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home - Miscellaneous - Infection - GI AIDS CMV Written by Dr Sebastian Zeki

GI AIDS CMV

AIDS-related cytomegalovirus gastrointestinal disease. CMV Latent (carriage of genome without replication) TriggersTNFalphaCatecholaminesProinflammatory prostaglandins Transmission Vertical Horizontal Kids Young Adults Age Reactivation Active Infection(detectable viral replication in peripheral blood on PCR or end organs or significant rise in CMV-specific antibodies Mechanisms to avoid Eradication1. Viral latency2.Inhibiting CMV co-infected cells3. Block antigen presentation by MHC4. Inhibitory cytokine production5. Neutralising host antibodies Primary infection: Cyclosporin, high dose steroids, tacrolimus all amplify CMV. CMV Infection Diagnostic tests:Histology (10-87%) H&E- inclusion bodies.Immunohistochemistry which is 78-93% sensitivity.CMV IgM has a sensitivity of 100%-Usually drops within 2-3 months after acute infection but can go on for 2 years.If immunocompromised may not mount immune response at all.CMV IgG sensitivity of 98-100%-Positivity is not informative as 70% are. Negativity means the patients doesn’t currently have it.CMV culture has a sensitivity of 45-78%- Poor sensitivity, high specificity. Blood CMV culture better than other fluids.CMV antigen test has a sensitivity of 60-100%-Usually for CSF. CMV DNA 65-100%- PCR- could be very useful particularly if applied to stool. Clinical Manifestations:Usually osophagus and the colon. Symptom presentation depends on the anatomic location of the infection. TEsophagitis — Fever, odynophagia, and nausea/ substernal burning pain. Can be diffuse or localised ulcersGastritis — Epigastic pain. GI bleeding rareEnteritis — Rare (4% of GI CMV). Get pain and diarrhoeaColitis — Most common GI manifesta-tion. (overall 2nd after retinitis)Pain diarrhoea and feverExtensive mucosal hemorrhage and perforation can be life-threatening complications.Other — Can cause painful oropharyn-geal ulceration DiagnosisHistology:Ulceration with inclusion bodies on histologyLaboratory evaluation — CMV PCR- although can be detected without invasive diseaseAntigen assaysBlood culture. CMV antibody not useful unless negative and most people will have been exposed Prevalence: 5% of patients with AIDS.Risk Factors:Viraemia (CMV detection in blood predicts invasive disease subsequentlyCD4 <50 cells/microL Natural History:If have GI CMV disease without HAART have a 4 month prognosis Side Effects:Ganciclovir- Neutropenia and thrombocytopenia Foscarnet - Reversible increases in serum creatinine Electrolyte disturbances are common with foscarnet, including symptomatic hypocalcemia.Cidofovir - NephrotoxicityNeutropeniaPeripheral neuropathyhypotony (abnormally low intraocular pressure), Anterior uveitisAlopecia. TreatmentGanciclovir and foscarnet are effective for the initial management of CMV gastrointestinal disease.Foscarnet has renal side effects but it is better if have thrombocytpoenia.Ganciclovir is cheaper with less renal effects.Overall treatment duration is 6 weeks.Oral therapy such as Oral valganciclovir (900 mg twice daily) can be used to complete induction once the patient has started to repond.Initiation of HAART should start once patient has begun to respond.Maintenance therapy is not recommended unless the patient is frequently relapsing. Pathology — CMV gastrointestinal disease is characterized histologically by mucosal inflammation, tissue necrosis, and vascular endothelial involvement. Cytomegalic cells (large cells containing eosinophilic intranuclear and frequently basophilic intracyto-plasmic inclusions) on H&EOphthalmologic evaluation — GI CMV predicts CMV retinitis so need it checked Disease (active disease plus clinical signs of infection (fever/ leucopoenia/ end organs involved).......is detection of viral inclusions or positive viral cultures necessary Chronic Written by Dr Sebastian Zeki Induction therapy — Salvage therapy —For relapsers or non-responders:a) Switching to the alternative agent b) Ganciclovir plus foscarnet.c) Cidofovir CMV may affect right side of colon in 30% Problems: Long incubation (up to 3 weeks), no quantification, low sensitivityShell vial culture- results in 24hours. Sensitivity of around 68-100%. Not widely used Results in 24 hours Semi-quantitative. Not done on blood as it is open to interpretation.

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