SUMMARY Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.

The first objective of this study was to describe the effect of on-farm heat treatment of colostrum on colostral bacteria counts and IgG concentrations. The second objective was to describe the effect of feeding heat-treated (vs. raw) colostrum on passive transfer of colostral immune and nutritional parameters in neonatal calves. Pooled batches of colostrum were mixed and divided equally: one half was fed raw whereas the other half was fed after heat treatment at 60 degrees C for 60 min using a commercial on-farm batch pasteurizer. Colostrum samples were cultured for total bacteria count and total coliform count and analyzed for total IgG concentration. Forty-nine Holstein calves were fed either raw colostrum (n = 24) or heat-treated colostrums (n = 25) within 1 to 2 h after birth. Serum samples collected from calves at 0 h (precolostrum) and 24 h (postcolostrum) were assayed for serum total protein; IgG, IgA, and IgM concentrations; peripheral total leukocyte counts; neutrophil counts; lymphocyte counts; lymphocyte phenotypes; vitamin A, vitamin E, cholesterol, and beta-carotene concentrations. Serum samples collected from 2- to 5-d-old calves were tested for immunoglobulin function via a bovine viral diarrhea virus type I serum neutralization titer and for neutrophil bacterial opsonization activity. On-farm batch heat treatment of colostrum at 60 degrees C for 60 min resulted in lower colostrum bacteria concentrations while maintaining colostral IgG concentration. Calves fed heat-treated colostrum had significantly greater serum total protein and IgG concentrations at 24 h, plus greater apparent efficiency of IgG absorption (total protein = 6.3 mg/dL; IgG = 22.3 mg/mL; apparent efficiency of absorption = 35.6%) compared with calves fed raw colostrum (TP = 5.9 mg/dL; IgG = 18.1 mg/mL; apparent efficiency of absorption = 26.1%). There was no effect of treatment on serum concentrations of IgA, IgM, vitamin A, vitamin E, cholesterol, beta-carotene or vitamin E:cholesterol ratio, or on serum bovine viral diarrhea virus type I serum neutralization titers. There was no difference between treatment groups when examining calf plasma total leukocyte counts, neutrophil counts, lymphocyte counts, or neutrophil opsonization activity. However, the latter results were considered inconclusive.

Abstract. One-, 4-, and lo-week-old pigs were exposed to porcine reproductive and respiratory syndrome virus (PRRSV) to determine the effect of age on clinical signs, hematologic alterations, the onset and duration of viremia, routes of virus shedding, antibody production, and microscopic lesions produced by PRRSV isolate ATCC VR-2332. The response to PRRSV infection was similar among age groups. Fever, usually prolonged, and a marked dyspnea with cutaneous erythema when restrained for sample collection were the most consistent clinical signs. Prolonged periocular edema was unique to the l-week-old pigs. The white blood cell count was decreased on day 4 postexposure (PE) due to decreases in neutrophils and lymphocytes. The virus was isolated from buffy coats at day 1 PE and was isolated from serum, buffy coat, or plasma at each sample collection period through the end of the trial (day 28 PE). Virus was most consistently isolated from lung, lymph node, spleen, and tonsil on day 7 PE and exclusively from lymph node, spleen, and tonsil on day 28 PE. Virus was infrequently isolated from urine and fecal and nasal swabs. Consistent microscopic changes in all age groups included interstitial pneumonia and lymph node hypertrophy and hyperplasia on days 7 and 28 PE, lymph node necrosis on day 7 PE, and subacute mononuclear myocarditis on day 28 PE. Findings presented here indicate that interstitial pneumonia, lymphoid necrosis, and mononuclear myocarditis are characteristic lesions of PRRSV isolate ATCC VR-2332 infection in 1-, 4-, and lo-week-old pigs.Porcine reproductive and respiratory syndrome (PRRS), a recently emerging disease of swine, causes pneumonia and late term abortion characterized by stillborn pigs, partially autolyzed fetuses, and weak live-born pigs. [8][9][10][11][14][15][16]18,24,25 In conventional pigs, this virus causes fever, marked dyspnea ("thumping"), flulike signs, and an increase in pneumonia from opportunistic bacteria. ll,14,l6,18 Clinical signs in PRRS virus (PRRSV)-infected gnotobiotic pigs are inappetence, fever, diarrhea, hyperpnea, dyspnea, and rough hair coats.9 Clinical signs of the disease are reported to be more severe in neonatal pigs. The disease is caused by a positive-strand enveloped RNA virus closely related to lactate dehydrogenase-elevating virus (LDEV), equine arteritis virus (EAV), and simian hemorrhagic fever virus (SHF) and will probably be classified in the family Arteriviridae. 4,17,20 To determine the effect of age on disease, l-, 4-, and 10-week-old pigs were intranasally exposed to PRRSV. Hematologic alterations, onset and duration of vireFrom the Departments of Veterinary Diagnostic Medicine (Rosmia, routes of virus shedding, antibody production, and gross and microscopic lesions were evaluated. Materials and methodsAnimals. Thirty-two pigs (16 4-wk-old pigs and 16 10-wk-old pigs) and 2 sows with litters (each litter containing 9 1-wk-old piglets) were obtained from a swine herd seronegative for PRRS. The source herd was also seronegative for antibodies to pseu...

Mycoplasma hyopneumoniae is the principal aetiological agent of enzootic pneumonia (EP), a chronic respiratory disease that affects mainly finishing pigs. Although major efforts to control M. hyopneumoniae infection and its detrimental effects have been made, significant economic losses in pig production worldwide due to EP continue. M. hyopneumoniae is typically introduced into pig herds by the purchase of subclinically infected animals or, less frequently, through airborne transmission over short distances. Once in the herd, M. hyopneumoniae may be transmitted by direct contact from infected sows to their offspring or between pen mates. The 'gold standard' technique used to diagnose M. hyopneumoniae infection, bacteriological culture, is laborious and is seldom used routinely. Enzyme-linked immunosorbent assay and polymerase chain reaction detection methods, in addition to post-mortem inspection in the form of abattoir surveillance or field necropsy, are the techniques most frequently used to investigate the potential involvement of M. hyopneumoniae in porcine respiratory disease. Such techniques have been used to monitor the incidence of M. hyopneumoniae infection in herds both clinically and subclinically affected by EP, in vaccinated and non-vaccinated herds and under different production and management conditions. Differences in the clinical course of EP at farm level and in the efficacy of M. hyopneumoniae vaccination suggest that the transmission and virulence characteristics of different field isolates of M. hyopneumoniae may vary. This paper reviews the current state of knowledge of the epidemiology of M. hyopneumoniae infection including its transmission, infection and seroconversion dynamics and also compares the various epidemiological tools used to monitor EP.

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Little is known about the participation of beta chemokines in inflammatory processes within the central nervous system. The release of three of these peptides (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and monocyte chemoattractant protein-1) from human fetal microglial cell and astrocyte cultures was assessed following stimulation by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha. Although striking differences were found between these two types of glial cells in their responsiveness to lipopolysaccharide and cytokines, both microglia and astrocytes produced all three beta chemokines. Only microglial cells, however, demonstrated an increased migratory response to the beta chemokines. The results of this in vitro study suggest that beta chemokines may play an important role in the trafficking of mononuclear phagocytes within the brain.

Various conditions were evaluated and modified to improve the sensitivity of the serum neutralization (SN) test for detecting antibody in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). Higher SN titers were consistently obtained by the addition of 20% fresh swine serum to the virus diluent and by the use of a permissive cell clone (MARC-145) derived from the MA-104 cell line. Test sera used to assess the SN test were obtained from 2 groups of 3-week-old pigs infected intranasally with PRRSV (MN-1b). Using the modified method, SN antibody was first detected 9-11 days postinoculation (PI), with a peak evident at 11-21 days PI. The antibody subsequently declined, and a second peak was observed between 41 and 45 days PI. The first antibody peak was not observed and the SN antibody was only detectable between 32 and 41 days PI when the test was done with 20% heated swine serum or without supplemental swine serum. The SN antibody during 2-3 weeks PI was found to be sensitive to 2-mercaptoethanol or anti-swine IgM treatment. The SN antibody titers were high when homologous PRRSV isolate was used in the test but were markedly low for heterologous PRRSV isolates. No difference in antibody titers was observed when homologous and heterologous PRRSV isolates were tested by indirect fluorescent antibody assay. These results indicate that the modified SN method is useful in detecting earlier and higher PRRSV antibody and that it can differentiate among PRRSV isolates.

Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.