An outbreak of human Leishmania (Viannia) braziliensis infection

The occurence of acute cutaneous leishmaniasis among inhabitants of 10 farms within 10 Km of the hamlet of Corte de Pedra, Bahia, Brazil was studied prospectively from 1984-l989. A mean population of 1,056 inhabitants living in 146 hourses were visited every 6 months and the numberof sKin ulcers recorded. A leishmanin skin test survey was done people with suggestive skin scars or active disease in l984. The incidence of skin ulcers due to Leishmania (Viannia) brasiliensis (Vlb) reached 83/1,000 inhabitants but declined sharply in the subsequent 2 years. Retrospective data shows that leishamiasis is a sporadic endemic disease. Although the reasons for this epidemic are unclear some possible aetiological factors are discussed

An outbreak of human Leishmania (Viannia) braziliensis infection.

The occurrence of acute cutaneous leishmaniasis among inhabitants of 10 farms within 10 Km of the hamlet of Corte de Pedra, Bahia, Brazil was studied prospectively from 1984-1989. A mean population of 1,056 inhabitants living in 146 houses were visited every 6 months and the number of skin ulcers recorded. A leishmanin skin test survey was done people with suggestive skin scars or active disease in 1984. The incidence of skin ulcers due to Leishmania (Viannia) braziliensis (Lvb) reached 83/1,000 inhabitants but declined sharply in the subsequent 2 years. Retrospective data shows that leishmaniasis is a sporadic endemic disease. Although the reasons for this epidemic are unclear some possible aetiological factors are discussed.

[Spontaneous healing of leishmaniasis caused by Leishmania viannia braziliensis in cutaneous lesions]. / Cura espontânea da leishmaniose causada por Leishmania viannia braziliensis em lesões cutâneas.

In field clinics in the communities of Três Braços and Corte de Pedra, Bahia, we have attended 1.416 patients with tegumentary leishmaniasis in fourteen years, the predominant species in transmission is Leishmania Viannia brasi liensis (LVB). Because of the danger of metastasis with this infection treatment was routinely recommended with Glucan-time. However sixteen patients refused injection therapy and six women were pregnant when seen and not treated. All patients were followed up in our clinic. All these patients closed their skin ulcers although one subsequently relapsed. Patients were followed up for variable periods (four to twelve years), after the diagnosis. In nine patients (40.9%) of the cohort, the time to healing after initiation of the lesion was calculated as six months of evolution. At twelve months, nineteen patients (86.3%) had complete healing of their lesions. In three patients an active lesion was present for longer than one year. The determinants of this variable natural evolution of human LVB lesion remains completely unknown. It is difficult for us to understand and compare the effects of therapeutic agents in mucocutaneous leishmaniasis.

[Information-related changes in attitude to mucocutaneous leishmaniasis of a population from an endemic region of the south of Bahia]. / Mudança do componente cognitivo da atitude de uma população de região endêmica do Sul da Bahia diante da leishmaniose tegumentar.

The mutilant nature of the mucosal form of leishmaniasis can cause alterations in personal relations. To identify the level of understanding of leishmaniasis and the psychological reaction to it patients and houseowners in an endemic area of Bahia were interviewed. Several false beliefs were identified and there was a strong tendency to reject mutilated patients among the population for a false fear of contagion. Possibly future clarification of the real nature of leishmaniasis could change such a negative attitude among the resident population.

Effect of very high-dose thymidine infusions on leukemia and lymphoma patients.

The physiological pyrimidine nucleoside thymidine (dThd) is cytotoxic to normal and neoplastic cells in culture that are exposed to concentrations in excess of 1 mM for prolonged periods. In order to explore the antileukemic potential of the compound, we have treated six patients with relapsed leukemia or lymphoma with marrow and blood involvement, by prolonged infusions of dThd, at dosages of 90 to 240 g/sq m/day for 14 to 29 days. Mean plasma dThd concentration ranged from 3.8 to 5.5 mM. Cerebrospinal fluid levels were measured on three occasions and ranged from 2 to 23.5% of simultaneous plasma levels. Diarrhea was dose limiting in one patient. The other side effects included nausea and vomiting in all patients, hepatotoxicity in two patients, electrolyte imbalance in one, progression of a pericardial effusion to tamponade in one, and mild central nervous system toxicity in five. In all cases, this therapy produced bone marrow aplasia. One patient with acute lymphoblastic leukemia, refractory to prior treatment, achieved a complete remission which lasted for 16 weeks. Another patient with lymphoblastic lymphoma had a greater than 50% reduction in his mediastinal mass which lasted for less than 1 month. At multiple points during therapy, the bone marrow S-phase fraction was measured by flow cytometry and autoradiography. In five patients, the proportion of cells in S phase increased during the first few days of the infusion but then returned to base line, concomitant with an overall reduction in the number of bone marrow blasts. Cytoreduction was evaluated by the technique of W. Hiddemann, B. D. Clarkson, T. Buchener, M. R. Melamed, and M. Andreeff (Blood, 59: 216-225, 1982). The magnitude of tumor cell kill ranged from 0.7 to 3.6 logs of blasts/cu mm of bone marrow. The data demonstrate that dThd is able to induce a complete remission in a patient with acute leukemia previously refractory to treatment. However, because of the very large drug quantities, fluid volumes, and the prolonged course required to produce the necessary tumor cell kill, this treatment approach is too impractical to be used extensively.

Thymidine as a kinetic and biochemical modulator of 1-beta-D-arabinofuranosylcytosine in human acute nonlymphocytic leukemia.

We have carried out a clinical trial in which patients with relapsed leukemia were treated with thymidine (dThd) prior to and concomitantly with the administration of 1-beta-D-arabinofuranosylcytosine (ara-C) in an effort to kinetically and biochemically modulate the leukemic cells with two objectives: (a) to increase the S-phase fraction before giving ara-C; and (b) to increase the uptake and phosphorylation of ara-C. Six patients with acute nonlymphocytic leukemia who had relapsed after conventional or experimental therapy were given continuous i.v. infusions of dThd in conjunction with ara-C. dThd was started at 75 g/sq m/day (producing 1 mM plasma levels) and was given for 5 to 8 days until the proportion of bone marrow cells in S-phase (measured by autoradiography and flow cytometry) had increased and/or stabilized; then ara-C at 200 mg/sq m/day was begun. Twenty-four hr after initiation of ara-C therapy, the dThd dose was reduced to 30 g/sq m/day (plasma dThd, 0.1 to 0.6 mM). Both drugs were continued for 6 to 12 days until marrow aplasia or unacceptable toxicity occurred. Four patients with a base-line labeling index lower than 30% experienced a sustained increase in the S-phase fraction; two patients with a base-line labeling index higher than 30% experienced a reduction in the S-phase compartment during dThd infusion, in one case followed by an increase. The degree of S-phase arrest did not correlate with remission induction. In 5 patients, the flash incorporation of labeled ara-C into nucleoside triphosphate and deoxycytidine into DNA of bone marrow cells was measured. Three patients had a significant increase in the incorporation of deoxycytidine into DNA. Two of them achieved a complete remission. Increases in ara-C uptake were less impressive. A new technique was used to measure the absolute number of blasts present in the bone marrow. A decrease in leukemic cells between 0.9 and 2.6 logs10/mm was found at the end of the infusions. Three patients experienced greater than 2-log reduction. Two of them entered complete remission that lasted 6 weeks and 3 months, respectively. These correlations should be interpreted with caution because of the small number of patients treated. This study suggests that dThd, although of very limited therapeutic value by itself, may have potentiated the antitumor activity of ara-C to some extent. Whether this effect is of significance can only be determined by further studies.

Phase I and clinical pharmacological evaluation of biochemical modulation of 5-fluorouracil with N-(phosphonacetyl)-L-aspartic acid.

5-Fluorouracil (FUra) is a clinically useful antineoplastic agent. Preclinical studies suggest that the therapeutic effects of FUra can be enhanced by pretreatment with N-(phosphonacetyl)-L-aspartic acid (PALA), an inhibitor of aspartate transcarbamylase. The objective of treatment with PALA is to increase the activation of FUra by inhibiting the normal pathway of de novo pyrimidine biosynthesis. Theoretically, the optimal dose of PALA should produce effective blockade of this pathway without increasing toxic effects of FUra. Using pyrazofurin-induced orotic aciduria and orotidinuria as a measure of this pathway, it as determined that PALA (250 mg/sq m) is effective in inhibiting total-body pyrimidine synthesis. Sixty-eight adult patients with cancer were treated with combinations of PALA and FUra. High doses of PALA (1 to 2 g/sq m) prevented the use of full dosage of FUra; however, PALA (250 mg/sq m) can be administered 24 hr before FUra (750 mg/sq m) once weekly for at least 3 weeks. The toxicity observed using that combination of doses was mild to moderate myelosuppression, mucositis, diarrhea, nausea, and vomiting. Further clinical studies are warranted.