Version May 2024
INTRODUCTION — Leishmaniasis consists of a complex of vector-borne diseases caused by a heterogeneous group of protozoa belonging to the genus Leishmania; it is transmitted by sand fly vectors. Clinical manifestations range from cutaneous ulcers to systemic multiorgan disease. The epidemiology and control of cutaneous leishmaniasis (CL) are reviewed here. The clinical manifestations, diagnosis, and treatment are discussed separately. (See "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Treatment".)
EPIDEMIOLOGY
General principles — Leishmania infection is endemic in scattered foci in more than 98 countries on five continents [1]. As of 2022, 99 countries reported endemic cutaneous leishmaniasis (CL) [2,3]. Globally, the annual incidence of CL is estimated to be 0.7 to 1 million new cases per year [4]. The 2019 Global Burden of Disease study estimated 4.6 million prevalent CL cases [5]. In 2022, approximately 85 percent of CL is reported from eight countries: Afghanistan, Algeria, Brazil, Colombia, Islamic Republic of Iran, Iraq, Peru, and the Syrian Arab Republic (figure 1) [2]. Detailed global distribution maps (1960 to 2020) have been published [6-8].
At least 23 species of Leishmania have been associated with human infection [9]. In general, leishmaniasis is transmitted by the bite of an infected female sand fly to mammalian reservoirs (typically rodents, sloths, marsupials, or wild or domestic canines) (figure 2). Humans are infected incidentally when they enter endemic areas. Anthroponotic (human-sand fly-human) transmission of Leishmania tropica in urban areas (Kabul, Afghanistan) has been described [10].
Emergence outside endemic areas — The number of CL cases imported into nonendemic developed countries increased during the 1990s and 2000s. Review of data from the GeoSentinel surveillance database demonstrated that between 1996 and 2004, CL was among the 10 most common dermatologic disorders among returning travelers from Central and South America [11,12]. Among United States GeoSentinel sites between 2008 and 2019, 111 CL cases and 6 mucosal leishmaniasis cases were reported [13]. Between 1997 and 2017 in the entire GeoSentinel study, 858 returned travelers had travel-acquired CL or mucosal leishmaniasis. Notably, 10 percent of the individuals with CL traveled for ≤2 weeks. Bolivia and Costa Rica were the destination countries associated with the highest number of CL cases (18 and 11 percent, respectively) [14].
Similarly, the Hospital for Tropical Diseases in London identified 223 patients with CL between 1998 and 2009 [15]. Old World CL was observed in 90 patients; it mostly occurred among travelers to the Mediterranean region and was caused by L.L. infantum (syn chagasi). New World CL was observed in 133 patients; 73 percent was caused by Leishmania Viannia species and it mostly occurred among backpackers or soldiers in jungle training. There were also 11 cases of mucosal leishmaniasis (ML); other reports have also described recognition of ML among young, healthy adventure travelers to Central and South America [15,16].
Military operations in Iraq and Afghanistan have been associated with outbreaks of Old World CL among military personnel. It is estimated that more than 2000 cases have occurred among United States personnel, based on samples submitted to the Leishmaniasis Diagnostics Laboratory at the Walter Reed Army Institute of Research. Infections acquired in Iraq are mainly due to L.L. major; infections acquired in Afghanistan are due to both L.L. major and L.L. tropica. Many cases of L.L. major infection acquired around Mazar-e-Sharif, Afghanistan, were complicated by lymphocutaneous invasion [17,18]. Rarely, cutaneous L.L. infantum (syn chagasi) infection has been observed.
Leishmaniasis and conflict have long been linked. Outbreaks in Afghanistan, Iran, Iraq, Colombia, and most recently the Syrian Arab Republic are illustrative of this. Conflict in the Syrian Arab Republic and the resultant effects on health infrastructure and mass displacement has led to epidemic CL [19-22]. This has caused outbreaks in Lebanon, Jordan, and Turkey among refugees [23-25]. Surveillance among adult Syrian refugees evaluated for migration-related illness found 32 percent had CL [26].
The clinical presentation of L.V. braziliensis in the Corte de Pedra area of northeast Brazil is evolving. Disseminated leishmaniasis is spreading rapidly in this area. This condition is distinct from diffuse CL; it consists of >10 (sometimes up to 300) pleomorphic, acneiform, nodular, or ulcerative lesions in more than two body areas. Frequently, it is much more severe and difficult to treat than localized CL caused by L.V. braziliensis [27,28]. Disseminated leishmaniasis has also been reported in Colombia [29].
In the United States, more than 80 cases of endemic human CL have been identified as of 2017; all were acquired in Arizona, Texas, or Oklahoma [30,31]. L.L. mexicana was identified in those with species identification, with a novel Leishmania noted in Arizona [31]. In 2014, a 27-month-old boy in North Dakota whose family had emigrated from endemic Nepal prior to his birth developed cutaneous L.L. donovani spp infection of the eyelid [32,33].
In Australia, CL due to a novel Leishmania species has been identified among red kangaroos, wallabies, and wallaroos; thus far, no human cases have been reported [34-36]. Transmission via a midge vector has been suggested.
In the French West Indies, a new species of parasite, L. Mundinia martiniquensis, has been reported to cause CL and VL [37,38]. Based on DNA sequence analysis, the parasite in Thailand known as L. Mundinia orientalis has been found to be the same subgenus, suggesting a broader geographic distribution than previously known [39]. In Ghana, CL caused by Leishmania enriettii complex was reported [40,41].
As use of biologic immunomodulating treatments expands, reports of CL associated with tumor necrosis factor-alpha inhibitor use and atypical presentations in travelers have been observed [42].
MICROBIOLOGY — CL in the New World is generally caused by L.L. mexicana and parasites from the Viannia complex (table 1). CL in the Old World is generally caused by L.L. major, L.L. tropica, or L.L. aethiopica. Species associated with visceral leishmaniasis, L.L. infantum (syn chagasi) and L.L. donovani, may also cause localized CL. (See "Visceral leishmaniasis: Clinical manifestations and diagnosis".)
LIFECYCLE — Leishmaniasis is transmitted by the bite of an infected female sand fly to a mammalian reservoir (typically rodents, sloths, marsupials, or wild or domestic canines) (figure 2).
Leishmania persist as obligate intracellular parasites (in the amastigote form) in macrophages of mammalian host tissues. Feeding sand fly vectors ingest amastigotes; over the next 4 to 14 days, amastigotes develop into motile, flagellated extracellular promastigote parasites in the gut of the sand fly. Promastigote parasites are subsequently regurgitated from the proboscis of the sand fly into the skin of the next mammalian host during feeding. These promastigotes are phagocytized and transformed to amastigotes within phagolysosomes, perpetuating the transmission cycle.
Sand fly vectors — Phlebotomine sand flies of two genera transmit CL: Lutzomyia in the New World and Phlebotomus in the Old World [43]. More than 90 sand fly species are proven or probable vectors [9].
Sand flies are generally nocturnal feeders, but some species in South America may feed preferentially during the day. Most species are capable of feeding during the day if disturbed. Sand flies are relatively poor fliers; they are easily disturbed by wind and live close to animal reservoirs for perpetuation of transmission.
Sand flies probe with slashing mouthparts that allow blood to pool below the skin surface. Infected sand flies regurgitate metacyclic Leishmania parasites, saliva, and promastigote secretory gel (PSG) into this blood pool. Sand fly saliva and PSG provide immunomodulatory changes at the infection site, which may exacerbate infection [44-47].
Transmission to humans — Transmission of CL can follow epidemic or endemic patterns. Outbreaks may occur when a sand fly habitat is disturbed (such as encroachment of settlements into forested areas of the Amazon) or when susceptible hosts move into areas of endemic transmission (for example, outbreaks of CL have occurred among military personnel deployed to Iraq and Afghanistan).
The global prevalence of CL is increasing because of many factors, including climate change, urbanization/deforestation, increasing rodent populations, decreasing insecticide use, war, mass population displacement/migration, adventure travel, and increasing numbers of immunosuppressed hosts.
Humans may represent a source of infection; viable parasites have been recovered from blood and uninvolved skin both before and after treatment [48-50]. The implications for transfusion/tissue donation remain to be explored, although the risk of human-to-human transmission is likely much lower than for visceral leishmaniasis.
CONTROL — Prevention of CL consists of individual protective measures and public health measures. There is no effective preexposure prophylaxis or effective vaccine. Prior infection confers some immunity against the infecting Leishmania species, which suggests promise for vaccine development [51]. Leishmanization, a strategy previously used in some regions at risk for L.L. major infection, consisted of injecting viable parasites to produce a controlled skin lesion and induce T cell immunity. This strategy had some efficacy, but there was variability between lots and not all skin lesions healed fully. A cost-effective analysis (using a societal perspective with costs per disability adjusted life year) found that a training program leading to improved CL early diagnosis and the interruption of vector transmission were cost effective [52].
Effective prevention requires health education regarding risk of infection and epidemiology of transmission. Infection is transmitted by sand fly bites usually between dusk and dawn. Covering skin with clothing is helpful as sand fly mouthparts do not penetrate clothing (in contrast, mosquito mouthparts do penetrate clothing). Clothing can be impregnated with an insecticide such as permethrin. An insect repellent such as DEET (NN-diethyl-3-methylbenzamide) can be applied to exposed skin areas. Use of fine mesh insecticide-treated bednets may also be helpful [53]. (See "Prevention of arthropod and insect bites: Repellents and other measures".)
Public health measures for prevention of CL consist of vector control (sand flies) and reservoir control (domestic and sylvatic animals) [54]. A review of preventive measures noted that few human-specific outcomes have been measured for any intervention [55]. One cluster-randomized clinical trial in Afghanistan showed that indoor residual spraying with lambdacyhalotrhin, insecticide-treated bednets, and insecticide-treated bedsheets were all associated with a significant reduction in CL cases [56]. In settings with peridomiciliary transmission, residual insecticide spraying may be effective; the efficacy depends on transmission dynamics in a local area [57]. A pilot comparative trial of insecticidal wall painting, insecticidal durable wall lining, insecticide impregnated bednets, and indoor residual spraying with deltamethrin suggested that insecticidal walling painting resulted in reduced sand fly numbers [58]. Effective interventions have included clearing vegetation, eliminating reservoir habitats such as rodent burrows, placing wall barriers, and using insecticide diffusers or coils in living areas [59,60]. Animal reservoir control may not be practical in areas where sylvatic rodents serve as the major reservoir. The use of deltametrin-impregnated collars in dogs has been associated with decreased seroconversion rates of visceral leishmaniasis in humans and dogs, but its efficacy for prevention of CL has not been evaluated [61].
SUMMARY
●Microbiology − Leishmaniasis consists of a complex of vector-borne diseases caused by protozoa belonging to the genus Leishmania (table 1). Cutaneous leishmaniasis (CL) in the New World is generally caused by L.L. mexicana and parasites from the Viannia complex. CL in the Old World is generally caused by L.L. major, L.L. tropica, or L.L. aethiopica. (See 'Microbiology' above.)
●Lifecycle − Leishmaniasis is transmitted by the bite of an infected female sand fly to a mammalian reservoir (figure 2). Sand flies are generally nocturnal feeders but are capable of feeding during the day. Transmission of CL can follow epidemic or endemic patterns. Outbreaks may occur when a sand fly habitat is disturbed or when susceptible hosts move into areas of endemic transmission. (See 'Lifecycle' above.)
●Epidemiology − Leishmania infection is endemic in scattered foci in more than 98 countries on 5 continents. Globally, the annual incidence of CL is estimated to be 0.7 to 1.0 million new cases per year. Approximately 85 percent of CL is reported from eight countries: Afghanistan, Algeria, Brazil, Colombia, Iraq, Islamic Republic of Iran, Peru, and the Syrian Arab Republic. (See 'Epidemiology' above.)
●Individual preventive measures − Individual protective measures for prevention of CL include covering skin with clothing; clothing can also be impregnated with insecticide such as permethrin. Insect repellent can be applied to exposed skin areas. Use of fine mesh insecticide-treated bednets may also be helpful. (See 'Control' above.)
●Vector and reservoir control − Public health measures for prevention of CL consist of vector control (sand flies) and reservoir control (domestic and sylvatic animals). Residual insecticide spraying may be effective in settings with peridomiciliary transmission. Other interventions have included clearing vegetation, eliminating reservoir habitats such as rodent burrows, placing wall barriers, and using insecticide diffusers or coils in living areas. (See 'Control' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Karin Leder, who contributed to an earlier version of this topic review.
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