Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system.

Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.

Suspected primary hypoparathyroidism in a domestic ferret (Mustela putorius furo).

CASE DESCRIPTION: A 4-year-old castrated male domestic ferret (Mustela putorius furo) was examined because of a 3-week history of intermittent seizures, signs of depression, hypocalcemia, and hyperphosphatemia. CLINICAL FINDINGS: Plasma biochemical analysis confirmed hyperphosphatemia (17.7 mg/dL) and low concentrations of total (4.3 mg/dL) and ionized (0.49 mmol/L) calcium. Serum parathyroid hormone concentration (2.30 pmol/L) was low or in the low part of the reference interval. TREATMENT AND OUTCOME: Calcium gluconate was administered (2.0 mg/kg/h [0.9 mg/lb/h], IV), followed by a transition to administration of calcium carbonate (53 mg/kg [24.1 mg/lb], PO, q 12 h) and dihydrotachysterol (0.02 mg/kg/d [0.009 mg/lb/d], PO). Attitude of the ferret improved and seizures ceased as blood calcium concentrations increased. The ferret was reexamined because of seizures approximately 1 year after oral maintenance administration of dihydrotachysterol and calcium was initiated. The ferret responded well to emergency and long-term treatment but then was lost to follow-up monitoring. The ferret died approximately 2 years after the initial evaluation and treatment. Hypertrophic cardiomyopathy was diagnosed during necropsy, but the parathyroid glands could not be identified. CLINICAL RELEVANCE: To the authors' knowledge, primary hypoparathyroidism has not previously been reported in a ferret. The condition should be considered for ferrets with hypocalcemia and hyperphosphatemia without azotemia. Treatment with dihydrotachysterol and oral supplementation of calcium appeared to be a viable option for long-term management.

Central diabetes insipidus in an African Grey parrot.

CASE DESCRIPTION: A 5.5-year-old sexually intact female African Grey parrot (Psittacus erithacus) was evaluated for a 1-year history of pronounced polyuria and polydipsia. The bird also had a 1-month history of signs of mild depression and mydriasis. CLINICAL FINDINGS: Physical examination revealed a thin body condition and incomplete bilateral mydriasis. Other examination findings as well as CBC and screening radiography results were unremarkable. Plasma biochemical analysis revealed mild hypernatremia. The bird had a 3.3% loss in body weight over 170 minutes during a water deprivation test, and urine osmolality remained low. After IM administration of 0.9 microg of desmopressin, the rate of weight loss decreased substantially and urine osmolality increased 300% over the following 200 minutes. TREATMENT AND OUTCOME: Initial attempts to treat the bird with orally administered desmopressin failed to correct the polydipsia and polyuria. Ultimately, IM administration of 24 microg of desmopressin/kg (10.9 microg/lb) every 12 hours yielded a noticeable reduction in water consumption and urine production over a 6- to 8-hour period. Eight months later, the bird was returned for a recheck examination, at which time it was in good health and continued to respond to the medication. Despite continued response to the medication, right-sided internal ophthalmoparesis was detected 16 months after the initial diagnosis. CLINICAL RELEVANCE: To the authors' knowledge, central diabetes insipidus in birds has not been reported. The condition should be considered in birds with clinical signs of disease similar to those in mammals. Long-term IM administration of desmopressin may be a viable treatment option.

Electrocardiography of the Asian elephant (Elephas maximus).

Electrocardiograms (ECGs) are infrequently performed on Asian elephants (Elephas maximus), and few studies have been reported in the literature. The aim of this study was to determine reference ranges of ECG parameters in Asian elephants and to ascertain if age, body weight, and position of the elephant significantly affected the ECG. Electrocardiograms were obtained from 27 captive, nonsedated apparently healthy Asian elephants while they were standing (ST), in right lateral recumbency (RL), and/or in left lateral recumbency (LL). Six-lead ECGs were obtained using novel clamps and long ECG cables (71 cm). From lead I, standard waveforms and intervals were analyzed, including PR interval, QT interval, ST segment, P, QRS, T, and U waves if they were present. One animal was determined to have a previously undiagnosed conduction abnormality and was not included in the study. Most elephants had a sinus arrhythmia in at least one position. With increasing age, there was a trend toward a slower heart rate and significantly longer P waves. Increasing body weight was significantly correlated with longer QT intervals and T waves with lower amplitude. Compared with measurements in ST, LL resulted in P waves and QRS complexes with shorter amplitude, U waves with greater amplitude, PR intervals with shorter duration, and an increased heart rate. Compared with measurements in LL, RL resulted in larger QRS complexes. U waves were most commonly detected in RL and LL. Mean electrical axis calculated in the frontal plane were as follows: standing range -125 to +141 degrees, mean -5 degrees; left lateral range -15 to +104 degrees, mean 27 degrees; right lateral range -16 to +78 degrees, mean 9 degrees. Position-specific reference ranges should be used when interpreting ECGs, and clinicians must be aware of how age and body weight may affect the ECG.

The role of dietary antioxidant insufficiency on the permeability of the blood-brain barrier.

Our previous studies implicated vitamin E deficiency as a risk factor for equine motor neuron disease, a possible model of human amyotrophic lateral sclerosis, and showed direct effects of this deficiency on brain vascular endothelium. To gain better understanding of the pathogenesis of equine motor neuron disease, we determined the effects of dietary antioxidant insufficiency and the resultant brain tissue oxidative stress on blood-brain barrier permeability. Rats (n = 40) were maintained on a diet deficient of vitamin E for 36 to 43 weeks; 40 controls were fed a normal diet. Permeability of the blood-brain barrier in the cerebral cortex was investigated using rhodamine B, and lipid peroxidation was measured as a marker for oxidative stress. Animals on the vitamin E-deficient diet showed less weight gain and had higher brain lipid peroxidation compared with the controls. Fluorometric studies demonstrated greater rhodamine B in the perivascular compartment and central nervous system parenchyma in rats on the deficient diet compared with controls. These results suggest that a deficiency in vitamin E increases brain tissue oxidative stress and impairs the integrity of the blood-brain barrier. These observations may have relevance to the pathogenesis of amyotrophic lateral sclerosis and other neurologic diseases.

Extrapyramidal side effects in a blue and gold macaw (Ara ararauna) treated with haloperidol and clomipramine.

A diagnosis of adverse extrapyramidal symptoms (EPS) was reached in a 14-year-old female blue and gold macaw (Ara ararauna) that presented with disseminated dystonia (manifesting as pacing, head bobbing, and circling), intermittent ataxia, and coarse-muscle tremors of 60 hours duration. The patient had been treated 23 days previously with haloperidol decanoate (1.7 mg/kg IM once), and for 3 days before hospitalization with clomipramine HCl at a prescribed dosage of 3.9 mg/kg PO q12h. The patient was treated with supportive care, a gradual reduction in the clomipramine dose, and intramuscular and oral diphenhydramine (2 mg/kg q12h). As commonly observed in human patients with drug-induced EPS, a dramatic resolution of clinical signs was observed within 2 hours after the first intramuscular administration of diphenhydramine. It is recommended that EPS be considered in macaws experiencing neurologic signs secondary to clomipramine administration and, in particular, in those treated concurrently or previously with haloperidol.

Pituitary-dependent hyperadrenocorticism in a cockatoo.

CASE DESCRIPTION: A 13-year-old female intact Moluccan cockatoo (Cacatua moluccensis) was evaluated because of coelomic distention, presumed to be secondary to an abdominal hernia. The patient also had a history of rapid weight gain and polyuria and polydipsia. CLINICAL FINDINGS: Ultrasonography was used to confirm the existence of a pseudohernia that appeared to contain the small intestines, pancreas, and reproductive tract. Results of plasma biochemical analysis revealed hyperglycemia, hypophosphatemia, and high nonfasting bile acid concentrations and aspartate aminotransferase activity. A CBC revealed a relative heterophilia with a concomitant lymphopenia and mild monocytosis. Histologic evaluation of a liver biopsy specimen indicated chronic hepatic lipidosis. Despite a strong clinical suspicion of hyperadrenocorticism, ACTH stimulation test results were equivocal. TREATMENT AND OUTCOME: The pseudohernia was strengthened with a prolene mesh. Despite ongoing medical and surgical care, the patient developed complications associated with the herniorrhaphy and was euthanatized. The clinical suspicion of hyperadrenocorticism was confirmed on the basis of histologic evaluation of the pituitary gland by use of special stains. CLINICAL RELEVANCE: To our knowledge, pituitary-dependent hyperadrenocorticism has not been previously confirmed in Psittaciformes. The condition should be considered in birds with clinical signs consistent with those observed in mammals. For the cockatoo of this report, ACTH stimulation test results were equivocal and additional diagnostic tests should be developed for avian patients.

Cryptosporidium and dairy cattle in the Catskill/Delaware watershed: a quantitative risk assessment.

We carried out a study to estimate the public health risk posed by dairy cattle located in New York City's Catskill/Delaware watershed, as measured by daily C. parvum-like oocyst loading. A Monte Carlo simulation model that takes into account the nature of the dairy cattle population within the target area, age-specific incidence/prevalence rates, as well as differential fecal production and oocyst-shedding intensity rates was used to address the objectives. Additionally, the model was designed to distinguish between zoonotic and nonzoonotic species/genotypes of Cryptosporidium. Total estimated daily C. parvum-like oocyst shedding across all age/production categories was estimated at 4.15 x 10(10). The zoonotic C. parvum comprised 93.5% of this load. It was estimated that preweaned calves produce 99.5% of the total daily C. parvum ocyst burden. The recently described nonzoonotic C. bovis was estimated to have a daily load of 2.2 x 10(9) oocysts across all age/production strata. C. parvum deer-like genotype was estimated to have a total daily load of 1.3 x 10(9) oocysts. The results of this study support earlier assertions that strategies aimed at reducing the cryptosporidial risk posed by dairy cattle to public health will be most efficacious if aimed at preweaned calves.

An outbreak of cryptosporidiosis among alpaca crias and their human caregivers.

CASE DESCRIPTION: 6 alpaca crias from a single farm were examined because of diarrhea (n = 4) or decreased fecal production (n = 2). CLINICAL FINDINGS: Cryptosporidium parvum was identified by means of fecal flotation in samples from 5 of the 6 crias, and a diagnosis of cryptosporidiosis was made. In the remaining cria, a presumptive diagnosis of cryptosporidiosis was made. Three people involved in caring for the crias from this farm were subsequently confirmed to have cryptosporidiosis, and 3 other people were suspected to have cryptosporidiosis. Sequence analysis of the ssu rDNA gene loci confirmed C parvum as the causative agent in 4 of the 6 crias. Subsequent evaluation of the farm revealed 2 additional crias confirmed to have cryptosporidiosis. Stocking densities on the farm were high, with approximately 20 adults/acre in some pastures. TREATMENT AND OUTCOME: All 6 hospitalized crias were given supportive treatment consisting of antimicrobials, gastroprotectants, and fluids. All but 1 survived. Farm owners were advised to decrease stocking density on the farm. CLINICAL RELEVANCE: Findings suggested that zoonotic transmission of C parvum from alpacas to humans can occur.

Factors associated with shedding of Cryptosporidium parvum versus Cryptosporidium bovis among dairy cattle in New York State.

OBJECTIVE: To isolate and speciate Cryptosporidium DNA from fecal samples obtained from dairy cattle in New York State and identify factors associated with whether cattle were shedding Cryptosporidium parvum versus Cryptosporidium bovis. DESIGN: Cross-sectional study. SAMPLE POPULATION: 115 fecal samples positive for DNA coding for the Cryptosporidium 18S rRNA gene from dairy cattle in New York State. PROCEDURES: A PCR assay was used to amplify DNA from fecal samples; amplification products were submitted for bidirectional DNA sequencing. Logistic regression was used to test for associations between various host factors and Cryptosporidium spp. RESULTS: 70 of the 115 (61%) fecal samples were found to have C parvum DNA, 42 (37%) were determined to have C bovis DNA, and 3 (3%) were found to have C parvum deer-type DNA. The presence of diarrhea at the time of fecal sample collection, oocyst count, and breed were associated with whether cattle were infected with C parvum or C bovis, with animals more likely to be infected with C parvum if they had diarrhea, had a high oocyst count, or were Holsteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that C parvum and C bovis can be isolated from dairy cattle in New York State and that various factors affect whether cattle infected with Cryptosporidium spp are infected with C parvum or C bovis. Findings also lend credence to the theory that C bovis may be more host adapted and thus less pathogenic to dairy cattle than C parvum.

Incidence of Cryptosporidium parvum in the dairy cattle population in a New York City Watershed.

A longitudinal study of 2-year duration was conducted to determine the risk, as measured by incidence rate, of Cryptosporidium parvum infection among dairy cattle in the Catskill/Delaware Watershed of New York City (NYC), and the factors that predispose animals to the likelihood of infection. A proportional sampling scheme with follow up at quarterly farm visits was employed for heifers and cows. Additionally, all calves born on the 39 study farms were sampled once during the first four weeks of life and at least once more before weaning. Samples were analyzed for the presence of C. parvum using a quantitative centrifugation concentration flotation technique and a C. parvum-specific enzyme-linked immunosorbent assay (ELISA). Of the 9914 fecal samples collected, 747 were found to contain C. parvum. The average number of oocysts detected was 1.3x10(5)/g (range: 1.0/g--8.2x10(6)/g). The average age at time of first detection of the organism was 15.0 days with a standard deviation of 6.59 days. The age range of animals infected with C. parvum in the study population was 3--60 days (inclusive). The unadjusted (crude) incidence rate of C. parvum among the entire study population was 2.05 per 1000 animal-days. The unadjusted incidence rate among pre-weaned calves was 15.55 per 1000 animal-days. After controlling for age and prior protozoal risk level, no seasonal impact on the incidence of C. parvum was detected among animals less than 61 days by negative binomial regression. A seasonal impact was identified among the oocyst counts of infected animals after controlling for age and prior protozoal risk level.