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LEISHMANIASIS
Presented by Emmanuel Saha
MBChB student
Kenyatta University
Outline
1. History
2. Epidemiology
3. Etiology
4. Disease manifestations
5. Lifecycle
6. Clinical features
7. Diagnosis
8. Differential diagnosis
9. Treatment and Prevention
History
● Leishmaniasis dates back to the 1st century AD.
● Initially known as “Dum dum” fever and later “kal- azar.”
● Was later named Leishmaniasis after Sir William Leishman discovered ovoid
bodies in the spleen of a British soldier who was experiencing bouts of fever,
anemia, muscular atrophy and swelling of the spleen, in 1901.
● It later acquired the name donovani when Charles Donovan discovered the
promastigotes in other kal-azar patients displaying similar symptoms. He named
these bodies donovan bodies.
● Hence gaining the name Leishmania donovani.
Epidemiology
● It is a neglected disease that affects 700 000 to 1 million new cases occur annually
(WHO, 2021).
● Causes 70,000 deaths annually.
● Prevalent in some parts of Asia, the Middle East, Africa (particularly in the tropical
region and North Africa, with some cases elsewhere), and southern Europe. It is not
found in Australia or the Pacific Islands.
● Endemic in Saudi Arabia.
Regional epidemiology
● In Kenya, Cutaneous Leishmaniasis is reported from the highland areas, including the
eastern slopes of Mt. Elgon in Bungoma county, the Aberdare Range, Baringo
county, and other parts of the Rift Valley region.
● Visceral Leishmaniasis is found in the Rift Valley region(Baringo, West Pokot, and
Turkana county), Eastern region (Machakos, Kitue, and Meru county), and North
Eastern region.
Etiology
● Leishmaniasis is a cutaneous disease caused by protozoan parasites belonging to the
genus Leishmania.
● It is transmitted by the bite of tiny 2 to 3mm long insect vector sandfly (known as
Phlebotomus species in the Old World and Lutzomyia in the New World)
● It is also known as Orient Boils, Baghdad Boil, kala azar, black fever, sandfly
disease, Aleppo boil, Dum-Dum fever or espundia.
Etiology
● Most forms of the disease are transmissible from animals (zoonosis). Some 70 animal
species, including humans, have been found as natural reservoir hosts of Leishmania
parasites.
● Human infection is caused by about 21 of 30 species that infect mammals. Most
common ones include:
○ Leishmania donovani
○ Leishmania mexicana
○ Leishmania tropica
○ Leishmania braziliensis
Disease manifestations
1.Visceral leishmaniasis: Most vicious form. Known as kala-azar and is fatal if left untreated in over 95%
of cases.
2. Mucocutaneous leishmaniasis: Leads to partial or total destruction of mucous membranes of the nose,
mouth and throat.
3. Localized Cutaneous leishmaniasis: It’s the most common form of leishmaniasis and causes skin
lesions, mainly ulcers, on exposed parts of the body, leaving life-long scars and serious disability or stigma.
4.Diffuse cutaneous leishmaniasis.
Life Cycle
In Human hosts:
● Leishmaniasis is transmitted by the bite of female phlebotomine sandflies.
● The sandflies inject the infective stage, metacyclic promastigotes, during blood
meals(1).
● Metacyclic promastigotes that reach the puncture wound are phagocytized by
macrophages (2) and transformed into amastigotes(3) in the macrophage
● Amastigotes multiply in infected cells and affect different tissues, depending in part on
which Leishmania species is involved (4).
● Different tissue specificities cause different clinical manifestations of various forms of
leishmaniasis.
Life Cycle
In Vector sand flies:
● Sandflies become infected during blood meals on infected host when they ingest
macrophages infected with amastigotes(5,6).
● In the sandfly's midgut, the parasites differentiate into promastigotes (7), which
multiply, differentiate into metacyclic promastigotes and migrate to the proboscis(8)
1. Localized cutaneous Leishmaniasis
● Also known as oriental sore, Aleppo boil, and Baghdad sore.
● It is the least drastic type of Leishmania.
● Weeks or months after being bitten by an infected sandfly, the host may notice an
itchy bump (lesion) on an arm, leg, or face.
● Lymph nodes near the bump may be swollen.
● Within months, the bump develops a crater (ulceration) in the center, with a raised,
reddened ridge around it.
2. Diffuse Cutaneous Leishmaniasis
● Lesions are very similar to those of localized cutaneous leishmaniasis, except
they are spread all over the body.
● The body's immune system is overwhelmed and allows parasite to freely spread
throughout.
● The characteristic lesions resemble leprosy.
● New lesions appear in the mouth and nose, and occasionally in the area between
the genitalia and the anus, years after the first lesion have healed.
3. Visceral Leishmaniasis
● Caused by Leishmania donovani species of parasites.
● Most fatal form of Leishmania.
● The natural habitat of L.donovani in man is the reticuloendothelial system of the
viscera, in which the amastigotes multiply by simple binary fission until the host cells
are destroyed,
● More macrophages are parasitized and destroyed thus the host defense system is
rendered ineffective.
● Infective stage for man is promastigote and amastigotes for the sandfly
Clinical features
● Night sweats, body weakness and anorexia are typical.
● Fever lasting for weeks or months.
● Weight loss
● Hepatomegaly (can be marked)
● Splenomegaly (often enormous)
● Pancytopenia (can lead to death from haemorrhage or infection)
● Hypergammaglobulinaemia
● Swollen lymph nodes
● Cough especially in immunocompromised patients.
Pathogenesis of Visceral Leishmaniasis
● The organisms proliferate & invade cells of the liver and spleen leading to marked
enlargement of the organs, weight loss, anemia, and emaciation.
● Reduced bone marrow activity, coupled with cellular distraction in the spleen, results
in anaemia, leukopenia and thrombocytopenia leading to secondary bacterial
infections and a tendency to bleed.
● Lymphadenopathy also occurs. Increased production of globulin results in
hyperglobulinemia.
Mucocutaneous Leishmaniasis
● Initial infection gives a persistent cutaneous lesion that eventually heals.
● Several years later the oral and respiratory mucosa is involved, with inflammation
and mutilation of the nose, mouth, oropharynx, and trachea.
● It may arise after inadequate treatment of some species.
● Respiratory difficulties and malnutrition can cause death.
Diagnosis
Routine diagnosis includes:
1. Complete blood count-(1)normocytic normochromic anemia, (2) leukopenia with
decreased neutrophils and a relative monocytosis and lymphocytosis, and (3)
thrombocytopenia may occur due to parasitic bone-marrow infiltration.
2. Liver function tests- Mild elevation in AST and ALT in VL.
3. The aldehyde test and the antimony test are used to detect hypogammaglobinemia
and diagnose visceral leishmaniasis. Findings include elevated gamma globulin levels
and a reversal of the albumin-globulin ratio
Diagnosis
Visceral Leishmaniasis
● The gold standard for diagnosing visceral leishmaniasis is parasite identification in
tissue smears, with splenic aspirate being more sensitive than bone marrow or lymph
node aspirates.
● Serological methods used where it is difficult to obtain examining tissues
● The direct agglutination test, in which stained parasites are agglutinated by serum
antibodies, is popular in Iran and Africa.
Diagnosis
Cutaneous and Mucocutaneous Leishmaniasis
● Touch smears or culture of exudates or scrapings from the lesions yield good results
in the diagnosis of cutaneous leishmaniasis.
● From a nodule, slit skin smears give good results. Tissue biopsy can be used for
impression smears, culture, or animal inoculation, especially for mucocutaneous
leishmaniasis.
● Microscopy and culture is about 85% sensitive.
● Dental scrapings or mucosal granuloma biopsy can be used but parasites may be
difficult to find.
Differential Diagnosis
1. Basal Cell Carcinoma
2. Chromoblastomycosis
3. Blastomycosis
4. Group A Streptococcal (GAS) Infections
5. Histoplasmosis
6. Impetigo
7. Leprosy
8. Syphillis
Treatment
1. Definitive treatment:
a. Antiparasitic pentavalent antimonials such as sodium stibogluconate (Pentostam)
or meglumine antimonate were the mainstay of treatment (Stark, 2020).
b. Liposomal amphotericin B is the drug of choice of VL.
c. Pentamidine and amphotericin B deoxycholate, as well as oral agents
ketoconazole, itraconazole, and fluconazole have acceptable cure rates though
not FDA approved.
d. Oral miltefosine.
Treatment
e. Allopurinol and Paramomycin can be used as adjunctive medication. Cannot be used
alone in treating Leishmaniasis.
f. Interferon gamma-1b (Actimmune)- Immunomodulator. Administered with sodium
antimony gluconate.
Treatment
Supportive treatment:
● Admit patients for laboratory and cardiac monitoring.
● Administer antibiotic therapy to treat superimposed bacterial wound infections.
● Rest, a high-protein and high-calorie diet, blood transfusions, and wound care are
vital for patients with VL and severe mucocutaneous leishmaniasis.
Prevention
● Immunization with live-attenuated L major promastigotes have been used in Russia
and middle East though not commercially available
● Protection against sandfly bites: Insect repellents and insecticides can be used around
homes, on clothing, on skin, and on bed nets.
● Reducing the population of sand flies by: Clearing the land of trees and bushes for at
least 984 ft (300m) around all villages, and destroying ant hills where sand flies hind
during the day.
● Rodents control to reduce reservoirs . Dogs, may carry the protozoan that causes
leishmaniasis, Simple blood test can be performed on dogs in endemic areas.
References
Stark C (2020). Leishmaniasis Treatment & Management: Approach Considerations,
Pharmacotherapy, Management of Cutaneous Leishmaniasis. (2022). Retrieved 15 January
2022, from https://emedicine.medscape.com/article/220298-treatment
WHO (2022). Leishmaniasis. Retrieved 15 January 2022, from https://www.who.int/news-
room/fact-sheets/detail/leishmaniasis
Leishmaniasis

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Leishmaniasis

  • 1. LEISHMANIASIS Presented by Emmanuel Saha MBChB student Kenyatta University
  • 2. Outline 1. History 2. Epidemiology 3. Etiology 4. Disease manifestations 5. Lifecycle 6. Clinical features 7. Diagnosis 8. Differential diagnosis 9. Treatment and Prevention
  • 3. History ● Leishmaniasis dates back to the 1st century AD. ● Initially known as “Dum dum” fever and later “kal- azar.” ● Was later named Leishmaniasis after Sir William Leishman discovered ovoid bodies in the spleen of a British soldier who was experiencing bouts of fever, anemia, muscular atrophy and swelling of the spleen, in 1901. ● It later acquired the name donovani when Charles Donovan discovered the promastigotes in other kal-azar patients displaying similar symptoms. He named these bodies donovan bodies. ● Hence gaining the name Leishmania donovani.
  • 4. Epidemiology ● It is a neglected disease that affects 700 000 to 1 million new cases occur annually (WHO, 2021). ● Causes 70,000 deaths annually. ● Prevalent in some parts of Asia, the Middle East, Africa (particularly in the tropical region and North Africa, with some cases elsewhere), and southern Europe. It is not found in Australia or the Pacific Islands. ● Endemic in Saudi Arabia.
  • 5. Regional epidemiology ● In Kenya, Cutaneous Leishmaniasis is reported from the highland areas, including the eastern slopes of Mt. Elgon in Bungoma county, the Aberdare Range, Baringo county, and other parts of the Rift Valley region. ● Visceral Leishmaniasis is found in the Rift Valley region(Baringo, West Pokot, and Turkana county), Eastern region (Machakos, Kitue, and Meru county), and North Eastern region.
  • 6. Etiology ● Leishmaniasis is a cutaneous disease caused by protozoan parasites belonging to the genus Leishmania. ● It is transmitted by the bite of tiny 2 to 3mm long insect vector sandfly (known as Phlebotomus species in the Old World and Lutzomyia in the New World) ● It is also known as Orient Boils, Baghdad Boil, kala azar, black fever, sandfly disease, Aleppo boil, Dum-Dum fever or espundia.
  • 7. Etiology ● Most forms of the disease are transmissible from animals (zoonosis). Some 70 animal species, including humans, have been found as natural reservoir hosts of Leishmania parasites. ● Human infection is caused by about 21 of 30 species that infect mammals. Most common ones include: ○ Leishmania donovani ○ Leishmania mexicana ○ Leishmania tropica ○ Leishmania braziliensis
  • 8. Disease manifestations 1.Visceral leishmaniasis: Most vicious form. Known as kala-azar and is fatal if left untreated in over 95% of cases. 2. Mucocutaneous leishmaniasis: Leads to partial or total destruction of mucous membranes of the nose, mouth and throat. 3. Localized Cutaneous leishmaniasis: It’s the most common form of leishmaniasis and causes skin lesions, mainly ulcers, on exposed parts of the body, leaving life-long scars and serious disability or stigma. 4.Diffuse cutaneous leishmaniasis.
  • 9. Life Cycle In Human hosts: ● Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. ● The sandflies inject the infective stage, metacyclic promastigotes, during blood meals(1). ● Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages (2) and transformed into amastigotes(3) in the macrophage ● Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved (4). ● Different tissue specificities cause different clinical manifestations of various forms of leishmaniasis.
  • 10.
  • 11. Life Cycle In Vector sand flies: ● Sandflies become infected during blood meals on infected host when they ingest macrophages infected with amastigotes(5,6). ● In the sandfly's midgut, the parasites differentiate into promastigotes (7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis(8)
  • 12. 1. Localized cutaneous Leishmaniasis ● Also known as oriental sore, Aleppo boil, and Baghdad sore. ● It is the least drastic type of Leishmania. ● Weeks or months after being bitten by an infected sandfly, the host may notice an itchy bump (lesion) on an arm, leg, or face. ● Lymph nodes near the bump may be swollen. ● Within months, the bump develops a crater (ulceration) in the center, with a raised, reddened ridge around it.
  • 13.
  • 14. 2. Diffuse Cutaneous Leishmaniasis ● Lesions are very similar to those of localized cutaneous leishmaniasis, except they are spread all over the body. ● The body's immune system is overwhelmed and allows parasite to freely spread throughout. ● The characteristic lesions resemble leprosy. ● New lesions appear in the mouth and nose, and occasionally in the area between the genitalia and the anus, years after the first lesion have healed.
  • 15.
  • 16. 3. Visceral Leishmaniasis ● Caused by Leishmania donovani species of parasites. ● Most fatal form of Leishmania. ● The natural habitat of L.donovani in man is the reticuloendothelial system of the viscera, in which the amastigotes multiply by simple binary fission until the host cells are destroyed, ● More macrophages are parasitized and destroyed thus the host defense system is rendered ineffective. ● Infective stage for man is promastigote and amastigotes for the sandfly
  • 17. Clinical features ● Night sweats, body weakness and anorexia are typical. ● Fever lasting for weeks or months. ● Weight loss ● Hepatomegaly (can be marked) ● Splenomegaly (often enormous) ● Pancytopenia (can lead to death from haemorrhage or infection) ● Hypergammaglobulinaemia ● Swollen lymph nodes ● Cough especially in immunocompromised patients.
  • 18.
  • 19. Pathogenesis of Visceral Leishmaniasis ● The organisms proliferate & invade cells of the liver and spleen leading to marked enlargement of the organs, weight loss, anemia, and emaciation. ● Reduced bone marrow activity, coupled with cellular distraction in the spleen, results in anaemia, leukopenia and thrombocytopenia leading to secondary bacterial infections and a tendency to bleed. ● Lymphadenopathy also occurs. Increased production of globulin results in hyperglobulinemia.
  • 20. Mucocutaneous Leishmaniasis ● Initial infection gives a persistent cutaneous lesion that eventually heals. ● Several years later the oral and respiratory mucosa is involved, with inflammation and mutilation of the nose, mouth, oropharynx, and trachea. ● It may arise after inadequate treatment of some species. ● Respiratory difficulties and malnutrition can cause death.
  • 21.
  • 22. Diagnosis Routine diagnosis includes: 1. Complete blood count-(1)normocytic normochromic anemia, (2) leukopenia with decreased neutrophils and a relative monocytosis and lymphocytosis, and (3) thrombocytopenia may occur due to parasitic bone-marrow infiltration. 2. Liver function tests- Mild elevation in AST and ALT in VL. 3. The aldehyde test and the antimony test are used to detect hypogammaglobinemia and diagnose visceral leishmaniasis. Findings include elevated gamma globulin levels and a reversal of the albumin-globulin ratio
  • 23. Diagnosis Visceral Leishmaniasis ● The gold standard for diagnosing visceral leishmaniasis is parasite identification in tissue smears, with splenic aspirate being more sensitive than bone marrow or lymph node aspirates. ● Serological methods used where it is difficult to obtain examining tissues ● The direct agglutination test, in which stained parasites are agglutinated by serum antibodies, is popular in Iran and Africa.
  • 24. Diagnosis Cutaneous and Mucocutaneous Leishmaniasis ● Touch smears or culture of exudates or scrapings from the lesions yield good results in the diagnosis of cutaneous leishmaniasis. ● From a nodule, slit skin smears give good results. Tissue biopsy can be used for impression smears, culture, or animal inoculation, especially for mucocutaneous leishmaniasis. ● Microscopy and culture is about 85% sensitive. ● Dental scrapings or mucosal granuloma biopsy can be used but parasites may be difficult to find.
  • 25. Differential Diagnosis 1. Basal Cell Carcinoma 2. Chromoblastomycosis 3. Blastomycosis 4. Group A Streptococcal (GAS) Infections 5. Histoplasmosis 6. Impetigo 7. Leprosy 8. Syphillis
  • 26. Treatment 1. Definitive treatment: a. Antiparasitic pentavalent antimonials such as sodium stibogluconate (Pentostam) or meglumine antimonate were the mainstay of treatment (Stark, 2020). b. Liposomal amphotericin B is the drug of choice of VL. c. Pentamidine and amphotericin B deoxycholate, as well as oral agents ketoconazole, itraconazole, and fluconazole have acceptable cure rates though not FDA approved. d. Oral miltefosine.
  • 27. Treatment e. Allopurinol and Paramomycin can be used as adjunctive medication. Cannot be used alone in treating Leishmaniasis. f. Interferon gamma-1b (Actimmune)- Immunomodulator. Administered with sodium antimony gluconate.
  • 28. Treatment Supportive treatment: ● Admit patients for laboratory and cardiac monitoring. ● Administer antibiotic therapy to treat superimposed bacterial wound infections. ● Rest, a high-protein and high-calorie diet, blood transfusions, and wound care are vital for patients with VL and severe mucocutaneous leishmaniasis.
  • 29. Prevention ● Immunization with live-attenuated L major promastigotes have been used in Russia and middle East though not commercially available ● Protection against sandfly bites: Insect repellents and insecticides can be used around homes, on clothing, on skin, and on bed nets. ● Reducing the population of sand flies by: Clearing the land of trees and bushes for at least 984 ft (300m) around all villages, and destroying ant hills where sand flies hind during the day. ● Rodents control to reduce reservoirs . Dogs, may carry the protozoan that causes leishmaniasis, Simple blood test can be performed on dogs in endemic areas.
  • 30. References Stark C (2020). Leishmaniasis Treatment & Management: Approach Considerations, Pharmacotherapy, Management of Cutaneous Leishmaniasis. (2022). Retrieved 15 January 2022, from https://emedicine.medscape.com/article/220298-treatment WHO (2022). Leishmaniasis. Retrieved 15 January 2022, from https://www.who.int/news- room/fact-sheets/detail/leishmaniasis

Editor's Notes

  1. It was depicted in pre-incan pottery in Ecuador and Peru in the 1st century.