Long-term cognitive effects of Lyme disease in children.

Most studies of adults infected with Lyme disease (LD) have found adverse cognitive effects from the disease. In contrast, the only controlled study investigating cognitive effects of LD in a pediatric population found no effects after a 2-year follow-up. However, it was questioned whether the negative effects might take longer than 2 years to emerge. Therefore, this investigation reports a 4-year follow-up of the original sample. Twenty-five children with strictly defined LD were compared with 17 sibling control children. A neuropsychological battery was utilized, including assessment of the cognitive areas of IQ, information processing speed, fine-motor dexterity, novel problem solving and executive functioning, short-term and intermediate memory, and acquisition of new learning. In addition, parents' subjective ratings were obtained on the disease's impact on their child's participation in everyday activities. No between-group differences were found for 17 of the 18 neuropsychological test measures, nor were there differences in parents' subjective ratings. Therefore, in contrast with studies of adults with LD, the results of long-term follow-up of the pediatric population continue to strongly support the finding that children treated appropriately for LD have an excellent prognosis for normal cognitive functioning.

Cognitive effects of Lyme disease in children: a 4 year followup study.

OBJECTIVE: To measure cognitive effects of Lyme disease (LD) in a pediatric population 4 years after disease onset. METHODS: Prospective, blinded, multivariable controlled study of cognitive skills in children who have been treated for LD. The setting was a children's hospital in an area endemic for LD. Twenty-five children with strictly defined LD were compared with 17 control children (6 disease-control and 11 sibling-control). OUTCOME MEASURES: An extensive set of neuropsychological measures was administered. These included assessment of the cognitive areas of IQ, information processing speed, fine-motor dexterity, novel problem solving and executive functioning, short term and intermediate memory, and acquisition of new learning. Parents' ratings were also obtained concerning disease impact upon everyday activities. RESULTS: Seventeen of the 18 neuropsychological test measures showed the LD and control groups similar at time of 4 year followup. There were no differences between the groups regarding parents' impressions of disease impact. CONCLUSION: In contrast to studies of adults with LD, the results of longterm followup of the pediatric population continue to strongly support the finding that children treated appropriately for LD have an excellent prognosis for normal cognitive functioning.

Cognitive effects of Lyme disease in children.

OBJECTIVE: To measure possible cognitive sequelae of Lyme disease (LD) within a pediatric population. DESIGN: Prospective, blinded, controlled study of cognitive skills in children who had been treated for LD. SETTING: A children's hospital in an area endemic for LD. PATIENTS: Forty-one children with strictly defined LD were compared with 14 control children who had subacute rheumatological diseases, and with 23 healthy sibling controls. OUTCOME MEASURES: Neuropsychologic measures were administered to each child to assess the following cognitive areas: IQ information processing speed, fine-motor dexterity, novel-problem solving and executive functioning, short-term and intermediate memory, and the ability to acquire new learning. Predisease and postdisease academic achievement test scores were also gathered. Impressions from parents concerning the disease's subsequent impact were also obtained. RESULTS: No differences between LD and control groups were found for any of the numerous neuropsychologic measures. Analyses also failed to show differences between LD patients grouped with respect to the presence or absence of known neurologic involvement, disease stage, duration of symptoms before therapy, or type of antibiotic treatment. No predisease versus post-disease difference in academic performance was found. No perceived long-term deterioration in cognitive, social, or personality areas was reported by parents. CONCLUSION: Children appropriately treated for LD have an excellent prognosis for unimpaired cognitive functioning.

Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus.

We report here on a series of vaccine trials to evaluate the effectiveness of an inactivated equine infectious anemia virus (EIAV) whole-virus vaccine and of a subunit vaccine enriched in EIAV envelope glycoproteins. The inactivated vaccine protected 14 of 15 immunized ponies from infection after challenge with at least 10(5) 50% tissue culture-infective doses of the homologous prototype strain of EIAV. In contrast, it failed to prevent infection in any of 15 immunized ponies that were challenged with the heterologous PV strain. Levels of PV virus replication and the development of disease, however, were significantly reduced in 12 of the 15 ponies so challenged. The subunit vaccine prevented infection from homologous challenge in four of four ponies tested but failed to prevent infection in all four challenged with the PV strain. Two of the four subunit vaccinates had more severe symptoms of equine infectious anemia than nonimmunized ponies infected in parallel. Both vaccines stimulated EIAV-specific cell-mediated immunity. The in vitro lymphoproliferative response was shown to be mediated by T lymphocytes and appeared to be indistinguishable from that induced by EIAV infection. Significant differences were observed in the in vivo lymphocyte responses following challenge with the two virus strains. While peripheral blood mononuclear cells from the inactivated virus vaccinates were equally stimulated by both the prototype and PV strains, the subunit vaccinates challenged with PV exhibited lower levels of spontaneous proliferation and serine esterase activity. This diminished cellular response to PV was correlated with more severe clinical disease in the same ponies. These studies demonstrate for the first time that both an EIAV inactivated whole-virus vaccine and a viral envelope glycoprotein-based subunit vaccine can provide protection against rigorous challenge levels of homologous virus but are unable to protect against similar challenge levels of a heterologous virus. Moreover, the data demonstrate that protection can be achieved in the absence of detectable levels of virus-specific neutralizing antibody in the vaccine recipients at the time of virus challenge. While vaccine-induced virus-specific cell-mediated immune responses were detected, their role in conferring protection was not obvious. Nevertheless, protection from disease appeared to be correlated with the induction of high levels of serine esterase activity following challenge. A significant observation is that while the whole-virus vaccine was usually capable of preventing or markedly moderating disease in the PV-infected ponies, the subunit vaccine appeared to have a high potential to enhance the disease induced by PV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Equine infectious anemia: prospects for control.

Equine infectious anemia has been managed in most countries by the imposition of testing and quarantine regulations. In the United States, about 700,000 of the more than 7,000,000 horses are tested annually. As long as the status of greater than 90% of the horse population remains unknown and horses are transported and congregate in a relatively unrestricted manner, EIA will continue to exact its toll. Therefore, it is incumbent on the scientific community to continue to develop and refine practical and sensitive diagnostic tests for EIA which will be used in an expanding market, to reduce the number of untested horses and to increase the accuracy of test results. Under ideal conditions, EIA can spread rapidly in a localized population with potentially devastating results. Although strict adherence to sanitary regulations will minimize the likelihood of epizootics, the existence of a large reservoir of untested horses with occasional contact with uninfected test-negative horses will ensure the continued transmission of EIAV. The change of this transmission occurring as a result of human intervention can be eliminated but it is not possible to eliminate the threat posed by blood feeding insects. If these "chance encounters" between an untested EIAV infected horse and a test-negative horse occur under field conditions where horse flies are abundant and the proximate distance between the horses is minimal, transmission is efficient if the quantity of EIAV in the blood of the donor horse is high.(ABSTRACT TRUNCATED AT 250 WORDS)

Equine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection.

Three ponies were inoculated with plasma containing 10(4.8) TCID50 of equine infectious anemia virus (EIAV) and observed for 165 to 440 days. Each pony developed a febrile response within 3 weeks of infection during which a plasma viremia greater than or equal to 10(3.5) TCID50/ml was observed. Analyses of four isolates from sequential febrile episodes in a single pony were conducted by two-dimensional tryptic peptide maps and with monoclonal antibodies in immunoblots. Structural and antigenic alterations were observed in the envelope glycoproteins gp90 and gp45, with greatest variation in gp90. Specific IgG to EIAV gp90, gp45, and p26 of homologous and heterologous isolates was detectable by immunoblots within one month after infection although IgG levels to gp45 at this time were relatively low. The group-specific determinants of gp90 and gp45 were more antigenic than those of p26; however, binding of IgG to these determinants did not correlate with neutralization of EIAV as assayed in fetal equine kidney cells. Neutralizing antibodies were first detectable within two months of infection and only neutralized viruses isolated prior to serum collection. Neutralizing activity of sera collected later in the infection was broadly reactive regardless of the number of clinical episodes the donor had suffered.

Learning problems in neurofibromatosis patients.

Learning problems in patients with neurofibromatosis (NF) are probably the most frequent characteristics after those that define the disorder. They are not secondary to the physical problems. A recent survey that compared children who have NF with their siblings revealed a 37% greater incidence of learning disabilities in the children with NF. Intelligence quotient (IQ) data from several studies indicate that almost all patients with NF have a normal IQ, but there is a progression from low normal to normal as these patients reach adulthood. The most common psychoeducational problems include visual-perceptual-motor delay, spelling and arithmetic disabilities, and a cluster of weaknesses related to cortical organization, similar to those seen in children with attention-deficit disorders. A type of learning disability unique to patients with NF has not been identified, and the diagnosis and treatment of the learning problems are generally the same as for children without NF.

Prospective study of progeny of inapparent equine carriers of equine infectious anemia virus.

Progeny of a band of horses, positive by the agar-gel immunodiffusion (AGID) test for equine infectious anemia (EIA) antibody, were observed through their weaning over a 4-year period. Sentinels (AGID test-negative) were allowed to mingle with EIA-infected mares and their foals in pasture situations in an area with high populations of potential vectors. Of 27 adult sentinels, 8 (30%) seroconverted in annual rates ranging from 0% to 75%. In contrast, only 2 of 31 (6%) foals weaned became infected. Difference in infection rates between adult sentinels and foals was significant (chi 2, P less than 0.05). Possible explanations for differences included protective value of colostral immunity and differences in attractiveness to blood feeding vectors. Detectable colostral immunity to EIA virus in the AGID test persisted for 25 to 195 days, with a mean of 124 days.

Observations of tabanid feeding on mares and foals.

The occurrence of tabanid feeding between mares and foals was observed. When mares and foals were observed freely moving within a pasture situation, foals had 2.43% (4 flies in 77 observations vs 297 flies in 139 observations) of the tabanid feeding occurrences of the mares. This difference in tabanid burden varied due to herd size, herd location, and tabanid species. Lower tabanid burden of foals was indicated as a practical protective mechanism against pathogenic agents mechanically transmitted by tabanids, such as equine infectious anemia virus.

Virulence and in vitro growth of a cell-adapted strain of equine infectious anemia virus after serial passage in ponies.

Five serial passages of a cell-adapted strain of equine infectious anemia (EIA) virus were conducted in Shetland ponies. The 13 recipient ponies became agar-gel immunodiffusion test-positive by 25 days after they were inoculated. The virulence of the cell-adapted strain of EIA virus markedly increased through 3 serial passages, although individual variation within passages was high. The 1st serial-passage recipient remained afebrile through 200 days, whereas a febrile episode occurred about every 185, 44, 35, and 33 days in the 2nd, 3rd, 4th, and 5th serial-passage recipients, respectively. Severe clinical signs of EIA were noted in the ponies at each serial passage, but the mean virulence rating of each passage, graded on frequency of febrile episodes and number of clinical signs evident within 200 days after ponies were inoculated, increased from 0 through 4, 21, 24, and 29 for the 1st through 5th serial passages, respectively. Isolates of EIA virus, made in fetal equine kidney cells, were obtained from plasma of 75% of the samples of blood collected during febrile episodes and from 45% of the samples collected during afebrile periods, indicating that the cell culture growth capacity of this strain of EIA virus may be relatively stable through 5 serial passages in Shetland ponies.

Transmission of equine infectious anemia virus from horses without clinical signs of disease.

Twenty seven adult horses positive to the agar gel immunodiffusion (AGID) test for equine infectious anemia (EIA), but with no history of clinical EIA, were used in transfusion studies to determine whether infectious EIA virus was present in 1 to 5 ml of their blood. Of 27 recipients, 21 (78%) became AGID test-positive at an average of 24 days after inoculation. Two horses that were initially negative when screened were retested and found to carry infectious virus in 5-300 ml of whole blood; the other 4 horses were not retested. Horse flies (Tabanus fuscicostatus Hine) were unable to transmit EIA virus from 10 AGID test-positive donors with no history of clinical EIA, but virus was transmitted from a pony with artificially induced acute EIA and from a horse that had recovered from a clinical attack of EIA 9 months earlier. Histopathologic changes indicative of EIA were noted in all test-positive recipients. The most consistent lesion was paracortical lymphoid hyperplasia in the splenic lymph node.

Detection of equine infectious anemia virus in a horse with an equivocal agar gel immunodiffusion test reaction.

A horse whose serum reacted equivocally in the agar gel immunodiffusion (AGID) test for equine infectious anemia was studied over a 3-year period. The horse remained afebrile and virus was detected in only 1 of 6 horse inoculation tests. The intensity of AGID test reactions increased temporarily following this evidence for virus. Although the AGID test reaction was equivocal and 5 of the 6 transmission attempts failed, the 1 successful transmission proved the horse was infected.

Studies with equine infectious anemia virus: transmission attempts by mosquitoes and survival of virus on vector mouthparts and hypodermic needles, and in mosquito tissue culture.

Biological and mechanical transmission trials with Psorophora columbiae (Dyar and Knab) and Aedes sollicitans (Walker) and ponies acutely infected with equine infectious anemia virus (EIAV) were negative. The EIAV antigen was detected by radioimmunoassay in Ae sollicitans immediately after the mosquitoes had fed on an acutely ill pony, but not 14 days after feeding. Psorophora columbiae mosquitoes had detectable EIAV antigen as determined by radioimmunoassay 24 hours after they fed on an acutely ill pony; this antigen was not detected again until 6 days after feeding and was still detected 14 days after feeding. The EIAV was detected on hypodermic needles held at 25 C for 96 hours, but was not detected 120 hours after the needles were dipped in solutions of EIAV. The virus was detected on the mouthparts of mosquitoes for 1 hour after they had fed on an EIAV-rich medium, but was not detected 4 hours after feeding. Culex pipiens quinquefasciatus Say ovarian cells maintained the infectivity of EIAV for 10 weekly passages, but no evidence for virus multiplication was obtained.

Serologic survey for equine infectious anemia virus in Louisiana.

In 1975, a survey was conducted in East Baton Rouge Parish, Louisiana, to determine the prevalence of equine infectious anemia. Using the agar gel immunodiffusion test, 94 of 1,398 horses (6.7%) were found to be infected. Infection rates were especially high in areas where clinical cases of equine infectious anemia had been diagnosed. Clinical signs compatible with the disease were noted in 1 of the 94 seropositive horses. The sample set of 1,398 horses represented 22% of the census population obtained during the 1971 Venezuelan equine encephalomyelitis vaccination campaign.

Spontaneous renal disease in beaver in Louisiana.

Interstitial nephritis was present in 13 of 25 adult beavers (Castor canadensis). Results of serum chemistry, serotyping, and culture for leptospires were compared with the extent of renal lesions. Although the pathogenesis of the nephritis was not determined, the survey provided baseline information on spontaneous renal disease in beavers.

Spontaneous renal disease in Louisiana armadillos (Dasypus novemcinctus).

Renal lesions were present in 34 (68%) of 50 armadillos (Dasypus novemcinctus) collected for a survey of the prevalence of leptospires in Louisiana wildlife. The renal lesions were not associated with elevations in the renal function tests of blood urea nitrogen or serum creatinine or with consistent serologic or cultural evidence of leptospires.

Renal lesions in striped skunks (Mephitis mephitis) from Louisiana.

Renal tissue from 100 striped skunks (Mephitis mephitis) examined microscopically showed evidence of inflammation in 74% of the kidneys. Azotemia was present in 20% of the skunks that had severe renal lesions. The cause of inflammation is unknown, but leptospires were cultured from kidneys or urine of 55% of these skunks.