Chagas disease in bone marrow transplantation: an approach to preemptive therapy.

The efficacy of preemptive therapy was evaluated in bone marrow transplantation (BMT) recipients associated with Chagas disease (CD). The criterion to include patients in the protocol was the serological reactivity for CD in recipients and/or donors before transplant. After BMT, the monitoring was performed using the direct Strout method (SM), which detects clinical levels of Trypanosome cruzi parasitemia, and CD conventional serological tests. Monitoring took place during 60 days in ABMT and throughout the immunosuppressive period in allogeneic BMT. Reactivation of CD was diagnosed by detecting T. cruzi parasites in blood or tissues. In primary T. cruzi infection, an additional diagnostic criterion was the serological conversion. A total of 25 CD-BMT patients were included. Two ABMT and four allogeneic BMT recipients showed CD recurrences diagnosed by SM. One patient also showed skin lesions with T. cruzi amastigotes. Benznidazole treatment (Roche Lab), an antiparasitic drug, was prescribed at a dose of 5 mg/kg/day during 4-8 weeks with recovery of patients. Primary T. cruzi infection was not observed. This report proves the relevance of monitoring CD in BMT patients and demonstrates that preemptive therapy was able to abrogate the development of clinical and systemic disease.

Recipients and donors of bone marrow transplants suffering from Chagas' disease: management and preemptive therapy of parasitemia.

We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.

Leishmania (Viannia) braziliensis: biological behavior in golden hamsters of isolates from Argentine patients.

This study reports intraspecific variations of native isolates of Leishmania (Viannia) braziliensis from patients with leishmaniasis from Salta, Argentina. These isolates induced skin lesions in golden hamsters, initially showing rapid development, reaching their largest size between 28 and 35 days postinfection (PI). Thereafter, the infections were self-limiting and total regression was observed at 80-150 days PI. The majority of the native isolates were characterized by low infectivity in the experimental animals, and a classic pattern of dissemination to systemic organs was established. However, unusual features for L. braziliensis were displayed by two isolates; one showed evidence of high infectivity in hamsters characterized by a short prepatent period and larger, severe and persistent lesions at the inoculation site. The other isolate, of low infectivity, showed cutaneous metastasis and recurrent systemic dissemination in the same animals, suggesting dissociation between infectivity and pathogenicity. Metastasis has been frequently described in hamsters infected with L. (V) guyanensis and L. (V) panamensis, but not in infections induced by L. (V) braziliensis, as was observed in this study. Active and/or regressive histopathologic lesions were observed, depending on the stage of the infection. An exudative and mixed inflammatory pattern with microabscesses and necrotic areas was observed during early infection, while well-defined granulomas and collagen formation were the predominant features detected at a later time. Amastigotes were easily detected in the tissues, although in low numbers. Schaumann bodies were always detected. The characterization of the unique features of these native isolates, and the verification of their reproducibility in vitro and in vivo will be useful tools in tests related to immunoprophylaxis and chemotherapy.

Natural Trypanosoma cruzi infection in dogs of endemic areas of the Argentine Republic.

The population dynamics and the prevalence of chagasic infection of 352 dogs living in 108 rural houses infested by triatomines were studied. The region was divided into three sections according to increasing distances to an urban area. Each animal was identified by means of its particular characteristics and built, and its owners gave information about its habits. By means of xenodiagnosis, serology and ECG studies, prevalences of infection, parasitological-serological correlation, percentage of altered electrocardiographic outlines and percentage of houses with parasitemic dogs, were determined. The rural area showed a characteristic T. cruzi infection pattern and differences in the canine population parameters with respect to the other areas were observed: a higher proportion of puppies than adult dogs, a more sedentary population, higher prevalences of infection, as measured by xenodiagnosis, in dogs, and the highest proportion of bedroom insects infected with T. cruzi. It is assumed that the sedentary characteristics of the human population in that rural area impinge in the blood offer to the triatomine population, and the high percentage of parasitemic dogs of the area, contribute to the rise of "kissing bugs" infected with T. cruzi found in bedrooms.

[Clinical features and diagnosis of mucocutaneous leishmaniasis in patients of an endemic area in Salta]. / Caracteristícas clínicas y diagnóstico de la leishmaniasis mucocutanea en pacientes de un área endémica de Salta.

A total of 39 patients with a clinical diagnosis of mucocutaneous leishmaniasis, in an endemic area for leishmaniasis in Salta, Argentina, were examined between June 1990 and December 1992. Of these cases, 87% (34/39) presented the cutaneous simple form, 10.3% the cutaneous multiple form and 2.6% the mucosal form. Lesions were more frequently located in legs and arms (71.8%), followed by trunk and multiple location (10.3%). Of the patients, 43% were housewives, students or children, suggesting that the infection could be contracted in the domestic or peridomestic environment. Of 39 patients diagnosed, in 22 (56.4%) the parasite was found. Direct microscopy (smear) permitted a diagnosis in 13 (59.4%) of these 22 patients. Among these, 5 (22.7%) had positive diagnosis by culture, and 9 (40.9%) by inoculation in hamsters. Ten parasite isolates (45.4%) were obtained. The smear is recommended as a diagnostic method for epidemiological surveillance due to the sensibility demonstrated herein and its easy application in the endemic area. The time of clinical evolution, from the appearance of the lesion up to the detection of the patient by Sanitary Agents, was approximately 90 days. This would be related to the frequency of the visits, usually every 3 months. Only one of 30 treated patients had a relapse at 6 months, due to non fulfillment of the treatment.

First visceral leishmaniasis focus in Argentina.

An eight-year old boy from Posadas (27 masculine 23'S, 55 masculine 54'W) was diagnosed with visceral leishmaniasis (VL) during 2006. Lutzomyia longipalpis was discovered in the backyard of his house, while the spread of canine visceral leishmaniasis was confirmed in Posadas. This is the southernmost report of a VL transmission focus and the first in Argentina.

Trypanosoma cruzi: T-cell-dependent mechanisms of resistance during chronic infection.

Effector mechanisms of resistance exerted by T cells from BALB/c mice chronically infected with Trypanosoma cruzi, Tulahuén strain, were studied. Spleen cells from chronically infected mice (Chro-SC) prestimulated with heat-killed trypomastigotes (HKT) and/or IL-2 destroyed PHA-labeled p-815 mastocytoma cells, HKT-pulsed macrophages, and normal peritoneal macrophages. However, HKT-stimulated Chro-SC did not affect the infectivity of free bloodstream forms of the parasite. Upon HKT stimulation, Chro-SC or their culture supernatant activated peritoneal macrophages for the destruction of intracellular amastigotes. The effect was abolished after Thy 1.2+ cell depletion. The addition of Cyclosporin A (CyA), which blocks T-cell activation, during HKT-stimulation of Chro-SC, diminished their ability to activate the trypanocidal activity of macrophages. CyA also inhibited the production of both macrophage-activating factors and interferon-gamma by HKT-stimulated Chro-SC. CyA administration to recipients of nylon-wool nonadherent spleen cells from chronically infected mice inhibited their adoptively acquired resistance against T. cruzi, suggesting that the conferred resistance depended on the effect of specifically activated cells. When administered during the chronic stage of the infection, CyA abrogated the antigen-specific delayed type hypersensitivity response but increased the levels of anti-T. cruzi IgG antibodies. Neither parasitemia, tissular parasitism in myocardium or skeletal muscle, nor mortality were detected after CyA treatment, suggesting the presence of a CyA nonsensitive mechanism(s) in the control of T. cruzi during the chronic phase of the infection.

Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys.

Twenty young male Cebus apella monkeys were infected with CA1 Trypanosoma cruzi strain and reinfected with CA1 or Tulahuen T. cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CA1 strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were performed with the virulent Tulahuén strain or high doses of CA1 strain. Clinical, electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic chronic myocarditis. All monkeys survived and no mortality was observed.

Reactivation of chronic Chagas' disease following allogeneic bone marrow transplantation and successful pre-emptive therapy with benznidazole.

This report shows the early detection of reactivation of chronic Chagas' disease (CCd) in a 27-year-old man with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation (ABMT). Pre-emptive therapy with benznidazole during a period of 7 weeks led to a rapid recovery of the patient, who remains free of parasitemia 2 years after the bone marrow transplantation.

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.

First visceral leishmaniasis focus in Argentina

An eight-year old boy from Posadas (27º 23'S, 55º 54'W) was diagnosed with visceral leishmaniasis (VL) during 2006. Lutzomyia longipalpis was discovered in the backyard of his house, while the spread of canine visceral leishmaniasis was confirmed in Posadas. This is the southernmost report of a VL transmission focus and the first in Argentina.

Anatomía aplicada de los senos esfenoidales: Consideraciónes clínico - quirúrgicas / Applied anatomy of the Sphenoid sinuses: Clinico - surgical considerations

Este trabajo resume los hallazgos obtenidos del estudio de cincuenta senos esfenoidales en material cadavérico, a través de al disección y la utilización de TAC. Se hallaron variedades en la localización, forma y tamaño de los mismos. Estas variaciones en la anatomía, provocan cambios en la relación de los enos con estructuras anatómicas de trascendental importancia en cirugía, tales como el nervio óptico, la arteria carótida intracavernosa, el nervio maxilar, el nervio pterigoideo y el nervio vidiano. Se remarca la importancia de este conocimiento anatómico para evitar complicaciones en la cirugía de la región selar por vía transesfenoidal, del clivus o del vértice orbitario.

Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys

Twenty young male Cebus apella monkeys were infected with CAl Trypanosoma cruzi strain and reinfected with CA l or Tulahuen T.cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CAl strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were perfomed with the virulent Tulahuén strain or high doses of CAl strain. Clinical electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic myocarditis. All monkeys survived and no mortality was observed.