus isolation = growth of virus in cell culture, chick embryo & animal inoculation Detection of antibodies in serum (serology) ▪ Detection of patient’s immune response e.g. Enzyme-Linked Immunosorbent Assay (ELISA) or Enzyme-Immuno Assay Types of specimens for virology Conjunctival swab Sample each eye with separate swabs (premoistened with sterile saline) by rolling over conjunctiva When only one eye is infected, sampling both can help distinguish indigenous microflora from true pathogens Blood Test for antibodies, antigen, viral genome Tears Corneal scrapings Collected by ophthalmologist by scraping ulcer/lesions Vitreous fluid Needle aspiration Unsure? Microbial flora of the normal eye Note: Viruses & Fungi are NOT normal flora Quiz: True or False Laboratory tests for viruses are perfect and correct every time Quiz: True or False A blood sample is the ideal sample type for ocular conditions Specific viruses affecting the eye 1. Adenovirus 2. Herpesviruses i. ii. iii. iv. HSV1/2 VZV CMV HHV8 3. Rubella 4. Measles 5. Entero / Coxsackievirus 6. Molluscum 7. Arboviruses 8. SARS-CoV-2 9. HIV 10. Human papillomavirus 11. Hepatitis B virus Next Lecture For healthcare workers Adenovirus Droplets from respiratory tract/direct contact eye secretions/urine/ contaminated surfaces/devices Non-enveloped – particularly resistant to inactivation Pathology is due to viral replication & cell lysis + host’s immune response Sporadic & epidemic forms Ocular manifestations are classified into 4 syndromes: Pharyngoconjunctival fever (PCF) Epidemic keratoconjunctivitis (EKC) Acute nonspecific follicular conjunctivitis (NFC) Chronic keratoconjunctivitis (CKC) = rare! Additionally, may cause acute haemorrhagic conjunctivitis Adenovirus Pharyngoconjunctival fever (PCF) Most commonly occurs in children & young adults (outbreaks) Spread rapidly as a result of respiratory tract to eye, eye to eye and via infected tissues, clothes, other fomites & contaminated swimming pools Sporadic cases are seen in all age groups Serotypes 3, 4 & 7 (common) Less common types: 1, 11, 14, 16-19, 37 IP of 6-12 days Fever & sore throat Conjunctivitis (usually bilateral), with burning, irritation, mild photophobia Punctuate keratitis may develop, followed by corneal infiltrates Adenovirus Epidemic keratoconjunctivitis (EKC) Occurs sporadically or in clusters & epidemics Common serotypes 8, 19 & 37 Less often: serotypes 3, 4, 7, 10, 11, 21 Highly contagious - transmitted via close personal contact as well as during non-sterile eye examinations with contaminated ophthalmic instruments More common during autumn & winter IP = 8-10 days Keratitis in approx. 80% of patients – discomfort, photophobia, tearing, mild blepharospasm Subepithelial corneal infiltrates are the hallmark - may lead to visual loss Tears & saliva are contagious for about 2 weeks Adenovirus Diagnosis: History & clinical features. Specimens: Conjunctival swabs, tears, throat swabs, urine Lab Tests: ▪ Virus isolation with IFA ▪ Serology Immunoflorescence staining showing the infected Adenovirus cells in direct smear of conjunctival swab Management: A. Most NB step of adenoviral conjunctivitis is prevention of transmission Povidone-iodine drops may reduce contagiousness B. Symptomatic: analgesia, lubricants, cold compresses. No specific antivirals C. Conjunctivitis complications e.g. pseudomembrane & membrane formation – surgical removal + careful administration of topical steroids D. No vaccine E. Contact lenses should be disposed Quiz: True or False Adenoviruses are very easily inactivated Herpesviruses HHV-1 Herpes simplex virus 1 HSV-1 HHV-2 Herpes simplex virus 2 HSV-2 HHV-3 Varicella zoster virus VZV HHV-4 Epstein-Barr virus EBV HHV-5 Cytomegalovirus CMV HHV-6 Human herpes virus 6 HHV-6 HHV-7 Human herpes virus 7 HHV-7 HHV-8 Human herpes virus 8 HHV-8/KSV The herpesviruses All herpesviruses are morphologically identical One of the most successful human parasites Infects majority of the world’s population by early adulthood Irrespective of age of primary infection, virus persists life-long Immune hosts can be re-infected Herpes simplex virus Most infections = asymptomatic Clinical: mainly vesicular eruptions of the skin/ mucus membranes HSV1: Face HSV2: Genital organs Spread by direct contact/sexual contact. Primary infection/Reactivation of previously dormant virus Clinical: Primary Gingivostomatitis Eczema herpeticum Pharyngitis/Tonsillitis Meningo-encephalitis Disseminated infection Reactivation: HSV1: Fever blisters HSV2: Genital ulcers Herpes simplex virus: Eye HSV1 > HSV2 Primary or reactivation Ocular manifestations of HSV-1 infection include: Blepharitis Conjunctivitis Infectious epithelial keratitis Neurotrophic keratopathy Necrotising stromal keratitis Immune stromal keratitis Endotheliitis Eyelid & periorbital vesicles Prodromal facial & lid tingling (24hrs) Associated conjunctivitis, discharge & lid swelling Duration: 6 – 8 days Herpes simplex virus: Eye The typical dendritic ulcer caused by HSV-1 is a form of infectious epithelial keratitis and occurs as a result of active viral replication Infection with HSV-1 causing keratitis is the single most frequent cause of infectious blindness in developed countries Other ocular manifestations include iridocyclitis, panuveitis and acute retinal necrosis (ARN), which is rare and usually occurs in immunocompetent hosts Herpes simplex virus: Eye Diagnosis: Clinical Vesicle fluid: Electron microscopy Virus Isolation Blood - antibodies PCR (vesicle fluid/anterior chamber or vitreous fluid/biopsy specimen) Treatment: Antiviral agents are the mainstay of Rx Topical or oral (depends on site, severity & patient immune status) Intravenous Varicella zoster virus ▪ HHV3 ▪ Spread via respiratory droplets ▪ Primary infection = Varicella (chickenpox) ▪ Reactivation = Zoster (shingles) ▪ Vesicles are virus-filled Varicella zoster virus Shingles: Single dermatome. Approximately 10%-20% of all herpes zoster presents as herpes zoster ophthalmicus Herpes zoster ophthalmicus Usually involves the upper lid and does not cross the midline. Typically affects elderly Herpes zoster ophthalmicus Diagnosis: ▪ Usually clinical ▪ Vesicle fluid: ▪ Electron microscopy ▪ Cell culture ▪ Blood for antibodies ▪ PCR: Vesicle fluid/anterior chamber fluid More severe in immune-compromised Prevention: ▪ Vaccine ▪ Immunoglobulin Treatment: ▪ Analgesia, good hydration, adequate personal hygiene to prevent 2ndry bacterial infections ▪ Antivirals: Oral or IV esp. immunocompromised patients Quiz: True or False All herpesviruses persist life-long Cytomegalovirus (CMV) ▪ HHV5 ▪ Ubiquitous ▪ Mostly asymptomatic ▪ Shed in urine & body fluids including saliva, breast milk, genital secretions ▪ Therefore congenital, oral and sexual routes most common ▪ Also transmitted by blood transfusion and organ transplant Congenital CMV infection ▪ Most prevalent viral cause of congenital infection ▪ Infection transplacental or ascending from cervix ▪ Highest risk of serious birth defects in primary maternal infection during pregnancy ▪ Cataracts ▪ Optic atrophy ▪ Macular scars ▪ Cortical visual impairment ▪ Strabismus Cytomegalovirus (CMV) CMV Retinitis ▪ Mainly in immunocompromised ▪ Begins with a slow onset of floaters with blurred vision over a few days or a blind spot in the center of vision. ▪ Usually starts in one eye but often progress to the other eye. ▪ Without treatment or improvement in the immune system, CMV retinitis destroys the retina & damages the optic nerve, resulting in blindness. Less common: anterior uveitis, corneal endotheliitis Diagnosis: ▪ Clinical ▪ Antibodies in blood ▪ PCR: blood/ocular fluids Prevention: ▪ No vaccine Treatment: ▪ Antiviral – Ganciclovir ▪ Oral/IV/intravitreal injection Kaposi’s Sarcoma (KS) ▪ HHV 8 ▪ Neoplasm almost exclusively seen in patients with AIDS ▪ Spread by saliva, possibly sexual transmission ▪ Commonest anterior segment lesion seen in AIDS; appears as a violaceous, non-tender nodule on the eyelid or conjunctiva ▪ Treatment: ▪ may be necessary for cosmesis and to relieve functional difficulties ▪ Mainly radiotherapy. ▪ Other options: cryotherapy /chemotherapy Quiz: True or False Primary VZV infection – chickenpox (varicella) Rubella ▪ German measles ▪ Enveloped, RNA virus ▪ Benign fever and rash ▪ Biggest threat of rubella virus is to foetuses of pregnant women who develop primary infection in the 1st trimester ▪ Result may be abortion, stillbirth or congenital rubella syndrome (CRS) ▪ Ocular manifestations of rubella virus are generally limited to CRS Epidemiology: ▪ Worldwide ▪ Man is the only host ▪ Affects mainly children ▪ Transmitted via respiratory route ▪ Congenitally infected babies: prolonged shedding of virus Congenital Rubella Syndrome ▪ Damage to foetal endothelial cells in early pregnancy is the result of viral replication, because the immune system has not developed by this time ▪ The virus also induces retardation of mitosis in infected cells ▪ Classic triad: Cataract, cardiac abnormalities, deafness. ▪ Ocular features: ▪ Cataract ▪ Microphthalmos, glaucoma, retinopathy, keratitis, anterior uveitis, iris atrophy. ▪ Refractive errors, pendular nystagmus, strabismus. Rubella Diagnosis: CRS Pregnant women: ▪ Serology (IgG & IgM): blood Prenatal: ▪ PCR: amniotic fluid Baby: ▪ Rubella-specific IgM antibodies synthesised by the foetus, will be present at birth. ▪ Cord blood or infant serum is the preferred specimen ▪ PCR: urine, respiratory specimens Virus isolation: blood, urine, throat swabs Management General: ▪ mild illness – symptomatic CRS: ▪ TOP: confirmed 1st trimester diagnosis ▪ Multidisciplinary team management ▪ Rx complications ▪ Cataract surgery ▪ Mx of 2ndry glaucoma Prevention: Vaccine Measles Rubeola RNA, enveloped virus Humans are the natural hosts of the virus Affects all races Males = Females Disease of childhood but infection can occur in unvaccinated or partially vaccinated persons Highly contagious Spread from person to person by respiratory droplets, via: coughing sneezing close personal contact direct contact with secretions Measles Clinical features Incubation period = 10 to 14 days Prodromal phase lasts for several days: Malaise Fever Loss of appetite ‘The three C’s’ & ‘P’: conjunctivitis, cough, coryza & photophobia Towards the end of the prodrome, just before the rash, Koplik’s spots may appear on the buccal mucosa Rash usually appears 3 – 5 days after the start of the prodrome Usually lasts about 5 days Measles Most important cause of blindness in children in developing countries, +/15,000 - 60,000 cases of blindness per year Acute infection depresses the serum retinol concentration, which can result in xerophthalmia, with corneal ulceration, keratomalacia, & subsequent corneal scarring, eventually resulting in blindness Blindness may also result from cortical damage from measles encephalitis Corneal ulceration in a young child following measles. Fluorescein staining demarcates a large area of ulceration. (Reproduced from The Child, Measles and the Eye by the WHO.) Measles Diagnosis Clinical Serology (IgG & IgM): blood PCR: blood, CSF, respiratory specimens Treatment Supportive: antipyretics & fluids Vitamin A, 200 000IU orally (to prevent blindness) Prevention Safe & effective vaccine available 95% protection rate Immunity persists for years Quiz: True or False Measles and German Measles are caused by the same virus Picornaviridae Family Large family of small, RNA viruses, unenveloped Polio-, entero-, coxsackie-, echo-, parecho-, rhino-, hepatitis A viruses Worldwide Transmitted by respiratory & faecal-oral routes Eye disease may result from direct inoculation via hand to eye contact Viral shedding persists long after sx cease: transmission in schools, childcare centers, with close contact Cause various illnesses: Common cold Herpangina Febrile rash illnesses (hand-foot-&-mouth disease) Hepatitis Myocarditis Encephalitis Picornaviruses & the eye Conjunctivitis, keratoconjunctivitis, uveitis Coxsackie A24, B2 Echo 7 and 11 Enterovirus 70 Enterovirus 70 & Coxsackie A24 can cause bilateral follicular conjunctivitis of sudden onset with conjunctival haemorrhages, transient keratitis. Acute haemorrhagic conjunctivitis: conjunctival congestion, vascular dilatation, & oedema Picornaviruses Diagnosis Specimens: Tears Eye swab Conjunctival scrapings Ocular fluids Blood Throat swab Tests: Serology Virus isolation PCR Management Symptomatic Bed rest Cold compressors Analgesia Avoid contact and sharing of towels etc. To be continued…