Visceral Leishmaniasis
Disease Details
Family Health Simplified
- Description
- Visceral leishmaniasis, also known as kala-azar, is a severe parasitic disease characterized by fever, weight loss, enlargement of the spleen and liver, and anemia, caused by the Leishmania parasite transmitted through the bites of infected sandflies.
- Type
- Visceral leishmaniasis, also known as kala-azar, is a parasitic disease caused by protozoa from the Leishmania genus, specifically Leishmania donovani and Leishmania infantum. It is not genetically transmitted. Instead, it is transmitted to humans through the bite of infected female phlebotomine sandflies.
- Signs And Symptoms
- When people develop visceral leishmaniasis, the most typical symptoms are fever and the enlargement of the spleen, with enlargement of the liver sometimes being seen as well. The blackening of the skin that gave the disease its common name in India does not appear in most strains of the disease, and the other symptoms are very easy to mistake for those of malaria. Misdiagnosis is dangerous, as without proper treatment the mortality rate for kala-azar is close to 100%. L. donovani itself is not usually the direct cause of death in people with kala-azar, however. Pneumonia, tuberculosis, and dysentery are omnipresent in the immuno-depressed regions where leishmaniasis thrives, and, as with AIDS, it is these opportunistic infections that are more likely to kill, flaring up in a host whose immune system has been weakened by the L. donovani infection. Progress of the disease is extremely variable, taking anywhere from one to twenty weeks, but a typical duration for the Sudanese strain of the disease is narrower, between twelve and sixteen weeks.Even with recovery, kala-azar does not always leave its hosts unmarked. Some time after successful treatment—generally a few months with African kala-azar, or as much as several years with the Indian strain—a secondary form of the disease may set in, called post kala-azar dermal leishmaniasis, or PKDL. This condition manifests first as small, measle-like skin lesions on the face, which gradually increase in size and spread over the body. Eventually the lesions may coalesce to form disfiguring, swollen structures resembling leprosy, and occasionally causing blindness if they spread to the eyes. (This disease is not the same as cutaneous leishmaniasis, a milder disease caused by another protozoan of the Leishmania genus which also causes skin lesions.)
- Prognosis
- Visceral leishmaniasis, also known as kala-azar, is a severe disease caused by protozoan parasites of the Leishmania genus. If left untreated, the disease can be fatal, with high mortality rates. However, with timely diagnosis and effective treatment, the prognosis significantly improves. Modern treatments can lead to cure rates of over 95%. Long-term outcomes are generally good if the disease is caught and treated early, but patients may suffer from residual health issues like splenomegaly (enlarged spleen) and malnutrition. Early treatment and follow-up care are crucial for a favorable prognosis.
- Onset
- Visceral leishmaniasis, also known as kala-azar, typically has an insidious onset, meaning symptoms develop gradually over weeks to months. This can include fever, weight loss, enlargement of the spleen and liver, and anemia.
- Prevalence
- Visceral leishmaniasis, also known as kala-azar, is most prevalent in parts of South Asia, East Africa, and South America. India, Bangladesh, Nepal, Sudan, and Brazil account for the majority of the world's cases. The disease affects an estimated 50,000 to 90,000 people annually, with a significant portion of cases going unreported.
- Epidemiology
- More than 90% of the global burden of visceral leishmaniasis (VL) was contributed by seven countries in 2015: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan. In India, more than 70% of VL cases are reported from the state of Bihar. North Bihar, India (including Araria, Purnea, and Kishanganj) is the endemic zone of this disease. The disease is endemic in more than 60 countries. In Iran this includes Ardabil, Fars, and North Khorasan.However, while the disease's geographical range is broad, it is not continuous. The disease clusters around areas of drought, famine, and high population density. In Africa, this has meant a knot of infection centers mostly in South Sudan, Sudan, Ethiopia, Kenya, and Somalia. Living conditions here have changed very little in the past century, and the people are not normally very mobile. Parts of South Sudan, in particular the Upper Nile region, are almost totally cut off from the rest of the country, and most people tend to remain at their place of birth although there have been huge population movements due to the civil war, leading to severe epidemics.
- Intractability
- Visceral leishmaniasis, also known as kala-azar, is not considered intractable, as it can be treated effectively with proper medical intervention. Treatment typically involves the use of antileishmanial medications such as amphotericin B, miltefosine, or pentavalent antimonials. Early diagnosis and prompt treatment are crucial to prevent severe complications and improve outcomes. However, access to treatment can be challenging in resource-limited settings, and drug resistance is an emerging concern.
- Disease Severity
- Visceral leishmaniasis can be severe and potentially life-threatening if left untreated. It primarily affects internal organs such as the liver, spleen, and bone marrow, leading to serious complications including severe anemia, swelling of the spleen and liver, and immunosuppression. Early diagnosis and appropriate treatment are crucial to prevent fatal outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:9146
- Pathophysiology
- Visceral leishmaniasis, also known as kala-azar, is caused by protozoan parasites of the genus Leishmania, typically Leishmania donovani and Leishmania infantum. The pathophysiology involves the transmission of the parasite through the bite of an infected female sandfly. Once inside the host, the parasites infect macrophages and multiply within them. This leads to widespread infection, predominantly affecting the liver, spleen, and bone marrow. The immune response becomes dysregulated, and the parasitized macrophages disseminate through the reticuloendothelial system, causing organomegaly, anemia, leukopenia, and hypergammaglobulinemia. The disease can be fatal if untreated.
- Carrier Status
- Visceral leishmaniasis, also known as kala-azar, is primarily transmitted by the bite of infected female phlebotomine sandflies. The disease does not have a "carrier" status in humans in the same way some other diseases do. However, humans can act as reservoirs of the parasite, especially in areas where the disease is endemic. The primary natural reservoirs are animals, particularly dogs and wild canids. There is no non-analytical term "nan" associated with visceral leishmaniasis.
- Mechanism
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Visceral leishmaniasis (VL), also known as kala-azar, is caused by protozoan parasites of the genus Leishmania, primarily Leishmania donovani and Leishmania infantum. The disease affects the internal organs, particularly the spleen, liver, and bone marrow.
**Mechanism:**
1. **Transmission:** VL is transmitted through the bite of infected female Phlebotomine sandflies. The parasites are ingested by the sandfly during a blood meal from an infected host.
2. **Infection in Sandfly:** In the sandfly’s gut, the parasites develop into promastigotes (the flagellated, motile form) and multiply.
3. **Transmission to Humans:** When an infected sandfly bites a human, it injects the promastigotes into the skin.
4. **Host Invasion:** The promastigotes are taken up by macrophages (a type of white blood cell). Inside the macrophages, they transform into amastigotes (the non-flagellated, intracellular form).
5. **Replication:** The amastigotes multiply, causing the macrophages to burst. The released amastigotes go on to infect new macrophages, spreading the infection throughout the reticuloendothelial system, including the spleen, liver, and bone marrow.
**Molecular Mechanisms:**
1. **Immune Evasion:** The parasites have evolved mechanisms to evade the immune response. They inhibit the production of reactive oxygen and nitrogen species by macrophages, which are crucial for killing intracellular pathogens.
2. **Modulation of Host Cell Signaling:** Leishmania parasites can manipulate host cell signaling pathways to promote their survival. For example, they can inhibit apoptosis (programmed cell death) of the host cell, ensuring the parasite's continued replication.
3. **Alteration of Cytokine Profiles:** The parasites can alter the host's immune response by modulating the production of cytokines. This includes increasing anti-inflammatory cytokines like IL-10 and TGF-β and decreasing pro-inflammatory cytokines like IL-12 and TNF-α.
4. **Reticuloendothelial System Impact:** The accumulation and replication of the parasites in macrophages lead to the enlargement of the spleen and liver (hepatosplenomegaly), and destruction of bone marrow cells, resulting in anemia, leukopenia, and thrombocytopenia.
Understanding these mechanisms and molecular interactions is crucial for developing effective therapies and vaccines against visceral leishmaniasis. - Treatment
-
Visceral leishmaniasis, also known as kala-azar, is treated with several medication options, including:
1. **Antimonial compounds**: These have been the traditional first-line treatments, specifically sodium stibogluconate or meglumine antimoniate.
2. **Amphotericin B**: Available in liposomal form, this is often preferred due to higher efficacy and fewer side effects.
3. **Miltefosine**: An oral medication that is useful in treating visceral leishmaniasis, though it may have teratogenic effects.
4. **Paromomycin**: An aminoglycoside antibiotic also used in combination therapies.
Treatment regimens can vary based on factors like regional drug resistance patterns, patient age, and side effects profile. - Compassionate Use Treatment
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For visceral leishmaniasis:
**Compassionate Use Treatment:**
- Compassionate use regulations allow access to medications not yet approved for public use. For visceral leishmaniasis, specific compassionate use programs may be available for experimental drugs like Miltefosine or other emerging treatments depending on local health authority regulations.
**Off-Label or Experimental Treatments:**
- **Miltefosine:** Originally approved for other types of leishmaniasis, it is sometimes used off-label for visceral leishmaniasis.
- **Liposomal Amphotericin B (AmBisome):** Mainstream treatment but also investigated in various dosing regimens and combinations.
- **Paromomycin:** May also be used in combination with other therapies.
- **Drug Combinations:** Research is ongoing into combinations of existing drugs to improve efficacy and reduce resistance, such as combining Miltefosine with Liposomal Amphotericin B.
- **Immunotherapy:** Experimental approaches include the use of immune-modulating agents to enhance the body’s defense against Leishmania parasites.
Availability and approval of these treatments depend on regional health regulations and ongoing clinical trials. - Lifestyle Recommendations
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For visceral leishmaniasis, lifestyle recommendations include:
1. **Preventive Measures:**
- Use insect repellent containing DEET or Picaridin.
- Wear protective clothing, such as long sleeves and pants, especially during dusk and dawn when sandflies are most active.
- Use bed nets treated with insecticide when sleeping.
2. **Environmental Modifications:**
- Stay in well-screened or air-conditioned areas to reduce exposure to sandflies.
- Use insecticide sprays or fumigants to kill sandflies in living areas.
- Remove organic waste (e.g., animal manure, leaf litter) from around homes to reduce breeding habitats for sandflies.
3. **Health Monitoring:**
- Be aware of symptoms such as fever, weight loss, enlarged spleen or liver, and anemia.
- Seek medical attention promptly if symptoms of visceral leishmaniasis appear, especially after travel to endemic areas.
4. **Travel Precautions:**
- Avoid traveling to regions known for high incidence of visceral leishmaniasis during peak transmission seasons.
- Stay informed about the areas where the disease is prevalent and take extra precautions if travel is necessary.
These lifestyle changes can help in preventing infection and managing the risk associated with visceral leishmaniasis. - Medication
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Visceral leishmaniasis, also known as kala-azar, is typically treated with antiparasitic medications. The primary treatments include:
1. **Liposomal Amphotericin B** - This is often the first-line treatment due to its effectiveness and safety profile.
2. **Miltefosine** - An oral medication used particularly in areas where other treatments may not be as effective.
3. **Paromomycin** - An aminoglycoside antibiotic used in combination with other treatments.
4. **Pentavalent antimonials (e.g., Sodium Stibogluconate)** - These have been traditional therapies but are less commonly used now due to resistance and adverse effects.
The choice of medication may depend on geographic location due to varying drug resistance patterns and availability. - Repurposable Drugs
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Visceral leishmaniasis, also known as kala-azar, can potentially be treated with several repurposable drugs. Some of these include:
1. **Miltefosine**: Originally developed for cancer treatment.
2. **Amphotericin B**: Initially used for fungal infections.
3. **Pentamidine**: Commonly used for treating certain types of pneumonia.
4. **Paromomycin**: An antibiotic for bacterial infections.
Research on repurposing other drugs and nanotechnology-based treatments is ongoing, as they may offer more effective and less toxic alternatives to conventional therapies. - Metabolites
-
Visceral leishmaniasis, also known as kala-azar, is a disease caused by the protozoan parasites of the genus Leishmania. The disease primarily affects internal organs such as the spleen, liver, and bone marrow. The specific metabolites associated with visceral leishmaniasis can include elevated levels of certain markers in the blood, such as:
1. **Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST)**: These liver enzymes may be elevated due to liver involvement.
2. **Bilirubin**: Elevated bilirubin levels may occur, indicating liver dysfunction.
3. **Gamma-globulins**: Increased levels of gamma-globulins, as part of a polyclonal increase in immunoglobulins.
4. **Renal function markers**: Altered levels of blood urea nitrogen (BUN) and creatinine can indicate kidney involvement or damage.
Research on nanoscale interventions (nanotechnology) for visceral leishmaniasis is ongoing and includes the development of nanoparticle-based drug delivery systems aimed at improving the efficacy and reducing the toxicity of anti-leishmanial drugs. These approaches may include:
1. **Liposomes**: Encapsulating drugs in liposomes to target macrophages where Leishmania parasites reside.
2. **Polymeric nanoparticles**: Using biodegradable polymers to facilitate sustained drug release and targeting.
3. **Metal nanoparticles**: Exploring the use of metal nanoparticles like gold and silver for their potential anti-parasitic properties.
These advances represent a promising frontier in the treatment and management of visceral leishmaniasis. - Nutraceuticals
- Research on nutraceuticals specifically for visceral leishmaniasis is limited. While there's no strong evidence supporting their use for treating this disease, maintaining overall good nutrition can support the immune system. The primary treatment for visceral leishmaniasis involves antiparasitic medications like amphotericin B and miltefosine.
- Peptides
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In the context of visceral leishmaniasis, peptides can be considered for their potential use in diagnostic assays and vaccines. Research is ongoing to identify specific peptide sequences that can elicit an immune response or serve as biomarkers for detecting infection.
Nanotechnology (nan) plays a significant role in developing advanced diagnostic tools and treatment options for visceral leishmaniasis. Nanoparticles can improve the delivery and efficacy of anti-leishmanial drugs, reduce side effects, and aid in creating more sensitive and specific diagnostic tests.
Overall, both peptides and nanotechnology offer promising avenues for enhancing the management of visceral leishmaniasis through better diagnostics and more effective treatments.