Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 29, Number 5—May 2023
Research

Leishmania donovani Transmission Cycle Associated with Human Infection, Phlebotomus alexandri Sand Flies, and Hare Blood Meals, Israel1

Liora StudentskyComments to Author , Laor Orshan, Fouad Akad, Irina Ben Avi, Debora Diaz, Shirly Elbaz, Orly Sagi, Gal Zagron, Lea Valinsky, Maya Davidovich-Cohen, and Gad Baneth
Author affiliations: Ministry of Health Central Laboratories for Public Health, Jerusalem, Israel (L. Studentsky, L. Orshan, I. Ben Avi, D. Diaz, S. Elbaz, M. Davidovich-Cohen); The Hebrew University of Jerusalem, Rehovot, Israel (L. Studentsky, G. Baneth); Ministry of Health National Laboratory for Public Health, Tel Aviv, Israel (F. Akad); Soroka University Medical Center, Beer-Sheba, Israel (O. Sagi); Israeli Ministry of Environmental Protection, Jerusalem (G. Zagron); Maccabi Healthcare Services, Tel Aviv (L. Valinsky)

Main Article

Figure 2

Phylogenetic analysis of Leishmania internal transcribed spacer 1 rRNA fragments in study of Leishmania donovani transmission cycle associated with human infection, Phlebotomus alexandri sand flies, and hare blood meals, Israel. Leishmania-specific internal transcribed spacer 1 rRNA fragments (201 bp) were amplified by PCR from P. alexandri sand flies, pooled female Phlebotomus spp. flies, and patient samples and then sequenced. Tree was constructed by using the maximum-likelihood method and Tamura 3-parameter model, estimated by using the Aikaike information criterion (33). Dendogram includes sequences from L. donovani and L. infantum isolated from sand flies and clinical samples in this study compared with Leishmania spp. reference controls and GenBank sequences from Israel and other countries. Tree shows substantial separate clustering of L. infantum (boostrap 94%) and L. donovani (bootstrap 89%) sequences. Empty circles are Leishmania international reference strains, black triangles are the 10 sequences from our study deposited in GenBank, and black circles are additional L. infantum–positive sand flies samples from Israel. Available GenBank sequences for L. major, L. tropica, L. infantum, and L. donovani from Israel and other countries are also included. GenBank accession numbers, Leishmania spp., isolate source, and country are indicated. Only bootstrap values >70% are shown. Not to scale.

Figure 2. Phylogenetic analysis of Leishmania internal transcribed spacer 1 rRNA fragments in study of Leishmania donovani transmission cycle associated with human infection, Phlebotomus alexandri sand flies, and hare blood meals, Israel. Leishmania-specific internal transcribed spacer 1 rRNA fragments (201 bp) were amplified by PCR from P. alexandri sand flies, pooled female Phlebotomus spp. flies, and patient samples and then sequenced. Tree was constructed by using the maximum-likelihood method and Tamura 3-parameter model, estimated by using the Aikaike information criterion (33). Dendogram includes sequences from L. donovani and L. infantum isolated from sand flies and clinical samples in this study compared with Leishmania spp. reference controls and GenBank sequences from Israel and other countries. Tree shows substantial separate clustering of L. infantum (boostrap 94%) and L. donovani (bootstrap 89%) sequences. Empty circles are Leishmania international reference strains, black triangles are the 10 sequences from our study deposited in GenBank, and black circles are additional L. infantum–positive sand flies samples from Israel. Available GenBank sequences for L. major, L. tropica, L. infantum, and L. donovani from Israel and other countries are also included. GenBank accession numbers, Leishmania spp., isolate source, and country are indicated. Only bootstrap values >70% are shown. Not to scale.

Main Article

References
  1. Jaffe  CL, Baneth  G, Abdeen  ZA, Schlein  Y, Warburg  A. Leishmaniasis in Israel and the Palestinian Authority. Trends Parasitol. 2004;20:32832. DOIPubMedGoogle Scholar
  2. Schlein  Y, Warburg  A, Schnur  LF, Gunders  AE. Leishmaniasis in the Jordan Valley II. Sandflies and transmission in the central endemic area. Trans R Soc Trop Med Hyg. 1982;76:5826. DOIPubMedGoogle Scholar
  3. Schlein  Y, Warburg  A, Schnur  LF, Le Blancq  SM, Gunders  AE. Leishmaniasis in Israel: reservoir hosts, sandfly vectors and leishmanial strains in the Negev, Central Arava and along the Dead Sea. Trans R Soc Trop Med Hyg. 1984;78:4804. DOIPubMedGoogle Scholar
  4. Anis  E, Leventhal  A, Elkana  Y, Wilamowski  A, Pener  H. Cutaneous leishmaniasis in Israel in the era of changing environment. Public Health Rev. 2001;29:3747.PubMedGoogle Scholar
  5. Jacobson  RL, Eisenberger  CL, Svobodova  M, Baneth  G, Sztern  J, Carvalho  J, et al. Outbreak of cutaneous leishmaniasis in northern Israel. J Infect Dis. 2003;188:106573. DOIPubMedGoogle Scholar
  6. Schnur  LF, Nasereddin  A, Eisenberger  CL, Jaffe  CL, El Fari  M, Azmi  K, et al. Multifarious characterization of leishmania tropica from a Judean desert focus, exposing intraspecific diversity and incriminating phlebotomus sergenti as its vector. Am J Trop Med Hyg. 2004;70:36472. DOIPubMedGoogle Scholar
  7. Svobodova  M, Votypka  J, Peckova  J, Dvorak  V, Nasereddin  A, Baneth  G, et al. Distinct transmission cycles of Leishmania tropica in 2 adjacent foci, Northern Israel. Emerg Infect Dis. 2006;12:18608. DOIPubMedGoogle Scholar
  8. Jacobson  RL. Leishmaniasis in an era of conflict in the Middle East. Vector Borne Zoonotic Dis. 2011;11:24758. DOIPubMedGoogle Scholar
  9. Ready  PD. Biology of phlebotomine sand flies as vectors of disease agents. Annu Rev Entomol. 2013;58:22750. DOIPubMedGoogle Scholar
  10. Gunders  AE, Foner  A, Montilio  B. Identification of Leishmania species isolated from rodents in Israel. Nature. 1968;219:856. DOIPubMedGoogle Scholar
  11. Gunders  AE, Lidror  R, Montilo  B, Amitai  P. Isolation of Leishmania sp. from Psammomys obesus in Judea. Trans R Soc Trop Med Hyg. 1968;62:465.
  12. Wasserberg  G, Abramsky  Z, Anders  G, El-Fari  M, Schoenian  G, Schnur  L, et al. The ecology of cutaneous leishmaniasis in Nizzana, Israel: infection patterns in the reservoir host, and epidemiological implications. Int J Parasitol. 2002;32:13343. DOIPubMedGoogle Scholar
  13. Faiman  R, Abbasi  I, Jaffe  C, Motro  Y, Nasereddin  A, Schnur  LF, et al. A newly emerged cutaneous leishmaniasis focus in northern Israel and two new reservoir hosts of Leishmania major. PLoS Negl Trop Dis. 2013;7:e2058. DOIPubMedGoogle Scholar
  14. Talmi-Frank  D, Jaffe  CL, Nasereddin  A, Warburg  A, King  R, Svobodova  M, et al. Leishmania tropica in rock hyraxes (Procavia capensis) in a focus of human cutaneous leishmaniasis. Am J Trop Med Hyg. 2010;82:8148. DOIPubMedGoogle Scholar
  15. Ya’ari  A, Jaffe  CL, Garty  BZ. Visceral leishmaniasis in Israel, 1960-2000. Isr Med Assoc J. 2004;6:2058.PubMedGoogle Scholar
  16. Singer  SR, Abramson  N, Shoob  H, Zaken  O, Zentner  G, Stein-Zamir  C. Ecoepidemiology of cutaneous leishmaniasis outbreak, Israel. Emerg Infect Dis. 2008;14:14246. DOIPubMedGoogle Scholar
  17. Azmi  K, Krayter  L, Nasereddin  A, Ereqat  S, Schnur  LF, Al-Jawabreh  A, et al. Increased prevalence of human cutaneous leishmaniasis in Israel and the Palestinian Authority caused by the recent emergence of a population of genetically similar strains of Leishmania tropica. Infect Genet Evol. 2017;50:1029. DOIPubMedGoogle Scholar
  18. Gandacu  D, Glazer  Y, Anis  E, Karakis  I, Warshavsky  B, Slater  P, et al. Resurgence of cutaneous leishmaniasis in Israel, 2001-2012. Emerg Infect Dis. 2014;20:160511. DOIPubMedGoogle Scholar
  19. Israel Ministry of Health. Annual report of central laboratories, 2019 (Hebrew) [cited 2021 Jan 5]. https://www.health.gov.il/PublicationsFiles/LAB_JER2019.pdf
  20. Nezer  O, Bar-David  S, Gueta  T, Carmel  Y. High-resolution species-distribution model based on systematic sampling and indirect observations. Biodivers Conserv. 2017;26:42137. DOIGoogle Scholar
  21. Stern  E, Gardus  Y, Meir  A, Krakover  S, Tzoar  H. Atlas of the Negev. Jerusalem (Israel): Keter Publishing House; 1986.
  22. Orshan  L, Szekely  D, Khalfa  Z, Bitton  S. Distribution and seasonality of Phlebotomus sand flies in cutaneous leishmaniasis foci, Judean Desert, Israel. J Med Entomol. 2010;47:31928. DOIPubMedGoogle Scholar
  23. Orshan  L, Elbaz  S, Ben-Ari  Y, Akad  F, Afik  O, Ben-Avi  I, et al. Distribution and dispersal of Phlebotomus papatasi (Diptera: Psychodidae) in a zoonotic cutaneous leishmaniasis focus, the northern Negev, Israel. PLoS Negl Trop Dis. 2016;10:e0004819. DOIPubMedGoogle Scholar
  24. Abonnenc  E. Les Phlébotomes de la région éthiopienne (Diptera, Psychodidae). In: Memoires ORSTOM series. Paris: Office de la Recherche Scientifique et Technique; 1972
  25. Lewis  DJ. A taxonomic review of the genus Phlebotomus (Diptera: Psychodidae). Bull Br Mus Nat Hist. 1982;45:121209.
  26. Lukes  J, Mauricio  IL, Schönian  G, Dujardin  JC, Soteriadou  K, Dedet  JP, et al. Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy. Proc Natl Acad Sci U S A. 2007;104:937580. DOIPubMedGoogle Scholar
  27. Talmi-Frank  D, Nasereddin  A, Schnur  LF, Schönian  G, Töz  SO, Jaffe  CL, et al. Detection and identification of old world Leishmania by high resolution melt analysis. PLoS Negl Trop Dis. 2010;4:e581. DOIPubMedGoogle Scholar
  28. Sagi  O, Berkowitz  A, Codish  S, Novack  V, Rashti  A, Akad  F, et al. Sensitive molecular diagnostics for cutaneous leishmaniasis. Open Forum Infect Dis. 2017;4:ofx037. DOIPubMedGoogle Scholar
  29. Ben-Shimol  S, Sagi  O, Horev  A, Avni  YS, Ziv  M, Riesenberg  K. Cutaneous leishmaniasis caused by Leishmania infantum in Southern Israel. Acta Parasitol. 2016;61:8558. DOIPubMedGoogle Scholar
  30. el Tai  NO, Osman  OF, el Fari  M, Presber  W, Schönian  G. Genetic heterogeneity of ribosomal internal transcribed spacer in clinical samples of Leishmania donovani spotted on filter paper as revealed by single-strand conformation polymorphisms and sequencing. Trans R Soc Trop Med Hyg. 2000;94:5759. DOIPubMedGoogle Scholar
  31. Haralambous  C, Antoniou  M, Pratlong  F, Dedet  JP, Soteriadou  K. Development of a molecular assay specific for the Leishmania donovani complex that discriminates L. donovani/Leishmania infantum zymodemes: a useful tool for typing MON-1. Diagn Microbiol Infect Dis. 2008;60:3342. DOIPubMedGoogle Scholar
  32. Valinsky  L, Ettinger  G, Bar-Gal  GK, Orshan  L. Molecular identification of bloodmeals from sand flies and mosquitoes collected in Israel. J Med Entomol. 2014;51:67885. DOIPubMedGoogle Scholar
  33. Kumar  S, Stecher  G, Li  M, Knyaz  C, Tamura  K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35:15479. DOIPubMedGoogle Scholar
  34. Ben-Ami  R, Schnur  LF, Golan  Y, Jaffe  CL, Mardi  T, Zeltser  D. Cutaneous involvement in a rare case of adult visceral leishmaniasis acquired in Israel. J Infect. 2002;44:1814. DOIPubMedGoogle Scholar
  35. Guan  LR, Xu  YX, Li  BS, Dong  J. The role of Phlebotomus alexandri Sinton, 1928 in the transmission of kala-azar. Bull World Health Organ. 1986;64:10712.PubMedGoogle Scholar
  36. Guan  LR, Zhou  ZB, Jin  CF, Fu  Q, Chai  JJ. Phlebotomine sand flies (Diptera: Psychodidae) transmitting visceral leishmaniasis and their geographical distribution in China: a review. Infect Dis Poverty. 2016;5:15. DOIPubMedGoogle Scholar
  37. Molina  R, Jiménez  MI, Cruz  I, Iriso  A, Martín-Martín  I, Sevillano  O, et al. The hare (Lepus granatensis) as potential sylvatic reservoir of Leishmania infantum in Spain. Vet Parasitol. 2012;190:26871. DOIPubMedGoogle Scholar
  38. Sevá  ADP, Martcheva  M, Tuncer  N, Fontana  I, Carrillo  E, Moreno  J, et al. Efficacies of prevention and control measures applied during an outbreak in Southwest Madrid, Spain. PLoS One. 2017;12:e0186372. DOIPubMedGoogle Scholar
  39. Tsokana  CN, Sokos  C, Giannakopoulos  A, Mamuris  Z, Birtsas  P, Papaspyropoulos  K, et al. First evidence of Leishmania infection in European brown hare (Lepus europaeus) in Greece: GIS analysis and phylogenetic position within the Leishmania spp. Parasitol Res. 2016;115:31321. DOIPubMedGoogle Scholar
  40. Rocchigiani  G, Ebani  VV, Nardoni  S, Bertelloni  F, Bascherini  A, Leoni  A, et al. Molecular survey on the occurrence of arthropod-borne pathogens in wild brown hares (Lepus europaeus) from Central Italy. Infect Genet Evol. 2018;59:1427. DOIPubMedGoogle Scholar
  41. Jambulingam  P, Pradeep Kumar  N, Nandakumar  S, Paily  KP, Srinivasan  R. Domestic dogs as reservoir hosts for Leishmania donovani in the southernmost Western Ghats in India. Acta Trop. 2017;171:647. DOIPubMedGoogle Scholar
  42. Hassan  MM, Osman  OF, El-Raba’a  FM, Schallig  HD, Elnaiem  DE. Role of the domestic dog as a reservoir host of Leishmania donovani in eastern Sudan. Parasit Vectors. 2009;2:26. DOIPubMedGoogle Scholar
  43. Dereure  J, El-Safi  SH, Bucheton  B, Boni  M, Kheir  MM, Davoust  B, et al. Visceral leishmaniasis in eastern Sudan: parasite identification in humans and dogs; host-parasite relationships. Microbes Infect. 2003;5:11038. DOIPubMedGoogle Scholar
  44. Bsrat  A, Berhe  M, Gadissa  E, Taddele  H, Tekle  Y, Hagos  Y, et al. Serological investigation of visceral Leishmania infection in human and its associated risk factors in Welkait District, Western Tigray, Ethiopia. Parasite Epidemiol Control. 2017;3:1320. DOIPubMedGoogle Scholar
  45. Bashaye  S, Nombela  N, Argaw  D, Mulugeta  A, Herrero  M, Nieto  J, et al. Risk factors for visceral leishmaniasis in a new epidemic site in Amhara Region, Ethiopia. Am J Trop Med Hyg. 2009;81:349. DOIPubMedGoogle Scholar
  46. Kalayou  S, Tadelle  H, Bsrat  A, Abebe  N, Haileselassie  M, Schallig  HDFH. Serological evidence of Leishmania donovani infection in apparently healthy dogs using direct agglutination test (DAT) and rk39 dipstick tests in Kafta Humera, north-west Ethiopia. Transbound Emerg Dis. 2011;58:25562. DOIPubMedGoogle Scholar
  47. Magri  A, Galuppi  R, Fioravanti  M, Caffara  M. Survey on the presence of Leishmania sp. in peridomestic rodents from the Emilia-Romagna Region (North-Eastern Italy). Vet Res Commun. 2023;47:2916. DOIPubMedGoogle Scholar
  48. Özbilgin  A, Çavuş  İ, Yıldırım  A, Gündüz  C. [Do the rodents have a role in transmission of cutaneous leishmaniasis in Turkey?] [in Turkish]. Mikrobiyol Bul. 2018;52:25972.PubMedGoogle Scholar
  49. Frézard  F, Aguiar  MMG, Ferreira  LAM, Ramos  GS, Santos  TT, Borges  GSM, et al. Liposomal amphotericin B for treatment of leishmaniasis: from the identification of critical physicochemical attributes to the design of effective topical and oral formulations. Pharmaceutics. 2022;15:99. DOIPubMedGoogle Scholar

Main Article

1Data from this study were presented at the Israeli Society for Parasitology, Protozoology and Tropical Diseases Annual Meeting; March 21, 2022; Kfar Hamaccabiah, Ramat Gan, Israel.

Page created: March 06, 2023
Page updated: April 18, 2023
Page reviewed: April 18, 2023
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external