Infectious agent
Leishmaniasis is attributable to obligate intracellular protozoan parasites; >20 Leishmania species trigger leishmaniasis. Leishmaniasis has totally different types, together with visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucosal leishmaniasis (ML). The presenting kind varies by Leishmania species. For instance, Leishmania infantum and Leishmania donovani are the most typical causes of VL, whereas ML is most frequently related to Viannia species.
Transmission
Leishmania parasites are most frequently transmitted via the bites of contaminated feminine phlebotomine sand flies. Transmission danger is biggest from nightfall to daybreak as a result of sand flies usually feed (i.e., chew) at night time and through twilight hours. Vector exercise would possibly simply be ignored as a result of sand flies are small and silent, and their bites can go unnoticed. Vacationers with doubtlessly elevated danger for leishmaniasis embody journey vacationers, chicken watchers, development staff, ecotourists, army personnel, missionaries, Peace Corps volunteers, and other people doing analysis or humanitarian work open air at night time or twilight. Nevertheless, even short-term vacationers in leishmaniasis-endemic areas have developed leishmaniasis. Immigrants and refugees from endemic areas additionally would possibly current with leishmaniasis. A much less frequent mode of transmission for each CL and VL is unintentional occupational (laboratory) exposures. For VL, unusual modes embody congenital transmission, blood transfusions, organ transplantation, and sharing of contaminated needles.
Epidemiology
In 2021, leishmaniasis was reported to be endemic in 99 international locations. An estimated 600,000 to 1,000,000 new circumstances of CL and 50,000 to 90,000 new circumstances of VL happen yearly. The ecologic settings for leishmaniasis transmission vary from rainforests to arid areas.
Within the Japanese Hemisphere, CL is present in Africa, notably the tropical area and North Africa; Asia, notably Central and Southwest Asia; southern Europe, together with southern France, Greece, Italy, Portugal, Spain, and the Mediterranean islands; and a few international locations of the Center East. Leishmaniasis from these areas is also known as “Previous World” leishmaniasis. Within the Western Hemisphere, CL is present in elements of Mexico, all international locations of Central America, and most of South America besides Chile and Uruguay. Endemic transmission in the US has been recognized in Texas, particularly amongst individuals residing in areas bordering northeastern Mexico, and presumably in Arizona and Oklahoma. Leishmaniasis from these areas is also known as “New World” leishmaniasis. Endemic transmission of CL is just not present in Canada. Go to the World Well being Group (WHO) cutaneous leishmaniasis endemicity map for extra info.
GeoSentinel Surveillance from 1997–2017 indicated that amongst sufferers with laboratory confirmed CL examined at specialised journey or tropical drugs clinics on 6 continents, together with North America, frequent supply international locations for travel-associated CL have been within the Amazon Basin (Brazil, Bolivia, Colombia, Ecuador, and Peru); Costa Rica; El Salvador; and Israel. Amongst immigrants, frequent supply international locations have been Afghanistan and Syria. Circumstances of CL in U.S. service personnel have mirrored army actions (e.g., in Afghanistan and Iraq). CL is normally extra frequent in rural than city areas however is present in some peri-urban and concrete areas (e.g., in Kabul, Afghanistan).
Though ML is unusual, it has occurred in vacationers and expatriates, together with in individuals whose circumstances of CL weren’t handled or have been handled inadequately. ML is mostly related to the Viannia subgenus present in Central and South America, notably in infections acquired in Bolivia, Brazil, or Peru. Nevertheless, ML has been documented on uncommon events with species of Leishmania present in numerous international locations of the Japanese Hemisphere.
VL is normally extra frequent in rural than city areas, however it’s present in some peri-urban areas (e.g., in northeastern Brazil). Within the Japanese Hemisphere, VL is present in Africa, notably East Africa; elements of Asia, notably the Indian subcontinent and Central and Southwest Asia; southern Europe; and the Center East. Within the Western Hemisphere, most circumstances happen in Brazil; some circumstances happen in scattered foci elsewhere in Latin America. General, VL is present in focal areas of >70 international locations. In 2021, 97% of reported VL circumstances have been from 11 international locations: Brazil, Eritrea, Ethiopia, India, Kenya, Nepal, Somalia, South Sudan, Sudan, Uganda, and Yemen. Go to the 2020 WHO visceral leishmaniasis endemicity map for extra info.
The geographic distribution of VL circumstances evaluated in the US and different international locations displays journey and immigration patterns. Though unusual in most U.S. vacationers, expatriates, and army personnel, VL has occurred in such short-term and long-term vacationers coming back from journey or deployment to endemic areas in European international locations (e.g., France, Greece, Italy, Macedonia, and Spain) and the Center East.
Medical presentation
Medical presentation is determined by the type of leishmaniasis (i.e., CL, ML, or VL). Not all individuals with Leishmania an infection develop signs.
Cutaneous leishmaniasis
CL can current with a broad number of dermatologic manifestations starting from small and localized pores and skin lesions to giant nodules or plaques protecting a number of physique surfaces. The medical spectrum can mimic different pores and skin situations (e.g., leprosy, squamous cell most cancers, fungal or different pores and skin infections).
Lesions usually develop on uncovered areas of the pores and skin inside a number of weeks after an infection. Nevertheless, lesions might first seem months or years later, typically within the context of trauma (e.g., pores and skin wounds, surgical procedure). The lesions can change in look and measurement over time, usually progressing from small, erythematous papules or nodular plaques to open sores with raised borders and central craters (i.e., ulcers), which may be lined with crusts or scales. Lesions normally are painless however may be painful if superinfected with micro organism. Satellite tv for pc lesions, regional lymphadenopathy, and nodular lymphangitis can happen. Even with out remedy, most lesions ultimately heal; they’ll final for months or years, nevertheless, and usually end in scarring.
Mucosal leishmaniasis
Some Leishmania species are a possible concern as a result of parasites would possibly unfold from the pores and skin to the mucosal surfaces of the nostril or mouth and trigger lesions in these areas. Most frequently, these are Leishmania Viannia species in Central and South America. ML regularly seems years after the unique pores and skin lesions have healed however can also happen together with the pores and skin lesions or because the preliminary presentation of a subclinical cutaneous an infection. The preliminary medical manifestations usually contain the nostril, with bleeding, power stuffiness, and infected mucosa or lesions; much less typically the mouth or larynx are concerned, manifesting as a brassy cough or hoarseness. In superior circumstances, ulcerative destruction of the mouth, nostril, larynx, and pharynx (e.g., perforation of the nasal septum, laryngeal harm, or tracheal harm) can happen.
Visceral leishmaniasis
Amongst symptomatic individuals, the incubation interval usually ranges from weeks to months. Sickness onset may be abrupt or gradual. Stereotypical medical manifestations of VL embody fever, hepatosplenomegaly (particularly splenomegaly), night time sweats, and weight reduction; lymphadenopathy can happen. Laboratory findings attribute of VL embody pancytopenia (anemia, leukopenia, thrombocytopenia), excessive complete protein, low albumin, and hypergammaglobulinemia. If untreated, extreme (superior) circumstances of VL usually are deadly. Latent an infection can clinically manifest years to many years after publicity in individuals who turn out to be immunocompromised via HIV an infection, biologic immunomodulatory remedy, or immunosuppressive remedy.
Prognosis
CDC can help with the diagnostic analysis of suspected leishmaniasis, together with parasite species identification. For consultative companies, contact CDC Parasitic Illnesses Inquiries (404-718-4745; parasites@cdc.gov). CDC’s Parasitology Lab (404-718-4175; parasiteslab@cdc.gov) can present useful info relating to assortment, storage, and delivery of samples for Leishmania diagnostic testing.
Cutaneous and mucosal leishmaniasis
Contemplate CL in individuals with power, non-healing pores and skin lesions who’ve been in areas the place leishmaniasis is discovered. Medical indicators and signs will not be sufficiently particular to distinguish CL from different situations. Receive an express journey historical past, together with, if potential, questioning fellow vacationers about comparable lesions. Receive details about length and development of signs, whether or not the lesions are painful, prior remedy, and present drugs (e.g., immunosuppressive brokers); images are useful to evaluate lesions over time. Conduct a cautious bodily examination, together with analysis of pores and skin, lymph nodes, and mucosal surfaces.
Any affected person with CL attributable to a species with danger of inflicting ML, primarily associated to the Viannia subgenus species (Leishmania (V.) braziliensis, Leishmania (V.) guyanensis, and Leishmania (V.) panamensis), but additionally hardly ever associated to some extra New World and Previous World species, ought to bear a cautious examination of mucosal surfaces, together with the vocal cords and oronasal pharynx, together with biopsy of any irregular showing tissue, to guage for ML. This mucosal examination ought to happen no matter different signs. Referral to a specialist in a position to conduct an endoscopic laryngeal examination is warranted if ML is suspected.
Laboratory affirmation of the analysis is achieved by detecting Leishmania parasites or DNA in contaminated tissue via light-microscopic examination of stained specimens, tradition methods, or molecular strategies (e.g., polymerase chain response); conducting a number of checks on the specimen improves diagnostic yield. As a result of totally different Leishmania species have totally different administration implications, species identification via molecular testing is vital, notably if >1 species is endemic to areas the place the affected person traveled. Serologic testing typically is just not helpful for CL as a result of the assays are insensitive and can’t distinguish between energetic and previous an infection.
Visceral leishmaniasis
Contemplate VL within the differential analysis of individuals with a related journey historical past, even within the distant previous, and a persistent, unexplained febrile sickness, particularly if accompanied by different suggestive manifestations (e.g., pancytopenia or splenomegaly). Hemophagocytic lymphohistiocytosis might be a complication and may immediate healthcare professionals to think about VL in sufferers with the suitable journey historical past.
Laboratory affirmation of the analysis is achieved by detecting Leishmania parasites or DNA in contaminated blood, bone marrow, liver, or lymph nodes via light-microscopic examination of stained specimens, molecular strategies, or tissue tradition methods. Serologic testing can present supportive proof for the analysis.
Remedy
Remedy of leishmaniasis may be complicated; healthcare professionals can obtain professional session from CDC employees about remedy approaches (see the “Prognosis” part of this chapter for contact info).
Cutaneous and mucosal leishmaniasis
The first purpose of CL and ML remedy is to forestall morbidity. Choices about whether or not and the way to deal with CL, together with whether or not to make use of a systemic (oral or parenteral) remedy moderately than an area or topical strategy, must be individualized. All circumstances of ML must be handled with systemic remedy. The response to a specific routine can range not solely amongst Leishmania species but additionally for a similar species in several geographic areas. Knowledgeable session is suggested for remedy of any affected person with CL, ML, or VL.
Some sufferers with CL could also be candidates for native remedy relying on the danger of mucosal dissemination, affected person traits, and the traits, quantity, and site of the lesion(s). Native remedy can embody cryotherapy, warmth remedy, topical paromomycin, or intralesional pentavalent antimonials. In the US, topical paromomycin could also be accessible via compounding pharmacies and its use is taken into account off-label. The oral agent miltefosine is permitted by the U.S. Meals and Drug Administration (FDA) to deal with CL attributable to 3 Western Hemisphere species of the Viannia subgenus: Leishmania (V.) braziliensis, L. (V.) guyanensis, and L. (V.) panamensis, in addition to for ML attributable to L. (V.) braziliensis in adults and adolescents ≥12 years previous who weigh ≥30 kg and will not be pregnant or breastfeeding throughout remedy or for five months after the final dose of miltefosine. Numerous parenteral choices, together with liposomal amphotericin B, are commercially accessible, though not FDA-approved to deal with CL or ML. The pentavalent antimonial compound meglumine antimoniate (Glucantime) is just not FDA-approved however may be acquired via an Investigational New Drug (IND) software. Glucantime may be administered intravenously, intramuscularly, or intralesionally; the route of administration must be individualized, and professional session is suggested. Pentostam is now not accessible, however sodium stibogluconate could also be accessible in some international locations exterior of the US.
Visceral leishmaniasis
All symptomatic sufferers with VL must be handled. Refer sufferers with VL to an infectious illness or tropical drugs specialist who might help direct care and supply individualized remedy. Threat for relapse and remedy failure is bigger in immunocompromised VL sufferers in contrast with immunocompetent VL sufferers, notably these residing with HIV. Due to this fact, remedy of VL can differ between immunocompromised and immunocompetent VL sufferers. Relapse and remedy failure hardly ever would possibly happen in immunocompetent sufferers.
Liposomal amphotericin B (AmBisome) is permitted by the FDA to deal with VL and is mostly the drug of alternative for U.S. sufferers. The oral agent miltefosine is permitted by the FDA to deal with VL in sufferers contaminated with L. donovani who’re ≥12 years previous, who weigh ≥30 kg, and who will not be pregnant or breastfeeding throughout remedy or for five months after remedy. Pentavalent antimonials (e.g., meglumine antimoniate [Glucantime], sodium stibogluconate) are utilized in endemic areas, aside from India, the place creating resistance is a priority. See the “Cutaneous and Mucosal Leishmaniasis” part above for additional info on the provision of pentavalent antimonials.
Prevention
No vaccines or medication to forestall an infection can be found. Vacationers can scale back the danger of CL through the use of private protecting measures to keep away from sand fly bites (see Mosquitoes, Ticks, and Different Arthropods chapter). Advise vacationers to keep away from out of doors actions, particularly from nightfall to daybreak when sand flies are essentially the most energetic; put on protecting clothes and apply insect repellent to uncovered pores and skin and underneath the sides of clothes (e.g., shirt sleeves, pant legs) in response to the producer’s directions; and sleep in air-conditioned or well-screened areas. Spraying sleeping quarters with insecticide would possibly present some safety, and followers or ventilators would possibly inhibit the motion of sand flies, that are weak fliers.
Sand flies are small (roughly 2–3 mm, <1/8 inch) and might cross via the holes in extraordinary mosquito nets. Though effective mesh nets can be found, these may be uncomfortable in sizzling climates. The effectiveness of mosquito nets may be enhanced by treating with a pyrethroid-containing (i.e., permethrin) insecticide. The identical remedy may be utilized to mattress sheets and clothes, curtains, and window screens.
