Infectious diseases: July 2008 Archives

A confirmed case of the uncommon LaCrosse encephalitis was reported recently in northern Virginia—a notable story (at least for the local news source), because the disease "typically occurs" further south in the state. The Virginia report and yesterday's news of several cases of West Nile disease in Los Angeles provide an opportunity to review here the mosquito-transmitted encephalitides that occur in the not-always-good-old summertime.

Causing about 70 cases of encephalitis per year in the United States, the LaCrosse virus belongs to the Bunyaviridae family of negative-stranded RNA viruses. The main transmission cycle is between small vertebrate hosts, like squirrels or chipmunks, and the treehole mosquito. LaCrosse encephalitis in humans occurs mainly in Appalachia and the Midwest (the disease was first recognized in 1963 in La Crosse, WI). Although most cases of infection are asymptomatic, the latency from mosquito bite to symptoms (either a flu-like illness or, less commonly, frank encephalitis) ranges from 5 to 15 days. Those who are especially susceptible to disease in endemic areas are persons engaged in outdoor activities and children younger than 16 years of age. The fatality rate, however, is less than 1%.

Both the West Nile and St. Louis viruses belong to the family Flaviviridae, genus Flavivirus—positive-stranded RNA viruses. The transmission cycle for these viruses, like that for most arboviruses, is between wild birds and mosquitoes. In 2003, there were more than 9800 cases of documented West Nile encephalitis in the United States, and the average annual number of cases of St. Louis encephalitis is approximately 110. West Nile encephalitis has spread rapidly throughout the United States, since its recognition in New York in 1999. St. Louis encephalitis occurs most often in the central and eastern parts of the country. The latency from bite to symptoms for both infections ranges from 3 to 15 days; although, the overwhelming majority of infected persons remain asymptomatic. For the less-than-1% of those who do develop encephalitis, the fatality rate is 50% for West Nile (2002-2003 data) and 5%-30% for St. Louis disease. Older individuals are particularly vulnerable.

The Eastern and Western Equine Encephalitis viruses belong to the family Togaviridae, genus Alphavirus— positive single-stranded RNA viruses. The main transmission cycle for these viruses is also between wild birds and mosquitoes, and, as the name implies, horses are common "dead-end" hosts. Infection with the Eastern Equine Encephalitis virus (EEEV) is most common in the eastern part of the United States, with the largest number of encephalitis cases in Florida, Georgia, Massachusetts, and New Jersey. Infection with the Western Equine Encephalitis virus (WEEV) is most prevalent in the plains regions. The average annual number of EEEV and WEEV encephalitis cases in the United States is 5 and 15, respectively. Like persons infected other arboviruses, those with EEEV and WEEV are mostly likely to remain asymptomatic. Symptoms, if manifest, occur approximately 3-10 days after a bite from a transmitting mosquito. Persons older than 50 years of age or younger than 15 years are at greatest risk for developing severe infection with either virus; although, the fatality rate with EEEV (33%) among symptomatic persons is much higher than that with WEEV (3%).

The most common and reportedly efficient way to diagnose infection with these viruses is to assay for neutralizing IgM antibodies in either serum or CSF. Care is purely supportive for symptomatic individuals. There are no vaccines to prevent human disease; although vaccines to prevent EEEV and WEEV in horses are evidently available.

Primary source: CDC

Photo of Culex quinquefasciatus, known to transmit St. Louis encephalitis virus, from Galveston County Mosquito Control.

Not exactly a US public health menace, but the rise of Balamuthia mandrillis encephalitis is something worth watching. The latest issue of the MMWR provides information on 10 cases identified between 1999 and 2007 by the California Encephalitis Project. Since the recognition of balamuthiasis in 1989 (in a pregnant mandrill baboon at the San Diego Zoo), 150 human cases have been identified worldwide.

What is Balamuthia mandrillis?
A free-living amoeba in soil.

How is disease transmitted?
Airborne cysts are inhaled, or skin lesions are directly contaminated.

Who or what is affected?
Immunocompetent or immunocompromised humans, nonhuman primates, horses, dogs, and sheep. People with occupational or recreational exposure to soil (agriculture, construction, dirt biking) may be especially vulnerable.

What are disease symptoms?
Those consistent with other forms of encephalitis—eg, fever, encephalopathy, cranial nerve palsies, seizures.

What does the CSF look like?
Markedly elevated protein (>100 mg/dL); elevated WBC with a predominance of lympocytes; normal or low glucose.

What does brain MRI look like?
Typically abnormal. In the California cases, multiple ring-enhancing lesions, white matter lesions, hypointense lesions, or hydrocephalus were noted.

How is disease definitively diagnosed?
Indirect immunofluorescence staining of formalin-fixed tissue—eg, brain. PCR testing for Balamuthia DNA in CSF or brain tissue has been used; although, the specificity and sensitivity of PCR testing for Balamuthia are unknown, as are the specificity and sensitivity of serologic testing.

Where are reference laboratories? 
At the CDC (gsv1@cdc.gov) and the California Department of Public Health (shilpa.gavile@cdph.ca.gov).

What is the treatment?
Three surviving patients in the United States received pentamidine isethionate, fluconazole, flucytosine, sulfadiazine, and a macrolide antibiotic (azithromycin or clarthromycin).

What is the survival rate?
In the California cases, approximately 10%.

Who or what is Balamuth?
Balamuthia co-discoverer Govinda S. Visvesvara, PhD, of the CDC, writes by e-mail that the organism was named after his major advisor, William Balamuth (1914-1981), Professor of Zoology at UC Berkeley. How's that for homage?

Photomicrograph of Balamuthia mandrillis trophozoites in brain tissue from the CDC.

So far this year, 127 Americans have contracted measles (rubeola), say Federal health officials, creating the largest measles outbreak in the United States since 1997. The current outbreak is believed to be the result of unvaccinated Americans acquiring the viral disease during overseas travel.

States with measles cases now include Arizona, Arkansas, California, Georgia, Hawaii, Illinois, Louisiana, Michigan, Missouri, New York, New Mexico, Pennsylvania, Virginia, Wisconsin, and Washington. The disease has also been reported in Washington, DC. Measles was acquired in Belgium, China, Germany, India, Israel, Italy, Pakistan, the Philippines, Russia, and Switzerland, according to the CDC.

The lack of vaccination among some American children is due to the increasing use of personal or religious exemptions by parents, owing to their unsubstantiated fears of the risk of autism. Reuters reports that, last month, measles was declared endemic in England for the first time since the mid-1990s, because parents declined vaccinations for their children.

Photo of child with measles rash from the CDC.

The World Health Organization (WHO) now recommends a line-probe assay (LiPA) for the rapid, 2-day detection of multidrug-resistant tuberculosis* (MDR-TB), according to yesterday's press release. LiPA (eg, GenoType MTBDRplus; Hain LifeScience) extracts and amplifies sputum-derived Mycobacterium tuberculosis DNA, which is then hybridized with oligonucleotide probes to detect genes conferring rifampin or isoniazid resistance (eg, rpoB, katG, inhA).

In a 2006 study, the sensitivity and specificity of a rifampin-resistance LiPA (INNO-LiPA.Rif; Innogenetics) or traditional 2-3-month culture were examined in 420 new or retreatment sputum specimens from Asia, Africa, Europe, or Latin America (Studies suggest that rifampin resistance is a reasonable indicator of MDR-TB, where the prevalence of disease is high.) The concordance between LiPA and culture for rifampin resistance was 99.6%.

Result	LiPA	Culture
Positive for M. tuberculosis DNA, %	92.6	74.3
Positive for rifampin-resistance DNA, %	30.6	30.8
Missed positive specimens	22	100

WHO estimates that only 2% of the world's MDR-TB cases are recognized and treated appropriately, and that the multimillion-dollar initiative to systematically implement LiPA testing in 16 countries will increase that percentage to 15% or higher by 2012. Designated countries will receive the tests and appropriate training through the Stop TB Partnership's Global Drug Facility. According to WHO, Lesotho is ready to implement the use of LiPA for rapid MDR-TB detection, and Ethiopia will be ready by the end of this calendar year.

Photomicrograph of M. tuberculosis in sputum smear stained with Ziehl-Neelson acid-fast stain. Courtesy of CDC/Ronald W. Smithwick.

* Defined as resistance to both rifampin and isoniazid.