Leishmaniasis, Cutaneous leishmaniasis and visceral leishmaniasis (Oriental Sore and Kala-azar)

Sample

1. 1. Prepare a smear from the lesion of the patient.
   2. Spleen, tissue or aspirate, and  (FNA) of lymph nodes.
      1. Splenic puncture.
      2. Nasal smears.
   3. Bone marrow aspirate.
   4. Culture from the above samples.
   5. Buffy coat of peripheral blood.

Indications

1. This helps in the diagnosis of Cutaneous Leishmaniasis or oriental sore.
2. For diagnosis of visceral leishmaniasis.

Pathophysiology

1. 1. Cutaneous Leishmania (CL) is transmitted by the sandfly.
   2. Genus of protozoa comprising parasites of worldwide distribution.
   3. Several species of which are pathogenic for humans. All species are morphologically indistinguishable.
   4. These are divided on the Clinical syndrome they produce:
      1. Visceral.
      2. Cutaneous.
      3. Mucocutaneous.
   5. Leishmania classified into :
      1. L. donovani.
      2. L. tropica.
      3. L. Mexicana.
   6. This is the summary of the Leishmania life cycle:

Cutaneous leishmaniasis

1. Leishmania tropica:
   1. L. Tropica complex consists of:
      1. L. tropica.
      2. L. major.
      3. L. aethiopica.
   2. This is complex causes Oriental sore, also called as Baghdadi boil, old world cutaneous leishmaniasis, or Delhi ulcer.
   3. This is transmitted by sandflies belonging to the genus Phlebotomus.
   4. Epidemiology: 
      1. These lesions are seen in the Mediterranean littoral, in Armenia, Azerbaijan, Uzbekistan, Turkmenistan, Afghanistan, India, Pakistan, and Iran.
      2. The dog may be the natural host but not looks an effective reservoir for a human.
   5. Incubation time is 2 months to 3 years.
   6. In general, cutaneous leishmaniasis causes skin lesions, which can persist for months, sometimes years.
   7. The skin lesions usually develop within several weeks or months after the exposure.
      1. These lesions are usually on the face.
      2. The lesions typically evolve from dry papules to nodular plaques to ulcerative lesions.
      3. These ulcers are usually 2 cm in Diameter or more with typical itching.
      4. These lesion has raised border and central depression, which can be covered by scab or crust.
   8. Rarely some lesions persist as nodules.
   9. These lesions are painless but some time may give rise to pain when these are infected.
   10. The healing process typically results in atrophic scarring.
2. Leishmania Major:
   1. It produces an acute infection with a duration of 3 to 6 months.
   2. The lesion primarily occurs on the lower limbs.
   3. These lesions are moist and tend to ulcerate very early.
   4. There may secondary and lesions on other sites.
   5. This disease is seen in Turkmenistan, Uzbekistan, Iran, Kazakhstan, Syria, Israel, Jordan, Africa, Algeria, Sahara, Tunisia, Sudden, Nigeria, Niger, Mali, Senegal, and Kenya.
3. Leishmania Mexicana:
   1. This causes new world cutaneous leishmaniasis
   2. It causes a Chiclero ulcer or Bay sore.
   3. It is found in the Belize, Yucatan peninsula, and in Guatemala.
   4. It is endemic in these areas.
   5. The amastigotes are found in the skin lesion of the humans, woodrats, and cats.
   6. Lesions are usually single and 40% involve ears.
   7. This may give rise to the diffuse cutaneous lesion.
4. Signs and symptoms:
   1. The first sign of the infection is a red papule.
   2. There is itching and this may grow to 2 cms or more in diameter.
   3. In L.major infection, the papule is covered with serous exudate and ulcerates early.
   4. In L. tropica papules are dry and ulcerate only after several months.
   5. This cutaneous form may be seen as:
      1. Diffuse cutaneous leishmaniasis and this may be due to lake cell-mediated immunity.
      2. Leishmaniasis recideva is due to good antibody and cellular response. In this case, the central lesion heals and the peripheral area is active.

Mucocutaneous Leishmaniasis:

1. L. braziliensis causes mucocutaneous leishmaniasis, also called espundia and uta.
   1. There is the formation of the ulcer on the oral-nasal mucosa.
   2. This is common in Brazil.
   3. The cutaneous lesions are multiple and large in size.
   4. Secondary infection plays a role in their persistence of the large size lesion.
   5. Sometimes it spreads to the mucous membranes.
      1. The entire nasal mucosa and the hard and soft mucosa are involved.
      2. The nasal septum will be destroyed.
      3. But unlike syphilis, the bone is not involved.
      4. The ulceration leads to loss of all soft parts of the nose, the lips, and soft palate.
      5. Death may occur in these patients due to secondary infection.
   6. A similar disease is also seen in Sudan and Ethiopia.

Visceral leishmaniasis

1. Leishmania donovani:
   1. There are three types of L. Donovani complex:
      1. L. Donovani donovani.
      2.  L. Donovoni chagasi.
      3. L. Donovani infantum
   2. It causes visceral leishmaniasis also called Kala-azar or black disease, Dumdum fever.
   3. This occurs in India, Burma, Bangladesh, Thailand, and Sumatra.
      1. Also seen in the Central African Republic, Sudan, Kenya, Gambia, Gabon, Northern Uganda, and Niger.
      2. This was seen in China but now it is controlled.
   4. Vector is Phlebotomus sandflies.
   5. In some cases, L.tropica has been found, in few cases in India and veterans from the Gulf war.
   6. The causative agent is a parasite of the reticuloendothelial system.
      1. This is not confined to the reticuloendothelial cells of the subcutaneous tissue and mucous membranes but may be found throughout the body.
   7. signs and symptoms:
      1. The Visceral leishmaniasis (also known as Kala-Azar).
      2. No skin lesions are seen, rarely except a papule at the site of the bite.
      3. Fever.
      4. weight loss (cachexia, wasting).
      5. Hepatosplenomegaly (usually, the spleen is more prominent than the liver).
         1. It returns to normal after the treatment.
      6. Bone marrow when involved, give rise to:
         1. Pancytopenia i.e., anemia, leukopenia, and thrombocytopenia.
         2. TLC is usually below 4000/cmm and is between 2000 to 3000/cmm.
         3. There is a monocytosis.
      7. High total protein level and a low albumin level, with hypergammaglobulinemia.
      8. Lymphadenopathy may be noted, particularly in some geographic regions, such as Sudan.
      9. HIV-coinfected patients may have atypical manifestations, such as involvement of the gastrointestinal tract and other organ systems.
   8. Kala-azar which means black (kala) fever (Azar). These are severe (advanced) cases of visceral leishmaniasis.
      1. Kala-azar or severe visceral leishmaniasis  untreated are typically  fatal due to:
         1. Directly from the disease.
         2. Indirectly from complications, such as hemorrhage or secondary bacterial infection.
         3. If left untreated the mortality rate may reach 100% within two years (WHO).

Pathogenesis of the lesion:

1. The fly when biting the host then amastigotes proliferates.
2. These are taken up by the macrophages and the endothelium of the small capillaries.
3. Macrophagic cells cause the lysis of amastigotes.
4. There is a chronic granulomatous reaction and it leads to local nodule formation which is due to the parasite-induced damage.
5. This may ulcerate and there is the possibility of pyogenic infection.

Mode of spread

1. Leishmania spread through the bite of the female sandfly (Phlebotomine).

2. Human is a natural source of a reservoir.

Laboratory Diagnosis of cutaneous Leishmania

Procedure how to make smear for cutaneous leishmaniasis:

1. 1. If the ulcer is on the arm or feet then first try to put pressure so that there is a stoppage of the blood supply to that area.
   2. Now prick and try to get yellow color material or serum like material.
   3. Make a smear from this material.
   4. Other Methods is to take a sample just like Fine needle aspiration (Author personal experience ).
   5. In the FNA method go into the periphery of the ulcer and most of the time get a good sample.

Result

1. 1. In a good smear, you will see a lot of LT bodies in the histiocytes and outside on the smear.

1. 2. Also,  can find a single separate LT body.

Diagnosis of Leishmaniasis:

1. Find amastigotes in:
   1. L.tropica is diagnosed by making the smear from the deeper area of the skin lesion.
      1. These smears are stained with Giemsa.
      2. Typical amastigotes are seen.
2. Material aspirated from the bone marrow (64 to 86% positive), spleen (95 to 98% positive), or enlarged lymph nodes (roughly 64% positive).
3. From nasal secretion.
4. From the buffy coat of peripheral blood (67 to 99% positive).
   • The culture of aspirates or peripheral blood.
   • Can find the Leishmania antibody using the known parasitic antigen.
5. Leishmania amastigotes (LT body) seen in the monocytes and few seen as single in the following diagrams.
6. ELIZA and indirect fluorescent antibody assay.

Treatment

1. The best drug is Sodium stibogluconate (antimony sodium gluconate (Pentostam).
   1. Pentostam 20 mg/Kg body weight is injected I/V or I/M for 20 days for cutaneous leishmaniasis.
      1. This dose can be repeated in the resistant cases at 10 days interval.
      2. A maximum of three courses can be given.
2. Another drug is:
   1. Meglumine antimonate (Glucantime).
      1. Initial 50 mg/Kg body weight given for 10 to 12 days for cutaneous leishmaniasis.
      2. For mucocutaneous give treatment for 15 days and repeat after 15 to 20 days if healing is not complete.
   2.  Pentamidine.
   3. Oral Ketoconazole 400 mg daily for 4 to 8 weeks is effective in the treatment of longstanding cutaneous leishmaniasis.
   4. Steroids

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