RESUMEN
Leishmaniasis is endemic in the Middle East, and both cutaneous and visceral forms are reported from the region ranging from the Levant to Afghanistan. The potential and proven phlebotomine sand fly vectors and reservoir hosts of the Leishmaniases species in Afghanistan, Iran, Iraq, Israel, Jordan, Lebanon, Saudi Arabia, Syria, Turkey, and Yemen are described. This region has seen a movement of populations across the area, due to both military and civilian strife. Refugees, armed forces, and multi-national contractors are particularly at risk to acquire this disease. There has been an upsurge in Leishmaniasis research, especially as new foci are exposed and the need to protect the naïve populations moving into endemic areas becomes a public health priority. New sand fly vectors and animal reservoirs have been discovered while novel control methods are being evaluated. Modern molecular techniques are now being used more routinely and revealing some unusual findings. The aim of this review is to collate the most recent data on the burden of the disease, diagnostic applications, eco-epidemiology of vectors, and reservoir hosts, and how the control projects have been developing in the Middle East.
Asunto(s)
Reservorios de Enfermedades/parasitología , Enfermedades Endémicas , Insectos Vectores/parasitología , Leishmania/fisiología , Leishmaniasis/epidemiología , Phlebotomus/parasitología , Animales , Humanos , Leishmaniasis/diagnóstico , Leishmaniasis/parasitología , Leishmaniasis/prevención & control , Medio Oriente/epidemiología , Salud Pública , ZoonosisRESUMEN
Despite world-wide efforts in fighting malaria, this mosquito-borne infectious disease is a huge burden for the population, especially in tropical and subtropical areas. The WHO recommends artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria. However, artemisinin resistance cannot now be ignored. Factors affecting the development of artemisinin resistance include uncontrolled use of artemisinin-based combination therapy (ACT), mobile populations and migrants, artemisinin monotherapy, the use of subtherapeutic levels of artesiminin, substandard and counterfeit drugs, high treatment cost, and co-use of artemisinin derivates as prophylactic agents. Promising herbal alternatives are already in the pipeline, but the only long-term solution for eradicating malaria would be the development of a successful vaccination.
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Resistencia a Medicamentos , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Quimioterapia Combinada , HumanosRESUMEN
An intraspecific study on Phlebotomus papatasi, the main proven vector of Leishmania major among the members of the subgenus Phlebotomus, was performed. The internal transcribed spacer 2 (ITS 2) of rDNA and the ND4 gene of mt DNA were sequenced from 26 populations from 18 countries (Albania, Algeria, Cyprus, Egypt, Greece, India, Iran, Israel, Italy, Lebanon, Morocco, Saudi Arabia, Spain, Syria, Tunisia, Turkey, Yugoslavia and Yemen), and compared. Samples also included three other species belonging to the subgenus Phlebotomus: P. duboscqi, a proven vector of L. major in the south of Sahara (three populations from Burkina Faso, Kenya and Senegal), P. bergeroti, a suspected vector of L. major (three populations from Oman Sultanate, Iran and Egypt), and one population of P. salehi from Iran. A phylogenetic study was carried out on the subgenus Phlebotomus. Our results confirm the validity of the morphologically characterized taxa. The position of P. salehi is doubtful. Variability in P. papatasi contrasts with that observed within other species having a wide distribution like P. (Paraphlebotomus) sergenti in the Old World or Lutzomyia (Lutzomyia) longipalpis in the New World. Consequently, it could be hypothesized that all populations of P. papatasi over its distribution area have similar vectorial capacities. The limits of the distribution area of L. major are correlated with the distribution of common rodents acting as hosts of the parasites.
Asunto(s)
ADN Mitocondrial/análisis , ADN Espaciador Ribosómico/genética , Variación Genética , NADH Deshidrogenasa/genética , Fiebre por Flebótomos/epidemiología , Phlebotomus/genética , Animales , Secuencia de Bases , Frecuencia de los Genes , Genética de Población , Geografía , Haplotipos , Humanos , Filogenia , Análisis de Secuencia de ADNRESUMEN
The sand fly Phlebotomus papatasi Scopoli, 1786, the vector of Leishmania major Yakimoff et Schokhor, 1914, is found in desert areas where sugars are scarce but also in habitats that abound in sugar sources. The sand flies require sugar meals from plant sources for their energy requirements and to hydrolyze these complex sugars, they need a repertoire of glycosidases. We presumed that there are differences in the levels of glycosidase activities in flies from such habitats and also assumed that they may be instrumental in modulating the flies' susceptibility to L. major infections. Phlebotomus papatasi originating from diverse ecological habitats ranging from an oasis to desert sites were colonized. They were analyzed for weight changes and glycosidase activities before and after feeding on 1M sucrose solution. Oasis flies were smaller than desert flies but took larger sugar meals. Homogenates of these flies hydrolyzed 16 synthetic and 2 natural glycoside substrates to varying degrees. The arid-region flies tended to produce more glycosidase activity than those originating in sugar-rich environments, especially sucrase, alpha- and beta-glucosidase, aalpha-fucosidase, alpha-mannosidase, and alpha- and beta-N-acetylgalactosaminidase. However, chitinolytic enzyme activities and particularly the beta-N-acetylhexosaminidase activity of oasis flies were higher than other flies tested. In comparing the desert flies, there were also significant differences in glycolytic enzyme activities between the spring-line (flowering season) of flies and the autumn-line (end of dry season) flies. A range of saccharide inhibitors was tested to demonstrate the specificity of the enzymes.
Asunto(s)
Quitina/metabolismo , Ecosistema , Enzimas/metabolismo , Insectos Vectores/metabolismo , Phlebotomus/metabolismo , Sacarosa/metabolismo , Análisis de Varianza , Animales , Peso Corporal , Enzimas/análisis , Femenino , Leishmania major , Masculino , Factores Sexuales , Sacarosa/administración & dosificaciónRESUMEN
Evidence is provided for genetic and biological variation among Leishmania major strains that correlates with their geographical origin. The host-parasite relationship also appears to be specific. Great gerbils, Rhombomys opimus, and fat sand rats, Psammomys obesus, are the main reservoir hosts in Central Asia and the Middle East, respectively. However, the Central Asian parasite failed to infect the Middle Eastern rodent host in the laboratory, and vice versa. A permissively primed intergenic polymorphic (PPIP)-PCR and a single-stranded conformation polymorphism (SSCP)-PCR exposed genetic polymorphism among 30 strains of L. major from different geographical regions. This was verified by subsequent sequencing of DNA from the same strains using four genomic targets: (a) the NADH-dehydrogenase (NADH-DH) gene, (b) the 6-phosphogluconate dehydrogenase (6PGD) gene, (c) the ribosomal internal transcribed spacers, and (d) an anonymous DNA sequence originally amplified with random primers. All the genetic markers indicated that the nine Central Asian strains were a separate homogenous genetic group. The Middle Eastern strains formed another geographical group that displayed heterogeneity corresponding with their different Middle Eastern locations. Molecular markers and host-parasite relationships confirmed that Central Asian and Middle Eastern strains are genetically and biologically distinct sub-populations of L. major. Three African strains of L. major were genetically closer to the Middle Eastern strains, and a representative one did infect fat sand rats, but they had distinct permissively primed inter-genic polymorphic PCR patterns and internal transcribed spacer 2 types.
Asunto(s)
Leishmania major/genética , Polimorfismo Genético , África , Animales , Asia Central , Secuencia de Bases , ADN Intergénico/análisis , ADN Espaciador Ribosómico/genética , Gerbillinae , Humanos , Leishmania major/aislamiento & purificación , Malato Deshidrogenasa/genética , Medio Oriente , Datos de Secuencia Molecular , NADH Deshidrogenasa/genética , Fosfogluconato Deshidrogenasa/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Alineación de Secuencia , Especificidad de la EspecieRESUMEN
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.
Asunto(s)
Insectos Vectores/parasitología , Leishmania tropica/crecimiento & desarrollo , Leishmaniasis Cutánea/parasitología , Phlebotomus/parasitología , Animales , Bioensayo , Cricetinae , ADN de Cinetoplasto/química , ADN de Cinetoplasto/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Clima Desértico , Electroforesis en Gel de Almidón , Femenino , Variación Genética , Humanos , Isoenzimas , Israel , Leishmania tropica/enzimología , Leishmania tropica/genética , Leishmaniasis Cutánea/transmisión , Mesocricetus , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Población Rural , SerotipificaciónRESUMEN
This study describes a new focus of cutaneous leishmaniasis (CL) due to Leishmania tropica, in the Galilee region of northern Israel. Thirty-three cases from 4 villages (northern part) and from the city of Tiberias (southern part) have been clinically diagnosed since 1996. Parasites from 13 patients and from 6 sand flies were characterized by isoenzyme electrophoresis, 2 immunological methods, and 3 polymerase chain reaction (PCR)-based methods. Isolates from the northern part were antigenically similar to Leishmania major and were different from other L. tropica isolates, including those from the southern part of the focus. They belonged to a newly reported zymodeme and were separable from all known Israeli L. tropica isolates, by use of 2 different PCR-based methods. Five (5.2%) of 97 Phlebotomus (Adlerius) arabicus and 2 (1.2%) of 162 Phlebotomus (Paraphlebotomus) sergenti females from the northern part of the focus were found to be infected with L. tropica. Three of 29 hyraxes (Procavia capensis) were positive for Leishmania ribosomal DNA. Thus, the northern part of this emerging focus of CL in Israel is distinct from all known L. tropica foci. P. arabicus is the main vector, and it transmits parasites that are different from other L. tropica isolates, with respect to antigenic, molecular, and biochemical parameters.
Asunto(s)
Brotes de Enfermedades , Leishmania tropica/enzimología , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Animales , Antígenos de Protozoos/sangre , ADN Protozoario/química , ADN Protozoario/genética , Reservorios de Enfermedades , Electroforesis en Gel de Almidón , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Damanes/parasitología , Inmunodifusión , Isoenzimas , Israel/epidemiología , Leishmania tropica/genética , Phlebotomus/parasitología , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Leishmania tropica is one of the causative agents of cutaneous leishmaniasis (CL), a disfiguring parasitic disease that recently was found to be viscerotropic. In urban areas it is transmitted from infected individuals by the bite of phlebotomine sand flies to naïve persons (anthroponotic CL). In rural areas animals are thought to be the reservoir, but the full life cycle is still under investigation (zoonotic CL). For many years L. tropica was either confused or merely grouped with L. major while Phlebotomus sergenti was the only proven vector. In recent years new foci have erupted, but few have been investigated. This review describes some of the history, recent findings, epidemiology, potential vectors, and the search for possible reservoir hosts besides man.