Case presentation

1
Case presentation

• Case 15
• Reporter I2 ???
• Date 94/11/14

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Chief complaint, present illness,
personal/past/family history

• A 24-year-old male Pakistani medical resident was
  seen in the emergency department at midnight he
  was acutely ill with weakness, fever, abdominal
  pain, and diarrhea.
• He had visited relatives in Pakistan several
  months earlier.
• He had recently lost 20 lb inexplicably.

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Physical examination

• Physical examination revealed hepatomegaly,
  splenomegaly, and lymphadenopathy.
• The patient had darkened areas of skin on his
  forehead and around his mouth.

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Laboratory tests

• Anemic, with a hemoglobin level of 10 g/dl.
• Leukopenia and thrombocytopenia.
• Liver enzyme levels were slightly elevated.
• Giemsa-stained buffy coat smears a few
  macrophages containing oval, nonflagellated
  protozoan forms, about 2 to 3 µm long(Fig.15.1).
  A large nucleus, a small kinetoplast, and an
  axoneme were visible in several parasites.

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Fig.15.1
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Leishmaniasis (??????)

• Intracellular amastigotes in macrophages of
  humans and other mammalian hosts .
• Extracellular promastigotes in the gut of sandfly
  vectors.

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Leishmaniasis (??????)

• In humans and other susceptible mammals in
  cells of reticuloendothelial origin as
  intracellular amastigotes, which are 2 to 3 ?m in
  length, oval or round, and lack an flagellum.

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Leishmaniasis (??????)

• In Wright- and Giemsa-stain
• ? the cytoplasm appears blue.
• ? the nucleus is relatively large, eccentrically
  located, and red.
• ? the distinct, rod-shaped, red-staining
  kinetoplast (a specialized mitochondrial
  structure) contains extranuclear DNA arranged as
  catenated minicircles and maxicircles.

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1. Amastigotes in a bone marrow specimen from a
patient with visceral leishmaniasis. 2. Each
amastigote has a nucleus and kinetoplast. 3.
Visualization of the kinetoplast is essential in
differentiating leishmaniasis from diseases such
as histoplasmosis.
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Leishmaniasis (??????)

• Anti-leishmanial antibodies and complement are
  deposited on the parasite surface.
• Promastigotes are phagocytosed by macrophages.
  Promastigotes convert within them to amastigotes.
  
• Amastigotes are released and infect other
  mononuclear phagocytes.
• Cell-mediated immune response (predominant Th1
  response).

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Visceral Leishmaniasis (?????????)

• Etiology
• ? Typical L. donovani (Indian subcontinent,
  northern and eastern China, Pakistan, Nepal,
  eastern Africa), L. infantum(Middle East,
  Mediterranean littoral, Balkans, central and
  southwestern Asia, northern and western China,
  North and sub-Saharan Africa), and L. chagasi
  (Latin America)
• ? Atypical L. amazonensis (Latin America) or L.
  tropica (Middle East or Africa).

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Visceral Leishmaniasis (?????????)

• The incubation period usually 3 to 8 months.
• Symptoms/Signs fever, weight loss, discoloration
  of skin (hands, feet, abdomen, or face), anemia,
  hepatosplenomegaly, leukopenia, and
  hypergammaglobulinemia.
• The condition is known as kala-azar (???).

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Question 1

• Which infection does this patient have? What is
  the name of the hemoflagellate? Which is causing
  his infection?

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Answer 1

• Due to the patients symptoms signs, visceral
  leishmaniasis causes the patients infection.

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Question 2

• Name the three species belonging to this complex.
  In which parts of the world are these species
  located?

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Answer 2

• L. donovani Indian subcontinent, northern and
  eastern China, Pakistan, Nepal, eastern Africa.
• L. infantum Middle East, Mediterranean littoral,
  Balkans, central and southwestern Asia, northern
  and western China, North and sub-Saharan Africa.
• L. chagasi Latin America

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Question 3

• Which vectors are responsible for the
  transmission of this infection?

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Answer 3

• Transmission is by Phlebotomus argentipes and
  other anthropophilic Phlebotomus spp. (??).

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Question 4

• List four forms of infection caused by this genus
  of hemoflagellates. How does this patient's
  infection differ from the other three?

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Answer 4

• Cutaneous leishmaniasis
• ? typically there is, first, a papule, which
  enlarges,
• becomes crusted, and then ulcerates. Ulcers
• have a diameter of about 2 cm and an indurated
• border.
• ? regional lymphadenopathy is common.
• ? patients usually have no fever,

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• 1. Ulcerative skin lesions with raised outer
  borders on the arm of a patient with New World
  (American) cutaneous leishmaniasis acquired in
  Costa Rica.

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• Diffuse cutaneous leishmaniasis
• ? observed in Ethiopia, Venezuela, Brazil, and
  the Dominican Republic.
• ? the lesions are widespread and typically remain
  as macules or papules without ulceration.
• ? the mucous membranes may be involved, but not
  the viscera.
• ? lesions contain sparse lymphocytes, and there
  is cutaneous anergy to leishmanial antigens.

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• Mucocutaneous leishmaniasis (espundia)
• ? caused by L. braziliensis and is especially
  prevalent in Brazil south of the Amazon.
• ? in patients with cutaneous lesions the
  likelihood of subsequent mucous membrane
  involvement is about 80.
• ? more than 90 of patients with espundia have
  scars of previous cutaneous involvement.
• ? nasal lesions tend to destroy the cartilage of
  the septum and spread to the buccal mucosa,
  pharynx, and larynx.

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Question 5

• How is the diagnosis of this infection made?

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Answer 5

• Definitive diagnosis amastigotes in tissue or
  the isolation of promastigotes in culture.
• Antileishmanial antibodies high titer in
  immunocompetent patients with visceral
  leishmaniasis.
• ELISA (recombinant L. chagasi antigen rk39)
  highly sensitive and specific in detecting
  visceral leishmaniasis in immunocompetent
  persons.

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• The leishmanin (Montenegro) skin test
• ? negative results in patients with progressive
  visceral leishmaniasis.
• ? the result becomes positive in the majority of
  persons in whom infection spontaneously resolves
  and in those who have undergone successful
  chemotherapy.

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Differential diagnosis

• Acute stage malaria, typhoid fever, typhus,
  acute Chagas' disease, schistosomiasis, miliary
  tuberculosis, or amebic liver abscess.
• Subacute or chronic stages brucellosis,
  Salmonella bacteremia, histoplasmosis, infectious
  mononucleosis, hepatosplenic schistosomiasis, and
  splenomegaly due to chronic malaria.

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Question 6

• What is the significance of the time of day
  (midnight) at which the patient was seen in the
  emergency department?

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Answer 6

• The incubation period is usually in the range of
  3 to 8 months.

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Question 7

• What causes the enlargement of the liver and
  spleen?

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Answer 7

• Large numbers of amastigote-infected mononuclear
  phagocytes in the liver and spleen result in
  progressive hypertrophy.
• The spleen massively enlarged as splenic
  lymphoid follicles are replaced by parasitized
  mononuclear cells.
• The liver marked increase in the number and size
  of Kupffer cells, many of which contain
  amastigotes.

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Question 8

• What causes the anemia and leukopenia
  characteristic of this infection?

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Answer 8

• Anemia
• ? severe normocytic and normochromic.
• ? hemolysis, marrow replacement with
  leishmania-infected macrophages, hemorrhage,
  splenic sequestration of erythrocytes,
  hemodilution, and effects of cytokines such as
  TNF-alpha.
• Leukopenia
• ? increased margination, splenic sequestration,
  or an autoimmune process.

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Question 9

• Which complication may occur in this infection?

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Answer 9

• Post-kala-azar dermal leishmaniasis
• ? follows the treatment of visceral leishmaniasis
  in a subset of persons in Africa and India.
• ? the skin lesions vary from hyperpigmented
  macules to frank nodules.
• ? they are found on the face, trunk, extremities,
  oral mucous membranes, and occasionally, on the
  genitals.

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Question 10

• How is this infection treated?

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Answer 10
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References

• Harrison's Principles of Internal Medicine - 16th
  Ed. (2005)
• Internal Medicine, Stein - 5th Ed. (1998)
• Schlossberg Current Therapy of Infectious Disease