RESUMO
The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana-complex and subgenus Viannia, ii) in suspected infections with L. mexicana-complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis.
Assuntos
Antiparasitários/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatologia/normas , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/terapia , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/terapia , Feminino , Alemanha , Humanos , GravidezRESUMO
The predominant sand fly species collected inside houses in Kfar Adumim, an Israeli village in the Judean Desert that is a focus of cutaneous leishmaniasis, was Phlebotomus papatasi, which was also caught attempting to bite humans. Phlebotomus sergenti, which is rarely seen inside houses, constituted the predominant sand fly species in caves near the village. Leishmania isolates from Ph. sergenti and humans typed as Leishmania tropica. Sand fly and human isolates produced similar small nodular cutaneous lesions in hamsters. Isolates produced excreted factor (EF) of subserotypes A(9) or A(9)B(2), characteristic of L. tropica and reacted with L. tropica-specific monoclonal antibodies. Isoenzyme analysis consigned the strains to the L. tropica zymodemes MON-137 and MON-275. Molecular genetic analyses confirmed the strains were L. tropica and intraspecific microheterogeneity was observed. Genomic fingerprinting using a mini-satellite probe separated the L. tropica strains into two clusters that were not entirely congruent with geographic distribution. These results support the heterogeneous nature of L. tropica and incriminate Ph. sergenti as its vector in this Judean Desert focus.
Assuntos
Insetos Vetores/parasitologia , Leishmania tropica/crescimento & desenvolvimento , Leishmaniose Cutânea/parasitologia , Phlebotomus/parasitologia , Animais , Bioensaio , Cricetinae , DNA de Cinetoplasto/química , DNA de Cinetoplasto/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Clima Desértico , Eletroforese em Gel de Amido , Feminino , Variação Genética , Humanos , Isoenzimas , Israel , Leishmania tropica/enzimologia , Leishmania tropica/genética , Leishmaniose Cutânea/transmissão , Mesocricetus , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , População Rural , SorotipagemRESUMO
This paper reports attempts to develop a sensitive and inexpensive procedure for rapid diagnosis of cutaneous leishmaniasis at the species level using skin scrapings from patients. The presence of 3 species (Leishmania major, L. tropica and L. infantum) in Israel and the West Bank demonstrates the need for a species-specific detection method in this region. The primer pair Uni21/Lmj4 was developed on the basis of an L. major minicircle sequence but it also amplified other 'Old World' species of Leishmania. Due to species-specific differences in the size of minicircles, these primers can be used in the polymerase chain reaction to answer diagnostic and epidemiological questions.
Assuntos
DNA de Cinetoplasto/genética , Leishmania major/classificação , Leishmania tropica/classificação , Leishmaniose Cutânea/diagnóstico , Adulto , Animais , Feminino , Humanos , Leishmania major/genética , Leishmania tropica/genética , Leishmaniose Cutânea/parasitologia , Masculino , Reação em Cadeia da Polimerase/métodos , Pele/parasitologia , Especificidade da Espécie , Manejo de Espécimes/métodosRESUMO
Objectives. To assess the immunogenicity of intradermal (ID) booster doses of Purified Chick Embryo Cell rabies vaccine (PCECV, Rabipur) administered to Thai schoolchildren one, three and five years after a primary ID pre-exposure (PrEP) vaccination series. Methods. In this follow-up study of a randomized, open-label, phase II clinical trial, two simulated post-exposure booster doses of PCECV were administered on days 0 and 3 intradermally to 703 healthy schoolchildren, one, three or five years after primary vaccination with either two or three ID doses of 0.1 mL PCECV. Blood was drawn immediately before and 7, 14 and 365 days after the first booster dose to determine rabies virus neutralizing antibody (RVNA) concentrations. Results. An anamnestic response of approximately 30-fold increase in RVNA concentrations was demonstrated within 14 days after booster. All children (100%) developed adequate RVNA concentrations above 0.5 IU/mL. No vaccine related serious adverse events were seen in any of the vaccinees. Conclusion. ID rabies PrEP with PCECV is safe and immunogenic in schoolchildren and the anamnestic response to a two booster dose vaccination series was found to be adequate one, three, and five years after a two- or three-dose primary PrEP vaccination series.
RESUMO
BACKGROUND: Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. METHODS: An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. RESULTS: The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience. CONCLUSION: This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic.
Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Administração Oral , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Aspartato Aminotransferases/sangue , Cápsulas/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas , Criança , Pré-Escolar , Creatinina/sangue , Esquema de Medicação , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Índia , Hepatopatias/sangue , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/uso terapêutico , Resultado do TratamentoRESUMO
In recent years, New World cutaneous leishmaniasis has been seen at a higher incidence among returning Israeli travelers. Leishmania braziliensis and related species cause unsightly cutaneous lesions possibly complicated with a mucosal disease. A total of 12 patients with New World cutaneous leishmaniasis were treated in our clinic, 11 of whom (92%) acquired the disease in the Bolivian Amazon Basin. Five (42%) had regional lymphadenopathy in addition to cutaneous lesions. Polymerase chain reaction was performed for 8 patients to identify the causative Leishmania species. In all, 9 patients (75%) were cured by a single course, and 3 (25%) after an additional course of intravenous sodium stibogluconate. The treatment was well tolerated clinically. Laboratory abnormalities, mainly elevation of liver enzymes (58%), were reversible. We concluded that polymerase chain reaction is a useful tool in establishing the species diagnosis of leishmaniasis and that sodium stibogluconate appears to be a safe and effective treatment for L braziliensis infection.