Viral opportunistic infections Joanna NikitorowiczBuniak Immunology background Cell

Viral opportunistic infections Joanna Nikitorowicz-Buniak

Immunology background ► Cell mediated immunity - CTL, NK cells and macrophages. ► Deficits in cell mediated immunity eg. - AIDS (CD 4 T cells ≤ 200 per μl of blood) - Di George syndrome (lack of thymus), - leukaemia/lymphoma - cancer therapy - immuno-suppression - malnutrition

Common opportunistic viruses ► Herpes family: HSV 1 and 2, CMV, Varicella zoster, EBV, HHV-8 ie. Kaposi sarcoma herpes virus ► Polyomaviruses: JC, BK ► Measles ► RSV ► Parainfluenza ► Adenovirus ► Papilomavirus ► Hep B

. ‘ 11 days old baby died of multiple organ failure caused by the herpes simplex virus. The newborn was infected by her mother kisses or breastfeeding’ Daily Mail 29 Feb 2009

Herpes simplex 1 & 2 ► Primary infection, latency in V cranial nerve. Secondary infection very mild, orofacial or genital lesions. ► Immunosuppressed: infections of lungs, oesophagus and brain or generalised (Herget et al, 2005); common lack of orofacial and genital lesions ► Detection: microscopy, virus cultivation, serology ► Treatment: 1 -2 weeks aciclovir, valacyclovir or famciclovir ► Prevention: antivirals for first 3 -4 weeks after transplantation.

CMV

CMV cont. ► Primary infection asymptomatic; latent in monocytes and lymphoid tissue. 60 -70% people acquire CMV by the age of 6 (Reuter et al. , 2004) ► Immundefficient: affect multiple organs causing: colitis, pneumonitis, retinitis (HIV, leads to blindness), mouth ulcers, hepatitis (liver transplants) ► Detection: culture, PCR, serology ► Treatment: intravenous ganciclovir, or foscarnet for 23 weeks; cidofovir and fomivirsen for retinitis. ► Prevention: up to 12 weeks ganciclovir, valganciclovir, foscarnet or acyclovir

JC virus Primary infection: late childhood and early adolescence, latent in kidney or brain. Infect 70% -90% of population (Padget and Walker, 1973). Mainly subclinical, some respiratory symptoms. ► Immunodeficient: demyelianation of CNS – progressive multifocal leucoencephalopaty. ►

JC virus cont. ► Symptoms: impairment of mental function and movement, disturbance of speech and vision. Rapid progress, severe disability, dementia, blindness and paralysis, coma and death. ► Diagnosis: examination of brain biopsy ► Treatement: some positive results with cytarabine, and cidofovir ► Prevention

Measles ► Causes fever, malaise, sneezing, rhinitis, congestion, conjunctivitis and cough, Koplik's spots and maculopapular rash. Usually selflimiting but some complications can occur.

Measles Immunosuppressed: severe illness, often without characteristic rash. Giant cell pneumonia, subacute measles encephalitis - most common in children with leukaemia. The incubation period 5 to 6 months and death within few weeks or months. Similar to SSPE but more rapid. Symptoms include convulsions, decline in mental status and consciousness. ► Diagnosis: examination of brain tissue and PCR ► Treatment: early administration of ribavirin ► Prevention: herd immunity ie. vaccination of large percent of population ►

General considerations ► patients education, OI symptoms awareness ► early detection (often atypical symptoms) and appropriate treatment ► controlling underlying disease eg. early treatment of HIV to avoid CD 4 T cells depletion ► treatment often suppressive not curative ► latency – problems with compliance in symptom free patients ► patients on drug cocktail, possible interactions ► problems with resistance

References Barron MA, Weinberg A, (2005). Common viral infections in transplant recipients, part 1. Herpesviruses. Clinical Microbiology Newsletter. 27, 99 -106 ► Mustafa MM, Weitman SD, Winick NJ, Bellini WJ, Timmons CF, Siegel JD, 1993. Subacute measles encephalitis in the young immunocompromised host: report of two cases diagnosed by polymerase chain reaction and treated with ribavirin and review of the literature. Clinical Infectious Diseases. 16, p. 654 -660 ► Padget BL, Walker DL, 1973. Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. Journal of Infectious Diseases. 127, p. 467 - 470 ► Reuter JD, Gomez DL, Wilson JH, van der Pol AN, 2004. Systemic immune deficiency necessary for cytomegalovirus invasion of the mature brain. Journal of Virology. 78, p 1473 -1487 ► UNAIDS, 1998. HIV-related opportunistic diseases: UNAIDS technical update. UNAIDS, Geneva ►