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Mucocutaneous Leishmaniasis

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Description: Mucocutaneous leishmaniasis is a parasitic disease caused by Leishmania protozoa that affects the skin, mucous membranes, and can lead to severe disfigurement.
Type: Mucocutaneous leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania. It is not genetically transmitted; rather, it is transmitted through the bite of infected female sandflies, specifically those from the genus Phlebotomus or Lutzomyia.
Signs And Symptoms: The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person is bitten by infected sand flies.
Leishmaniasis may be divided into the following types:
Cutaneous leishmaniasis is the most common form, which causes an open sore at each bite site, which heals in a few months to a year and half, leaving an unpleasant-looking scar.Diffuse cutaneous leishmaniasis produces widespread skin lesions which resemble leprosy, and may not heal on their own.

Mucocutaneous leishmaniasis causes both skin and mucosal ulcers with damage primarily of the nose and mouth.
Visceral leishmaniasis or kala-azar ('black fever') is the most serious form, and is generally fatal if untreated. Other consequences, which can occur a few months to years after infection, include fever, damage to the spleen and liver, and anemia.Leishmaniasis is considered one of the classic causes of a markedly enlarged (and therefore palpable) spleen; the organ, which is not normally felt during examination of the abdomen, may even become larger than the liver in severe cases.
Prognosis: Mucocutaneous leishmaniasis is a serious form of leishmaniasis that can cause significant morbidity. The prognosis depends on various factors including the timeliness of diagnosis, the patient's overall health, and the effectiveness of treatment. If left untreated, it can lead to severe disfigurement and complications. Early and appropriate treatment generally improves the prognosis significantly.
Onset: Mucocutaneous leishmaniasis typically has an insidious onset, developing weeks to months, and sometimes even years, after the initial infection with the Leishmania parasite. The initial phase often begins with a cutaneous ulcer, which can then progress to affect mucous membranes of the nose, mouth, and throat. The exact timing of onset can vary depending on the specific Leishmania species involved and the individual's immune response.
Prevalence: The prevalence of mucocutaneous leishmaniasis varies by region. It is primarily found in South America, particularly in countries such as Brazil, Peru, and Bolivia. Although considered less common than cutaneous leishmaniasis, mucocutaneous leishmaniasis can cause significant morbidity in affected regions. Exact prevalence data are not readily available, and reporting rates may vary based on surveillance and diagnostic capabilities.
Epidemiology: Out of 200 countries and territories reporting to WHO, 97 countries and territories are endemic for leishmaniasis. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in western Asia and the Middle East. It affects as many as 12 million people worldwide, with 1.5–2.0 million new cases each year. The visceral form of leishmaniasis has an estimated incidence of 500,000 new
cases. In 2014, more than 90% of new cases reported to WHO occurred in six countries: Brazil, Ethiopia, India, Somalia, South Sudan and Sudan. As of 2010, it caused about 52,000 deaths, down from 87,000 in 1990. Different types of the disease occur in different regions of the world. Cutaneous disease is most common in Afghanistan, Algeria, Brazil, Colombia, and Iran, while mucocutaneous disease is most common in Bolivia, Brazil, and Peru, and visceral disease is most common in Bangladesh, Brazil, Ethiopia, India, and Sudan.Leishmaniasis is found through much of the Americas from northern Argentina to South Texas, though not in Uruguay or Chile, and has recently been shown to be spreading to North Texas and Oklahoma, and further expansion to the north may be facilitated by climate change as more habitat becomes suitable for vector and reservoir species for leishmaniasis. Leishmaniasis is also known as papalomoyo, papa lo moyo, úlcera de los chicleros, and chiclera in Latin America. During 2004, an estimated 3,400 troops from the Colombian army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with leishmaniasis. Allegedly, a contributing factor was that many of the affected soldiers did not use the officially provided insect repellent because of its disturbing odor. Nearly 13,000 cases of the disease were recorded in all of Colombia throughout 2004, and about 360 new instances of the disease among soldiers had been reported in February 2005.The disease is found across much of Asia, and in the Middle East. Within Afghanistan, leishmaniasis occurs commonly in Kabul, partly due to bad sanitation and waste left uncollected in streets, allowing parasite-spreading sand flies an environment they find favorable. In Kabul, the number of people infected was estimated to be at least 200,000, and in three other towns (Herat, Kandahar, and Mazar-i-Sharif) about 70,000 more occurred, according to WHO figures from 2002. Kabul is estimated as the largest center of cutaneous leishmaniasis in the world, with around 67,500 cases as of 2004. Africa, in particular the East and North, is also home to cases of leishmaniasis. Leishmaniasis is considered endemic also in some parts of southern parts of western Europe and spreading towards north in recent years. For example, an outbreak of cutaneous and visceral leishmaniasis was reported from Madrid, Spain, between 2010 and 2012.Leishmaniasis is mostly a disease of the developing world, and is rarely known in the developed world outside a small number of cases, mostly in instances where troops are stationed away from their home countries. Leishmaniasis has been reported by U.S. troops stationed in Saudi Arabia and Iraq since the Gulf War of 1990, including visceral leishmaniasis.
In September 2005, the disease was contracted by at least four Dutch marines who were stationed in Mazar-i-Sharif, Afghanistan, and subsequently repatriated for treatment.
Intractability: Mucocutaneous leishmaniasis can be challenging to treat and may require prolonged or multiple treatments, particularly if it becomes advanced. While it is not universally intractable, some cases can be more resistant to standard therapies, necessitating specialized approaches. Prompt diagnosis and treatment are crucial for better outcomes.
Disease Severity: Mucocutaneous leishmaniasis can cause severe and disfiguring outcomes. It affects the mucous membranes of the nose, mouth, and throat, leading to significant tissue destruction. Although not usually fatal, the condition can result in substantial morbidity, necessitating complex medical and sometimes surgical treatments.
Healthcare Professionals: Disease Ontology ID - DOID:9155
Pathophysiology: Mucocutaneous leishmaniasis is caused by parasites of the Leishmania genus, primarily Leishmania braziliensis. The disease typically progresses from a cutaneous lesion to affect the mucous membranes of the nose, mouth, and throat. Pathophysiologically, it involves the parasite's invasion and destruction of mucosal tissues, leading to dysfunction and disfigurement. The host's immune response contributes significantly to tissue damage, involving a complex interplay of immune cells and cytokines that fail to control the infection effectively.
Carrier Status: Mucocutaneous leishmaniasis does not have human carriers in the traditional sense. The disease is primarily transmitted through the bite of infected female sandflies, which serve as the primary vectors. Once infected, humans can develop symptoms, but they do not serve as carriers that can directly infect other humans.
Mechanism: Mucocutaneous leishmaniasis (MCL) is caused by the protozoan parasites of the genus *Leishmania*, primarily *Leishmania braziliensis*.

**Mechanism:**
The disease is transmitted to humans through the bite of infected female phlebotomine sandflies. Once the parasite enters the host, it infects macrophages and other cells of the immune system. The infected cells then disseminate and cause lesions, primarily affecting mucosal tissues of the nose, mouth, and throat.

**Molecular Mechanisms:**
1. **Parasite Entry and Infection:** *Leishmania* promastigotes enter host cells via receptor-mediated phagocytosis. Key receptors on macrophages include the complement receptor 3 (CR3) and other opsonic receptors.

2. **Immune Evasion:** The parasites evade the host immune system by inhibiting the fusion of phagosomes with lysosomes, thus avoiding degradation. *Leishmania* also modulates host cell signaling pathways to reduce the immune response, such as by impairing antigen presentation.

3. **Destruction of Tissue:** The immune response to the infection, involving Th1 cells and production of cytokines (e.g., IFN-γ, TNF-α), leads to an inflammatory response that can damage mucosal tissues. The chronic inflammation driven by these immune responses results in tissue destruction and ulceration characteristic of MCL.

Understanding these mechanisms is crucial for developing targeted therapies and effective treatment strategies for mucocutaneous leishmaniasis.
Treatment: The treatment is determined by where the disease is acquired, the species of Leishmania, and the type of infection.
For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within three months of getting pregnant. It does not appear to work for L. major or L. braziliensis.The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for L. major, L. tropica, L. mexicana, L. panamensis, and L. braziliensis. Pentamidine is effective for L. guyanensis. Oral fluconazole or itraconazole appears effective in L. major and L. tropica. There is limited evidence to support the use of heat therapy in cutaneous leishmaniasis as of 2015.There are no studies determining the effect of oral nutritional supplements on visceral leishmaniasis being treated with anti-leishmanial drug therapy.
Compassionate Use Treatment: Compassionate use treatments for mucocutaneous leishmaniasis may include experimental drugs or therapies not yet approved for general use but are provided to patients with serious conditions when no comparable or satisfactory alternative therapy options are available. Off-label or experimental treatments for mucocutaneous leishmaniasis might involve:

1. **Miltefosine**: Though primarily approved for visceral and cutaneous leishmaniasis, it is occasionally used off-label for mucocutaneous cases.
2. **Imiquimod**: This immune response modifier, typically used for skin conditions, has been experimentally used in combination with other treatments for mucocutaneous leishmaniasis.
3. **Pentamidine**: Generally used for different forms of leishmaniasis, it may be considered off-label for mucocutaneous types.
4. **Liposomal Amphotericin B**: While approved for visceral leishmaniasis, it may be used experimentally for mucocutaneous forms.
5. **Thermotherapy**: Controlled heating may be used as an experimental treatment to kill the parasite locally.

These treatments should be administered under the guidance of a healthcare professional experienced in managing leishmaniasis.
Lifestyle Recommendations: For mucocutaneous leishmaniasis, some lifestyle recommendations include:

1. **Avoid Sandfly Bites**: Use insect repellent, wear long-sleeved clothing, and use bed nets, especially in endemic areas.
2. **Personal Hygiene**: Maintain regular hygiene practices to prevent secondary infections.
3. **Early Detection and Treatment**: Seek medical attention promptly if symptoms develop to ensure early and effective treatment.
4. **Wound Care**: Properly clean and care for any lesions to prevent secondary infections.
5. **Healthy Diet**: Maintain a balanced diet to support overall health and immune function.
6. **Follow Medical Advice**: Adhere strictly to the treatment regimen prescribed by healthcare providers.
Medication: Medication for mucocutaneous leishmaniasis typically includes antimonial compounds such as sodium stibogluconate or meglumine antimoniate. Other treatment options may involve amphotericin B, miltefosine, or pentamidine. Treatment choice can depend on the specific Leishmania species, the geographical region, and the patient's overall health.
Repurposable Drugs: Currently, there is no widely accepted nanotechnology-based treatment for mucocutaneous leishmaniasis. Research is ongoing in this area, with some studies exploring nanoparticle delivery systems to enhance the efficacy and reduce the toxicity of traditional medications, but these are still in experimental stages. Standard treatments primarily include antimonial compounds, amphotericin B, and miltefosine.
Metabolites: Mucocutaneous leishmaniasis, caused by the Leishmania parasite, primarily affects the skin and mucous membranes. While specific metabolites associated with this disease might not be extensively documented, metabolic changes generally involve alterations in host metabolic pathways due to infection. Key aspects include:

1. **Energy Metabolism**: Infected macrophages can show altered glucose metabolism, impacting glycolysis and the tricarboxylic acid (TCA) cycle.
2. **Amino Acid Metabolism**: There can be changes in amino acid levels, affecting arginine and polyamine synthesis which are crucial for parasite survival and replication.
3. **Lipid Metabolism**: Alterations in lipid metabolism may occur, affecting membrane lipid composition and signaling pathways.

"NAN" usually indicates that the requested information may not be available or documented specifically in the context of mucocutaneous leishmaniasis.
Nutraceuticals: There is limited scientific evidence on the efficacy of nutraceuticals in treating mucocutaneous leishmaniasis. Traditional treatments primarily include antiparasitic medications. Nutraceuticals such as antioxidants, vitamins, and immune-boosting supplements may support overall health but should not replace conventional therapy. Always consult with a healthcare professional before starting any new treatment.
Peptides: Mucocutaneous leishmaniasis is treated primarily with antimonial compounds, such as sodium stibogluconate or meglumine antimoniate, as well as amphotericin B in refractory cases. Peptides and nanoparticles (nan) are areas of ongoing research. Peptide-based vaccines and therapeutic peptides targeting specific aspects of the Leishmania parasite's biology are being explored. Additionally, nanoparticles are being investigated for their potential to improve drug delivery, enhance drug efficacy, and reduce toxicity. However, these are not yet standard treatments.