DEPARTMENT OF PATHOLOGY
The Johns Hopkins Medical Institutions
 
Vol. 18, No. 8
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, February 22, 1999
 
  1. Provided by Leslie Edwards Reger, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
  2. Week of Feb 8-12 - 16 outbreaks total reported to DHMH: 11 influenza-like illness outbreaks in nursing homes, 1 outbreak of influenza-like illness with pneumonia in a nursing home, 1 confirmed influenza A outbreak in a N.H., 1 gastroenteritis in a food-service facility, and 2 gastroenteritis outbreaks in nursing homes

    Week of Feb 15-19 - 32 outbreaks reported to DHMH: 18 outbreaks of influenza-like illness in nursing homes, 3 gastroenteritis outbreaks in nursing homes/health care facilities, 1 case investigation of Legionella, 2 outbreaks of scabies in nursing homes, 4 outbreaks of foodborne gastroenteritis, 1 outbreak of pneumonia at a nursing home, 2 influenza-like illness with pneumonia outbreak in a nursing home, and 1 outbreak of rash illness reported in a middle school
     

  3. The Johns Hopkins Hospital. Information provided by Dr. Michael Dardik, Department of Pathology.
Clinical History: A 29 year old HIV positive woman with a history of oral thrush but no AIDS-defining illness presented with gastrointestinal, gynecologic and ophthalmologic complaints. She had lost ten pounds over three months, with mildly decreased appetite, early satiety, epigastria pain after swallowing, and intermittent watery diarrhea. She had been treated two months ago for genital herpes with intravenous acyclovir, but has had metrorrhagia exacerbated by sexual intercourse. Three weeks prior to admission, she became blind in the left eye, and has had progressively decreasing vision in the right eye. On physical examination , she was in no acute distress. Laboratory studies revealed a CD4 count of 3 and a viral load of 750,000. Ophthalmologic exam revealed n papillary response to light and only trace light perception in the left eye and 20/40 vision in the right eye. Fundoscopic examination revealed retinal changes consistent with Cytomegalovirus retinitis and she was treated with an intravitreous injection of ganciclovir. Gynecologic exam revealed two labial and multiple cervical ulcers. Cervical biopsies demonstrated numerous cells containing intranuclear and cytoplasmic inclusions consistent with cytomegalovirus infection. Endoscopy revealed diffuse edema and colonic biopsies demonstrated inflammation and cytomegalovirus infection. The patient completed a 14 day induction regimen of intravenous ganciclovir and then switched to a maintenance intravenous ganciclovir regimen.

Cytomegalovirus

Cytomegalovirus (CMV) is an enveloped DNA virus that is a family of species-specific viruses. As a member of the herpesvirus group, CMV is capable of establishing latency after primary infection. CMV is rarely pathogenic in healthy adults, but when host resistance falls below a critical threshold. CMV can reactivate.

CMV is a pathogen in a variety of patients. In immunocompetent individuals, it can occasionally cause a mononucleosis-like infection. In pregnant women, primary infection can cause severe generalized organ manifestations with high mortality and vertical transmission can cause congenital infection manifested as mental retardation. CMV is an important pathogen in immunocompromised patients, in particular, in transplant recipients and HIV positive patients.

 

CMV in HIV infection

Epidemiology: CMV is present in 90% to 99% of HIV positive patients. However, in most of these patients the virus is latent. Approximately 30% to 40% of HIV positive patient will develop serious CMV disease. The incidence of CMV disease appears to be increasing as patients with HIV live longer with more profound degrees of immunosuppression.

Clinical Features: Reactivation typically does not occur until the CD4 count drops below 100. The most common manifestation is retinitis. Other frequent manifestations include esophagitis, colitis, polyradiculopathy and disseminated (multiple organ) infection.

Diagnosis: Although the documentation of past CMV infection is relatively straightforward by detection if IgG antibodies to CMV, the diagnosis of active disease is more complicated. As most infection in this patient population is reactivation and not primary, the correlation between IgM antibodies and symptomatic disease is poor, and therefore serology is not a reliable indicator of disease. Excretion in the urine for months after infection means a positive urine culture is an unreliable indicator of infection. CMV can be culture from blood or tissue specimens on human fibroblasts, but cytopathic changes may not be detected for one to four weeks and sensitivity is low. A more rapid detection can be achieved by culturing the specimen on monolayers and staining with a fluorescein labeled antibody directed to a CMV protein expressed early in replication' results can be achieved in 3 days but sensitivity is still low. Polymerase chain reaction (PCR) can be performed in the laboratory on cerebrospinal fluid, amniotic fluid and vitreous humor and has an analytical sensitivity of 20-200 copies. In sites not amenable to PCR, culture and histologic examination can be performed. Characteristic histopathologic findings include markedly enlarged cells with large purple intranuclear inclusions surrounded by a halo with smaller basophilic cytoplasmic inclusions. An immunohistochemical stain for CMV is also available for cases where routine (H&E) stains are equivocal. Of note, the diagnosis of CMV retinitis remains a clinical diagnosis based on characteristic appearance on fundoscopic examination, although the use of CMV PCR is increasingly performed.

Therapy: CMV retinitis can be treated with oral ganciclovir, intraocular ganciclovir implant, intravitreal ganciclovir injection, foscarnet or cidofovir. Unfortunately, most patients with CMV retinitis relapse. Disseminated infection is typically treated with 3 to 6 weeks of induction therapy with ganciclovir followed by lifelong maintenance therapy with ganciclovir. Ganciclovir has serious marrow toxicity, including granulocytopenia and thrombocytopenia; these effects are usually reversible.

References:

    1. Bowen EF, Griffiths PD, Davey CC, Emery BC, Johnson MA. Lessons from the natural history of cytomegalovirus. AIDS 10 S1:S37-41, 1996.
    2. DalMonte P, Lazzarotto T, Riplati A, Landini MP. Human cytomegalovirus Infection: A complex diagnostic problem in which molecular biology has induced a rapid evolution. Intervirology 39:192-203, 1996.
    3. Danner SA. Management of cytomegalovirus disease. AIDS 9 S2: S3-8, 1995.
    4. Jacobson MA. Drug Therapy: Treatment of Cytomegalovirus Retinitis in Patients with the Acquired Immunodeficiency Syndrome. New England Journal of Medicine 337(2): 105-114, 1997.


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