Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates Section Editor, HIV, is Associate Editor for Infectious Disease Alert
Monkeypox Strain Differences
Chen N, et al. Virulence Differences Between Monkeypox Virus Isolates From West Africa and the Congo Basin. Virology. 2005;340:46-63.
Researchers have identified 2 distinct strains of monkeypox virus, one of which appears to be significantly less virulent than the other, possibly explaining the lack of deaths in the 2003 Midwestern outbreak. That out-break was spread by US prairie dogs, sold as pets or exchanged at swap meets, which had become infected with monkeypox virus when housed by animal distributors next to imported Gambian rats. A total of 72 suspected and confirmed human cases were reported in Wisconsin, Illinois, Indiana, Kansas, Ohio, and Missouri. Sixteen people required hospitalization, some for infection control purposes, although 2 children required intensive care. No deaths occurred, and many cases were relatively asymptomatic, with a localized crop of blisters or rash resembling smallpox. This experience, which physicians in the United States attributed to the quality of their care, was distinct from reports suggesting that monkeypox in Africa is associated with a 10% case fatality rate.
It turns out that the 2003 outbreak was the result of infection with a West African strain of virus that appears less virulent than the Congolese strain. Researchers from the US Army Research Institute of Infectious Diseases, the Centers for Disease Control and Prevention, and 4 other Universities in the United States and Canada worked together on this project, comparing strains of West African monkeypox similar to that responsible for the Midwestern outbreak (MPXV-COP-58) with a strain of Congo monkeyvirus (MPXV-ZA1-V79) banked back in the 1990s during earlier smallpox vaccine research. Cynomolgus monkeys infection with the West African strain developed clinically mild symptoms. In contrast, 5 of 6 monkeys infected with Congolese strain developed severe illness, and 3 died. Molecular analysis identified a number of potential virulence genes, including one similar to vaccinia complement protein (D14L). This finding also explains why more than 90% of human cases in African are reported from the Congo, and deaths from monkeypox are not seen outside of this region.
Voriconazole-Induced Christmas Music
Agrawal AK, Sherman LK. Voriconazole-Induced Musical Hallucinations. Infection. 2004;32:293-295.
Auditory hallucinations are uncommon, but can be due to a whole host of unusual conditions, including schizophrenia, post-traumatic stress disorder, psychosis secondary to hypothyroidism, various dementias, Parkinson’s disease, and rarely migraines. They can also occur with dopamine agonists and sympathomimetic agents, such as cocaine and methamphetamines, and may be inhibited by dopamine antagonists. Musical hallucinations, in particular, tend to occur in patients with various temporal lobe insults, such as strokes, tumors, head injuries, and temporal lobe seizures.
A 78-year-old man suddenly developed musical hallucinations while receiving voriconazole 300 mg twice daily for fungal prophylaxis during induction for acute myelogenous leukemia. On the second day of voriconazole treatment, he began hearing Christmas songs. The music was sufficiently irritating that he wrote a letter of complaint to hospital administration. He could even hear specific lyrics and knew some of the titles, although he insisted that he had no conscious memory of some of them. He weighed 103 kg, had normal renal and hepatic function, and there was no reason to suspect abnormally high drug levels, although levels were not obtained. He had recently completed a course of idarubicin and cytarabine, and verapamil was the only other medication with a possible drug interaction (verapamil is a P-glycoprotein inhibitor, which could increase voriconazole levels). A neuropsychiatric evaluation was unremarkable. Radiographic studies of the head and eggs were not obtained. Once the voriconazole was discontinued, the music became sporadic and was gone by the third day. The music did not recur when he was switched to itraconazole.
Reversible visual disturbances are common in patients receiving voriconazole, but this is the first report of possible drug-induced auditory hallucinations related to voriconazole. Curiously, songs are the most frequent kind of musical hallucinations, they are often religious or patriotic in nature, and the individual often has no recollection of the music, as if some locked-away memory is being triggered.
Wisconsin Teen Survives Rabies
Willoughby RE Jr., et al. Survival After Treatment of Rabies with Induction of Coma. N Engl J Med. 2005;352:2508-2514.
Rabies in humans is a universally fatal illness, characterized by encephalopathy, paresis, and autonomic dysfunction. Death typically occurs within 5-7 days of onset of symptoms, although aggressive intervention has prolonged survival for up to 120 days. Only 5 well-documented cases have survived rabies encephalitis, all of whom received rabies vaccine before the onset of symptoms.
Now there is a sixth and most remarkable case. A 15-year-old girl presented about one month after a bat bite with symptoms of acute rabies encephalitis. Her presentation is typical for half of the cases of rabies reported in the United States during the past 25 years: she was bitten by a bat, although thought she had just been scratched. She washed the area with peroxide and did not seek medical attention. She remained well and healthy, participating in school and sports until about 4 weeks later, when she developed parathesis, quickly followed by diplopia, nausea and vomiting, blurred vision, and gait abnormality. By the 5th day of symptoms, she developed fever and progressive neurological deterioration, and was hospitalized.
Once the history of a bat bite was ascertained, she was quickly transferred to Pediatric Critical Care at the Medical College of Wisconsin in Milwaukee, where multiple blood, saliva, cerebrospinal, and skin tissue samples for rabies were forwarded to the CDC; they were unable to demonstrate viral antigen or amplify or culture rabies virus from any specimen. On the second day of hospitalization (the sixth day of symptoms), rabies specific antibody was demonstrated in the serum and cerebrospinal fluid, and confirmed by the CDC. For this reason, rabies vaccine and immunoglobulin were not administered. After induction of coma with ketamine and midazolam, ribavirin was added on the 3rd hospital day (because of a possible systemic antiviral effect), and amantadine was added on the 4th hospital day (because of in vitro activity against rabies virus). Each drug was administered for about one week. Over the next several days, she developed autonomic instability, high fever that lasted for several days without an apparent bacterial etiology.
Remarkably, there were signs of improvement by the twelfth hospital day, with development of patellar reflexes. By the fourteenth day, she could blink, open her mouth, and move her eyebrows. On the sixteenth day, she wiggled her toes and, by the 19th day, responded to her mother. She was discharged to home after 11 weeks of hospitalization, and was back in school after 4 months, although continued to have neurologic impairment with choreoathetosis and dystonia.
Why this teen survived, and what aspect of her treatment may be have been essential to her survival, is not clear. Interestingly, the reason why rabies is virtually uniformly fatal is not known. All 6 survivors uniquely demonstrated evidence of serologic response to virus—although the other 5 had received vaccine before the onset of symptoms—and virus could not be detected in any. It is possible that this young woman had an attenuated rabies virus or variant strain; various rabies virus variants have been isolated from nearly all of the 41 bat species found in the United States, and strains of bat-associated Lyssavirus have newly been described. Although rabies virus infection of neurons is marked, the degree of inflammation and cell death is typically mild compared with, for example, herpes encephalitis, where there may be frank destruction of tissue. One theory holds that rabies infection may induce sustained or permanent neuronal dysfunction, long after virus has been successfully cleared by the immune system. For this reason, it was hypothesized that aggressive support may improve the chance of survival from rabies. To this end, a group of physicians and researchers met in 2003, to develop a treatment protocol for acute rabies infection, which included rabies vaccine, human rabies immunoglobulin, ribavirin, interferon, and ketamine. Vaccine would not need to be given if the patient had evidence of rabies-specific virus at the time of diagnosis.
Another interesting tidbit: most cases of human rabies in the United States occur in the fall. Assuming an incubation period of 4-8 weeks, this suggests the greatest risk of exposure to rabid bats occurs during the late summer months. Although rare, clinicians should consider rabies as a cause of acute encephalitis, especially in the late summer and fall.
Researchers have identified 2 distinct strains of monkeypox virus, one of which appears to be significantly less virulent than the other, possibly explaining the lack of deaths in the 2003 Midwestern outbreak.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content