Cutaneous and visceral leishmaniasis is a parasitic disease diagnosed through lab tests. Leishmaniasis symptoms include an enlarged spleen and liver and bleeding.

Leishmaniasis

Humza Khizer

Overview

Leishmaniasis, also known as Kala-azar or black fever, is caused by a protozoan parasite. The parasite is commonly carried by a female phlebotomine sandfly and the bite from the fly transfers the parasite into the body. The species responsible for visceral leishmaniasis are L. donovani and L. infantum. The disease is known to affect internal organs especially spleen, liver and bone marrow<a href="#accordion">[3]</a>.&nbsp;

&nbsp;

Leishmaniasis is most commonly found in tropical and subtropical areas. Children under the age of 5 and people with compromised immune systems are most likely to fall victim to this chronic systemic disease. The disease is found in some areas of Mexico, South America, Central America, certain parts of Asia, southern Europe, North Africa, and some regions of South Africa.

Visceral Leishmaniasis is believed to be prevalent in Pakistan, especially in the areas of Gilgit-Baltistan, Azad Jammu &amp; Kashmir, etc. but even then, the overall cases of visceral leishmaniasis are low in number, hence making the diagnosis difficult.

Cutaneous Leishmaniasis is the most common type of leishmaniasis with over 700,000 to 1.2 million cases reported every year<a href="#accordion">[2]</a>. In Pakistan, 90 cases were registered in the course of a year from 2012 to 2013 only in the district Jhelum, and is considered a highly neglected yet prevalent disease in Pakistan. However, research on&nbsp; Leishmaniasis is currently underway<a href="#accordion">[1]</a>.

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There are two main types of leishmaniasis namely visceral leishmaniasis and the cutaneous leishmaniasis which has a sub-type called mucocutaneous leishmaniasis.

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<h5>Visceral Leishmaniasis</h5>

Also known as systemic leishmaniasis or kala-azar, this is the most severe form of leishmaniasis and is almost always fatal if left untreated. The infection affects your organs including your spleen and liver. Your bone marrow and immune system are also left severely damaged by the parasite.

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<h5>Cutaneous And Mucocutaneous Leishmaniasis</h5>

Cutaneous leishmaniasis is known to cause ulcers on your skin. It is the most common type of leishmaniasis and depending on the severity of the symptoms, treatment may or may not be necessary. It goes away on its own in many cases but some therapeutic measures can speed up the healing process.

Mucocutaneous leishmaniasis on the other hand is comparatively rare and is often regarded as the worsened form of cutaneous leishmaniasis. This often occurs months after the treatment and the healing of the ulcers. Mucocutaneous leishmaniasis spreads to your nose, throat, and mouth causing partial or complete destruction of the mucous membranes in those parts. Mucocutaneous leishmaniasis is far more serious and requires treatment for it to heal.&nbsp;

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Signs And Symptoms

Being the most severe form of leishmaniasis (Visceral Leishmaniasis), the disease victimizes people mostly from lower socioeconomic classes in low-income countries. Some people may experience a &lsquo;silent infection&rsquo; i.e., the disease may not show any symptoms or signs and may even go undiagnosed<a href="#accordion">[3]</a>. The symptoms of Visceral Leishmaniasis occur progressively over a week or sometimes even months and they may include:

&nbsp;

<ul>
	<li>Severe weight loss</li>
	<li>Fever</li>
	<li>Spleen and liver enlargement</li>
	<li><a href="https://www.merisehat.pk/disease/anemia" target="_blank">Anemia </a>(low red blood cell count)</li>
	<li>Leukopenia (low white blood cell count)</li>
	<li>Thrombocytopenia (low platelet count)</li>
</ul>

&nbsp;

Following are the symptoms of cutaneous and mucocutaneous leishmaniasis:

<ul>
	<li>Painless skin ulcers or crusted papules</li>
	<li>Runny or stuffy nose</li>
	<li>Trouble breathing</li>
	<li>Nosebleeds</li>
</ul>

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Causes

Leishmaniasis is caused by the infection of the leishmania parasite. This is contracted through the bite of a carrier female sandfly<a href="#accordion">[6]</a>. However, considering its higher prevalence in low-income countries, poor living standards, unsanitary environments, and poor housing. Hence, anything that acts as an ideal breeding ground for the sandflies, becomes a cause of the contraction of the parasite. Nevertheless, sandfly bite is not the only reason, other modes of transmission include:

&nbsp;

<ul>
	<li>Blood transfusion&nbsp;</li>
	<li>Intercourse</li>
	<li>Use of contaminated needles</li>
	<li>Inoculation of cultures</li>
</ul>

&nbsp;

While most cases of leishmaniasis consist of canines like wolves, dogs, and raccoons acting as a reservoir for the parasite which is later transferred to the sandfly where it multiples. In many regions especially in India, the transmission is mostly due to human-sandfly-human interaction<a href="#accordion">[5]</a>.&nbsp;&nbsp;

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The requirement for screening is not due to early detection or to predict the disease before it shows its symptoms but it is to determine if a patient is asymptomatic to the infection which may have the risk of worsening into visceral leishmaniasis. Around 10-20% of asymptomatic individuals are known to eventually develop visceral leishmaniasis.

The leishmanin skin test (LST) or the Montenegro test is based on a delayed hypersensitivity test. This test plays no role in the diagnosis of the disease, and in active visceral leishmaniasisit is usually negative. A positive test indicates cell-mediated immunity, and it is believed that there runs a massive risk of getting visceral leishmaniasis in immunocompromised individuals despite a positive LST test due to the use of immunosuppressants.&nbsp;

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Diagnosis

Symptoms of visceral leishmaniasis resemble other diseases which are why an accurate diagnosis is difficult but crucial; owing to the fatal complications associated with the disease.&nbsp;

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<ul>
	<li>Bone Marrow Aspirate &ndash; This is one of the best diagnostic tests for leishmaniasis. However, considering that the disease is more prevalent in low-income countries, the availability of the test is a common limitation. While cultures from bone marrow aspirate are always accurate but the extraction of bone marrow aspirate itself can be a challenge, especially in environments that are not highly controlled or equipped. Even though the test is invasive, to&nbsp;date it is regarded as the gold standard for the diagnosis of visceral leishmaniasis.</li>
</ul>

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<ul>
	<li>rK39 Immunochromatographic Strip Test (ICT) And Direct Agglutination Test (DAT) &ndash; These tests are very commonly used due to their low cost, but they lack specificity, especially in the differentiation between clinically active and asymptomatic infections. The tests also tend to show false positive results even after the disease has been cured. Regardless, both tests have comparable reliability but rK39 is considered to be more user-friendly.&nbsp;</li>
</ul>

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<ul>
	<li>PCR &amp; Real-Time PCR &ndash; Not as widely used due to their associated high costs, these tests do however provide accurate results, due to high sensitivity and specificity. Hence, these molecular diagnostic tools are still highly employed for the diagnosis of visceral leishmaniasis.&nbsp;</li>
</ul>

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<ul>
	<li>Indirect Fluorescent Antibody Test (IFAT) &ndash; This test is effective for detecting antibodies that appear during the initial stages of the infection but the test itself requires certain strict laboratory conditions, which can&rsquo;t be replicated in the field.&nbsp;</li>
</ul>

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<ul>
	<li>ELISA &ndash; Enzyme-Linked Immunosorbent Assay is also one of the commonly used diagnostic tests for the diagnosis of visceral leishmaniasis. The key component of this test is the type of antigen used and rk39 is known to show the highest specificity.</li>
</ul>

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Treatment

Treatment of leishmaniasis focuses on the disease and its symptoms as well as providing supportive care for the body to be able to endure the medications and fight the parasite. The treatment is often personalized e.g. therapy for malnutrition, anemia, and ART (antiretroviral therapy) is recommended for HIV-coinfected patients.

Currently employed therapies are not considered ideal, due to their high toxicity, resistance issues, prices, and the dedicated commitment required to continue a long-term treatment.

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The treatment for visceral leishmaniasis includes:

<ul>
	<li>Liposomal Amphotericin B: This is the treatment of choice in immunocompetent patients and has been approved by the FDA. However, this drug is used mostly in the Mediterranean region; owing to its high efficacy against the parasite strain found in that region. This is the drug of choice in coinfected HIV/VL patients.</li>
</ul>

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<ul>
	<li>Pentavalent Antimonial (Sbv) Therapy: This therapy is highly effective in many regions except for South Asia, as in certain parts of South Asia e.g. north of Bihar in India, Sbv resistance is high<a href="#accordion">[3]</a>. However, there are severe side effects associated with this therapy.</li>
</ul>

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<ul>
	<li>Paromomycin: This aminoglycoside antibiotic has found its use in the treatment of visceral leishmaniasis but it is highly dose-dependent and hence the patient is monitored closely for their response to the doses and the overall efficacy. Unfortunately, many patients are found to be resistant to paromomycin.</li>
</ul>

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A lot of the complications are associated with visceral leishmaniasis due to the severe symptoms that characterize the disease. These complications include:

&nbsp;

<ul>
	<li>Uncontrolled bleeding</li>
	<li><a href="https://www.merisehat.pk/disease/pneumonia" target="_blank">Pneumonia&nbsp;</a></li>
	<li><a href="https://www.merisehat.pk/disease/tuberculosis" target="_blank">Tuberculosis</a></li>
	<li>Septicemia (widespread blood poisoning by bacteria)</li>
	<li>Edema</li>
	<li>Hyperpigmentation&nbsp;</li>
	<li>Disfigurement of lips, nose or palate&nbsp;</li>
	<li>Splenic rupture</li>
	<li>Metastatic lesions in the nasopharynx</li>
</ul>

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Post Kala-azar Dermal Leishmaniasis:&nbsp;PKDL occurs a while after visceral leishmaniasis is cured. This complication causes a macular, maculopapular, and nodular rash. The rash starts around the mouth and spreads to different parts of the body<a href="#accordion">[7]</a>. The symptoms may vary depending on the geographical location and the control of the parasite. When it comes to treatment, SSG (sodium stibogluconate) intramuscular injections are the only treatments available. These injections are very painful and include the risk of cardiac arrest.&nbsp;

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You can contract leishmaniasis from any place that is humid and serves as an ideal breeding ground for sandflies. However, several other factors also contribute to the contraction of the disease:

&nbsp;

<ul>
	<li>Rapid Urbanization&nbsp;&ndash; This involves the cutting down of forests, formation of dams, construction of roads, mining, etc. Urbanization increases the chances of exposure to sandflies.&nbsp;</li>
</ul>

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<ul>
	<li>Large-Scale Migration &ndash; Migration in large numbers to endemic areas serves as a massive risk factor. This was observed in 1996 in Kabul, Afghanistan where around 270,000 cases of leishmaniasis were reported in a population of 2 million.&nbsp;</li>
</ul>

&nbsp;

<ul>
	<li>Coinfection In Immunodeficient Individuals &ndash; Your body is more susceptible to contracting infections with a weakened immune system. Patients with <a href="https://www.merisehat.pk/disease/hiv-61" target="_blank">HIV </a>are the most vulnerable to getting leishmaniasis.&nbsp;</li>
</ul>

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To date, there is no vaccine out there to immunize people against the infection. The following steps can be taken to avoid possible exposure to a sandfly and the parasite itself:

&nbsp;

<ul>
	<li>Reduce Contact With Vectors &ndash; This involves avoiding going out at times during which insects are active. The use of mosquito nets, insect repellent, and protective clothing is also recommended.</li>
</ul>

&nbsp;

<ul>
	<li>Vector Control &ndash; Mass sanitization is required to eradicate any possible breeding grounds for sandflies.&nbsp;</li>
</ul>

&nbsp;

<ul>
	<li>Maintenance Of&nbsp; Urban Reservoirs &ndash; With dogs serving as the main reservoir for the parasite, it is important to keep a check on your canines. A serological survey is recommended for dogs and appropriate measures should be taken in case of a positive result for the parasite.</li>
</ul>

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&nbsp;

<ul>
	<li>A review article published in Frontiers in Cellular and Infection Microbiology (Section: Parasite and Host) discusses precision medicine. The article&nbsp;discussed the possibility of the usage of precision medicine to treat visceral leishmaniasis especially since the current regimen for the disease is a hit or miss. The geographical specificity and individual resistance further complicate the situation. Precision medicine refers to the diagnostic methods and therapy regimens that are modified and targeted specifically to the individual based on their health, lifestyle, and environment.</li>
	<li>WHO published new proven drug regimens for the treatment of visceral leishmaniasis. Studies were conducted by M&eacute;decins Sans Fronti&egrave;res and partners in India, while the Drugs for Neglected Diseases initiative and partners were responsible for the research carried out in Ethiopia. The updated treatment suggests the use of daily liposomal amphotericin B injections over&nbsp;38 days.</li>
	<li>Recent research suggests that the nectar of plants like sunflower contain several bioactive agents that have a limiting action on the growth of leishmania and further research, could lead to the next breakthrough that may equip us with the knowledge and drugs to completely fight leishmaniasis<a href="#accordion">[8]</a>.</li>
</ul>

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Key Points

<ul>
	<li>Visceral Leishmaniasis is the most severe type of leishmaniasis that is comparatively uncommon yet can prove to be fatal if left untreated or treated poorly, whereas other types of leishmaniasis including cutaneous and mucocutaneous are not fatal and comparatively more prevalent.</li>
	<li>Endemic countries or regions have a few things in common: they are humid and low-income places where unsanitary conditions are highly prevalent.</li>
	<li>The disease is characterized by <a href="https://www.merisehat.pk/disease/anemia" target="_blank">anemia</a>, thrombocytopenia, severe weight loss,&nbsp;leukopenia &amp; liver and spleen enlargement.</li>
	<li>Visceral Leishmaniasis is contracted through sandflies which become a carrier for it through canines like dogs, wolves, etc. that act as a reservoir for the parasite.</li>
	<li>Current treatments for visceral leishmaniasis are not considered ideal since their efficacy is highly dependent on the geographical location. This is because different populations are exposed to other different diseases and hence contain different types of resistance to antimicrobials in their body. The parasite itself responds differently to different therapies based on geographical location.&nbsp;</li>
	<li>The preventive measures strictly focus on reducing possible interaction with the vector i.e., by taking measures to improve sanitation and cleanliness of the environment along with the use of insecticides.</li>
</ul>

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[1] Behzad Kayani, S. S. H. B. R. N. A. A. M. M. S. K. R. M. H. R. S. H. M. H. M. U.-u.-R. Z. &. M. C., 2021. Cutaneous Leishmaniasis in Pakistan: a neglected disease needing one health strategy. BMC Infectious Diseases, p. Article number: 622.