Neuroinvasion of Toxocara canis- and T. cati-larvae mediates dynamic changes in brain cytokine and chemokine profile.

BACKGROUND: Neurotoxocarosis (NT) is induced by larvae of the dog or cat roundworm (Toxocara canis or T. cati) migrating and persisting in the central nervous system of paratenic hosts, including humans, and may be accompanied by severe neurological symptoms. Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis, but detailed data on pathogenic mechanisms and involvement of signalling molecules during cerebral Toxocara species infections are scarce. METHODS: To elucidate alterations in immunomodulatory mediator pattern, comprehensive multiplex bead array assays profiling comprising 23 different cytokines and chemokines were performed during the course of T. canis- and T. cati-induced NT. To this end, cerebra and cerebella of experimentally infected C57Bl/6 J mice serving as paratenic host models were analysed at six different time points (days 7, 14, 28, 42, 70 and 98) post infectionem (pi). RESULTS: Brain-body mass ratios of T. canis and T. cati-infected mice were significantly lower than those of the uninfected control group at day 14 pi, and also at day 28 pi for T. canis-infected mice. Both infection groups showed a continuous decrease of pro-inflammatory cytokine concentrations, including TNF-α, IFN-γ, GM-CSF and IL-6, in the cerebrum over the course of infection. Additionally, T. canis but not T. cati-induced neurotoxocarosis was characterised by significantly elevated levels of anti-inflammatory IL-4 and IL-5 in the cerebrum in the acute and subacute phase of the disease. The higher neuroaffinity of T. canis led to a prominent increase of eotaxin and MIP-1α in both the cerebrum and cerebellum, while in T. cati-infected mice, these chemokines were significantly elevated only in the cerebellum. CONCLUSIONS: The direct comparison of T. canis- and T. cati-induced NT provides valuable insights into key regulatory mechanisms of Toxocara species in paratenic hosts. The cerebral cyto-/chemokine milieu is shifted to a predominantly anti-inflammatory immune response during NT, possibly enabling both survival of the parasite and the neuroinfected paratenic host. Alteration of eotaxin and MIP-1α concentrations are congruent with the higher neuroaffinity of T. canis and species-specific tropism of T. canis to the cerebrum and T. cati to the cerebellum.

Biochemical and immunopathological changes in experimental neurotoxocariasis.

Toxocariasis is a widespread soil-transmitted parasitic disease. Toxocara canis larvae migrate through the tissues with a special predilection for the central nervous system. Recently, neurotoxocariasis is being diagnosed in humans with increasing frequency due to improved diagnostic tools. The present study aimed at exploring the biochemical and immunopathological alterations in the brain in experimental T. canis infection. For this purpose, 75 Toxocara-infected mice were sacrificed at 2, 5, and 16 weeks post-infection. The brains were removed and assayed for total larval count, pro-inflammatory cytokines (TNF-alpha, IL-6), and central neurotransmitters (gamma-aminobutyric acid, glutamate, dopamine, norepinephrine, and serotonin). Brain sections were also stained for histopathological study, and for assessment of the expression of inducible nitric oxide synthase (iNOS), and glial fibrillary acidic protein (GFAP) by immunohistochemical methods. We found that larval recovery showed progressive increase over the course of infection. Furthermore, the infected mice displayed increased expression of pro-inflammatory cytokines and iNOS, as well as significant disturbances in neurotransmitter profile. Astrocytic activation, evidenced by enhanced expression of GFAP, was also manifest in infected animals. These changes were maximal in the chronic stage of infection or intensified over time. In conclusion, experimental neurotoxocariasis is associated with significant biochemical, immunological, and pathological changes.

Strongyloides stercoralis hyperinfection: difficulties in diagnosis and treatment.

Immunocompromised patients who are infected with Strongyloides stercoralis may develop a potentially fatal auto-infection syndrome characterised by non-specific pulmonary and gastrointestinal symptoms and Gram negative sepsis. We present the case of one such patient who underwent a negative laparotomy for a presumed intra-abdominal surgical catastrophe with a subsequent protracted stay on the intensive care unit. Once the diagnosis of strongyloidiasis was made, the patient was successfully treated with subcutaneous antihelminthic drugs. With appropriate screening for and eradication of strongyloides in those with immune compromise, or in those about to start immunosuppressive therapy, potentially fatal episodes of hyperinfection could be avoided. In the absence of screening, severe strongyloidiasis should be suspected in immunosuppressed individuals who have travelled to or resided in an endemic area and present with the characteristic features. Awareness of the signs of hyperinfection amongst those involved in acute care could prevent unnecessary morbidity and mortality in these patients.

[C3c activation and intrathecal biosynthesis in children suffering from eosinophilic meningoencephalitis due to Angiostrongylus cantonensis]. / Activación y biosíntesis intratecal de C3c en niños con meningoencefalitis eosinofilica por Angiostrongylus cantonensis.

INTRODUCTION: Eosinophilic meningoencephalitis due to Angiostrongylus cantonensis is an emergent infectious disease in our area. The objective of the present paper is to determine if the activation of the complement system was taken placed with the C3c production in cerebrospinal fluid. PATIENTS AND METHODS: 14 patients with an average age 4.5 years were studied. In such patients a lumbar punction was performed. C3c was quantified in serum and cerebrospinal fluid by radial immunodiffusion. RESULTS: Median cell number was 396 x 10(-6)/L with an average of 8.8% of eosinophils. Main symptoms were headache, vomiting and fever. Meningeal signs were present in 50% of the patients. C3c intrathecal synthesis occurred in 13 patients (92.8%). CONCLUSION: It was demonstrated the participation of complement system in third-stage larvae destruction in cerebrospinal fluid.

Central nervous system involvement in Chagas disease: a hundred-year-old history.

This review gives an account of central nervous system (CNS) involvement in Chagas disease, as confirmed by pathological studies. The fundamental histopathological finding associated with the acute nervous form of the disease is nodular encephalitis in multiple foci. CNS involvement probably does not occur in patients with the mild symptomatic acute form; or, in some cases, mild encephalitis in sparse foci may be present. Reactivation of chronic Chagas disease (reactivated acute nervous form), although uncommon, has been reported in immunosuppressed patients with malignant neoplasms of the hematopoietic-lymphoid system, after renal, heart and bone marrow transplantation and especially after the emergence of AIDS. Three aspects differentiate CNS involvement in immunosuppressed chagasic patients from the neuropathological picture described in the acute nervous form: the encephalitis in multiple foci tends to acquire a necrotizing feature; numerous amastigotes are always present; and many patients have the tumoral or pseudotumoral form (brain 'chagoma'). Ischemic cerebral changes associated with chronic chagasic cardiopathy (e.g. cerebral infarcts) are common. These changes, which are similar to those found in heart diseases with other causes, are considered secondary to hypoxemia following congestive heart failure, abrupt transitory fall of systemic arterial pressure and cerebral blood flow, cardiac arrhythmias and thromboembolism.

Apoptosis in meningoencephalitis of Angiostrongylus cantonensis-infected mice.

A hallmark of eosinophilic meningoencephalitis is infiltration of leukocytes into brain parenchyma and subarachnoid space infected by Angiostrongylus cantonensis. Apoptosis, a process that eliminates useless cells and counterbalances tissue homeostasis, is important for homeostasis of the immune system. In this study, we investigated the characteristics of cell death induced in BABL/c mice infected with A. cantonensis. We observed increased expression of the apoptotic proteins, caspase-3, caspase-8, caspase-9, and cytochrome c, and decreased expression of anti-apoptotic proteins, B-cell leukemia 2 and inhibitor of apoptosis protein 1. On immunohistochemistry, apoptotic proteins were localized within the leukocytes infiltrate. A terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling assay to detect DNA fragmentation confirmed these observations. The infiltration of leukocytes present in the brain parenchyma and subarachnoid space in vivo may also express these apoptotic regulatory molecules, which demonstrates the capacity of these cells to undergo apoptosis.

Establishment of adult Parelaphostrongylus tenuis, patent infections, and acquired immunity after experimental infection of white-tailed deer (Odocoileus virginianus) and red deer (Cervus elaphus elaphus).

Experimental Parelaphostrongylus tenuis infections were established in white-tailed deer (Odocoileus virginianus) and an atypical host, red deer (Cervus elaphus elaphus). Groups of deer were fed 10, 25, or 100 third-stage larvae (L3) of P. tenuis and received a single equivalent challenge exposure at varying intervals. Infections were monitored up to 6 yr in white-tailed deer and up to 2.8 yr in red deer. The prepatent period in white-tailed deer varied from 91 to 1,072 days (381 +/- 374) and in red deer from 105 to 358 days (167 +/- 77). Adult worms lived for up to 6 yr in white-tailed deer. Although most had patent infections until necropsy, latent periods were observed regardless of season. Adult worms lived for up to 2.8 yr in red deer, and patent infections persisted for 20-363 days (152 +/- 106). Patent infections were correlated with the presence of adult worms in blood vessels and sinuses of both deer species. Worms were restricted to the subdural space in all deer with latent and occult infections. Adult worm recovery in white-tailed deer fed 10 or 25 L3 corresponded to the mean intensities reported in natural infections of white-tailed deer Recovery from deer fed 100 L3 was not typical of natural infection intensities. Adult P. tenuis established in all groups of red deer, but neurologic disease was restricted to animals fed 100 L3. Acute neurologic disease was associated with subdural hemorrhage and occurred at 11 mo postinfection in 2 red deer. The absence of postchallenge patent periods and the persistence of occult infections indicated that challenge exposures did not establish. These data indicate that acquired immunity to P. tenuis was established by 6 mo postinfection in both white-tailed and red deer. Latent periods in white-tailed deer and latent infections in red deer reinforce the need for a reliable diagnostic assay.

The severity of mouse pathologies caused by the bird schistosome Trichobilharzia regenti in relation to host immune status.

Cercariae of the nasal bird schistosome Trichobilharzia regenti are able to penetrate into mammalian skin and migrate to the mouse central nervous system (CNS) causing tissue injury in certain cases. Our study shows that the severity of T. regenti pathologies in the CNS closely depends on the host immune status. During the primary infection of immunocompetent mice, the parasites evoked an acute inflammatory reaction in the skin and the CNS involving focal oedema and cellular infiltration of the tissue. Challenge infections resulted in the development of extensive inflammatory foci in the host skin which precluded the subsequent migration of the schistosomula to the CNS. On the other hand, during primary as well as challenge infections of immunodeficient mice (SCID), no significant immune response against the parasites was detected in any of the host organs examined; however, in contrast to immunocompetent mice, the infections were frequently manifested by severe leg paralysis.

Immunodiagnosis of human eosinophilic meningitis using an antigen of Angiostrongylus cantonensis L5 with molecular weight 204 kD.

An antigen from Angiostrongylus cantonensis fifth-stage larvae was purified by immuno-affinity chromatography with a specific monoclonal antibody. The purified antigen showed only a single band with a molecular weight of 204 kD in SDS-PAGE, and no cross-reactivity to antibodies induced by several other species of helminths were observed in ELISA. When the purified antigen was used to examine serum and cerebrospinal fluid (CSF) specimens by ELISA, the antibody levels in patients with eosinophilic meningitis or meningoencephalitis (EME) were significantly higher than those of control subjects. The antibody levels in serum were slightly higher than those in CSF, and the levels in serum were positively correlated with the levels in CSF. The reliability in detection of antibodies in serum was slightly higher than that in the detection of antibodies in CSF specimens. The purification of a specific A. cantonensis antigen and its subsequent use in the development of an ELISA for detection of A. cantonensis specific antibodies in serum specimens constitute an important step towards improvement in the accuracy of diagnosis for A. cantonensis infections.