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Possible Congenital Infection with La Crosse Encephalitis Virus --- West Virginia, 2006--2007

La Crosse encephalitis virus (LACV) is a mosquitoborne bunyavirus of the California encephalitis serogroup (1). During 2003--2007, West Virginia had the greatest number of cases (95) and highest incidence of LACV disease (5.1 cases per 100,000 population) of any state.* The majority of persons infected with LACV either have no symptoms or a mild febrile illness; a limited number experience encephalitis (2). Although only 1%--4% of those infected with LACV develop any symptoms, children aged <16 years are at highest risk for severe neurologic disease and possible long-term sequelae (2,3). The effects of LACV infection during pregnancy and the potential for intrauterine transmission and adverse birth or developmental outcomes are unknown. This report describes the first known case of LACV infection in a pregnant woman, with evidence of possible congenital infection with LACV in her infant, based on the presence of immunoglobulin M (IgM) antibodies in umbilical cord serum at delivery. The infant was born healthy with normal neurologic and cognitive functions and no LACV symptoms. Further investigation is needed to confirm the potential for intrauterine LACV transmission and to identify immediate and long-term health risks posed to infants. Because of the potential for congenital infection, pregnant women in areas where LACV is endemic should be advised to avoid mosquitoes; health-care providers should monitor for LACV infection and sequelae among infants born to women infected with LACV during pregnancy.

In August 2006, a previously healthy woman aged 43 years in week 21 of her pregnancy was admitted to a West Virginia hospital after experiencing severe headaches, photophobia, stiff neck, fever, weakness, confusion, and a red papular rash. The patient had reported a 3-month history of severe headaches, which were diagnosed initially as migraines and treated with morphine for pain. Two previous pregnancies had proceeded without complication, and each resulted in delivery of a healthy infant. The patient's medical history included anxiety, depression, and hypothyroidism, for which she received ongoing thyroid hormone replacement therapy.

After hospital admission, analysis of cerebrospinal fluid revealed an elevated white blood cell count (556 cells/mm3 [94% lymphocytes, 5% monocytes, and 1% polymor-phonuclear neutrophilic leukocytes]), elevated protein (66 mg/dL), and normal glucose (55 mg/dL). A diagnostic panel for viral encephalitis was performed, and the patient's serum was determined positive for the presence of LACV-specific IgM and immunoglobulin G (IgG) antibodies by immunofluorescence assay and for IgM by capture enzyme-linked immunosorbent assay (ELISA) (Table). The patient's serum was negative for IgM and IgG antibodies to the other three diseases in the diagnostic panel: eastern equine encephalitis, western equine encephalitis, and St. Louis encephalitis. A diagnosis of La Crosse encephalitis was made, and supportive therapy was initiated. During hospitalization, the patient experienced a low-grade fever and exhibited panleukocytosis (absolute neutrophil count: 12,800/µL), which persisted after discharge despite resolution of clinical signs.

After reporting the case to the West Virginia Department of Health and Human Resources, active follow-up of the patient and her fetus was initiated in collaboration with the patient's primary-care providers and CDC. With her consent, the patient's medical and prenatal histories were reviewed. Because guidelines for evaluating pregnant women infected with LACV do not exist, interim guidelines for West Nile virus were used to direct maternal and infant follow-up (4). Specifically, collection of blood and tissue products at time of delivery was arranged with the patient's obstetrician. Umbilical cord serum and maternal serum were tested for LACV-specific antibodies by ELISA and serum-dilution plaque-reduction neutralization test (PRNT). Sera also were tested for neutralizing antibodies to the closely related Jamestown Canyon virus by PRNT to rule out potential cross-reactivity. Umbilical cord and placental tissue were tested for LACV RNA by reverse transcription--polymerase chain reaction (RT-PCR). Data were collected regarding the infant's health at delivery and through routine well-child visits during the first 6 months of life.

The patient had a normal, spontaneous, vaginal delivery of a healthy girl at approximately 40 weeks gestation. The child had normal birth weight (2,970 g), length (52 cm), and head circumference (33 cm). Apgar scores at 1 minute and 5 minutes postpartum were within normal limits (8 and 9, respectively). LACV-specific IgM antibodies were detected in umbilical cord serum, although no evidence of LACV RNA was detected in umbilical cord tissue or placental tissue by RT-PCR (Table).

The mother declined collection of additional specimens of infant serum for confirmation of congenital LACV infection. Maternal serum collected at 11 weeks postpartum was positive for LACV IgG antibodies but negative for IgM. Except for intermittent nasal congestion associated with upper respiratory infections, the infant remained healthy and exhibited appropriate growth and development through the first 6 months of life. No neurologic abnormalities or decreased cognitive functions were observed.

Reported by: A Hinckley, PhD, Div of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; A Hall, DVM, EIS Officer, CDC.

Editorial Note:

This report summarizes the first case of symptomatic LACV infection identified during pregnancy. Congenital LACV infection of the fetus was suggested through identification of IgM antibodies in umbilical cord serum, although the newborn was asymptomatic and development was normal. Although unlikely to cross the placental barrier, LACV IgM antibodies detected in cord serum might have been attributable to transplacental leakage induced by uterine contractions that disrupt placental barriers during labor, which has been documented for anti-Toxoplasma IgM antibodies (5). Because specificity of standard laboratory techniques used to detect LACV IgM antibodies in cord serum or newborn serum is unknown, a follow-up evaluation of infant serum is necessary to confirm congenital infection. However, in this case, the mother declined collection of any additional specimens from her infant.

Certain infectious diseases have more severe clinical presentations in pregnant women (6). Symptomatic LACV infection is rare among adults; therefore, effects of pregnancy on the risk for or severity of illness are unknown. Because LACV-specific IgM can be present for as long as 9 months after infection (1), LACV might not have been responsible for the symptoms reported during this woman's pregnancy. However, the woman resided in an area where LACV is known to be endemic; during 2006, 16 (24%) of 67 LACV cases in the United States reported to CDC occurred in West Virginia, including three other cases from the same county as this patient. Although antimicrobial treatment of pregnant women often is controversial because of limited information regarding efficacy and risk to the developing infant (7), certain in vitro evidence indicates that the antiviral agent ribavirin might be useful for treating LACV infection in nonpregnant patients (2). However, supportive treatment continues as the standard of care for managing all LACV patients (2).

Congenital infection with other arboviral diseases has been reviewed and documented previously (8). Although no human congenital infection with a bunyavirus of the California serogroup has been reported, congenital infection with other bunyaviruses of the Bunyamwera serogroup has been associated with macrocephaly. In addition, animal studies have determined that infection with LACV during pregnancy can cause teratogenic effects in domestic rabbits, Mongolian gerbils, and sheep (9,10).

Pregnant women in areas where LACV is endemic should take precautions to reduce risk for infection by avoiding mosquitoes, wearing protective clothing, and applying a mosquito repellent to skin and clothing. Additionally, health-care providers serving areas where LACV is endemic should consider LACV in the differential diagnosis of viral encephalitis. As a nationally notifiable disease, all probable and confirmed cases of LACV should be reported to the appropriate state and local public health authorities. When LACV infection is suspected in a pregnant woman or infant, appropriate serologic and virologic testing by a public health reference laboratory is recommended. Testing breast milk for the presence of LACV also might be reasonable to evaluate the potential for maternal-infant transmission and to determine the suitability for continued breastfeeding. Additional investigations are needed to confirm the potential for congenital infection with LACV and to identify immediate and long-term health risks LACV poses to infants.

Acknowledgments

This report is based, in part, on contributions by the collaborating physicians and health-care providers; D Bixler, MD, and M del Rosario, MD, West Virginia Dept of Health and Human Resources; E Hayes, MD, N Lindsey, MS, O Kosoy, MA, A Lambert, J Laven, and R Lanciotti, PhD, Div of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; and D Bensyl, PhD, Office of Workforce and Career Development, CDC.

References

  1. McJunkin JE, Minnich LL, Tsai TE. La Crosse encephalitis and other California serogroup viruses. In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious diseases. 5th ed. Philadelphia, PA: W.B. Saunders; 2004:2403--11.
  2. McJunkin JE, Khan RR, Tsai TF. California-La Crosse encephalitis. Infect Dis Clin North Am 1998;12:83--93.
  3. Kappus KD, Monath TP, Kaminski RM, et al. Reported encephalitis associated with California serogroup virus infections in the United States, 1963--1981. In: Thompson WH, Calisher CD, eds. California serogroup viruses. New York, NY: Alan R. Liss; 1983:31--41.
  4. CDC. Interim guidelines for the evaluation of infants born to mothers infected with West Nile virus during pregnancy. MMWR 2004;53:154--7.
  5. Pinon JM, Dumon H, Chemla C, et al. Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies. J Clin Microbiol 2001;39:2267--71.
  6. Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections and pregnancy. Emerg Infect Dis 2006;12:1638--43.
  7. Cono J, Cragan JD, Jamieson DJ, Rasmussen SA. Prophylaxis and treatment of pregnant women for emerging infections and bioterrorism emergencies. Emerg Infect Dis 2006;12:1631--7.
  8. Tsai TF. Congenital arboviral infections: something new, something old. Pediatrics 2006;117:936--9.
  9. Osorio JE, Schoepp RJ, Yuill TM. Effects of La Crosse infection on pregnant domestic rabbits and Mongolian gerbils. Am J Trop Med Hyg 1996;55:384--90.
  10. Edwards JF, Karabatsos N, Collisson EW, de la Concha Bermejillo A. Ovine fetal malformations induced by in utero inoculation with Main Drain, San Angelo, and LaCrosse viruses. Am J Trop Med Hyg 1997;56:171--6.

* Confirmed and probable California serogroup viral (mainly La Crosse) encephalitis cases, human, United States, 1964--2007, by state. Available at http://www.cdc.gov/ncidod/dvbid/arbor/pdf/cal_lac.pdf.

La Crosse encephalitis, human: cumulative 2006 data. Available at http://diseasemaps.usgs.gov/2006/lac_us_human.html.

Table

TABLE. Summary of laboratory test results during investigation and follow-up of possible congenital infection with La Crosse encephalitis virus (LACV) — West Virginia, 2006–2007
Collection date
Specimen
Test
Result
August 20, 2006
Maternal serum
LACV IgM*capture ELISA†
Positive
Maternal serum
LACV IgM IFA§
Positive
Maternal serum
LACV IgG¶ IFA
Positive
Maternal serum
LACV neutralizing antibodies PRNT**
Positive
Maternal serum
JCV†† neutralizing antibodies PRNT
Negative
January 5, 2007
Placental tissue
LACV RNA RT-PCR§§
Negative
Umbilical cord tissue
LACV RNA RT-PCR
Negative
Umbilical cord serum
LACV IgM capture ELISA
Positive
Umbilical cord serum
LACV IgG capture ELISA
Equivocal
Umbilical cord serum
LACV neutralizing antibodies PRNT
Positive
Umbilical cord serum
JCV neutralizing antibodies PRNT
Negative
March 23, 2007
Maternal serum
LACV IgM capture ELISA
Negative
Maternal serum
LACV IgG capture ELISA
Positive
* Immunoglobulin M.
† Enzyme-linked immunosorbent assay.
§ Immunofluorescence assay.
¶ Immunoglobulin G.
** Plaque-reduction neutralization test.
†† Jamestown Canyon virus.
§§ Reverse transcription–polymerase chain reaction.
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Date last reviewed: 1/14/2009

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