First Month Of Infection Research Articles

Experimental Chronic Lyme Borreliosis in Lewis Rats

The course of Lyme borreliosis in LEW/N rats inoculated intraperitoneally as infants with 10(6) Borrelia burgdorferi was followed for 360 days. Spirochetes were detected in the blood through 30 days, in the brain through 60 days, and persisted in the spleen, liver, kidneys and articular tissue through 360 days. Acute exudative arthritis, tendonitis, and bursitis were evident in multiple joints by day 30. Arthritis regressed thereafter but capsular fibrosis and lymphoplasmacytic infiltrates persisted throughout the study. Several rats developed exacerbations of acute arthritis within days 180-360, a pattern similar to that encountered in human Lyme disease. Rats had a high prevalence of nonsuppurative myocarditis and vasculitis during days 90-360. Spirochetes were visualized by microscopy in joints and other tissues during the first month of infection, but were seen only sporadically thereafter. All rats seroconverted to B. burgdorferi by day 30. IgM titers persisted and IgG titers rose progressively through day 360. Immunoblots revealed IgM reactivity to a single 41 kDa protein until 360 days, when reactivity to a 60 kDa protein emerged. IgG reactivity occurred against progressively more proteins with time, indicating continued antigenic stimulation. Chronic and recurrent arthritic lesions and myocardial involvement suggest that the rat is a reliable model for further investigation.

Chronic murine toxoplasmosis: clinicopathologic characterization of a progressive wasting syndrome

Nya:NYLAR albino mice infected with Toxoplasma gondii gradually developed a chronic and progressive wasting syndrome characterized by facial and body alopecia, corneal opacities, necrotic lesions of ears and tail, signs of neurologic disease and death within six to eight months after infection. Haematologic changes included a transient normochromic, normocytic anaemia, and persistent lymphopenia and neutrophilia. Changes in serum proteins were manifested by hypoalbuminaemia and pronounced hypergammaglobulinaemia. Serum thyroxine concentrations fell sharply during the first month of infection, then gradually returned to control concentrations. Gross changes included loss of body weight, hepatosplenomegaly, ovarian and uterine atrophy, and a marked involution of the thymus. The predominant histopathologic change in the brain was a mononuclear cell vasculitis, particularly affecting the hippocampus and the choroid plexus, ependyma, and periventricular areas of the lateral and third ventricles. These preliminary observations indicate that mice can serve as a practical animal model of great potential for study of the pathogenesis of chronic toxoplasmosis.

The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice.

Theiler's murine encephalomyelitis virus (TMEV) gives rise to a biphasic disease of the central nervous system (CNS) following intracranial inoculation of susceptible strains of mice. The early phase, during the first month, resembles poliomyelitis and in the late phase the mice suffer from inflammatory demyelination reminiscent of multiple sclerosis. In order to investigate the role of helper T cells in the acute and chronic phases of the disease we depleted mice of their L3T4 T cells in vivo with rat monoclonal antibodies, prior to infection and prior to the onset of clinical signs of demyelination. Mice depleted of their helper cells failed to produce antibodies to TMEV and consequently were unable to clear virus from the CNS and died within the first month of infection. Depletion of T cells before the demyelinating phase of the disease resulted in a marked decrease in the incidence of disease from 77% of the immunocompetent animals with clinical signs of paralysis to 36%. Immunocompetent TMEV-infected mice also developed antibodies against myelin suggesting that autoimmune mechanisms may play a role in TMEV-induced demyelination.

Serum IgG antibodies in patients with cystic fibrosis with early Pseudomonas aeruginosa infection.

Serum IgG antibodies to Pseudomonas aeruginosa surface antigens were measured by enzyme linked immunosorbent assay in all patients with cystic fibrosis from whom P. aeruginosa was isolated for the first time during a study period of 18 months. In 15 patients the titre of serum IgG antibodies was greater than control values before or at the time of the first bacteriological isolation of P. aeruginosa. The presence of serum antibodies specific to P. aeruginosa suggests exposure to infection by that organism for some months before its isolation in significant numbers from the respiratory tract. In the other two patients serum titres were within the control range before isolation of P. aeruginosa but had increased to above the control range within the next month. Longitudinal studies on the entire group of patients showed further increases in titre concurrently with further isolations of P. aeruginosa. These results suggest that this assay may be an indicator of the beginning of pulmonary infection by P. aeruginosa and may prove to be a sensitive monitor of the progress of infection, and response to treatment, during the first months of infection by that organism.

Phospholipase B in the brains and meninges of nonsensitized and sensitized rats after challenge with Angiostrongylus cantonensis.

After a primary infection with 100 Angiostrongylus cantonensis larvae, infected rats showed elevated phospholipase B activity in meningeal and brain homogenates beginning with the first week and continuing through the first month of infection. The rise in phospholipase B values through the first 4 weeks, with a prolonged peak spanning days 30 to 31, coincided with the invasion and maturation of the parasites in the brain, and the ensuing sharp decline in phospholipase B levels, shown by the readings on day 45, coincided in turn with the known migration of the worms from the brain to the lungs, which begins about 5 weeks after infection. In the meninges, the pattern of enzyme elevation was generally similar to that in the brain samples except that the highest activity was seen earlier at days 8 to 9, followed by a gradual decline by days 30 to 31 and a sharper drop by day 45. Rats challenged with 100 larvae 53 days after the primary infection exhibited an almost immediate rise of phospholipase B activity in both the brain and meninges; the peaks of activity occurred at day 1 for the meninges and day 25 for the brain, and levels above control values were still present at day 50. Comparison of the total enzymatic content of the cerebral tissue and meninges revealed that a remarkably high proportion of the phospholipase B activity was contained in the meninges. The inference that elevated levels of this enzyme in the cerebral tissue of A. cantonensis-infected rats are due to inflammatory reactions within the meningeal envelopes was confirmed by histochemical demonstration of specific sites of enzymatic activity limited to the meninges. It is of interest that 80% of the cells positive for the enzyme were clearly identifiable as eosinophils since an association of bone marrow eosinophilia and high phospholipase B levels in rats infected with A. cantonensis was shown in our earlier study of rats infected with this parasite.

Nonspecific suppressor cell activity and specific cellular unresponsiveness in rat schistosomiasis.

AbstractSpleen cells from inbred Fischer rats infected with Schistosoma mansoni were cultured with S. mansoni antigen, phytohemagglutinin (PHA) or concanavalin A (Con A). During the first 3 weeks of infection, both a significant proliferative response and a delayed cutaneous hypersensitivity to S. mansoni antigen were observed. In contrast, during the fourth to the seventh week both responses were reduced to a nonsignificant level, and the proliferative response to PHA or Con A also decreased during this period. At the time of minimal reactivity to PHA or Con A, the depletion of cells adherent to nylon wool (but not depletion of mononuclear phagocytic cells by plating on plastic) restored a significant response to Con A. At this time, infected rat lymphocytes reduced the proliferative response of noninfected syngeneic cells induced by Con A. This inhibition was not observed when infected cells were previously passed through a nylon wool column. Inversely, nylon wool depletion of day‐28 or 35‐infected spleen cells did not restore lymphocyte response to S. mansoni antigen. Serum (or the dialyzable fraction thereof) from day‐29‐infected rats inhibited thymidine incorporation of PHA‐stimulated normal lymphocytes and the response to S. mansoni of spleen cells from infected rats. This information suggests that at the end of the first month of infection in the rat, lymphocyte unresponsiveness to S. mansoni antigen could not be related to a demonstrable suppressor cell activity. Low molecular weight inhibitory factor(s) released by the parasite and acting directly on lymphocytes could partly account for this unresponsiveness in rat schistosomiasis.