Literature

Clinical Pearls & Morning Reports


By Carla Rothaus

Published October 9, 2019

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What drugs have been used off label for the treatment of adenovirus-associated infectious diseases?

Adenoviruses can cause meningitis or meningoencephalitis as a primary infection or as a complication of systemic or respiratory infection in immunocompromised adults. Read the latest Case Records of the Massacusetts General Hospital here.

Clinical Pearls

Q: Can a tickborne viral infection be implicated as the cause of meningoencephalitis during the winter?

A: Tickborne infections can occur in winter. Ticks are generally inactive if the air temperature falls below 2°C; however, if the ground is not covered by snow and the soil temperature reaches 7°C, ticks will search for blood hosts, and Ixodes scapularis remains active if the temperature is above freezing.

Q: Is adenovirus encephalitis common?

A: Adenovirus encephalitis is extremely rare and is seen almost exclusively in immunocompromised hosts.

Morning Report Questions

Q: What are some of the neuropathological features of adenovirus meningoencephalitis?

A: Published reports of the neuropathological features of adenovirus meningoencephalitis are scarce, but reported cases show bilateral, sometimes symmetric, necrotizing lesions with a striking predilection for medial and paramedian structures (e.g., the mesial temporal lobe, basal forebrain, and brain stem) and the ventricular system. Lymphocytic infiltrates, microglial nodules, and intranuclear inclusions are the most common microscopic findings.

Q: What drugs have been used off label for the treatment of adenovirus-associated infectious diseases?

A: There are no approved antiviral agents for the prevention or treatment of adenovirus-associated infectious diseases. An oral, live-attenuated vaccine against adenovirus serotypes 4 and 7 is available for U.S. military use only. Prevention of adenovirus infection relies on personal hygiene, including hand washing, contact precautions, and water chlorination. Cidofovir has been used off label for the treatment of adenovirus-associated infectious diseases in immunocompromised hosts since its approval for the treatment of AIDS-related cytomegalovirus retinitis. Cidofovir therapy is frequently associated with renal tubular cellular injury and nephrotoxicity. Protocols for the administration of cidofovir include the use of aggressive intravenous hydration and the concurrent use of probenecid to prevent concentration of cidofovir in renal tubules and to minimize the risk of kidney injury. With the development of molecular methods to detect adenoviruses, DNA surveillance with PCR testing and preemptive off-label treatment with cidofovir have been increasingly used in high-risk immunocompromised populations. The development of brincidofovir for the treatment of adenovirus-associated infectious diseases was recently terminated. Brincidofovir remains available through an expanded-access program for the treatment of adenovirus infection in certain patients.

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