Unusual histopathologic features in thymic corpuscles associated with porcine periweaning failure-to-thrive syndrome.

Six, 5-6-wk-old pigs, from 3 farms of the same company, with significant loss of body condition were submitted for postmortem evaluation. Macroscopically, the main lesion observed in all of the pigs was thymic atrophy. Microscopically, all of the pigs had thymic atrophy, superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, and neutrophilic and lymphocytic rhinitis, leading to a diagnosis of porcine periweaning failure-to-thrive syndrome. In the pigs from 2 of the farms, many of the thymic corpuscles had infiltrates of neutrophils and degenerate cells, in some cases infiltrating the surrounding parenchyma.

Exploratory metagenomic analyses of periweaning failure-to-thrive syndrome-affected pigs.

Modern pig farming is characterised by the emergence of several syndromes whose aetiology is unclear or has a multifactorial origin, including periweaning failure-to-thrive syndrome (PFTS). In fact, its specific aetiology remains elusive, although several causes have been investigated over time. The present study aimed to investigate the potential role of viral agents in PFTS-affected and healthy animals by evaluating the virome composition of different organs using a metagenomic approach. This analysis allowed demonstrating a higher abundance of Porcine parvovirus 6 (PPV6) in healthy subjects while Ungulate bocaparvovirus 2 (BoPV2), Ungulate protoparvovirus 1 (PPV) and Porcine circovirus 3 (PCV-3) were increased in pigs with PFTS. No differential abundance of RNA viruses was found between PFTS-affected and control pigs. Remarkably, this is the first molecular characterisation of PPV6 and BoPV2 in Spain and one of the few all around the world, supporting their apparent widespread circulation. Interestingly, PCV-3 has been recently identified in several clinical-pathological conditions as well as in healthy pigs, while BoPV2 pathogenic potential is unknown. Although obtained results must be taken as preliminary, they open the door for further studies on the potential role of these viruses or their combination as predisposing factor/s for PFTS occurrence.

Genomic investigation of porcine periweaning failure to thrive syndrome (PFTS).

Porcine periweaning failure to thrive syndrome (PFTS) can be defined by anorexia, lethargy, progressive debilitation and compulsive behaviours that occur in seemingly healthy pigs within two to threeweeks of weaning in the absence of any known infectious, nutritional, management or environmental factors. A genetic component has been hypothesised for this syndrome. In the present study, 119 commercial pigs (80 cases and 39 controls) were genotyped with the porcine 80K single nucleotide polymorphism-chip and were analysed with logistic regression and two Fixation Index-based approaches. The analyses revealed several regions on chromosomes 1, 3, 6 and 11 with moderate divergence between cases and controls, particularly three haplotypes on SSC3 and 11. The gene-based analyses of the candidate regions revealed the presence of genes that have been reported to be associated with phenotypes like PFST including depression (PDE10A) and intestinal villous atrophy (CUL4A). It is important to increase the effort of collecting more samples to improve the power of these analyses.

Genome-wide association study of periweaning failure-to-thrive syndrome (PFTS) in pigs.

Porcine periweaning-failure-to-thrive syndrome (PFTS) is a condition that affects newly weaned piglets. It is characterised by a progressive debilitation leading to death, in the absence of infectious, nutritional, management or environmental factors. In this study, we present the first report of PFTS in South America and the results of a genome-wide association study to identify the genetic markers associated with the appearance of this condition in a crossbred swine population. Four chromosomal regions were associated with PFTS predisposition, one located on SSCX, one on SSC8, and the two other regions on SSC14. Regions on SSC8 and SSC14 harbour important functional candidate genes involved in human depression and might have an important role in PFTS. Our findings contribute to the increasing knowledge about this syndrome, which has been investigated since 2007, and to the identification of the aetiology of this disease.

Evidence that periweaning failure-to-thrive syndrome (PFTS) has a genetic predisposition.

Genetic susceptibility or resistance to diseases is currently drawing increasing attention. This work describes two different breeding herds showing signs of periweaning failure-to-thrive syndrome (PFTS), an emergent swine disease. The disease was diagnosed based on clinical picture and confirmed by histopathology. The possibility of main infectious pathogens was ruled out by immunohistochemistry and PCR. In a simple approach, sires of the affected piglets have been determined using microsatellite paternity analysis, including a healthy group in each case. In each of the two farms, a single boar was found to have sired 45-50 per cent sick animals. Removal of this sire from two farms resulted in a significant decrease in the prevalence of the disease among the offspring, in accordance with other two cases diagnosed, although without including a control group. Since the analysed animals belonged to three different genetic lines, these findings point to the existence of individual genetic susceptibility to this syndrome.

Pathological features and proposed diagnostic criteria of porcine periweaning failure-to-thrive syndrome.

Porcine periweaning failure-to-thrive syndrome (PFTS) is a clinical syndrome characterized by anorexia and progressive debilitation of newly weaned pigs. The objectives of the current case-control study were to describe the histopathologic features of PFTS in North America and test for selected pathogens in case and control pigs on 8 farms allegedly fulfilling the clinical definition of PFTS. Based on observations during farm visits, 5 farms fully met the case definition (PFTS farms), whereas 3 farms only partially fulfilled the definition (NON-PFTS farms). Necropsy and histopathologic examination were performed on case (n = 8 or 9) and control (n = 4) pigs from each farm. Superficial gastritis, which was mainly localized in the fundus and characterized by attenuation of superficial foveolar cells, was significantly more frequent in case pigs from PFTS farms compared with all the other pigs (odds ratio [OR], 16.7). The same was found for thymic atrophy (OR, 30.1) and small intestinal (SI) villous atrophy in the duodenum (OR, 28.7), jejunum (OR, 67.4), and ileum (OR, 56.3). All pigs with PFTS had at least 2 of these 3 lesions: gastritis, thymic atrophy, and SI villous atrophy. PFTS was not associated with any relevant porcine pathogen tested. We propose the diagnosis of PFTS be based on the fulfillment of the clinical case definition, the presence of the above lesions, and exclusion of other common swine diseases and pathogens. However, PFTS can be ruled out if debilitated pigs do not have at least 2 of the above 3 lesions.

Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.

Diagnostic investigation of porcine periweaning failure-to-thrive syndrome: lack of compelling evidence linking to common porcine pathogens.

Porcine periweaning failure-to-thrive syndrome (PFTS), an increasingly recognized syndrome in the swine industry of North America, is characterized by the anorexia of nursery pigs noticeable within 1 week of weaning, and progressive loss of body condition and lethargy during the next 1-2 weeks. Morbidity caused by PFTS is moderate, but case fatality is high. The etiology of PFTS is presently unknown and may include infectious agent(s), noninfectious factors, or both. PFTS was identified in a high health status farm with good management in early 2007. A diagnostic investigation was undertaken to identify the pathological lesions of, and infectious agents associated with, pigs demonstrating typical clinical signs. Affected (PFTS-SICK) and unaffected (PFTS-HLTHY) pigs from an affected farm, and unaffected pigs from 2 unaffected farms, were examined. The most prevalent lesions in PFTS-SICK pigs were superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, lymphocytic and neutrophilic rhinitis, mild nonsuppurative meningoencephalitis, and thymic atrophy. Rotavirus A and Betacoronavirus 1 (Porcine hemagglutinating encephalomyelitis virus) were identified only in PFTS-SICK pigs, but the significance of the viruses is uncertain because PFTS is not consistent with the typical presentation following infection by these pathogens. Porcine reproductive and respiratory syndrome virus, Porcine circovirus-2, Influenza A virus, Alphacoronavirus 1 (Transmissible gastroenteritis virus), Torque teno virus 1, Brachyspira hyodysenteriae, and Brachyspira pilosicoli were not identified in PFTS-SICK pigs. Suid herpesvirus 2 (Porcine cytomegalovirus), Porcine enteric calicivirus, Torque teno virus 2, pathogenic Escherichia coli, and coccidia were detected in both PFTS-SICK and PFTS-HLTHY pigs. It was concluded that there is a lack of compelling evidence that PFTS is caused by any of these pathogens.

Defects in small intestinal epithelial barrier function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine.

The objective of this study was to investigate intestinal function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine. Jejunum and distal ileum from control and pigs exhibiting PFTS was harvested at weaning, 4 and 11 days post-weaning (PW) for intestinal barrier function studies and histological analyses (n=6 pigs per group). Marked disturbances in intestinal barrier function was observed in PFTS pigs, compared with controls, indicated by lower (p<0.05) TER and increased (p<0.01) permeability to FITC dextran (4 kDa). Intestines from weaned pigs, subjected to a 4-day fast, exhibited minor disturbances in intestinal barrier function. Villus atrophy and crypt hyperplasia were observed in the PFTS intestine compared with control and fasted pigs. These data demonstrate that PFTS is associated with profound disturbances in intestinal epithelial barrier function and alterations in mucosal and epithelial morphology in which anorexia is not the sole factor.

Presumptive copper deficiency in hand-reared captive pronghorn (Antilocapra americana) fawns.

Presumptive copper deficiency was diagnosed in hand-reared captive pronghorn (Antilocapra americana) at the Los Angeles Zoo. Clinical signs, which were manifested in growing fawns, included anemia, anorexia, diarrhea, progressive paresis/recumbency, and aortic rupture. The range of serum copper concentrations in fawns born during the 1989 season (0.08-0.67 ppm) was below levels considered normal for domestic sheep and goats (0.7-2.0 ppm) and below concentrations measured in adult pronghorn (0.4-1.43 ppm). Copper sulfate supplementation of the hand-rearing formula, which was initiated in 1989, resulted in a significant increase in mean (+/- SD) serum copper levels from 0.45 +/- 0.18 ppm before supplementation to 0.68 +/- 0.05 ppm after supplementation (P < 0.05). Fawns born in subsequent seasons (April 1990-August 1993) continued to be supplemented with copper in the hand-rearing formula. Mean serum copper concentration from these fawns (0.68 +/- 0.22 ppm) was similar to the mean values from supplemented 1989 fawns and adult pronghorn in this herd (0.85 +/- 0.34 ppm; P > 0.05). No clinical signs of copper deficiency were detected in any fawns after supplementation was started. Analyses of the herd's diet revealed marginal dietary copper levels. Suspected dietary deficiency was confirmed by marginal tissue and serum copper concentrations in some of the herd's adult animals. Dietary copper levels were corrected to prevent future cases of clinical copper deficiency.

Hypophosphatemia associated with hypovitaminosis-D in Speke's gazelles (Gazella spekei).

Two juvenile male Speke's gazelles (Gazella spekei) at the St. Louis Zoo showed poor body condition, slowed growth, hunched stance, rough hair coat, and profound hypophosphatemia. The first gazelle was treated with parenteral phosphorous supplements but continued to deteriorate clinically and was euthanatized. The second gazelle had serum 25-hydroxyvitamin D levels of 0 nmol/L and was treated with i.m. injections of vitamin D. It died shortly after starting therapy. The only significant necropsy finding was multiple rib fractures in various stages of healing. Hypovitaminosis D has been confirmed in multiple Speke's gazelles in this collection, indicating possible deficiencies in the diet or in the amount of ultraviolet light available to the gazelles.

Efficacy of a single dose of oral antibiotic given within two hours of birth in preventing watery mouth disease and illthrift in colostrum-deficient lambs.

An antibiotic with a product licence limited to the treatment and control of infectious bacterial enteritis associated with Escherichia coli in piglets was tested for its ability to control watery mouth disease in neonatal lambs. Three groups of lambs were kept in conditions commonly encountered in intensive lambing systems, where high levels of environmental bacterial contamination may be expected. They were allocated at birth to: a control group (group 1) consisting of 18 colostrum-deprived lambs; group 2, consisting of 17 lambs given one feed of colostrum when they were two hours old; and group 3, consisting of 18 colostrum-deprived lambs given spectinomycin orally when they were two hours old. Nine group 1 lambs became diseased and were killed for humane reasons. Blood biochemical changes included hyperglycaemia followed by hypoglycaemia, lactacidaemia, hypoproteinaemia and metabolic acidosis, and postmortem examination of the diseased lambs showed signs consistent with endotoxaemia and a clinical diagnosis of watery mouth disease. Coliforms were isolated from the blood of all group 1 lambs and from half the lambs in groups 2 and 3, but endotoxaemia and watery mouth disease occurred only in group 1 lambs. The results for groups 2 and 3 showed that neither colostrum nor antibiotic at the rates and frequency used prevented bacteraemia, although consecutive samples were positive only on three occasions. Group 3 lambs consistently grew more rapidly than the surviving group 1 lambs and as rapidly as group 2 lambs. There was no evidence that male lambs were more prone to watery mouth disease than female lambs. The results indicated that the antibiotic spectinomycin did not induce endotoxaemia during low-grade bacteraemia and that a single oral dose given within two hours of birth protected colostrum-deprived lambs delivered into a contaminated indoor environment against watery mouth disease.

Fading kitten syndrome and neonatal isoerythrolysis.

Fading kitten syndrome includes noninfectious and infectious causes for neonatal death (birth to weaning age). Noninfectious causes are mostly responsible for mortality in the first week of life and include congenital disorders, low birth weights, trauma, malnutrition, environmental causes, and neonatal isoerythroylsis. Infectious causes are more prevalent at 3-4 weeks of age. This article discusses the causes, clinical signs, and management of fading kitten syndrome.

Failure to grow.

Failure to grow in pups and kittens can be the result of many factors. Dietary, metabolic, endocrine, parasitic, neoplastic, and genetic diseases may be responsible for a failure to thrive alone or in concert with other disorders. A complete history, physical examination, complete blood cell count, biochemistry profile, and urinalysis are the initial steps to define the underlying disorder(s). Subsequent tests may be needed based on these initial diagnostic results.

Health and growth of water-buffalo calves in Nueva Ecija, the Philippines.

This prospective observational study was undertaken in the province of Nueva Ecija in the Philippines to assess current levels of health and growth achieved by a defined cohort of water-buffalo calves raised by smallholder farmers and to identify factors associated with the performance of these animals during the first 6 months following birth. Seventy two animals were enrolled, including 16 Philippine native water-buffalo and 54 crossbred (F1, F2 or backcrosses) animals. Dullness (which was associated with manual assistance at birth and inadequate milk supply subsequently) and scouring were the main signs of morbidity in this cohort, and the crude morbidity and mortality rates during the first 6 months following birth were 2.9 cases and 0.31 deaths per 1000 calf-days at risk, respectively. Average daily gain was significantly influenced both by the breed of the calf and whether the calf developed dullness at any time during the period of observation. The results of this study suggest that the problem of dullness in water-buffalo calves deserves further research attention. Management procedures are likely to be important determinants of growth in these animals.

Protein deficiency in a colony of western lowland gorillas (Gorilla g. gorilla)

A syndrome of alopecia and weight loss in a colony of 10 western lowland gorillas (Gorilla gorilla gorilla) in Gabon during a 3-yr period was apparently due to a dietary protein deficiency, with nine individuals affected to some extent. The most severely afflicted was a 4-yr-old female who eventually died as a result of acute gastroenteritis caused by Shigella flexneri. Clinical signs included chronic alopecia, hair discoloration, failure to thrive, and weight loss, and their severity was directly correlated with the degree of hypoalbuminemia (12 g/L in the most extreme case) and normocytic normochromic anemia. Preliminary clinical tests and autopsy results suggested a dietary protein or amino acid deficiency as the cause of the hypoalbuminemia, and further analyses of serum amino acid and protein levels were consistent with a diagnosis of dietary protein deficiency. Supplementation of the colony diet with a protein preparation for humans produced a rapid amelioration of signs and improvement in body and coat condition, a normalization of serum albumin and total protein levels, and disappearance of the anemia in all affected animals except a 12-yr-old male, who responded well to treatment with anabolic steroids. The natural diet of western lowland gorillas is surprisingly high in protein, and the dietary protein requirement of captive gorillas may be increased as a result of the absence of commensal gastrointestinal ciliates.

Diminished reproduction, failure to thrive, and altered immunologic function in a colony of T-cell receptor transgenic mice: possible role of Citrobacter rodentium.

Citrobacter rodentium from an undetermined source was detected in a breeding colony of T-cell receptor transgenic mice housed in a conventional mouse facility in which murine hepatitis virus had been endemic and Helicobacter spp. had been detected. Citrobacter rodentium, isolated from blood, spleen, and colon, correlated with a significant increase in mortality and morbidity in this breeding colony. Transgenic mice of all ages were affected by chronic debilitation, loss in reproductive efficiency, rectal prolapse, and acute death, resulting in the near loss of these noncommercially available strains. Several alterations in immunologic parameters were observed, including outgrowth of an unusual population of cells in the spleen and blood, reduction in ascites production, loss of the capacity of peritoneal exudate cells to serve as feeders for the cloning of long-term T-cell lines, and inhibition of antigen-specific cytotoxic T-cell activity. These altered immune functions also were apparent in commercially-derived nontransgenic mice cohoused with the infected colony and in overtly healthy transgenic and nontransgenic littermates. Citrobacter rodentium and murine hepatitis virus were eliminated ultimately on rederivation of the affected strains by embryo transfer. However, the rapid decrease in the health of the colony necessitated more immediate action. To reduce mortality and allow breeding to continue during rederivation of the transgenic lines, animals were treated with enrofloxacin and moved to a barrier facility. Antibiotic therapy significantly reduced morbidity and mortality, markedly increased litter size and frequency, and resulted in the normalization of many of the immunologic assays. The involvement of C. rodentium in altering viability of the colony and perturbing immunologic assays is suggested by correlation of the onset of the syndrome with the appearance of Citrobacter sp. and its resolution with the elimination of Citrobacter sp. from the colony. Whether infection with Citrobacter alone is causative or whether superinfection of murine hepatitis virus- and Helicobacter-infected mice is required remains to be determined.