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Biomedical subjects

L Gradoni

Publications and source records attributed to L Gradoni.

At least 55 records · Page 3Linked to original sources

Visceral leishmaniasis in HIV infected patients: treatment with high dose liposomal amphotericin B (AmBisome).

Visceral leishmaniasis (VL) in patients coinfected with human immunodeficiency virus (HIV) is often atypical, and characteristically relapses after treatment. We treated 10 HIV infected patients (9 men) with parasitologically confirmed VL with liposomal amphotericin B ("AmBisome': L-AMB) at a dose of 4 mg/kg/day on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38. Patients were hospitalized for the first 5 days, and were monitored during, and 1 week and 1, 3 and 6 months after, L-AMB therapy. There were no serious adverse events, and L-AMB was well tolerated. 9/10 patients completed therapy, one patient defaulted at day 24. Clinical improvement was seen in all nine patients and the bone marrow aspirate was cleared of visible/culturable parasites in 8/9 patients. During follow-up, one patient defaulted. The seven remaining patients relapsed at 2, 3, 3, 5, 5, 6 and 7 months. Re-treatment with a variety of antileishmanial drugs was unsatisfactory. The time from first diagnosis of VL to death in six patients was 5-40 months (mean 18.8 months). Only one patient remained alive 26 months after treatment. L-AMB is safe and provides a good initial clinical response. Intermittent dosing enables a short period of hospitalization. However, relapse is probably inevitable.

AIDS-Related Opportunistic Infections↗

Short-course treatment of visceral leishmaniasis with liposomal amphotericin B (AmBisome).

We evaluated liposomal amphotericin B (AmBisome; Vestar, San Dimas, CA) administered to 88 immunocompetent patients (56 children) with visceral leishmaniasis (VL) caused by Leishmania infantum. Thirteen patients received 4 mg/kg on days 1-5 and 10 (total dose, 24 mg/kg), and all were cured; 42 received 3 mg/kg on days 1-5 and 10 (18 mg/kg), and 41 were cured; 32 received 3 mg/kg on days 1-4 and 10 (15 mg/kg), and 29 were cured (amastigotes were not cleared from 1 child, and 2 relapsed). One adult was cured with a total dose of 12mg/kg. The four children who were not cured received 3 mg/kg for 10 days; none had further relapses. There were no significant adverse events. For VL due to L. infantum, we recommended a total dose of AmBisome of > or = 20 mg/kg, given in > or = 5 doses of 3-4 mg/kg over > or = 10 days.

Adolescent↗

Epidemiological surveillance of leishmaniasis in HIV-1-infected individuals in Italy.

OBJECTIVE: To actively detect leishmaniasis in HIV-1-infected individuals in Italy, to describe the epidemiological features of the disease in these patients, and to compare them with epidemiological features of leishmaniasis in HIV-negative patients. DESIGN: Retrospective and prospective surveillance study. PATIENTS: Italian patients with HIV-1 infection and leishmaniasis diagnosed between 1985 and 1994. RESULTS: We recorded 116 leishmaniasis cases (115 visceral leishmaniasis), of which 94 (81%) were diagnosed over the last 4 years. Seventy-eight patients (67%) fulfilled the 1993 Centers for Disease Control and Prevention AIDS criteria. Leishmaniasis was passively reported in only 18% of cases. Leishmania incidence estimated among approximately 2700 AIDS patients living in leishmaniasis endemic areas averaged 1.6%, with a maximum of 4.9% in Sicily. These rates were up to 500-fold higher than among HIV-negative individuals living in the same areas, and were similar to those of ubiquitous opportunistic agents indicative of AIDS condition. Data from two major endemic regions indicated that overlap of HIV-1 and Leishmania infections has focal characteristics. The occurrence of small case clusters would suggest occasional modes of Leishmania transmission different from the insect vector. The isoenzyme characterization of 38 Leishmania stocks showed a zymodeme spectrum qualitatively and quantitatively different from that of the parasitic agent of visceral leishmaniasis in HIV-negative adults. CONCLUSIONS: Active surveillance provided reliable evaluation on the occurrence of HIV-Leishmania coinfections in Italy, although it was limited to hospital-based cases in this study due to general under-reporting of cases. Biological and epidemiological spectrum of the disease suggests that visceral leishmaniasis should be included among AIDS-defining pathologies.

Acquired Immunodeficiency Syndrome↗

[Eco-epidemiological study of Phlebotomus perniciosus in foci of visceral leishmaniasis in Campania].

An entomological survey was carried out during the sandfly season (June-October) of 1993 in three of the main visceral leishmaniasis (VL) foci of the Campania region of Italy. During the period 1989-1993, 39 VL cases were recorded in the three foci: 19 in Maddaloni, 14 in Ercolano and 6 in Ischia. For each focus, collecting stations representative of sandfly habitats (domestic, peri-domestic and sylvatic) located in urban, peri-urban and rural areas were selected for the sandfly investigation. Three monthly captures by means of sticky traps (20 x 20 cm) were carried out in each station. A total of 2,773 sandfly specimens were caught and identified as belonging to 4 species: Phlebotomus perniciosus (66.2%). P. mascittii (0.4%). P. papatasi (0.2%) and Sergentomyia minuta (33.2%). P. perniciosus, the proven vector of VL in Italy, showed the highest prevalence in all foci studied, Maddaloni (61.0%). Ercolano (62.5%) and Ischia (88.2%); the absolute density of the species (number of specimens/m2 of sticky trap) was not so high in all areas and habitats sampled, the values observed being between 0.14 and 22.05/m2. The relationship between the eco-epidemiological aspects and the distribution of P. perniciosus in the foci investigated is discussed.

Animal Diseases↗

Heterogeneity among zymodemes of Leishmania infantum from HIV-positive patients with visceral leishmaniasis in south Italy.

Eleven zymodemes of Leishmania infantum were identified among 38 parasite stocks isolated from Italian HIV-positive patients with visceral leishmaniasis (VL). Only one zymodeme is a common agent of Mediterranean VL in HIV-negative individuals, five zymodemes usually cause simple, self-resolving cutaneous leishmaniasis (CL), and five belong to unique genotypes which have not been previously reported from either VL or CL cases in immunocompetent individuals. This last group of parasites showed reassortment patterns within electromorphs frequently observed in dermotropic L. infantum zymodemes. The highest zymodeme heterogeneity was found in south Italy (Sicily), with six zymodemes identified among 12 HIV-positive patients surveyed.

Animals↗

Induction of interleukin 1 alpha in murine macrophages infected in vitro with different species and strains of Leishmania.

It is now generally agreed that several cytokines released by immunocompetent cells such as macrophages play a crucial role in the outcome of infections caused by protozoa belonging to the genus Leishmania. In particular, tumor necrosis factor (TNF) induction during the course of cutaneous leishmaniasis has been related to resistance to L. major infection in mice. However, the role played by interleukin 1 (IL-1) in the host response to leishmaniasis has yet to be completely elucidated. The aim of this work was to study whether different species and strains of Leishmania could induce IL-1 alpha in murine macrophages in vitro. Resident peritoneal macrophages of BALB/c and C3H/HeN mice were infected with L. donovani, L. major, or different strains of L. infantum. It was found that L. donovani did not induce IL-1 alpha in macrophages from either mice strain. Infection with L. major or with three out of six strains of L. infantum induced consistent amounts of IL-1 alpha, but only in macrophages from genetically resistant C3H/HeN mice. No relationship was found between the rate of infection of macrophages and the amount of IL-1 alpha detected in the supernatants of infected macrophages. Data obtained confirm that the release of IL-1 alpha by murine macrophages infected in vitro with Leishmania is influenced by the genetic background of the cells as well as by the parasite species.

Animals↗

Activity of liposomal amphotericin B (AmBisome) in dogs naturally infected with Leishmania infantum.

Thirteen dogs naturally infected with Leishmania infantum showing viscero-cutaneous signs of disease were treated with different dosages of liposomal amphotericin B (AmBisome). The animals were followed clinically and parasitologically over a period of eight months. Dogs which received three to five administrations of AmBisome 3-3.3 mg/kg showed rapid clinical improvement, with regression of lymphadenomegaly and splenomegaly, and cure of skin lesions. The clinical response was similar to that obtained with 14-21 doses of conventional antileishmanial drugs. However, follow-up lymph node aspirates remained positive for Leishmania in all dogs except one, which was treated with the total dose of AmBisome 15 mg/kg. The failure in parasitological cure may be due to inadequate drug targeting to parasitized cells, or to T-cell immune depression characteristic of patent cases of canine leishmaniasis, or to both.

Amphotericin B↗

Treatment of Mediterranean visceral leishmaniasis.

Up-to-date information is given on the epidemiological situation of zoonotic visceral leishmaniasis (ZVL) in nine Mediterranean countries, and on drug regimens adopted in the management of ZVL patients in each country. Results of experimental and clinical trials on the efficacy and tolerability of liposomal amphotericin B in laboratory animals and in patients with ZVL are presented, as well as conclusions and recommendations on drug regimens to be used in the treatment of ZVL.

Adolescent↗

Leishmania infantum tropism: strain genotype or host immune status?

In apparently immunocompetent patients, Leishmania infantum provokes a spectrum of disease, ranging from simple skin lesion to severe visceral leishmaniasis, that is determined mainly by the protozoan genotype. In HIV-positive individuals, leishmanial infection results almost exclusively in visceral disease. In this review, Luigi Grodoni and Marina Gromiccia discuss the role o f the intrinsic virulence of L. infantum strains and the immune condition of the host, and focus on recently described mechanisms of immunological control of leishmanial infection.

Journal Article↗

Mediterranean visceral leishmaniasis in pregnancy.

Visceral leishmaniasis (VL) in pregnancy is rare in Mediterranean countries. We report here 2 cases of VL in pregnant women who acquired the infection in Italy. In the first case, the disease was diagnosed and treated with liposomal amphotericin B during the pregnancy. In the second case, diagnosis was established and treatment with meglumine antimoniate both undertaken shortly after delivery. The 2 infants were followed clinically and serologically for 8-9 months after birth, but no evidence of congenital VL was observed.

Adult↗

[Visceral leishmaniasis in Italy. Its epidemiology, clinical picture and therapy].

Visceral leishmaniasis (VL) is a public health problem in most countries bordering the Mediterranean sea. The disease has been found in central and southern Italy, Sicily, Sardinia; some pockets are present in Liguria. Dogs are the reservoirs and the vectors are some species of sandfly (Phlebotomus species). The incubation period is usually between 2 and 8 months; children and adults may become infected; lethality may be high and depends upon a correct diagnosis and treatment. The diagnosis should be suspected on the basis of the epidemiological data and clinical picture and confirmed by the detection of specific antibodies by appropriate techniques. Leishmaniasis can be detected in splenic or bone marrow aspirates. Patients with HIV infection and VL may lack specific antibodies; parasitological diagnosis is mandatory for these patients. Antimonials are the classic therapeutic agents for VL. Recently liposomal amphotericin B (Ambisome) has been successfully used, with negligible toxicity.

Animals↗

Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a multi-centre trial.

Thirty-one patients with visceral leishmaniasis (VL) caused by Leishmania infantum received liposomal amphotericin B (AmBisome) in a multi-centre study. Ten immunocompetent patients (six children) received 1-1.38 mg/kg/day for 21 days, and ten (nine children) received 3 mg/kg/day for 10 days. All were cured without significant adverse events and without relapse during 12-24 months of follow-up. Eleven immunocompromised adults, including seven co-infected with HIV (four with AIDS) received 100 mg (1.38-1.85 mg/kg) daily for 21 days. All were initially considered cured, but eight relapsed clinically and parasitologically at 3-22 months. Liposomal amphotericin B is a new, safe and effective drug for the treatment of VL.

AIDS-Related Opportunistic Infections↗

The epidemiology and surveillance of visceral leishmaniasis in the Campania region of Italy. The value of zymodeme typing.

Although human visceral leishmaniasis (VL) is a notifiable disease in Italy, there is evidence that the actual number of cases is far higher than that notified. A programme for active surveillance of VL in the 14 Italian endemic regions was launched by the Istituto Superiore di Sanità. We report data collected during a 3-year period of active surveillance in Campania, a south Tyrrhenian region covering 4.5% of the Italian territory. Out of 120 clinically suspected cases referred to medical and diagnostic references centres, there were 52 confirmed VL cases (17.3/year), i.e. 10-fold more than previously notified. Most of the infection sites were in rural areas or peripheral districts of towns in hilly parts of Naples province. An epidemic cluster of 10 cases was identified in a microfocus of Caserta province. The biochemical analysis of 23 Leishmania stocks showed a zymodeme composition indicating Campania as an old and well-established focus of VL. The data obtained emphasize that the present notification system for VL in Italy is inadequate.

Adolescent↗