Survey of Lymphocytic Choriomeningitis Virus Diagnosis and Testing --- Connecticut, 2005

Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne virus that can be transmitted to humans through exposure to rodent urine, feces, saliva, or blood. LCMV infection is often asymptomatic or mild but can cause aseptic meningitis, encephalitis, life-threatening infections in immunosuppressed persons, and severe congenital defects (1,2). In May 2005, LCMV was implicated in the deaths of three organ-transplant recipients who had received organs from a common donor who had likely been infected from a pet rodent (3). In August 2005, the Connecticut Department of Public Health conducted surveys of hospital laboratories and infectious disease (ID) physicians in Connecticut to determine recent incidence of confirmed LCMV infection, the level of awareness of LCMV, and the frequency of LCMV testing. This report summarizes the results of those surveys, which indicate that awareness of LCMV is high among ID physicians; however, testing for LCMV is infrequent, and ID physicians might not be aware of the need to consider LCMV among the most susceptible populations even when a history of rodent contact is not initially evident. In part because of these findings, LCMV infection is now a physician- and laboratory-reportable disease in Connecticut. More systematic efforts are needed to determine the frequency of LCMV infection and to monitor for pet rodent infection.

All acute care hospital laboratories in Connecticut were surveyed by telephone and asked 1) whether LCMV testing is available on site, 2) whether specimens are sent to another laboratory for testing, 3) which tests are offered to detect the virus, 4) the number of test requests made during the preceding 5 years, and 5) the results of testing. A second survey of a group of sentinel ID physicians in the state was performed via e-mail. This group consists of mostly hospital-based ID physicians who regularly receive information via e-mail from the Connecticut Department of Public Health through the Connecticut Health Alert Network. They were asked how often in the preceding 5 years they had considered a diagnosis of LCMV and tested for the virus. They were also asked if they would consider LCMV in the differential diagnosis of ill patients described in specific epidemiologic and clinical scenarios. Physicians were sent a second e-mail message if they did not return the survey within a few weeks of the initial request.

Of the 30 acute care hospital laboratories in Connecticut, none perform LCMV testing on site; 29 (97%) reported referring samples to either the state public health laboratory or another referral laboratory. During the preceding 5 years, two laboratories received requests. Only the state laboratory and one other referral laboratory performed LCMV testing for Connecticut hospitals. Testing was performed on approximately 29 serum or cerebrospinal fluid (CSF) samples using a complement fixation test at the state public health laboratory and one CSF sample using an immunoflorescent antibody assay at another referral laboratory; none were positive.

Among the 35 ID physicians contacted, 28 (80%) responded to the e-mail questionnaire. Among the respondents, 17 (61%) reported considering a diagnosis of LCMV during the preceding 5 years; of these, nine (53%) ordered a test. None confirmed a diagnosis of LCMV. Among the 24 physicians who answered questions based on the scenarios, most would consider LCMV in the differential diagnosis among patients exposed to wild mice (92%), healthy pet rodents (96%), or sick pet rodents (96%). However, only six (25%) would consider LCMV in an immunocompromised patient with an unexplained febrile illness and no known exposure history.

Reported by: JL Hadler, MD, R Nelson, DVM, P Mshar, MPH, Connecticut Dept of Public Health. LE Sosa, MD, EIS Officer, CDC.

Editorial Note:

Outbreaks of LCMV in humans were first reported in the 1960s. Initial reports documented disease mostly in laboratory personnel working with mice and hamsters (4). The largest outbreak of LCMV occurred in 1973--1974 and resulted in 181 human cases in 12 states; this outbreak was associated with pet hamsters supplied by a single distributor (4). The likely source of LCMV in a transplant-associated outbreak in May 2005 was also determined to be a pet hamster (3). Although the wild house mouse (Mus musculus) is the natural reservoir for the virus, hamsters and other pet rodents can acquire the virus through exposure to infected mice and become an important source of human exposure. Given the association of recent outbreaks with pet rodents, control and monitoring of LCMV among rodent populations in breeding and retail facilities is needed. Until this can be achieved by the pet industry, other measures (e.g., human surveillance) need to be instituted to monitor for pet rodent infection and to minimize transmission of LCMV to humans.

The current incidence of clinically significant LCMV infection among humans is unknown. Two separate studies have demonstrated the prevalence of LCMV-specific antibodies in urban human populations exposed to wild rodents to range from 1% to 5% (5,6). During a 1974 outbreak in New York associated with pet hamsters, enhanced case finding identified 60 persons with serologically confirmed LCMV, 12 (20%) of whom had severe central nervous system disease (e.g., meningitis or meningoencephalitis) (2). Given these reports, morbidity associated with LCMV infections might be substantially higher than generally believed, and even severe LCMV infection is likely underdiagnosed, as evidenced by the infrequent testing for LCMV detailed in these surveys. Based in part on the findings in this report, beginning in 2006, LCMV infection became health-care provider and laboratory reportable in Connecticut, with supportive diagnostic testing offered at no charge by the state laboratory. The objectives of this reporting are to 1) ensure that patients with suspect cases, especially those with pet rodent exposure, get optimum testing for LCMV infection, 2) determine the epidemiology of and trends in LCMV infection, and 3) raise physician awareness. Optimum serologic testing includes paired acute and convalescent serum specimens, the latter obtained approximately 21 days after symptom onset.

The findings in this report suggest that hospital-based ID physicians in Connecticut are aware of the association of LCMV with exposure to mice and other rodents but not likely to consider LCMV-related illness in the most susceptible populations without a clear rodent exposure history. Although disease is rarely reported, infection can be particularly severe in immunocompromised persons (e.g., organ recipients) and can cause developmental defects in fetuses (1,3). Physicians in specialties likely to evaluate patients with illness associated with LCMV infection should know how the infection might manifest in immunocompromised persons; clinical disease in these patients might not include symptoms of meningitis or encephalitis but might be more generalized (3). These physicians should also be knowledgeable about risk factors for infection so they can counsel susceptible patients. CDC previously published guidance on minimizing risk for LCMV infection and recently issued an update on LCMV infection in pregnancy and newborns intended for physicians (7,8).

The findings in this report are subject to at least four limitations. First, although all of the acute care hospital laboratories in Connecticut participated, the questions were posed to multiple persons in each laboratory. Thus, the person with the most knowledge regarding LCMV might not have been contacted at each location. Second, these surveys focused on inpatient diagnoses and might have missed outpatient if physicians sent specimens directly to a referral laboratory. Third, only ID physicians were surveyed, which might have neglected diagnoses made by other groups of physicians. Finally, this survey is not representative of the knowledge and awareness of all ID physicians in Connecticut or physicians in other specialties who might evaluate patients with LCMV-related illness.

Monitoring for LCMV infection should continue to minimize the potential for outbreaks and to determine the effectiveness of personal and industry-level prevention measures. In the absence of regular testing for LCMV in the pet industry, surveillance for human infection, as has begun in Connecticut, is an alternative method of monitoring for LCMV disease both in humans and pet rodent populations. If human surveillance is conducted, it should occur in a setting of physician education and active encouragement for testing, especially for persons with a clinically compatible illness (e.g., encephalitis and aseptic meningitis) and epidemiologic risk factors.

Acknowledgments

The findings in this report are based, in part, on contributions by L Lobianco, MPH, A Morrison, MPH, D Mylnarski, MPH, A Nepaul, MS, K Purviance, MPH, T Rabatsky-Ehr, MPH, Connecticut Dept of Public Health.

References

1. Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol 2002;187: 1715--6.
2. Deibel R, Woodall JP, Decher WJ, Schryver GD. Lymphocytic choriomeningitis virus in man: serologic evidence of association with pet hamsters. JAMA 1975;232:501--4.
3. CDC. Lymphocytic choriomeningitis virus infection in organ transplant recipients---Massachusetts, Rhode Island, 2005. MMWR 2005;54:537--9.
4. Gregg MB. Recent outbreaks of lymphocytic choriomeningitis in the United States of America. Bull World Health Organ 1975;52:549--53.
5. Childs JE, Glass GE, Ksiazek TG, et al. Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an inner-city population. Am J Trop Med Hyg 1991;44:117--21.
6. Riera L, Castillo E, del Carmen Saavedra MC, et al. Serological study of the lymphochoriomeningitis virus (LCMV) in an inner city in Argentina. J Med Virol 2005;76:285--9.
7. CDC. Interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with rodents. MMWR 2005;54:747--9.
8. CDC. Lymphocytic choriomeningitis virus (LCMV) and pregnancy: facts and prevention. Atlanta, GA: US Department of Health and Human Services, CDC; December 2005. Available at http://www.cdc.gov/ncbddd/bd/lcmv.htm.

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Date last reviewed: 4/13/2006