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Case presentation
Case 15
Reporter: I2 姚信宇
Date: 94/11/14
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.
Physical examination

Physical examination revealed hepatomegaly,
splenomegaly, and lymphadenopathy.
 The patient had darkened areas of skin on his
forehead and around his mouth.
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.
Fig.15.1
Leishmaniasis (利什曼原蟲病)

Intracellular amastigotes in macrophages of
humans and other mammalian hosts .
 Extracellular promastigotes in the gut of sandfly
vectors.
Leishmaniasis (利什曼原蟲病)

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.
Leishmaniasis (利什曼原蟲病)

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.
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.
Leishmaniasis (利什曼原蟲病)

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).
Visceral Leishmaniasis (內臟型利什曼原蟲
病)

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).
Visceral Leishmaniasis (內臟型利什曼原蟲
病)

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 (黑熱病).
Question 1

Which infection does this patient have? What is
the name of the hemoflagellate? Which is causing
his infection?
Answer 1

Due to the patient’s symptoms & signs, visceral
leishmaniasis causes the patient’s infection.
Question 2

Name the three species belonging to this complex.
In which parts of the world are these species
located?
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
Question 3

Which vectors are responsible for the transmission
of this infection?
Answer 3

Transmission is by Phlebotomus argentipes and
other anthropophilic Phlebotomus spp. (白蛉).
Question 4

List four forms of infection caused by this genus
of hemoflagellates. How does this patient's
infection differ from the other three?
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,
1. Ulcerative skin lesions with raised outer borders
on the arm of a patient with New World
(American) cutaneous leishmaniasis acquired in
Costa Rica.

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.

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.
Question 5

How is the diagnosis of this infection made?
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.

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.
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.
Question 6

What is the significance of the time of day
(midnight) at which the patient was seen in the
emergency department?
Answer 6

The incubation period is usually in the range of 3
to 8 months.
Question 7

What causes the enlargement of the liver and
spleen?
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.
Question 8

What causes the anemia and leukopenia
characteristic of this infection?
Answer 8

Anemia:
 severe; normocytic and normochromic.
 hemolysis, marrow replacement with leishmaniainfected macrophages, hemorrhage, splenic
sequestration of erythrocytes, hemodilution, and
effects of cytokines such as TNF-alpha.
 Leukopenia:
 increased margination, splenic sequestration, or
an autoimmune process.
Question 9

Which complication may occur in this infection?
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.
Question 10

How is this infection treated?
Answer 10
References

Harrison's Principles of Internal Medicine - 16th
Ed. (2005)
 Internal Medicine, Stein - 5th Ed. (1998)
 Schlossberg: Current Therapy of Infectious
Disease