### Microbiology A protozoa, there are numerous species depending on where it was acquired. There is Old World predominantly *L*. *donovani* and New World, of which there are TNTC. Well, someone counted 53 species and around 20 can infect humans. ### Epidemiologic Risks Old World: India, Mideast, S. Europe, Asia, and N. Africa. The wild Gorilla may be a reservoir, [^1] is it a killa of Magilla? [^2] 20 of Iraq vets may have asymptomatic visceral leishmaniasis due to *Leishmania* *infantum*. [^3] New World: All over C. and S. America. Spread by the sand fly. The organisms is moving North with global heating [^4] and ain't no wall going to stop it..  In the US dogs are the likely reservoir of *L*. *infantum*, especially hounds. *Leishmania* *panamensis* is the most common species of *Leishmania* in Panama. *Leishmania* *mexicana* in endemic in Texas. [^5] There was a case of *Leishmania* *donovani* in North Dakota in a child that had never been out of the state. [^6] Poor kid. A life in North Dakota. > "We detected Leishmania infantum in 98 Norway rats (Rattus norvegicus) trapped in parks and sewers of Barcelona, Spain. The 84 rats from the sewers showed a prevalence of 33.3% and up to 2,272 estimated parasites." [^7] The fault, dear Brutus, is not in our stars / But in ourselves: > Interferon gamma variant rs2069705 seems to be a genetic modifier of clinical outcome of *Leishmania* infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL." [^8] ### Syndromes Cutaneous disease: a large, ragged, dry ulcer at the site of the bite, 2 weeks to 2 months after the bite. With *L*. *braziliensis*, the mucous membranes can be involved to cause destruction of the nose, face, etc. Diabetes leads to > "atypical cutaneous lesions characterized by large superficial ulcers without defined borders"and a poorer response to antimony therapy. [^9] Kala-azar or visceral disease: fever, weight loss, hepatosplenomegaly, anemia, and leukopenia. It can be a major problem in AIDS patients. It also sounds like a Ricardo Montalban character who fights Kirk. ### Treatment The ins and outs of *Leishmania* are too complicated for this guide; the few cases I have treated have always been with the help of the CDC. Stibogluconate sodium. Some Indian strains are resistant, perhaps due to arsenic in the water. [^10] Liposomal Amphotericin B is probably the preferred treatment for visceral disease and should cure 95% [^11], ketoconazole and itraconazole have activity against some *Leishmania*. Fluconazole at low dose cured 75% of patients and higher dose, the cured 100% of *Leishmania* (*Vianna*) *braziliensis* in Brazil. [^12] Although when compared head to head against stibogluconate, fluconazole was markedly inferior. [^13] Paromomycin was noninferior to Amphotericin B for visceral leishmaniasis (kala-azar). [^14] [^19] Miltefosine is used in the Indian subcontinent, but resistance may be increasing [^15] with one in 5 failing therapy. [^16] It is way expensive. " You can buy Impavido at the discounted price of $49,760.20 by using the WebMDRx coupon, a savings of 20%" [^17] I guess that is better than $62,385.59 With cutaneous disease, pentoxifylline [^18] increases healing and decreases relapse and in one small study Rimiquimod 7.5% cream administered topically every other day with intravenous meglumine antimoniate was superior to either agent alone. For cutaneous *L*. *major* topical paromomycin-gentamicin or paromomycin alone daily for 20 days ((15% paromomycin--0.5% gentamicin cream) or paromomycin alone (15% paromomycin cream)) are effective. [^20] For cutaneous *L*. *braziliensis* 15% paromomycin-aquaphilic is effective. [^21] Heat is also effective for cutaneous *Leishmania* *major*. [^22] ### Notes If you suspect a case, call the CDC. They are extremely helpful, will aid in getting the ulcer cultured, the specific species identified and help guide therapy. Invaluable. > "The first _Leishmania_-like fossil was found in the proboscis and alimentary tract of a blood-filled female of the extinct sand fly _Palaeomyia burmitis_ preserved in a 100 million-year-old Cretaceous Burmese amber...The second _Leishmania_-like fossil was described as _Paleoleishmania neotropicum_ and was found in the extinct sand fly _Lutzomyia adiketis_ in a 20–30 million-year-old Dominican amber" [^23] Lobomycosis can mimic *Leishmania* cutaneous disease. So consider the Main Man in your differential diagnosis. [^24] ### Puswhisperers [Hanging Chad](http://www.pusware.com/PW1/HangingChad.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1.mp3) [Belize Boil](http://www.pusware.com/PW6/BelizeBoil.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop808.mp3) [The sandfly is the vector but the gerbil is the reservoir.](http://www.pusware.com/PW10/SandFlyGerbil.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1138.mp3) ### Rationalizations [^1]: Hamad I, Forestier CL, Peeters M, Delaporte E, Raoult D, Bittar F. Wild gorillas as a potential reservoir of Leishmania major. J Infect Dis. 2015 Jan 15;211(2):267-73. doi: 10.1093/infdis/jiu380. Epub 2014 Jul 7. PMID: 25001460; PMCID: PMC4342692. [^2]: https://www.youtube.com/watch?v=KMiDf3Q1QfI [^3]: Rupal M Mody, Ines Lakhal-Naouar, Jeffrey E Sherwood, Nancy L Koles, Dutchabong Shaw, Daniel P Bigley, Edgie-Mark A Co, Nathanial K Copeland, Linda L Jagodzinski, Rami M Mukbel, Rebecca A Smiley, Robert C Duncan, Shaden Kamhawi, Selma M B Jeronimo, Robert F DeFraites, Naomi E Aronson, Asymptomatic Visceral _Leishmania infantum_ Infection in US Soldiers Deployed to Iraq, _Clinical Infectious Diseases_, Volume 68, Issue 12, 15 June 2019, Pages 2036–2044, [https://doi.org/10.1093/cid/ciy811](https://doi.org/10.1093/cid/ciy811) [^4]: Clarke CF, Bradley KK, Wright JH, Glowicz J. Case report: Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg. 2013 Jan;88(1):157-61. doi: 10.4269/ajtmh.2012.11-0717. Epub 2012 Nov 26. PMID: 23185078; PMCID: PMC3541728. [^5]: McIlwee BE, Weis SE, Hosler GA. Incidence of Endemic Human Cutaneous Leishmaniasis in the United States. JAMA Dermatol. 2018 Sep 1;154(9):1032-1039. doi: 10.1001/jamadermatol.2018.2133. PMID: 30046836; PMCID: PMC6143046. [^6]: McIlwee BE, Weis SE, Hosler GA. Incidence of Endemic Human Cutaneous Leishmaniasis in the United States. JAMA Dermatol. 2018 Sep 1;154(9):1032-1039. doi: 10.1001/jamadermatol.2018.2133. PMID: 30046836; PMCID: PMC6143046. [^7]: Galán-Puchades M, Gómez-Samblás M, Suárez-Morán JM, et al. Leishmaniasis in Norway Rats in Sewers, Barcelona, Spain. _Emerging Infectious Diseases_. 2019;25(6):1222-1224. doi:10.3201/eid2506.181027. [^8]: George A V da Silva, Tirza G Mesquita, Victor C Souza, José do Espírito Santo Junior, Mara Lúcia Gomes de Souza, Anette Chrusciak Talhari, Sinésio Talhari, Felipe G Naveca, Rajendranath Ramasawmy, A Single Haplotype of _IFNG_ Correlating With Low Circulating Levels of Interferon-γ Is Associated With Susceptibility to Cutaneous Leishmaniasis Caused by _Leishmania guyanensis_, _Clinical Infectious Diseases_, Volume 71, Issue 2, 15 July 2020, Pages 274–281, [https://doi.org/10.1093/cid/ciz810](https://doi.org/10.1093/cid/ciz810) [^9]: Alexsandro S Lago, Filipe R Lima, Augusto M Carvalho, Camilla Sampaio, Neuza Lago, Luiz H Guimarães, Jamile Lago, Paulo R L Machado, Lucas P Carvalho, Sérgio Arruda, Edgar M Carvalho, Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis, _Open Forum Infectious Diseases_, Volume 7, Issue 12, December 2020, ofaa491, [https://doi.org/10.1093/ofid/ofaa491](https://doi.org/10.1093/ofid/ofaa491) [^10]: Perry MR, Wyllie S, Prajapati VK, Feldmann J, Sundar S, Boelaert M, Fairlamb AH. Visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the Indian subcontinent? PLoS Negl Trop Dis. 2011 Sep;5(9):e1227. doi: 10.1371/journal.pntd.0001227. Epub 2011 Sep 27. PMID: 21980542; PMCID: PMC3181240. [^11]: Bern C, Adler-Moore J, Berenguer J, Boelaert M, den Boer M, Davidson RN, Figueras C, Gradoni L, Kafetzis DA, Ritmeijer K, Rosenthal E, Royce C, Russo R, Sundar S, Alvar J. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis. 2006 Oct 1;43(7):917-24. doi: 10.1086/507530. Epub 2006 Aug 28. PMID: 16941377. [^12]: Sousa AQ, Frutuoso MS, Moraes EA, Pearson RD, Pompeu MM. High-dose oral fluconazole therapy effective for cutaneous leishmaniasis due to Leishmania (Vianna) braziliensis. Clin Infect Dis. 2011 Oct;53(7):693-5. doi: 10.1093/cid/cir496. PMID: 21890773.Sousa AQ, Frutuoso MS, Moraes EA, Pearson RD, Pompeu MM. High-dose oral fluconazole therapy effective for cutaneous leishmaniasis due to Leishmania (Vianna) braziliensis. Clin Infect Dis. 2011 Oct;53(7):693-5. doi: 10.1093/cid/cir496. PMID: 21890773. [^13]: Prates FV, Dourado ME, Silva SC, Schriefer A, Guimarães LH, Brito MD, Almeida J, Carvalho EM, Machado PR. Fluconazole in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis: A Randomized Controlled Trial. Clin Infect Dis. 2017 Jan 1;64(1):67-71. doi: 10.1093/cid/ciw662. Epub 2016 Nov 1. PMID: 27803094. [^14]: Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med. 2007 Jun 21;356(25):2571-81. doi: 10.1056/NEJMoa066536. PMID: 17582067. [^15]: Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, Boelaert M, Dujardin JC, Chakravarty J. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis. 2012 Aug;55(4):543-50. doi: 10.1093/cid/cis474. Epub 2012 May 9. PMID: 22573856. [^16]: Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, Karki P, Singh R, Boelaert M, Dujardin JC. Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis. 2013 Jun;56(11):1530-8. doi: 10.1093/cid/cit102. Epub 2013 Feb 20. PMID: 23425958. [^17]: https://rx.webmd.com/drug-prices/impavido [^18]: Machado PR, Lessa H, Lessa M, Guimarães LH, Bang H, Ho JL, Carvalho EM. Oral pentoxifylline combined with pentavalent antimony: a randomized trial for mucosal leishmaniasis. Clin Infect Dis. 2007 Mar 15;44(6):788-93. doi: 10.1086/511643. Epub 2007 Feb 2. PMID: 17304449. [^19]: Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med. 2007 Jun 21;356(25):2571-81. doi: 10.1056/NEJMoa066536. PMID: 17582067. [^20]: Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, Gharbi A, Belhadj Hamida N, Boukthir A, Chlif S, Abdelhamid K, El Ahmadi Z, Louzir H, Mokni M, Morizot G, Buffet P, Smith PL, Kopydlowski KM, Kreishman-Deitrick M, Smith KS, Nielsen CJ, Ullman DR, Norwood JA, Thorne GD, McCarthy WF, Adams RC, Rice RM, Tang D, Berman J, Ransom J, Magill AJ, Grogl M. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med. 2013 Feb 7;368(6):524-32. doi: 10.1056/NEJMoa1202657. PMID: 23388004. [^21]: Jaime Soto, Paula Soto, Andrea Ajata, Carmelo Luque, Carlos Tintaya, David Paz, Daniela Rivero, Jonathan Berman, Topical 15% Paromomycin-Aquaphilic for Bolivian _Leishmania braziliensis_ Cutaneous Leishmaniasis: A Randomized, Placebo-controlled Trial, _Clinical Infectious Diseases_, Volume 68, Issue 5, 1 March 2019, Pages 844–849, [https://doi.org/10.1093/cid/ciy619](https://doi.org/10.1093/cid/ciy619) [^22]: Aronson NE, Wortmann GW, Byrne WR, Howard RS, Bernstein WB, Marovich MA, Polhemus ME, Yoon IK, Hummer KA, Gasser RA Jr, Oster CN, Benson PM. A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection. PLoS Negl Trop Dis. 2010 Mar 9;4(3):e628. doi: 10.1371/journal.pntd.0000628. PMID: 20231896; PMCID: PMC2834752. [^23]: Steverding, D. The history of leishmaniasis. _Parasites Vectors_ **10**, 82 (2017). https://doi.org/10.1186/s13071-017-2028-5 [^24]: https://www.dc.com/characters/lobo