Leishmaniasis

http://www.austincc.edu/microbio/2321/ld.htm

Leishmaniasis
By Leo E. Larios

Disease Etiologic Agent Leishmaniasis (leesh-muh-nahy-uh-sis) [1] is a vector-borne tropical/subtropical disease caused by intracellular protozoan species of the genus Leishmania. Infection in humans is caused by 21 different species of Leishmania, all of them morphologically indistinguishable from each other, and all of them causing the spectrum of clinical manifestations (cutaneous/mucosal and visceral) collectively known as Leishmaniasis. [1] [4]

Disease Transmission It is spread through the bite of infective female sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World [5]. In humans and other mammals infection is produced by the promastigote form of the parasite; once inside the host the protozoan is taken up by macrophages in the host, where it transforms into the amastigote form and multiply inside this leucocyte to later rupture it. The amastigotes released infect other macrophages and the cycle continues when a female sandfly feeds from the infected host [5], [6]. Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral (a.k.a. Kala-azar) leishmaniasis results. [4]

1 of 4

8/10/2013 9:37 PM

Leishmaniasis

http://www.austincc.edu/microbio/2321/ld.htm

Reservoir

Both anthroponotic and zoonotic foci exist; humans are the reservoir in anthroponotic cutaneous leishmaniasis; in zoonotic cases, wild rodents, marsupials and dogs are the reservoir for the species of Leishmania. In visceral leishmaniasis humans, wild members of canidae and dogs [4],[6] are reservoirs. In Bangladesh the only known reservoir for visceral leishmaniasis are humans. [6] Specific Microbial Characteristics The genus Leishmania is an obligate intracellular parasite, member of the trypanosomatid protozoa whose distinguishing feature is the possession of a single flagellum [5]. The variety of Leishmania species that cause leishmaniasis is one of the important factors that determine the type of leishmania infection (mucocutaneous or visceral) that can manifest in the host. [6] In the eastern hemisphere L. tropica, L. major, L. aethiopica are prevalent, and in the western hemisphere the L.mexicana and the L. braziliensis complexes are responsible for infection. Members of the L. braziliensis complex are likely to cause the mucosal form of the disease; and L. tropica causes usually the cutaneous form. The visceral manifestation is produced in the eastern hemisphere by members of the L. donovani complex and in the western hemisphere by L. chagasi/infantum. Taxonomy and groups are summarized in the two tables below. [6] [7] [8]

Specific Tests for Identification Diagnosis is through microscopic identification of the intracellular amastigote form in Giemsa stained slides from lesions, and through culture of the motile promastigote in suitable media [6]. Antibody detection can prove useful in visceral leishmaniasis but is of limited value in cutaneous disease, where most patients do not develop a significant antibody response [6].

2 of 4

8/10/2013 9:37 PM

Leishmaniasis

http://www.austincc.edu/microbio/2321/ld.htm

Species identification is done through monoclonal antibody testing, DNA techniques and biochemical isoenzyme assays. [4] Signs and Symptoms The most common forms of leishmaniasis are two, these are known as mucocutaneous leishmaniasis which causes skin sores, and visceral leishmaniasis which affects several internal organs (usually spleen, liver, and bone marrow) [6]. Cutaneous infection is localized and diffuse [5], it starts with a macule, then a papule and enlarges to a painful or painless ulcer. Lesion may be single or multiple, and these lesions may heal spontaneously within weeks or several months, sometimes lasting a year or more [6]. Visceral leishmaniasis is a chronic disease characterized by fever of sudden or gradual onset, liver and spleen enlargement, anemia, leukopenia, emaciation and weakness [6]. This form of the disease is usually fatal if left untreated. Historical Information The parasite was named in 1903 after the Scottish pathologist William Boog Leishman, who developed one of the earliest stains of the parasite in 1903 [9] [3]. Pre-Incan pottery in the first century AD depicts lesions consistent with mucocutaneous leishmaniasis; in Africa and India texts dating from the eighteenth century describe visceral leishmaniasis [3]. The origin of the genus Leishmania is uncertain. A proposed origin, evolution and dispersal of Leishmania, suggests a predecessor of L. donovani group and L. major would have evolved from parasites of insects in South America between 46 and 36 million years ago, and migrated to Asia via the Bering strait. The ancestor of the L. donovani complex diverged from other Leishmania species approximately between 14 and 24 million years ago. This predecessor arrived in central Asia and approx. 1 million years ago and later diverged into L. infantum, and L. donovani . Leishmania infantum was later introduced in South America by the European colonization. [10]

Virulence Factors Susceptibility is general [6]. Leishmania virulence is generally consequence of 1- Intrinsic virulence (drug resistance components, surface secretory components, and efficiency of the parasitic housekeeping system); 2- parasite burden in host (consequence in part of intrinsic virulence); 3- Host factors (immune response). [11] These components interact with each other and determine the global virulence of Leishmania. Parasites drug resistance, type of strain, and human host coinfection with HIV are examples of how these factors can affect virulence. Control and Treatment Patient treatment, periodic spraying with insecticides, destruction of rodent population in zoonotic areas and insecticide impregnated collars in the canine population foci are effective control measures. In anthroponotic foci, prompt and effective chemotherapy treatment of patients can help control transmission. [6] In mucocutaneous infections, pentavalent antimonials is the drug of choice. Pentamidine is used as a second line drug. In visceral or kala-azar leishmaniasis the most effective and expensive chemotherapy is amphotericin B. In developing countries the high cost of amphotericin B makes the pentavalent antimonials (Sb5) first line treatment of choice. [6] Prevention/Vaccines Currently there are no vaccines or drugs that prevent infection with Leishmania. Infection confers lifelong immunity; therefore a vaccine might be an effective method for prevention in the future. Protection from sand fly bites is best to avoid infection. Limiting outdoor activities in endemic areas from dusk to dawn, minimizing area of uncovered skin, use of insect repellant, and the use of bed nets treated with pyrethroids are practices that minimize exposure to the vector. Effective chemotherapy is becoming increasingly difficult due to emergence of drug resistance. [6] [12] [15] Local Cases/Outbreaks Although rare in Texas, native leishmaniasis infections have occurred in the past. From 1903 to 1989 a total of 27 native cases have been identified [13]. The distribution of these cases closely matches that of the wood rat (Neotoma micropus). In 2006-2007 nine cases were identified over the north Texas area, mostly rural locations in proximity to wooded or brushy areas where wild rodents, such as the wood rat, live. [14] Global Cases/Outbreaks The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new total leishmania cases each year [6] [15]. There are 2 million new cases of mucocutaneous leishmania infections worldwide each year. Visceral leishmaniasis cases amount to an incidence of 500,000 cases, with over 90% of the burden in India, Nepal, Sudan and Brazil [6]. Worldwide distribution maps for cutaneous and visceral leishmaniasis are shown below. [2] [3] a) Cutaneous Leishmaniasis distribution. [3]

3 of 4

8/10/2013 9:37 PM

Leishmaniasis

http://www.austincc.edu/microbio/2321/ld.htm

b) Visceral Leishmaniasis distribution. [2]

References [1] "Leishmaniasis." Dictionary.com Unabridged. Random House, Inc, n.d. Web. 13 Feb. 2013. <Dictionary.com http://dictionary.reference.com/browse/leishmaniasis>. [2] Anon. "Essential leishmaniasis maps." World Health Organization Leishmaniasis home. World Health Organization, n.d. Web. 14 Feb 2013. <http://www.who.int/leishmaniasis /leishmaniasis_maps/en/index1.html>. [3] Narciso, Heather, and Josuel Ruelan. "Leishmaniasis." Parasites & Pestilence:ParaSite Webpages. Stanford University, n.d. Web. 14 Feb 2013. <http://www.stanford.edu/class /humbio103/ParaSites2006/Leishmaniasis/Index.htm>. [4] Anon. "Leishmaniasis." DPDx-Laboratory Identification of Parasites of Public Health Concern. Centers for Disease Control and Prevention (CDC), 20 Jul 2009. Web. 14 Feb 2013. <http://dpd.cdc.gov/dpdx/HTML/Leishmaniasis.htm>. [5] Wikipedia contributors. "Trypanosomatid." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 12 Feb. 2013. Web. 25 Feb 2013. <http://en.wikipedia.org /w/index.php?title=Trypanosomatid&oldid=537900951> [6] Heymann M.D., David L. United States. American Public Health Association and WHO. Control of Communicable Diseases Manual. Washington, DC: American Public Health Association, 2008. Print. [7] McCall L-I, Zhang W-W, Matlashewski G (2013) Determinants for the Development of Visceral Leishmaniasis Disease. PLoS Pathog 9(1): e1003053. doi:10.1371/journal.ppat.1003053. Web.18 Feb 2013. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536654/> [8] Bhuwan B. Mishra, Raju R. Kale, Rakesh K. Singh, Vinod K. Tiwari. Alkaloids: Future prospective to combat leishmaniasis. Fitoterapia, Volume 80, Issue 2, March 2009, Pages 8190. Web.23 Feb 2013. <http://dx.doi.org/10.1016/j.fitote.2008.10.009> [9] Wikipedia contributors. "Leishmania." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 24 Feb. 2013. Web. 25 Feb 2013. <http://en.wikipedia.org /wiki/Leishmania> [10] Julius Lukes et al. Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy PNAS 2007 104 (22) 9375-9380; published ahead of print May 21, 2007,doi:10.1073/pnas.0703678104. Web. 22 Feb 2013. <http://www.pnas.org/content/104/22/9375.abstract> [11] Luis Rivas et al. Virulence and disease in leishmaniasis: what is relevant for the patient?. Trends in Parasitology, Volume 20, Issue 7, 1 July 2004, Pages 297301. Web. 22 Feb 2013. <http://dx.doi.org/10.1016/j.pt.2004.05.005> [12] Anon. United States. Centers for Disease Control and Prevention. Leishmaniasis. CDC, Update 01/10/2013. Web. Accessed 24 Feb 2013.<http://www.cdc.gov/parasites /leishmaniasis/epi.html>. [13] McHugh, CP. "Leishmaniasis in Texas: epidemiology and clinical aspects of human cases." Am J Trop Med Hyg. Nov 55.5 (1996): 547-55. Web. 24 Feb. 2013. <http://www.ncbi.nlm.nih.gov/pubmed/8940988>. [14] Jacobson, Sherry. NEWSclips." Rare, nonfatal skin infection found in N. Texas. Dallas Morning News, 28 Jun 2010. Web. 24 Feb 2013. <http://online.dshs.state.tx.us/Consumerand-External-Affairs/newsclips/September-2007/Rare,-nonfatal-skin-infection-found-in-N--Texans.aspx> [15] L. KEDZIERSKI, Y. ZHU and E. HANDMAN (2006). Leishmania vaccines: progress and problems. Parasitology, 133, pp S87-S112. doi:10.1017/S0031182006001831. Web. 2011. 24 Feb 2013. <http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=680888>

http://www.google.com/url?q=http%3A%2F%2Fdx.doi.org%2F10.1016%2Fj.pt.2004.05.005&sa=D&sntz=1&usg=AFQjCNHz0QJAvO3TC7E0Ex4uuLD4I5cjLA

4 of 4

8/10/2013 9:37 PM