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Cutaneous leishmaniasis in Bolivia. A study of 185 human cases from Alto Beni (La Paz Department). Isolation and isoenzyme characterization of 26 strains of Leishmania braziliensis braziliensis [corrected].

A clinical, serological, parasitological and therapeutic study of cutaneous leishmaniasis was carried out in a low sub-andean area (250-800 metres) of the La Paz Department, Bolivia. A team of seismic prospectors (350 workers) was surveyed for 12 months. Of 200 suspected cases of cutaneous leishmaniasis, 185 were serologically or parasitologically confirmed (incidence 52.8%). Those exposed to the greatest risk of infection were working in a virgin forest environment. Leishmanial organisms were isolated from 26 of the workers, either by in vitro cultivation or inoculation into hamsters. Isoenzyme characterization of the organisms by cellulose acetate electrophoresis showed them to be Leishmania braziliensis braziliensis [corrected]. The results of treatment of 168 patients with a pentavalent antimonial drug are also reported.

Animals↗

Studies on canine leishmaniasis control. 1. Evolution of infection of different clinical forms of canine leishmaniasis following antimonial treatment.

81 dogs naturally infected with Leishmania infantum in the Isle of Elba, Italy, were treated with meglumine antimoniate (Glucantime). 36 of them (45.5%) were asymptomatic cases. 4-24 months after treatment the dogs were clinically and serologically examined; the recovery rates were 47.2% for asymptomatic cases, 33.3% for oligosymptomatic cases, and 11.1% for symptomatic cases. Furthermore, treatment had prevented the development of patent disease in 90% of non-recovered asymptomatic cases, whereas it had produced only slight improvement of clinical condition in patent dogs which were still infected after drug administration. Treatment with antimonial drugs is therefore recommended in canine leishmaniasis control if non-patent or sub-clinical forms of the disease are detected by seroepidemiological surveys.

Animals↗

Studies on canine leishmaniasis control. 2. Effectiveness of control measures against canine leishmaniasis in the Isle of Elba, Italy.

A serological and parasitological survey carried out in 1985 in the Isle of Elba, Italy, revealed a high prevalence of canine leishmaniasis. This focus was considered ideal for the evaluation of effectiveness of treating infected dogs with meglumine antimoniate, applied as a control measure during 1985 and 1986. New data on prevalence were obtained for the years 1986 and 1987. Incidence of new canine leishmaniasis cases after the transmission seasons 1984, 1985 and 1986 were determined by examining 2 cohorts: cohort I, dogs born within 2 transmission seasons, and cohort II, adult dogs examined and found to be negative before each transmission season. Over 2000 tests were carried out on 1500 dogs. Prevalence analysis showed a reduction of infective dogs (symptomatic and oligosymptomatic) from 14.4% in 1985 to 5.2% in 1987. Incidence analysis showed a decrease of new cases from 12.4% after transmission season 1984 to 4.6% after transmission season 1987. The results indicate a two-thirds reduction of the disease frequency in dogs of the Isle of Elba after a 2-year period of control measures.

Animals↗

Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime.

Seventy-nine patients with cutaneous (62) or mucosal (17) infection with Leishmania (Viannia) braziliensis in Três Braços, Bahia, Brazil, were followed for at least 4 years after initiating treatment with antimony. Cutaneous relapses occurred in 6/62 (10%), mucosal relapse after cutaneous infection in 2/62 (3%), and mucosal relapse after mucosal disease in 2/17 (17%). It is concluded that relapse (cutaneous and mucosal) is rare after adequate antimony therapy and that no definite prediction of relapse (clinical, serological or by skin reaction) is possible.

Adolescent↗

A randomized trial comparing a pentavalent antimonial drug and recombinant interferon-gamma in the local treatment of cutaneous leishmaniasis.

In a randomized prospective trial N-methyl-glucamine antimoniate (Glucantime) and human recombinant interferon-gamma were infiltrated around lesions of cutaneous leishmaniasis caused by Leishmania tropica in Syria. A previous trial had shown that intradermal application of interferon-gamma promoted the healing of similar lesions in the study area. Twenty patients with 38 lesions received 1-3 ml Glucantime and 20 patients with 37 lesions received 25 micrograms of interferon-gamma intradermally once weekly for 5 consecutive weeks. While all lesions treated with Glucantime were free of parasites after the third injection, only 69% of those treated with interferon-gamma were parasitologically cured by week 10. Within 10 weeks, lesions treated with Glucantime healed completely in 29/38, and partially in 9/38, cases, whereas 1/37 and 13/37 lesions treated with interferon-gamma healed completely and partially, respectively. Perilesional application of Glucantime was highly effective and superior to interferon-gamma for treatment of cutaneous leishmaniasis caused by L. tropica.

Administration, Cutaneous↗

Cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis in Amazonian Brazil, and the significance of a negative Montenegro skin-test in human infections.

The clinical and epidemiological features of 62 cases of cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis, from Pará State, Amazonian Brazil, are discussed. The parasite, isolated in hamster skin and/or blood-agar culture medium, was in each case identified by both biological characteristics and a monoclonal antibody specific for promastigotes of L. (L.) amazonensis. Of the 62 patients, 46 (74.2%) presented with a single cutaneous lesion, and on no occasion was evidence found indicating metastatic spread to either the naso-pharyngeal mucosae or the viscera. Recent claims that this parasite may be responsible for both mucocutaneous leishmaniasis and typical visceral leishmaniasis are discussed. Meglumine antimoniate (Glucantime) proved highly efficient in the treatment of all patients. Of the 62 patients examined by the Montenegro skin test, only 32 (51.6%) gave a positive reaction. The significance of this finding is considered and the hypothesis made that the parasite itself may induce an immunoinhibition. Field studies amply confirmed the role of Lutzomyia flaviscutellata as the major sandfly vector of L. (L.) amazonensis in Amazonia.

Adolescent↗

Antimonial treatment of hamsters infected with Leishmania (Viannia) panamensis: assessment of parasitological cure with different therapeutic schedules.

The objective of the study was to establish the effective dose and route of administration of Glucantime for treating hamsters infected with Leishmania (Viannia) panamensis and to use this method to test new treatment regimens to attain clinical and parasitological cure. In the first experiments animals were inoculated subcutaneously in the hind foot with 5 x 10(6) promastigotes of L. panamensis (HOM/COL/84/1099) from a 6 d culture. One month after inoculation, Glucantime was administered intramuscularly (i.m.) at 20, 40 or 60 mg/kg/d for 20 d to groups of hamsters. Only 60 mg/kg/d resulted in both clinical improvement and parasite elimination from the skin and draining lymph node. In the second set of experiments, i.m., local and combined antimonial regimens were compared. The local regimen, of 4 intralesional (i.l.) injections of 4 mg of antimony at 5 d intervals, and the combined regimen (i.m. and i.l.), were more efficient at clearing parasites than the systemic (i.m.) schedule, especially when a low dosage of Glucantime (30 mg/kg/d x 20 d) was used. The results suggest that combining local treatment and low systemic dosages of antimonials results in clearance of L. panamensis.

Animals↗

Exploitation of parasite-derived antigen in therapeutic success against canine visceral leishmaniosis. Veterinary Group of Lupino.

In an attempt to obtain therapeutic success against canine visceral leishmaniosis, the potential of LiF2 antigen (Leishmania infantum-derived Fraction 2, 94-67 kDa), given alone or in combination with the chemotherapeutic agent N-methylglucamine antimonate, was compared with conventional chemotherapy with that drug. Absence of any parasite in direct microscopic examination of bone-marrow aspirates in treated dogs was considered a parasitological cure, i.e. therapeutic success. Results showed that the disappearance of clinical symptoms did not always indicate parasitological healing in dogs. The parasitological healing rates with chemotherapy and immunotherapy alone were 37.5% and 25% respectively, in contrast to the 100% cure rate observed with chemotherapy combined with immunotherapy. The development of a protective response in dogs, as measured by the in vitro leishmanicidal activity of monocyte-derived macrophages in the presence of autologous lymphocytes, was found to correlate well with the success of therapy. The overall findings of this study give an important insight into the immunotherapeutic strategy by which therapeutic success can be achieved in canine visceral leishmaniosis.

Animals↗

[Resistance of Leishmania infantum to Glucantime: risk factors and therapeutic management].

BACKGROUND: Resistance to antimonial drugs is rarely observed in immunocompetent patients. CASE REPORT: A 1-year-old girl was admitted suffering from persistent fever. A diagnosis of visceral leishmaniasis was made. The patient was given two courses of meglumine antimoniate (Glucantime) (60 mg/kg/d for 15 days) and one course of 12 injections of pentamidine (4 mg/kg). She relapsed 8 months later and failed to respond to Glucantime. Immunological tests performed during the relapse showed a suppression of the T cell response to Leishmania antigen and no production of interferon gamma. The patient was then successfully given liposomal amphotericin B (3 mg/kg/d for 10 days). She was asymptomatic 9 months later and had acquired specific cellular immunity against Leishmania. CONCLUSION: Deficient cell-mediated immunity and interferon gamma production are some factors responsible for decreased sensitivity to antimonial drugs. The WHO recommendations treating visceral leishmaniasis with prolonged administration of Glucantime may prevent relapses. Liposomal amphotericin B could be an alternative treatment.

Animals↗

Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis.

The randomized, controlled study compared the therapeutic efficacy and safety of two paromomycin-containing topical preparations with the gold treatment standard, meglumine antimoniate, and with each other in 120 Ecuadorian patients with ulcerated lesions. The two paromomycin treatment comparisons were double-blinded. Group 1 (n = 14) received 15% paromomycin plus 12% methylbenzonium chloride (PR-MBCL) dissolved in a soft white paraffin base, applied twice daily for 30 days. Group 2 (n = 40) was also treated for 30 days with 15% paromomycin plus 10% urea (PR-U) dissolved in the same paraffin base. Group 3 (n = 40) received 20mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per Ecuadorian Ministry of Public Health recommendations at the time of the study. The 10-day treatment was completed by 90% of the MA group compared to 72.5% of the PR-MBCL (X2 = 4.0, P = 0.045) and 75% of the PM-U (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days longer than the MA treatment. Post-treatment lesion burning, redness, inflammation, and soreness were more common in the two paromomycin groups compared to MA group (P < 0.05). The frequency of treatment-related side effects in the two paromomycin groups was similar. Six weeks after the start of treatment, 80.6% of MA subjects were clinically cured compared to 48.3% in the PR-MBCL (X2 = 6.1, P = 0.014) and 40% in the PM-U groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of clinically cured subjects in the MA (91.7%) compared to PM-MBCL (79.3%) or PM-U (70%) groups was not significantly different (P > 0.05). MA-treated subjects clinically cured by 12 weeks had a faster mean healing time (29.5 +/- 12.2 days) compared to those in the PM-MBCL (versus 43.1 +/- 14.4 days, t = -3.7, P = 0.001) or PR-U groups (43.5 +/- 17 days; t = -3.2, P = 0.002). During the 48-week post-treatment follow-up period, infection reactivation was observed in 15.2% of the MA subjects compared to 17.4% in the PM-MBCL and 10.5% PM-U of subjects diagnosed as clinically healed by 12 weeks (P > 0.05). The results suggest that although the time required for the clinical healing of ulcerated lesions takes longer, topical paromomycin may be an acceptable therapeutic alternative in endemic areas where meglumine antimoniate is not available, is too costly or medically contraindicated.

Administration, Topical↗

Antibody response in patients with cutaneous leishmaniasis infected by Leishmania (Viannia) braziliensis or Leishmania (Viannia) guyanensis in Brazil.

The antibody response against Leishmania (Leishmania) amazonensis crude antigen was measured through the indirect immunofluorescent assay (IFA) and the immunoenzymatic assay (ELISA) in 114 patients with cutaneous leishmaniasis (CL) in Brazil. Fifty-four patients were infected by Leishmania (Viannia) braziliensis, and 60 patients had L. (V.) guyanensis infection. Patients were comparable by age, sex, disease duration and the Montenegro skin test diameter. L. (V.) braziliensis-infected patients showed significant lower number of ulcerated lesions, greater ulcerated area and higher proportion of lymph node enlargement. Sensitivity of IFA was 79.6% (95% CI 66.1-88.9) and 71.7% (95% CI 58.4-82.2) for L. (V.) braziliensis and L. (V.) guyanensis-infected patients, respectively (P=0.324). Sensitivity of ELISA was 98.2% (95% CI 88.8-99.9) and 85.0% (95% CI 72.9-92.5) for L. (V.) braziliensis and L. (V.) guyanensis-infected patients, respectively (P=0.018). Significant differences were observed in the magnitude of the antibody response before treatment with higher levels detected in L. (V.) braziliensis-infected patients by both serologic techniques. Eighty-four patients had serologic evaluations before and 12 weeks after treatment with meglumine antimoniate, 20 mg/kg/day for 20 days. Significant lower optic density values were observed after treatment with both species independent of cure or failure. Our data showed that L. (V.) braziliensis induces a higher antibody response against L. (L.) amazonensis antigens than L. (V.) guyanensis and that down-modulation of the antibody response occurs shortly during disease evolution after treatment. Moreover the data support the use of ELISA as a better tool for detection of antibodies in CL.

Adolescent↗