# data[].attributes.attachment_link.title
Leishmaniasis - StatPearls - NCBI Bookshelf

# data[].attributes.attachment_link.description
Leishmaniasis is a disease caused by the protozoa Leishmania and is most commonly transmitted by infected sandflies. It has been historically widespread in tropical climates across multiple continents including Europe, Africa, Asia, and America. In humans, these parasites replicate intracellular and…

# data[].attributes.attachment_link.readable_text
The .gov means it's official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Abstract

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results.

Keywords: leishmania; leishmania treatment; recombinant antigens; vaccine.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Similar articles

Identifying vaccine targets for anti-leishmanial vaccine development.

Sundar S, Singh B. Sundar S, et al. Expert Rev Vaccines. 2014 Apr;13(4):489-505. doi: 10.1586/14760584.2014.894467. Expert Rev Vaccines. 2014. PMID: 24606556 Free PMC article. Review.

DNA based vaccination with a cocktail of plasmids encoding immunodominant Leishmania (Leishmania) major antigens confers full protection in BALB/c mice.

Ahmed SB, Touihri L, Chtourou Y, Dellagi K, Bahloul C. Ahmed SB, et al. Vaccine. 2009 Jan 1;27(1):99-106. doi: 10.1016/j.vaccine.2008.10.013. Epub 2008 Oct 23. Vaccine. 2009. PMID: 18951941

How to master the host immune system? Leishmania parasites have the solutions!

Rossi M, Fasel N. Rossi M, et al. Int Immunol. 2018 Mar 10;30(3):103-111. doi: 10.1093/intimm/dxx075. Int Immunol. 2018. PMID: 29294040 Free PMC article. Review.

Successful vaccination against Leishmania chagasi infection in BALB/c mice with freeze-thawed Leishmania antigen and Corynebacterium parvum.

Vilela Mde C, Gomes DC, Marques-da-Silva Ede A, Serafim TD, Afonso LC, Rezende SA. Vilela Mde C, et al. Acta Trop. 2007 Nov-Dec;104(2-3):133-9. doi: 10.1016/j.actatropica.2007.08.007. Epub 2007 Aug 31. Acta Trop. 2007. PMID: 17919443

References

Cabezas Y, Legentil L, Robert-Gangneux F, et al. Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates. Org Biomol Chem. 2015;13(31):8393-8404. - PubMed

de Freitas EO, Leoratti FM, Freire-de-Lima CG, Morrot A, Feijó DF. The contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis. Front Immunol. 2016;7:153. - PMC - PubMed

de Vries HJ, Reedijk SH, Schallig HD. Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol. 2015;16(2):99-109. - PMC - PubMed

Pearson RD, Sousa AQ. Clinical spectrum of leishmaniasis. Clin Infect Dis. 1996:1-11. - PubMed

Savoia D. Recent updates and perspectives on leishmaniasis. J Infect Dev Ctries. 2015;9(6):588-596. - PubMed

# data[].attributes.attachment_link.keywords[]
leishmaniasis vaccines / adverse effects

# data[].attributes.attachment_link.keywords[]
leishmaniasis vaccines / therapeutic use*

# data[].attributes.attachment_link.keywords[]
national center for biotechnology information

# data[].attributes.attachment_link.title
Leishmaniasis in humans: drug or vaccine therapy? - PubMed

# data[].attributes.attachment_link.description
The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

# data[].attributes.headline
Peer Review Article: Understanding Cutaneous Leishmaniasis

# data[].attributes.subject
Peer Review Article: Understanding Cutaneous Leishmaniasis

# data[].attributes.attachment_link.readable_text
Leishmaniasis is a neglected disease, World Health Organization (WHO) declared it as high priority worldwide. Colombia is one of the 98 countries in which the disease caused more than 17.000 cases per year. There is a need to explore novel therapies to reduce the side effects of the current treatments. For this reason, this study was aimed to evaluate Galleria mellonella hemolymph for potential peptides with anti-parasitic activity. Larvae were challenged with Leishmania (V) panamensis promastigotes and hemolymph was analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), reversed-phase chromatography (RP-HPLC), two-dimensional gel electrophoresis and liquid chromatography-mass spectroscopy (LC/MS). The immunological response of Galleria mellonella was followed by SDS-PAGE, immunized hemolymph was fractionated by RP-HPLC where fractions 5 and 11 showed the highest antileishmanial activity. From these fractions 15 spots were isolated by 2D gel electrophoresis and evaluated by LC/MS to identify the peptides present in the spots. After the analysis Moricin-B, Moricin-C4, Cecropin-D and Anionic Peptide 2 were identified due to the immune challenge with Leishmania promastigotes. Anionic peptide 2 and Cecropin-D were synthesized and evaluated for antileishmanial activity. The results showed that Anionic peptide 2 presented more anti-parasitic activity. This study showed for the first time the anti-parasitic potential of peptides derived from hemolymph of Galleria mellonella.

View all citing articles on Scopus

# data[].attributes.attachment_link.title
Cutaneous Leishmaniasis: The Truth about the 'Flesh-Eating Disease' in Syria

# data[].attributes.attachment_link.description
Leishmaniasis is a neglected disease, World Health Organization (WHO) declared it as high priority worldwide. Colombia is one of the 98 countries in which the disease caused more than 17.000 cases per year. There is a need to explore novel therapies to reduce the side effects of the current treatments.

# data[].attributes.headline
World Health Organization on Leishmaniasis

# data[].attributes.subject
World Health Organization on Leishmaniasis

# data[].attributes.attachment_link.readable_text
Overview

Leishmaniasis is caused by a protozoa parasite from over 20 Leishmania species. Over 90 sandfly species are known to transmit Leishmania parasites. There are 3 main forms of the disease:

Visceral leishmaniasis (VL), also known as kala-azar, is fatal if left untreated in over 95% of cases. It is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anaemia. Most cases occur in Brazil, east Africa and India. An estimated 50 000 to 90 000 new cases of VL occur worldwide annually, with only 25-45% reported to WHO. It has outbreak and mortality potential.

Cutaneous leishmaniasis (CL) is the most common form and causes skin lesions, mainly ulcers, on exposed parts of the body. These can leave life-long scars and cause serious disability or stigma. About 95% of CL cases occur in the Americas, the Mediterranean basin, the Middle East and central Asia. It is estimated that 600 000 to 1 million new cases occur worldwide annually but only around 200 000 are reported to WHO.

Mucocutaneous leishmaniasis leads to partial or total destruction of mucous membranes of the nose, mouth and throat. Over 90% of mucocutaneous leishmaniasis cases occur in Bolivia (the Plurinational State of), Brazil, Ethiopia and Peru.

Transmission

Leishmania parasites are transmitted through the bites of infected female phlebotomine sandflies, which feed on blood to produce eggs. Some 70 animal species, including humans, can be the source of Leishmania parasites.

WHO regional specificities

WHO African Region

Cutaneous Leishmaniasis is highly endemic in Algeria whereas in west Africa the epidemiological information is scarce. In east Africa all forms are endemic with outbreaks of visceral leishmaniasis occurring frequently.

WHO Region of the Americas

Cutaneous leishmaniasis is the main form and the epidemiology is complex, with several animals being the source of the parasite, and numerous types of sandflies and multiple Leishmania species in the same geographical area. Brazil is the main country endemic for VL in that region.

WHO Eastern Mediterranean Region

This region accounts for 80% of the cutaneous leishmaniasis cases reported worldwide. Visceral leishmaniasis is highly endemic in Iraq, Somalia, Sudan and Yemen.

WHO European Region

Cutaneous and visceral leishmaniasis are endemic. Imported cases are common, coming mainly from Africa and the Americas.

WHO South-East Asia Region

Visceral leishmaniasis is the main form of the disease, which is also endemic for cutaneous leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL)

Post-kala-azar dermal leishmaniasis (PKDL) is usually a sequel of visceral leishmaniasis that appears as macular, papular or nodular rash usually on face, upper arms and trunk. It occurs in east Africa (mainly in Sudan) and on the Indian subcontinent, where 5-10% of patients with kala-azar are reported to develop the condition. Although uncommon, it has also been reported from Brazil and also in HIV coinfected VL cases caused by L. infantum. It usually appears 6 months to 1 or more years after kala-azar has apparently been cured but can occur earlier. People with PKDL are considered a potential source of Leishmania infection.

Leishmania-HIV co-infection

People living with HIV and who are infected with leishmaniasishave high chances of developing the full-blown disease, high relapse and mortality rates. Antiretroviral treatment reduces the development of the disease, delays relapses and increases the survival. As of 2021, Leishmania-HIV coinfection has been reported from 45 countries. High coinfection rates are reported from Brazil, Ethiopia and the state of Bihar ( India). In 2022, WHO published new treatment recommendations for Leishmania-HIV coinfected patients in east Africa and South-East Asia.

Major risk factors

Socioeconomic conditions

Poverty increases the risk for leishmaniasis. Poor housing and domestic sanitary conditions (lack of waste management or open sewerage) may increase sandfly breeding and resting sites, as well as their access to humans. Sandflies are attracted to crowded housing because it is easier to bite people and feed on their blood. Human behaviour, such as sleeping outside or on the ground, may increase risk.

Malnutrition

Diets lacking protein-energy, iron, vitamin A and zinc increase the risk that an infection will progress to a full-blown disease.

Population mobility

Epidemics of leishmaniasis often occur when many people who are not immune move into areas where the transmission is high.

Environmental and climate changes

The incidence of leishmaniasis can be affected by changes in urbanization, deforestation or the human incursion into forested areas.

Climate change is affecting the spread of leishmaniasis though changes in temperature and rainfall, which affect the size and geographic distribution of sandfly populations. Drought, famine and flood also cause migration of people into areas where the transmission of the parasite is high.

Diagnosis and treatment

People suspected of suffering from visceral leishmaniasis should seek medical care immediately. In visceral leishmaniasis, diagnosis is made by combining clinical signs with parasitological or serological tests (such as rapid diagnostic tests). In cutaneous and mucocutaneous leishmaniasis serological tests have limited value and clinical manifestation with parasitological tests confirms the diagnosis.

The treatment of leishmaniasis depends on several factors including type of disease, concomitant pathologies, parasite species and geographic location. Leishmaniasis is a treatable and curable disease, which requires an immunocompetent system because medicines will not get rid of the parasite from the body, thus the risk of relapse if immunosuppression occurs. All patients diagnosed with visceral leishmaniasis require prompt and complete treatment. Detailed information on the treatment is available in the WHO technical report series 949, Control of leishmaniasis and the latest guidelines published on HIV-VL in east Africa and South-East Asia and the guideline for the treatment of leishmaniasis in the Americas.

Prevention and control

Preventing and controlling the spread of leishmaniasis is complex and requires many tools. Key strategies include:

Early diagnosis and effective prompt treatment reduce the prevalence of the disease and prevents disabilities and death. It helps to reduce transmission and to monitor the spread and burden of disease. There are highly effective and safe anti-leishmanial medicines particularly for visceral leishmaniasis, although they can be difficult to use. Access to medicines has significantly improved thanks to a WHO-negotiated price scheme and a medicine donation programme through WHO.

Vector control helps to reduce or interrupt transmission of disease by decreasing the number of sandflies. Control methods include insecticide spray, use of insecticide-treated nets, environmental management and personal protection.

Effective disease surveillance is important to promptly monitor and act during epidemics and situations with high case fatality rates under treatment.

Control of animal reservoir hosts is complex and should be tailored to the local situation.

Social mobilization and strengthening partnerships - mobilization and education of the community with effective behavioural change interventions must always be locally adapted. Partnership and collaboration with various stakeholders and other vector-borne disease control programmes is critical.

WHO response

WHO's work on leishmaniasis control involves:

supporting national leishmaniasis control programmes technically and financially to update guidelines, ensure access to quality-assured medicines, design disease control plans, surveillance systems, and epidemic preparedness and response systems;

monitoring disease trends and assessing the impact of control activities through the web-based global surveillance system which will allow for raising awareness and advocacy on the global burden of leishmaniasis and promoting equitable access to health services;

developing evidence-based policy strategies and standards for leishmaniasis prevention and control, including capacity building such as online courses at Neglected Tropical Diseases (openwho.org);

strengthening collaboration and coordination among partners and stakeholders;

promoting research including safe, effective and affordable medicines, as well as diagnostic tools and vaccines; and

supporting the South-East Asia Region, the only one with an initiative for the elimination of visceral leishmaniasis as a public health problem through 2022-2026, defined as less than one case per 10 000 inhabitants at the district level in Nepal and subdistrict level in Bangladesh and India. As per NTD road map 2023 milestone, only one country has been validated for elimination as public health problem. The region launched Regional strategic framework for accelerating and sustaining elimination of kala-azar in the South-East Asia Region 2022-2026.

# data[].attributes.attachment_link.description
Bites of infected female sand flies causes the disease. The visceral form attacks internal organs; the cutaneous form causes facial ulcers, disfiguring scars and disability. #BeatNTDs

# data[].attributes.headline
Peer Review Video: Afghan cities hit by disease caused by the sand fly

# data[].attributes.subject
Peer Review Video: Afghan cities hit by disease caused by the sand fly

# data[].attributes.body
https://video.ebscohost.com/c/4xjy4h/details/1_ds0t2h18?q=Cutaneous%20Leishmaniasis&deviceId=2421d5b1-3467-4151-80b3-d6d2af19197f&lang=en&minDate=&maxDate=

# data[].attributes.attachment_link.description
Sign in with your credentials to access the EBSCOhost premium information resources provided by your subscribing institution.

# data[].attributes.attachment_link.title
Bill & Melinda Gates Foundation Awards $15.1 Million To Treat African Sleeping Sickness And Leishmaniasis

# data[].attributes.attachment_link.description
CHAPEL HILL, N.C. -- The Bill & Melinda Gates Foundation has awarded $15.1 million to an international consortium of researchers, led by a University of North Carolina at Chapel Hill scientist, to develop new drugs to fight African sleeping sickness and leishmaniasis -- two diseases that are killing and infecting millions of people in developing nations.

# data[].attributes.attachment_link.readable_text
Soon after the first cases of COVID-19 were detected in Pakistan, in March, 2020, the government shut down all non-essential services, including outpatient care for an array of diseases not requiring emergency treatment. As a result, Médecins Sans Frontières was forced to close its clinics for people with cutaneous leishmaniasis.

Many patients, unaware of the extent of the shutdown and desperate for care, showed up to clinics anyway. But MSF-the only organization providing care for the disease in the country-had no choice but to turn them away, with nowhere else to go. Even hospitals would not accept patients for supportive treatment, since the disease is not considered life-threatening.

Suzette Kämink, a medical researcher focused on cutaneous leishmaniasis with MSF in Peshawar, Pakistan, witnessed the confusion and worry among patients in the early stages of the pandemic. Some traveled hundreds of kilometers for treatment-only to find clinics shuttered for reasons they struggled to understand, with little information about COVID reaching poorer, rural communities. "We had crying patients on the doorstep, begging for us to treat them," she said.

Pre-pandemic, in early 2020, MSF clinics in Pakistan were receiving over 250 new patients each week to start treatment for cutaneous leishmaniasis, a parasitic disease transmitted by the bite of a sandfly that causes large, painful ulcers on exposed skin.

It is a disease of poverty: Sandflies easily breed in areas with poor sanitation and hygiene, leading to the disease's disproportionate effect on poor communities.

The disease is also heavily stigmatized in Pakistan. The highly visible wounds on the hands or face cause significant discrimination and isolation-making the disease even more devastating for those already burdened by poverty. "It's really a heartbreaking disease," Kämink said, describing patients unable to find jobs because of large wounds on their faces, or being isolated from their families out of misplaced fear that the disease is contagious.

Even before COVID-19, such neglected diseases of poverty led to undue suffering because treatments are outdated and mediocre, at best, and research has been vastly underfunded.

But now, researchers express concern that stalled progress over the last year has further set back much-needed advancements to treatments. With the pandemic in its second year, doctors and researchers around the world are seeing the alarming effects of stalled health care and clinical trials on diseases affecting the world's most vulnerable populations.

Pakistan's reported 50,000+ cases of cutaneous leishmaniasis in 2019 is likely an undercount, given Pakistan's limited diagnostic capacity. The few treatment facilities are unevenly distributed throughout the country, rendering them tougher for more remote communities to reach. Traveling long distances every day for a 3-week course of treatment means a significant loss of income, in addition to transportation costs. Many who cannot afford the costs end up delaying treatment or skipping doses, which increases the likelihood that the lesion will leave a lifelong scar.

Some patients were unable to find any form of transportation to reach treatment centers once they reopened in September of 2020, after 6 months of closure. Rughia, a female patient at an MSF clinic, said, "I couldn't go to the clinic because roads were blocked and there was no bus, and there I was with my children and my own wound. I was scared as I saw it growing (the lesion) and couldn't do anything. I fear for my children."

The pandemic not only exacerbated the obstacles to care-it also set back efforts to develop better treatments. Currently, the only treatment available-the standard for over 70 years-consists of a series of painful injections administered daily for 3 weeks. Kämink and other neglected disease advocates believe new drugs are essential for reducing the burden of leishmaniasis, and MSF had long planned a clinical trial to improve treatments and potentially spare patients long journeys to clinics to cure their wounds.

MSF plans to study 2 potential therapies in its clinical trial. One, an oral drug, would entail a 1- month course of treatment-but it could be taken from the comfort of home rather than requiring patients to travel to the treatment facility each day. The other, in the form of thermotherapy, utilizes heat to treat the parasitic infections, and would only require patients to travel to the clinic once. If either of these therapies is found to be effective, Kämink says, it could significantly improve treatment access.

While MSF is the only organization focusing on leishmaniasis in Pakistan, other NGOs such as the Drugs for Neglected Diseases initiative are working on similar clinical trials for leishmaniasis treatments in different regions of the world. Not surprisingly, though, studies on neglected diseases have taken a back seat to COVID-19 in the pandemic era.

And the dire situation illustrated by cutaneous leishmaniasis in Pakistan holds true for other neglected diseases, too. Professor Ahmed Musa, a tropical infectious disease researcher in Sudan, studies tuberculosis, schistosomiasis, and visceral leishmaniasis (which affects internal organs rather than the skin). He said that funders see his projects and clinical trials as "second priority" to COVID-19 research. Musa and his team have accepted painful budget cuts for their clinical trials because, he said, "otherwise we have to stop them altogether."

Transportation challenges meant patients were not able to travel to clinics for weeks, and by the time they reached the treatment centers, many were ineligible to participate in Musa's clinical trials: Either too much time had passed from the start of their illness, or they were too ill from delaying treatment to be able to safely enter the clinical trial. Musa said the pandemic "markedly" impacted recruitment and delayed data analysis, pushing back the timeline for any potential drug approval process.

Skyrocketing costs for materials forced Musa and his team to seek alternative options. During a fuel shortage in Khartoum, they had to resort to the black market to purchase gasoline in order to travel the 6-plus hours it takes to reach clinical trial sites in the countryside-creating logistical headaches for Musa, as the principal investigator of multiple studies.

Despite the challenges, Musa's clinical trials have been able to continue in at least some capacity during the pandemic. MSF's clinical trials in Pakistan have not had as much luck.

Since September 2020, when clinics reopened, MSF's priority has been safely resuming treatment for patients whose progress was interrupted by the pandemic, and ensuring new patients are able to be treated. But more than a year after its planned debut, the clinical trial has not yet started.

In the meantime, MSF will continue to advocate for reduced costs and increased availability of drugs to treat cutaneous leishmaniasis in Pakistan. They are hopeful that new treatments on the horizon will drastically influence global efforts to control the disease. However, it is always in the back of the mind that as a neglected tropical disease, leishmaniasis carries less weight than other health issues regarded as more pressing by the international community. Since cutaneous leishmaniasis is not very life-threatening, Kämink said, "no priority is given to it."

With the unpredictability of COVID-19, the timeline for approving new treatments is anything but certain. Still, those working on neglected diseases believe in the work they are doing. "I always say that if we don't help our neglected people with all the neglected diseases," Musa said, "who is going to help them?"

Natalie Wodniak is a 2020 Pulitzer Center Campus Consortium Reporting Fellow. She holds a Master of Public Health in Global Health Epidemiology and Disease Control from The George Washington University.

Join the 50,000+ subscribers in 170+ countries who rely on Global Health NOW for the latest public health news. Sign up for our free , and please share the link with friends and colleagues.

# data[].attributes.attachment_link.title
Covid-19 Hinders Pakistan's Progress on Cutaneous Leishmaniasis

# data[].attributes.attachment_link.description
Soon after the first cases of COVID-19 were detected in Pakistan, in March, 2020, the government shut down all non-essential services, including outpatient care for an array of diseases not requiring emergency treatment. As a result, Médecins Sans Frontières was forced to close its clinics for people with cutaneous leishmaniasis.

# data[].attributes.attachment_link.title
The Mark of Neglect: Cutaneous Leishmaniasis