Viral Infections of the Skin and Mucus Membranes

1. Viral Infections of the Skin and Mucus Membranes

2. Maculopapular Rash Measles virus Rubella virus Parvovirus Human Herpes 6 Vesicular Rash Herpes simplex virus Varicella zoster virus Coxsakievirus

3. Measles Measles virus is a paramyxovirus Paramyxoviruses : Enveloped virus, ssRNA genome as a single piece. The family includes parainfluenza virus, mumps virus, measles virus and respiratory syncytial virus. Parainfluenza and mumps virus have a surface hemagglutinin and neuraminidase, while measles have a hemagglutinin, but not neuraminidase. The virion structure includes: Spikes F protein Matrix protein M, below the envelope Only one serotype

4. Measles Disease Acute febrile illness, mostly in childhood Incubation period: 10 – 12 days Onset is flu-like: high fever, cough, conjunctivitis Koplik's spots: red spots with bluish-white centre on the buccal mucosa 1 – 2 days later, acute symptoms decline with appearance of a widespread maculopapular rash Over 10 – 14 days, recovery is usually complete as the rash fades

6. Complications Giant cell pneumonia, more common in adults Otitis media Post-measles encephalitis Subacute sclerosing panencephalitis (SSPE): progressive and fatal degenerative disease within the infected cells, there is a defective form of the virus which because it can not produce functional M protein, is not released as complete virus from the cells.

7. Laboratory Diagnosis Most cases are diagnosed clinically NPA, immunofluorescence

8. Epidemiology Transmission: person to person by respiratory droplets. Malnutrition contributes to high mortality. Control Live attenuated vaccine, combined with mumps and rubella (MMR) Administration: between 12 – 18 months.

9. Rubella (German Measles) Rubella Virus Classified as togavirus ssRNA virus with an envelope pleomorphic in appearance, 50 – 60 nm in diameter nucleocapsid is icosahedral in symmetry ssRNA is infective and replication occurs in the cytoplasm three major polypeptides: C and envelope glycoproteins E1 and E2 single serotype

10. Postnatal Rubella Incubation period: 12 – 21 days Macular rash, appears first on the face, then spreads to the trunk and limbs Minor pyrexia, malaise and lymphadenopathy with suboccipital nodes most commonly enlarged and tender Arthralgia is uncommon in children, but may occur in up to 60% of adult females, involving the fingers, wrists, ankles and knees Encephalitis and thrombocytopenia are rare complications

11. Pathogenesis Virus is transmitted by air-borne route URT Viremia Skin, joints, placenta cross the barrier Infect fetal differentiating cells Early in pregnancy: this will cause congenital abnormalities

12. Laboratory Diagnosis Clinical diagnosis is unreliable Investigation by virus isolation is not indicated (unreliable and time-consuming) Serological diagnosis is the method of choice, detecting rubella specific IgG and rubella specific IgM. These tests are also used for screening to ascertain susceptibility and whether rubella immunization is indicated. Congenital rubella syndrome: serological testing for specific IgM. Maternal IgM does not cross the placenta so detection of specific IgM is diagnostic of intrauterine infection

13. Control Attenuated live vaccine (MMR) Seroconversion occurs in over 95% Protection persists for more than 20 years Administration in pregnancy is contra-indicated Pregnancy should be avoided for the month following vaccination

14. Human Parvovirus Only parvovirus B19 is the cause of diseases in humans Genus: Erythrovirus

15. The Virus 20 – 25 nm in diameter icosahedral symmetry, no envelope the capsid consists of two proteins, VP1 and VP2 specific viral receptors such as blood group P antigen; explains narrow host range infection is followed by life-long immunity Genome: ssDNA

16. Replication Dependent on cellular factors expressed transiently in the cell during late S or early G2 phase of mitosis. All parvoviruses require dividing cells for replication

17. Clinical Diseases Rash illness (Erythema infectiosum) Erythematous maculopapular rash Common in children aged 4 – 11 years Very similar to rubella Joint disease 80% in adult females 10% in childhood cases arthritis involving small joints of the hands with wrists, knees and ankles affected in some cases

18. Aplastic crisis A transient acute event which complicates chronic hemolytic anemia Fall in hemoglobin Disappearance of reticulocytes from peripheral blood Erythropoiesis cessation lasts for 5 – 7 days Symptoms of worsening anemia B19 infection is responsible for 90% of the cases Occurs most commonly in children with sickle cell anemic B19 in the immunocompromized Persistent infection that leads to persistent anemia

19. Laboratory Diagnosis Virus detection Serum, detecting viral antigens using ELISA detecting viral genome using nucleic acid hybridization and PCR Antibody detection Recent infection can be diagnosed by detecting B19-specific IgM or increasing amounts of specific IgG.

20. Epidemiology Endemic throughout the year in temperate climates Transmission occurs by respiratory route High-titre viremia enables transmission by blood Congenital transmission (vertical) Treatment Most cases are mild and self-limiting Aplastic crisis: blood transfusion Immunosuppressed: blood transfusion and human normal immunoglobulin Intrauterine infection: intrauterine blood transfusion

21. Human Herpesvirus 6 (HHV 6) Sequence analysis revealed two variants: HHV 6A: no clear disease association HHV 6B: exanthema subitum or roseola infantum

22. Roseola Infantum The disease is common between 6 months and 3 years Sudden onset of fever Throat congestion and cervical lymphadenopathy Widespread macular rash occurs in 10% of the cases Some cases are associated with HHV-7 infection HHV-6 and -7, both infect T lymphocytes

23. Vesicular Rash Herpes simplex virus Varicella zoster virus Coxsakievirus

24. Herpes Simplex Viruses Ubiquitous virus, infecting the majority of world’s population Two types: HSV-1 and HSV-2 Type 1 is associated primarily with mouth, eye and CNS Type 2 is found mostly in the genital tract Transmission: direct contact

25. Herpes Simplex Structure Icosahedral virus Lipoprotein envelope, derived from the nuclear membrane Genome: linear, ds DNA Replicate in the nucleus

26. HSV Glycoproteins At least 11 glycoproteins are known Three are essential for production of infectious virus: gB and gD : penetration into the cells gH: release of the virus

27. Pathogenesis Primary Infection The typical lesion is the vesicle; ballooning degeneration of intra-epithelial cells. The roof of the vesicle breaks down, forming ulcer During the replication phase at the site of entery in the epithelium, virus particles enter through the sensory nerve endings and transported along the axon to the nerve body (neurone) in the sensory (dorsal root) ganglion by retrograde axonal flow. Latent infection occurs in the survived neurons that still harbor the viral genome Antibodies reduce the severity of the infections, although it does not prevent recurrences.

28. Latent Infection About 1% of cells in the affected ganglion carry the viral genome. Viral DNA exists as free circular episomes (20 copies / cell). Latency-associated transcripts (LAT) are present HSV-1: causes latency in trigeminal ganglion HSV-2: causes latency in sacral ganglion

29. Reactivation Known triggers for recurrences are accompanied by a local increase in prostaglandin levels and depression of cell-mediated immunity. Reactivation can be induced by UV light Fever Trauma Stress Interval between the stimulus and lesion appearance is 2 – 5 days.

31. Clinical Features Oral infection Acute febrile gingivostomatitis in preschool children Vesicular lesions ulcerate rapidly Skin infections Herpetic whitlow: primary lesion on the fingers or thumb of the toddler with herpetic stomatitis, due to autoinoculation. It also occurs as accidental inoculation in health care workers. Eczema herpeticum: severe form of cutaneous herpes. It may occur in children with atopic eczema.

32. Clinical Features Eye infection Conjunctivitis or keratoconjunctivitis associated with corneal ulceration. This will result in corneal scarring and vision impairment. The majority are caused by HSV-1 Most patients with recurring eye disease are aged over 50 years CNS infection The most likely route of infection is central spread from trigeminal ganglion HSV encephalitis CSF collected in the acute stage should be used for PCR amplification of HSV DNA. More commonly due to HSV-1

33. Clinical Features Genital tract infection Both types can infect genital tract, but HSV-2 is more common. The lesions are vesicular at first but rapidly ulcerate Male: affects the glans and shaft of the penis Female: affects the labia and vagina or cervix Fever and malaise are accompanied by regional lymphadenopathy, urethritis and vaginal discharge

34. Clinical Features Recurrent genital herpes Can be as frequent as six or more episodes a year. Attacks are milder and shorter than first episodes HSV-1 genital infection recurs less often than HSV-2 Either type is capable of transmission from mother to infant. Transplacental passage has been recorded but is very rare. Ascending infection from the cervix is more significant especially when the membranes are ruptured prematurely.

35. Laboratory Diagnosis Isolation of HSV in cultures of human diploid fibroblast cells. Growth is rapid. CPE includes rounded, ballooned cells in foci and giant cell formation Detection of viral antigens in cell (by immunofluorescence), scraped from the base of lesions Detection of amplified viral DNA by PCR in CSF

36. Giant cell formation induced by Herpes simplex infection

37. Treatment Acyclovir: inhibits viral DNA synthesis Acute HSV infections Latency is not eradicated by this agent Prophylactic to prevent reactivation in the immunocompromized (transplant recipients) Available for topical, oral and intravenous route

38. Varicella Zoster Virus Two forms Primary infection is a generalized eruption (chicken pox) Reactivation is localized to one or few dermatomes (shingles, Varicella Zoster) Only one antigenic type

39. Pathogenesis of Chicken Pox Children, vesicular skin eruption Virus enters through URT or conjunctiva The virus causes viremia The vesicles lie in the middle of the epidermis. The fluid becomes cloudy with the influx of leucocytes. These pustules dry up, scabs form and desquamate. Lesions in all stages are present at any time while new ones are appearing.

40. Pathogenesis of Varicella Zoster VZV stays latent in the sensory ganglia Reactivation can occur at any age but the rate is much increased in persons aged 60 years or over. Zoster is usually limited to one dermatome; in adults most commonly in the thoracic or upper lumbar region.

42. Clinical FeaturesChicken Pox Incubation period: 14 – 15 days The patient is infectious for 2 days before and up to 5 days after onset The rash is most dense on the trunk and head Macules ---- Papules ---- Vesicles ---- Pustules

43. Chicken Pox

44. Complications Secondary bacterial infection (commonest) Pneumonia CNS cerebellar ataxia syndrome acute encephalitits

45. Herpes Zoster Reactivated VZV infection Localized eruption, unilateral, typically confined to one dermatome Prodromal paraesthesia and pain in the area supplied by affected nerve are common before skin lesions develop Postherpetic neuralgia Most common complication of zoster 50% risk in patients aged over 60 years pain persisting for 1 month or more after the rash

46. Herpes Zoster

47. Ophthalmic zoster Involvement of ophthalmic division of the trigeminal nerve corneal ulceration, stromal keratitis permanent scarring and loss of sight

48. Laboratory Diagnosis Early vesicular lesions are the best diagnostic material Virus isolation takes from 5 days to 3 weeks More rapid detection is possible with centrifugation-enhanced cultures (shell vials) Direct immunofluorescence VZV DNA amplification by PCR

49. Treatment Acyclovir Given to high-risk of complication Neonates (first 3 weeks of life) Ophthalmic zoster Immunocompromized

50. Epidemiology Spread: respiratory route, in winter and early spring Varicella is highly infectious to susceptible close contacts Mortality is high in normal adults, particularly smokers who develop pneumonia Zoster is associated with decreased T cell function: Old age Pre-AIDS phase Organ transplant recipients

51. Control Passive immunization: varicella zoster immunoglobulin (VZIG): Neonates Non-immune pregnant contacts Immunocompromized contacts A live attenuated vaccine, IM injection

52. Coxsackieviruses Picornavirus Icosahedral, positive sense, linear, ssRNA Two groups: A and B Group A: Herpangina (vesicular pharyngitis) Hand – Foot – and – Mouth disease Acute hemorrhagic conjunctivitis Group B: Pleurodynia (epidemic myalgia) Myocarditis Meningoencephalitis

53. Herpangina Severe febrile pharyngitis The pharynx is usually hyperemic and discrete vesicles occur on the posterior half of the palate, pharynx, tonsils or tongue Self-limited and most frequent in small children Hand – Foot – and – Mouth disease Oral and pharyngeal ulcerations Vesicular rash on the palm and soles

54. Hand – Foot – and – Mouth disease