Comments on the letter by Ribeiro et al.: impairment of parasympathetic-mediated autonomic modulation of the heart in Chagas' cardiomyopathy: parasympathetic modulation vs. tonus.

Chagas' disease is complex immune-mediated disease originated after Trypanosome cruzi transmission, and a major cause of heart failure in Latin American continent. Auto-antibodies directed to type 2 muscarinic parasympathetic (M2) receptors seem to play key roles on the pathogenesis of heart disease, in particular in the impairment of the cardiac autonomic modulation. When talking about M2 agonistic effects, one should first argue about the differences between the terms 'modulation' and 'tonus' before describing possible autonomic influences on the heart.

Vitamin E deficiency enhances pathology in acute Trypanosoma cruzi-infected rats.

Micronutrient malnutrition is usually highly prevalent in areas endemic for Chagas disease. Nevertheless, the contribution of micronutrient deficiency to the immunopathology of this infection is often overlooked. In the present work, we assessed the effects of vitamin E deficiency on acute Trypanosoma cruzi (Y strain) infection of Holtzman rats. At 20 days post infection, vitamin E deficiency induced changes in leukocyte levels and exacerbated the myocarditis and sympathetic denervation of ventricular hearts. Vitamin E-deficient infected rats displayed significant leukopenia, evidenced by the decline in the numbers of CD45RA(+)CD3(-) B-cells and CD3(+)CD4(+) T-lymphocytes in the peripheral blood compared with infected control rats. In contrast, vitamin E deficiency induced monocytosis as well as an increased differentiation rate of monocytes to macrophages, as revealed by immunohistochemical analysis.

Cyclophosphamide-induced immunosuppression protects cardiac noradrenergic nerve terminals from damage by Trypanosoma cruzi infection in adult rats.

Trypanosoma cruzi-infected juvenile rats develop severe cardiac sympathetic denervation in parallel with acute myocarditis. This aspect has not been studied in adult rats, thought to be resistant to this infection. The mechanism involved in T. cruzi-induced neuronal damage remains to be completely elucidated. In juvenile rats, the mortality during the acute phase depends on T. cruzi populations, ranging from 30% to 100%. Therefore, studies of mechanisms through hazardous procedures such as immunosuppression are restricted. The current paper shows that adult rats infected with T. cruzi (Y strain) develop severe acute myocarditis and cardiac sympathetic denervation, despite null mortality and virtual absence of patent parasitaemia followed by negative haemoculture. Recovery from the myocarditis and denervation occurred but PCR studies showed persistence of parasite DNA at least until day 111 post inoculation. Immunosuppression by cyclophosphamide treatment increased the parasitaemia, prevented the acute myocarditis and the sympathetic denervation without significant alteration of the myocardial parasitism. These results argue against a direct role for parasite-derived products and implicate the inflammatory cells in the denervation process. As previous studies in juvenile animals have discarded an essential role for radiosensitive cells, the macrophages remain as the possible effectors for the T. cruzi-induced neuronal damage.

Autonomic dysfunction in Chagas disease: lack of participation of the vagus nerve.

To evaluate the possible role of the vagus nerve in the development of the dysautonomia in Chagas disease, we examined 18 nerves from chagasic patients and 8 from non-chagasic patients, autopsied at the Department of Pathology, Ribeirão Preto School of Medicine, Brazil. Histological analysis showed mild inflammatory infiltrate composed predominantly of T lymphocytes, in epi-, peri- and endoneurium. No parasites were observed. Semithin sections showed swollen unmyelinated fibres, occasional thinly myelinated fibres, degenerated and atrophic axons, related to myelinated fibres. These findings were confirmed by electron microscopy, and in teased fibres. The changes were observed both in chagasic and in non-chagasic patients. Statistical analysis of the morphometric findings (myelinated fibre density, axonal and fibre diameters) failed to show significant differences between the 2 groups. The frequency of myelinated fibres of various diameters was also similar in the 2 groups. The morphological and morphometrical findings in chagasic patients are mild, non-specific, and could be related to the age of the patients, or with artefacts, since they have also been observed in non-chagasic patients. Retrograde changes due to the ganglionic lesions in the innervated organs cannot be completely ruled out. Our results do not allow us to implicate the vagus nerve in the dysautonomia in Chagas disease.

[Severe forms of eosinophilic meningitis in infants of Mayotte. Apropos of 3 cases]. / Formes graves de méningites à éosinophiles chez le nourrisson à Mayotte. A propos de 3 observations.

BACKGROUND: Eosinophilic meningitis caused by Angiostrongylus cantonensis is widespread in Southeast Asia and the Pacific islands. Adults develop transient meningitis with a benign course, whilst severe or fatal disease may occur in pediatric patients. CASE REPORTS: Three infant girls, aged 8 to 11 months, living on the island of Mayotte, developed fever, hypotonia, coma (2 cases), and, for one of them, seizures. Eosinophilia was detected in the peripheral blood and cerebrospinal fluid. Secondary, flaccid quadraplegia (1 case) or paraplegia (2 cases) with absence of deep tendon reflexes, urinary retention and anal incontinence were noted. Three patients had autonomic dysfunction. Computerized tomography showed enlarged ventricles and cerebral subarachnoid spaces. One patient had sequelae. Two patients could not be followed. Retrospectively, the diagnosis of angiostrongylus infection was established for two infants by a serological study. CONCLUSION: We report three new cases of infants with severe Angiostrongylus cantonensis infection in the French island of Mayotte (Comoro Islands). In this Indian Ocean area, eosinophilic meningitis seems to occur exclusively in infants and with severe radiculomyeloencephalitic forms.

Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study.

To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo.