Linda L. Minnich

La Crosse Encephalitis in Children

BACKGROUND La Crosse encephalitis is a mosquito-borne disease that can be mistaken for herpes simplex encephalitis. It has been reported in 28 states but may be underrecognized. METHODS We investigated the manifestations and clinical course of La Crosse encephalitis in 127 patients hospitalized from 1987 through 1996. The diagnosis was established by serologic testing for IgM and IgG antibodies to La Crosse virus. Data were collected by chart review. RESULTS Most of the patients were school-aged children (mean [+/-SD] age, 7.8+/-3.5 years; range, 0.5 to 15.0). Symptoms included headache, fever, and vomiting (each in 70 percent or more of the patients), seizures (in 46 percent), and disorientation (in 42 percent). Thirteen percent had aseptic meningitis. Hyponatremia developed in 21 percent, and there were signs of increased intracranial pressure in 13 percent. Six patients, including three with cerebral herniation, underwent intracranial-pressure monitoring. The 13 patients (11 percent) whose condition deteriorated in the hospital had decreases in serum sodium levels (P=0.007), and increases in body temperature (P=0.003) at the time of deterioration. At admission, these patients more often had a history of vomiting (P=0.047) and a score of 12 or lower on the Glasgow Coma Scale (P=0.02) than the others; a trend toward a greater prevalence of seizures at admission was also evident in this group (P=0.07). All the patients survived, but 15 of them (12 percent) had neurologic deficits at discharge. Follow-up assessments, performed in 28 children, suggested an increase in cognitive and behavioral deficits 10 to 18 months after the episode of encephalitis. CONCLUSIONS La Crosse virus infection should be considered in children who present with aseptic meningitis or encephalitis. Hyponatremia and increasing body temperature may be related to clinical deterioration.

Gastrointestinal Norovirus Infection Associated With Exacerbation of Inflammatory Bowel Disease

Objective:In this study we aimed to determine, in pediatric patients, whether norovirus infection could be associated with exacerbations of inflammatory bowel disease (IBD) and ascertain whether the clinical expression of norovirus gastroenteritis was similar in patients with IBD compared with non-IBD controls. Materials and Methods:We performed a case-control retrospective chart review, over a 10-month interval, of patients with IBD with an exacerbation of their disease. The presence of norovirus in stool and/or rectal swab samples, as determined by an enzyme-linked immunoassay, was assessed. In addition, sex, age, type of IBD, presence or absence of diarrhea, hematochezia, and the need for hospitalization were determined. A similar number of control patients who did not have IBD were used as controls. Results:Nine patients with IBD (8 ulcerative colitis/1 Crohn disease) had exacerbations with diarrhea. Eight had norovirus antigen in at least 1 sample. All 9 patients with IBD presented with bloody diarrhea and 6 of the 8 norovirus-positive patients with IBD required hospitalization. All of the control patients experienced diarrhea; however, no hematochezia was noted and no hospitalization was required. Several patients with IBD and controls remained positive for norovirus months after the initial positive stool and/or rectal swab sample. The virus appeared to be more common during winter months. Conclusions:We conclude that norovirus may be associated with exacerbations of IBD. When norovirus accompanies IBD it is more likely to be associated with hematochezia than when the infection occurs in the absence of IBD.

Respiratory syncytial virus-associated lower respiratory illnesses : possible influence of other agents

Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Childrens Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.

Acute lower respiratory illnesses during the first three years of life : potential roles for various etiologic agents

Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Childrens Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.

An eight-year study of the viral agents of acute gastroenteritis in humans: ultrastructural observations and seasonal distribution with a major emphasis on coronavirus-like particles.

Abstract During an 8-yr period, 862 stool specimens from patients with gastroenteritis were examined by electron microscopy after negative staining with 2% phosphotungstic acid (pH 6.5). Forty-one percent of the specimens submitted over an 8-yr period were determined to be positive for virus or viruslike particles belonging to one or more of seven morphologically distinct viral groups. Coronavirus-like particles (CVLPs) were present in 69.8% of the positive stool specimens. Membranous profiles containing “complement-type” holes (10 nm in diameter) were identified in some preparations containing CVLPs. The second most prevalent viral agent found in stool specimens was the rotavirus (17% of all positive stools). The incidence of other viruses identified in the survey were as follows: adenovirus 4.5%, picorna/parvovirus agents 2.9%, Norwalk-like agent 2.9%, astrovirus 1.9%, and calicivirus 0.5%. Unclassified small round viruses (≈25–30 nm in diameter) represented 0.5%. It was also determined that there was a seasonal distribution in excretion of all viruses except for CVLPs. A greater number of viruses were identified in the cooler, drier months of the year.

Pleomorphic, Enveloped, Virus-Like Particles Associated with Gastrointestinal Illness in Neonates

Abstract Pleomorphic, enveloped, virus-like particles were detected by electron microscopy in the stools of symptomatic infants during an outbreak of gastrointestinal illness in a neonatal intensive-care unit. To determine the incidence of virus-like particles in the stool and their relation to gastrointestinal symptoms, eight surveys of stools for the particles were conducted over 40 weeks. The incidence of virus-like particles in the stool decreased from 69% to <10% over the study period. Most infants surveyed were premature; overall, 32 (36%) of 88 neonates were positive for virus-like particles. Statistically significant associations were found between virus-like particles in the stool and gastrointestinal symptoms within one week of each survey. These symptoms included water-loss stools, blood in the stool, gastric retention, bilious gastric aspirates, and abdominal distention. Several infants with virus-like particles whose mothers had gastrointestinal or “flu-like” symptoms before delivery were identified in the community (not part of the survey study).

Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis.

Background: La Crosse viral encephalitis (LACVE) is associated with residual epilepsy and neurocognitive deficits in survivors. This report summarizes 3 phases of clinical studies of children treated with intravenous (IV) ribavirin (RBV), each one exploring a different phase (I, IIA, IIB) of clinical trial development. Methods: In phase I, 7 children with life-threatening LACVE were treated with emergency use RBV using a moderate IV dose (8.33 mg/kg/dose q 8 hours day 1, 5 mg/kg/dose q 8 hours days 2–10). In phase IIA, 12 children with severe LACVE were enrolled: 8 treated with RBV (same dose as phase I) and 4 with placebo. In phase IIB an escalated dose was used (33 mg/kg dose 1, then 16 mg/kg/dose q 6 hours for 4 days, and 8 mg/kg/dose q 8 hours for 3 days). Results: In a group of 15 children treated in phase I and phase IIA, RBV appeared safe at moderate dose, but based on steady-state RBV levels of 9.3 &mgr;M, estimated cerebrospinal fluid levels were less than 20% of the EC50 of RBV for LACVE. At the escalated dose used in phase IIB, adverse events occurred, likely related to RBV, and therefore the trial was discontinued. Nevertheless, valuable pharmacokinetic (PK) and safety data were obtained at moderate dose, with potential treatment implications for other indications. Conclusions: Although the results do not support the use of RBV for LACVE, this nevertheless is the largest study of antiviral treatment for LACVE to date and the largest pharmacokinetic analysis of IV RBV in children for any indication.

Atypical neonatal respiratory syncytical virus infection

may include fibrinous pleuritis or pleural effusions, but empyema has not been reported. In several reports, the organisms have been identified in hilar lymph nodes, and in the sinusoids of the spleen and liver1~ no cellular reaction or inflammatory response to the organisms was documented. In our patient, the lesions in the liver and brain resembled those found in the lungs, indicating that under certain circumstances the bacilli may become disseminated and cause multisystem disease. The precipitating factors in our patient likely include the profound immunodeficiency associated with SCID, and potentially the co-presence of parainfluenza virus and Pneumocytis carinii. The present case illustrates severat important points. It documents Legionella pneumophila infection in an infant. The features not reported thus far include disseminated infection with marked tissue reaction in several organs, including liver and brain. Immunocompromise d patients appear to be at the h ighest risk. Since many of these patients develop mixed infections, Legionella pneumophila should be included in the differential diagnosis, with appropriate studies being carried out when confronted with progressive respiratory failure of unknown etiology.

Viral gastroenteritis in Charleston, West Virginia, in 2007: from birth to 99 years of age.

OBJECTIVE To describe factors associated with a rectal swab or stool sample positive for norovirus, rotavirus, or adenovirus. DESIGN Retrospective study. SETTING Charleston Area Medical Center, a regional academic medical center in Charleston, West Virginia. METHODS Rectal swab or stool samples were obtained from patients suspected of having viral gastroenteritis. These samples were sent to the Charleston Area Medical Center virology laboratory for testing in 2007. Viral antigen in rectal swab and stool samples is detected by use of commercially available immunoassay kits for each virus. Data were extracted from the virology laboratory database for the following 1-year time period: January 1, 2007, through December 31, 2007. When necessary, additional information was obtained from electronic administrative data on patients. RESULTS There were 2,867 rectal swab and stool samples available for viral testing. Of these samples, 1,261 (44%) were positive for a virus. Of these positive samples, 972 (77%) were positive for norovirus, 182 (14%) were positive for rotavirus, and 110 (9%) were positive for adenovirus. The patients in the youngest age group had the highest number of test results positive for all 3 viruses. When the test results for the youngest age group (0-9 years) were compared with those for all the other age groups combined (10-99 years), the proportion of positive cases was highest for the youngest age group (P<.001). There were significant seasonal trends for all 3 viruses. Multivariate analysis of norovirus showed that season, source, sex, and age were significant predictors of a positive test result. Multivariate analysis of rotavirus showed that season and source were significant predictors of a positive test result. Multivariate analysis of adenovirus showed that season and age were significant predictors of a positive test result. CONCLUSIONS We conclude (1) that these 3 viruses are common causes of gastroenteritis in Charleston, West Virginia; (2) that infants and young children are more likely to test positive for these viruses than are older individuals; (3) that norovirus was the most common cause of gastroenteritis; and (4) that there are seasonal trends for all 3 viruses.

Gastrointestinal norovirus in the Charleston, West Virginia area-2007: birth to 99 years of age.

Data were collected on all patients in the Charleston, WV area tested for norovirus gastroenteritis during 2007. Of the 2687 rectal swab/stool samples, 60% were from individuals <20 years of age. Stool samples were more likely to be positive compared with rectal swab samples and if obtained from January to July and from patients <5 years of age.