Introduction
Leishmaniasis is a protozoal disease caused by Leishmania species. This infection is usually transmitted by sandflies of Lutzomyia and Phlebotomus species. 1.6 million people are affected by Leishmaniasis every year worldwide. Leishmaniasis typically involves clinical presentations, namely cutaneous leishmaniasis, visceral leishmaniasis, and mucocutaneous leishmaniasis. However, a new term called mucosal leishmaniasis describes the mucosal involvement of Leishmania species. Mucocutaneous leishmaniasis is associated with braziliensis, panamensis, and, less frequently, amazonensis species of Leishmania.
What Is Mucosal Leishmaniasis?
Mucosal leishmaniasis indicates an infection of the mucous membranes caused by Leishmania species. Mucosal leishmaniasis affects the mucous membranes of the oral cavity and the upper respiratory tract (a portion of the respiratory tract from the inner nostril wall to the larynx). Mucosal leishmaniasis usually manifests days or years after cutaneous leishmaniasis. Therefore, mucosal leishmaniasis can be either accompanied or preceded by cutaneous or visceral leishmaniasis. Mucosal leishmaniasis generally becomes evident within several years of untreated or suboptimally treated cutaneous lesions. Mucosal leishmaniasis is usually caused by Leishmania donovani complex species, namely Leishmania infantum.
What Are the Causative Organisms of Mucosal Leishmaniasis?
Researchers have identified twenty-one species of Leishmania that cause human infections. Mucosal leishmaniasis is caused by all major complexes of Leishmania species all over the world. It has been reported that L.braziliensis is responsible for the highest number of mucosal leishmaniasis cases all over the world.
Other members of Leishmania braziliensis complex species that have been associated with mucosal leishmaniasis include L. panamensis and L. guyanensis. L. amazonensis has also been found to be associated with mucosal leishmaniasis. Other Leishmania species that cause mucosal leishmaniasis include L. infantum, L. donovani, L. tropica, and L. major. Mucosal leishmaniasis is more common in adult men compared to adult women and children due to occupational exposure. Mucosal leishmaniasis can also be caused by endocrinal factors.
How Does Mucosal Leishmaniasis Develop?
Leishmaniasis is typically transmitted by Phlebotomine sandflies that belong to two different genera, namely, Phlebotomus and Lutzomyia. The life cycle of Leishmania species presents in two stages; a promastigote stage that occurs in the gut of the sandfly, then an amastigote stage that occurs in the mammalian host after the bite of a female sandfly. The pathogenesis of mucosal leishmaniasis is complex and remains partially unknown.
The saliva of the sandfly contains substances with a potential immunoregulatory ability. The contemporary inoculation of Leishmania species and the salivary substances exacerbate the mucosal infection. Hence, mucosal leishmaniasis develops due to insufficient or misled host immune responses in the early stages of cutaneous leishmaniasis. In addition, it has been reported that mucosal leishmaniasis is associated with uncontrolled and self-feeding inflammation, which is enhanced immunodeficiency. Several immunosuppressive factors, such as smoking, upper respiratory tract diseases, and corticosteroid therapy, may contribute to mucosal leishmaniasis.
The Leishmania species may reach the mucous membranes via three routes; as a direct extension of facial skin infections, involvement of mucous membranes subsequent to skin ulcers, or via direct mucosal infiltration of the parasite through sandfly bite.
What Are the Signs and Symptoms Associated With Mucosal Leishmaniasis?
Mucosal leishmaniasis typically becomes evident within several years of the cutaneous lesions that were left untreated or were suboptimally treated. However, skin and mucosal lesions may be present concomitantly, and some patients may have subclinical skin infections. The initial manifestations may include persistent, unusual symptoms, such as nasal stuffiness or bleeding. In some cases, oral or pharyngeal symptoms may be noticed first. Mucosal leishmaniasis can progress to cause destructive ulcers in the naso-oropharyngeal mucosa if left untreated. These ulcers can worsen, resulting in perforation of the nasal septum.
The signs and symptoms of mucosal leishmaniasis can vary according to the causative pathogens and the complexity of the pathogenesis. Mucosal leishmaniasis typically starts with non-specific symptoms of inflammation, such as erythema, edema, nasal congestion, epistaxis, and serous rhinorrhea, which worsens and progresses toward the lower respiratory tract. In addition, oral mucosal leishmaniasis can cause severe damage resulting in tooth loss and severe respiratory obstruction. Mucosal leishmaniasis may involve mucous membranes of the cheeks, nose, lips, oropharynx, palate, and larynx. The most common symptoms include dysphagia (difficulty swallowing), dysphonia (difficulty speaking), and oral discomfort.
How Is Mucosal Leishmaniasis Diagnosed?
The diagnosis of mucosal leishmaniasis depends on the presence of Leishmania amastigotes in the mucosal lesions and the following laboratory tests.
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Histological Diagnosis - Itdepends on the presence of amastigotes in mucosal samples that were obtained to visualize Leishmania bodies.
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Immunohistochemical Identification and Isoenzyme Profiling - It helps confirm the diagnosis of mucosal leishmaniasis and the type of Leishmania species.
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Polymerase Chain Reaction (PCR) - Polymerase chain reaction helps detect the presence of Leishmania in DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) in culture or tissue specimens.
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ELISA (Enzyme-Linked Immunosorbent Assay) - It is a highly sensitive serological test that helps detect anti-Leishmania IgG (immunoglobulin G) or Leishmania antigens.
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The Montenegro Skin Test - Itis a highly sensitive test that helps diagnose mucocutaneous leishmaniasis. However, it does not distinguish current and previous Leishmania infections.
How Is Mucosal Leishmaniasis Treated?
There is no specific treatment for mucosal leishmaniasis. It includes the following treatment strategies:
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The World Health Organization (WHO) recommends the use of pentavalent antimony and its derivatives, such as sodium stibogluconate and meglumine antimoniate, in the treatment of mucocutaneous leishmaniasis. These drugs are effective on the amastigotes. However, these drugs are associated with severe side effects, such as hepatic, cardiac, haematic, pancreatic, and renal toxicity.
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The addition of Pentoxifylline to pentavalent antimony causes a significant reduction in healing time compared to the isolated use of pentavalent antimony in mucosal leishmaniasis. In addition, the concomitant use of Pentoxifylline and pentavalent antimony has been associated with a high cure rate of 90 percent in patients with mucosal leishmaniasis.
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Pentamidine is highly effective against Leishmania braziliensis. Other drugs, such as Amphotericin B and Paromomycin, are highly effective against Leishmania species. Miltefosine has marked efficacy against visceral leishmaniasis.
Conclusion
Mucosal leishmaniasis is a worldwide disease that is difficult to prevent. The risk of incidence of mucosal leishmaniasis may increase due to environmental and throponotic changes that may arise. All the complexes of Leishmania species are the causative agents of mucosal leishmaniasis. Also, the sandfly is significantly responsible for the transmission of the disease and also contributes to the pathogenesis of mucosal leishmaniasis. The diagnosis depends on histological examination, but PCR plays a significant role. In addition, large randomized trials are required to determine the effective therapeutic protocol for the management of mucosal leishmaniasis.
