MIDTERM: LEISHMANIA Flashcards by Sunwoo's Berry

Leishmania spp. 4 MAIN COMPLEXES

o Leishmania braziliensis complex
o Leishmania donovani complex
o Leishmania mexicana complex
o Leishmania tropica complex

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Leishmania braziliensis complex

o Leishmania braziliensis
o Leishmania panamensis
o Leishmania peruviana
o Leishmania guyanensis

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Leishmania donovani Complex

o Leishmania donovani
o Leishmania infantum
o Leishmania chagasi

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Leishmania mexicana Complex

o Leishmania mexicana
o Leishmania amazonensis
o Leishmania venezuelensis
o Leishmania pifanoi
o Leishmania garnhami

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Leishmania tropica Complex

o Leishmania aethiopica
o Leishmania major
o Leishmania tropica

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Old world Leishmania:

L. tropica (Asia and Eastern)
L. aethiopica (Africa)
L. major

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New world Leishmania:

 L. Mexicana
 L. amazonensis
 L. guyanensis
 L. braziliensis
 L. chagasi

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Causative agent of LEISHMANIASIS

Leishmania spp.

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a general term used to describe diseases caused by the hemoflagellate genus Leishmania (a diploid protozoa)

Leishmaniasis

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4 categories of Leishmaniasis:

▪ Cutaneous leishmaniasis (CL)
▪ Diffuse cutaneous leishmaniasis (DCL)
▪ Mucocutaneous leishmaniasis (MCL)
▪ Visceral leishmaniasis (VL)

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vectors of Leishmania spp.

Sandflies of genus (female)

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vectors of old world Leishmania spp.

Phlebotomus

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vectors of new world Leishmania spp.

Lutzomyia

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Primary reservoir:

o Dogs (urban)
o Rodents (urban and rural)

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Mode of transmission:

o Congenitally
o Bite of sandfly
o Through blood transfusion
o Contamination of bite wounds
o Direct contact with contaminated
specimens

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The immune response of the host against
the infection depends on:

▪ Leishmania-specific Th1-type CD4+ T-cells
▪ Macrophages
▪ Cytokines

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However, other factors such as _________, ___________ and _______________may affect the outcome of infection

genetics, nutritional status, environmental factors

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Symptoms manifested by leishmaniasis is often
compared to?

LEPROSY

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Early descriptions of leishmaniasis have been
found as early as the first century A.D., where
they documented the disease in POTTERY FIGURES

American Indians

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studied the “Delhi boil” in India

A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)

Cunningham (1885)

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properly identified the intracellular parasites

A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)

Leishman (1903)

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o later identified Leishmania braziliensis

A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)

Gaspar Viana (1911)

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identified the insect vector which transmitted the parasite

A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)

Henrique Aragao (1922)

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Leishmania spp. is actually divided into_________, differentiated from one another by the location of their development inside the insect vector,
as well as the areas in which they are endemic.

2 subgenera

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Currently there are about ___ species of Leishmania which cause clinical manifestations in humans

15 SPECIES

Currently there are about 15 species of Leishmania which cause clinical manifestations in humans. * Historically divided and classified based on their:

- BIOLOGICAL - CLINICAL - GEOGRAPHIC - EPIDEMIOLOGICAL CHARACTERISTICS

infective stage to humans

PROMASTIGOTE

INFECTIVE STAGE TO VECTORS (SANDFLY)

AMASTIGOTE

DIAGNOSTIC STAGE

AMASTIGOTE

Leishmania spp. produce amastigotes intracellularly in the ________host

mammalian

Leishmania spp. produce promastigotes in the parts of the insect vector (what parts?)

o HINDGUT(Viannia subgenus), o MIDGUT(Viannia and Leishmania subgenera), and; o PROBOSCIS (Viannia and Leishmania subgenera)

Shape: OVOID or ROUNDED ▪ Size: 2 to 3 μm in length ▪ Habitat: Monocytes, Polymorphonuclear Leukocytes, or; Endothelial Cells ▪ Nucleus: Large ▪ Axoneme: arises from the kinetoplast and extends to the anterior tip.

AMASTIGOTE

▪ have a SINGLE FREE FLAGELLUM arising from the kinetoplast at the anterior end. ▪ Size: 15 to 20 μm in length;1.5 to 3.5 μm in width

PROMASTIGOTE

It is a NEW WORLD LEISHMANIASIS that is mainly distributed in the SOUTH AMERICA. Particularly in the RAINFOREST REGIONS, where CHICLE SAP for chewing gum is harvested (associated with the chiclero ulcer)

Leishmania braziliensis complex

Leishmania braziliensis complex Commonly associated diseases and conditions:

o Mucocutaneous leishmaniasis o Chiclero ulcer o Espundia o Forest yaws o Pian bois o Uta

Leishmania braziliensis complex VECTOR?

Lutzomyia & Psychodopygus (Sandflies)

Leishmania braziliensis complex TARGETS?

Reticuloendothelial cells

INFECTION SITE OF Leishmania braziliensis complex

SKIN AND THE MUCOUS MEMBRANE

- Affects 2-5% of people infected with L. braziliensis, either concurrently or even several years after the resolution of skin lesions. o It may be also due to the contiguous spread of cutaneous leishmaniasis caused by L. tropica. o Infects the NASAL and ORAL CAVITIES o Also called as "Uta" in the Peruvian Andes o Starts as skin lesions  nasal stuffiness, epistaxis, and destruction of the nasal septum (disfiguration called espundia) - Incubation period: few weeks – months

MUCOCUTANEOUS LEISHMANIASIS (MCL)

destruction of the nasal septum

Espundia

Progression into the pharynx and larynx may threaten the airway passage that may lead to:

 Dysphonia (unable to talk)  Dysphagia (difficulty to eat)  Aspiration pneumonia

_______is strong in cases of MCL, with increased levels of peripheral mononuclear cells in the blood

Systemic Th1 response

o Causative agent: L. guyanensis o The principal cause of mucocutaneous leishmaniasis in Guianas, parts of Brazil, and Venezuela.

FOREST YAWS (PIAN BOIS)

It can be classified as a NEW WORLD or OLD WORLD Leishmaniasis because of its location * TARGETS: Reticuloendothelial cells * INFECTION SITE: Visceral organs (internal organs of the body)

Leishmania donovani complex

VECTORS of Leishmania donovani complex

Lutzomyia; Phlebotomus (Sandflies)

o MOST SEVERE TYPE o is a disseminated parasitosis primarily caused by L. donovani complex o Incubation period: 2-8 months o Patients are asymptomatic, but symptoms appear if immunocompromised o Affects the bone marrow, spleen, and liver

VISCERAL LEISHMANIASIS (VL)

VISCERAL LEISHMANIASIS (VL) also known as the ?

kala azar (black fever), or dum dum fever

In patients with VL, Leishmania-specific Th1 response is usually _________

LOW/ABSENT

VISCERAL LEISHMANIASIS (VL) co-infects with HIV TRUE OR FALSE?

TRUE ▪ Visceral leishmaniasis is an important OPPORTUNISTIC INFECTION in AIDS patients. ▪ VL infection ACCELERATES HIV replication and PROGRESSION to AIDS.

- early stage (may resemble malaria or typhoid fever w/ the development of fever and chills) ▪ Twice-daily fever spikes (double quotidian) accompanied by chills ▪ Weight loss and emaciation (abnormally thin and weak) ACUTE OR CHRONIC STAGE?

ACUTE STAGE

- late stage o Include fever, weakness, loss of appetite, weight loss, hemorrhage, and abdominal enlargement associated with hepatosplenomegaly ACUTE OR CHRONIC STAGE?

CHRONIC STAGE (SUBACUTE)

▪ Kidney damage (glomerulonephritis) ▪ Granulomatous areas of skin

ADVANCE STAGES

 Sequela of visceral leishmaniasis  Seen in endemic areas  Manifests as a CUTANEOUS ERUPTION resulting in hypopigmented macules, malar erythema, nodules, and ulcerations  Manifest a few months to several years after treatment

POST – KALA AZAR DERMAL LEISHMANIASIS (PKDL)

consequence of a previous disease or injury

sequela

* NEW WORLD * PRIMARY VECTORS: Sandfly (Lutzomiya spp.) o Identical to that of L. braziliensis and L. donovani complex * AFFECTS: SKIN

Leishmania mexicana complex

Common associated disease of Leishmania mexicana complex and condition names:

o New World cutaneous leishmaniasis ▪ Also known as Chiclero ulcer and Bay sore o Diffuse Cutaneous Leishmaniasis

o MOST COMMON FORM of the disease o Caused by L. tropica, L. major & L. Mexicana o in case of New World leishmaniasis, it may progress to other forms of leishmaniasis. o usually characterized by a single pus-containing ulcer, which is generally self-healing o ORIENTAL BUTTON o Incubation period: 2 weeks to several months

CUTANEOUS LEISHMANIASIS (CL)

▪ It is an erythematous papule or nodule, produced at the inoculation site. ▪ papule forms a violaceous ulcer as it enlarges in size. The lesion may heal spontaneously after a few months, leading to a disfiguring scar ▪ may cause pruritis (intense itching).

ORIENTAL BUTTON

the inability of an individual to mount an adequate immune response

ANERGIC

o Also called anergic or lepromatous leishmaniasis o rare in NEW WORLD (rare form) o LESION: characterized by a localized, non-ulcerating papule, eventually developing numerous diffuse satellite lesions that affect the face and extremities.

DIFFUSE CUTANEOUS LEISHMANIASIS (DCL)

DIFFUSE CUTANEOUS LEISHMANIASIS (DCL) may be initially diagnosed as _____________________ - This latter form of cutaneous leishmaniasis usually occurs when the patient is anergic.

LEPROMATOUS LEPROSY

the initial lesion appears, ulcerates or disappears and, after a period of months to years, appears in local and distant areas from the bite site with lepromatous appearing lesions.

L. pifanoi infections

have been known to progress to an incurable diffuse cutaneous form of the disease.

L. amazonensis infections

* OLD WORLD * VECTOR: Sandfly (Phlebotomus spp.) * PRIMARILY ATTACKS: human lymphoid tissue of the skin

Leishmania tropica complex

Leishmania tropica complex Common associated diseases and condition names:

Old World cutaneous leishmaniasis Also known as:  Oriental sores  Delhi boils  Baghdad boils  dry or urban cutaneous leishmaniasis

o MOST COMMON FORM of the disease o Caused by L. tropica & L. Mexicana o One or more pus-containing ulcers that self-heal o Sometimes self-healing does not occur because of the thick plaques of skin along with multiple lesions/nodules o Small red papule occurs at bite site often, with intense itching. o 2 cm or larger in diameter o Incubation and appearance vary with subspecies.

CUTANEOUS LEISHMANIASIS (CL)

DIAGNOSIS OF Leishmania spp.

- MICROSCOPIC DEMONSTRATION - GIEMSA AND HEMATOXYLIN-EOSIN STAINS - CULTURES - NOVY, MACNEAL, AND NICOLLE MEDIUM (NNN) - SCHNEIDER’S MEDIUM - ANIMAL INOCULATION USING HAMSTERS - MONTENEGRO SKIN TEST - IMMUNOLOGIC ASSAYS such as ELISA and rk39 antigen dipstick test - FLOW CYTOMETRY & MOLECULAR DIAGNOSTIC MODALITIES - Restriction Fragment Length Polymorphism (RFLP)

often used in microscopic and histologic samples, and the demonstration of amastigotes confirms the diagnosis of leishmaniasis

GIEMSA AND HEMATOXYLIN-EOSIN STAINS

are unreliable due to the difficulty of isolating the parasites, especially in old lesions.

CULTURES

There are reports of successful primary isolation of the NEW WORLD cutaneous Leishmania using this medium

NOVY, MACNEAL, AND NICOLLE MEDIUM (NNN)

could detect low intensity of infection.

ANIMAL INOCULATION USING HAMSTERS

o leishmanin skin test o used to identify exposure to the parasite.

MONTENEGRO SKIN TEST

MONTENEGRO SKIN TEST is _____ in cases of CL and MCL

POSITIVE

MONTENEGRO SKIN TEST is _____ in cases of DCL and kala azar.

NEGATIVE

have demonstrated HIGH SENSITIVITY and specificity for VL in certain immunocompetent patient populations.

IMMUNOLOGIC ASSAYS such as ELISA and rk39 antigen dipstick test

o Primary pharmacologic treatment o notably the pentavalent antimonials

ANTIMONY COMPOUNDS

PENTAVALENT ANTIMONIALS:

o Sodium stibogluconate o n-methyl-glucamine (meglumine)

o DRUG OF CHOICE in cases where there is treatment failure with antimonials, or in area where resistance is high o has a HIGH CURE RATE o but has side effects o cost and availability of the drug are significant limiting factors.

INTRAVENOUS AMPHOTERICIN B

▪ Lipid-based preparations of the Amphotericin B ▪ highly effective ▪ better tolerated ▪ overall cost-effective drug formulation for cutaneous and visceral leishmaniasis

AmBisome

o An antineoplastic drug o Was introduced in 2002 where sodium pentavalent antimony resistance is high in India o only oral drug currently given to VL patients.

MILTEFOSINE

o another SECOND-LINE drug for CUTANEOUS as well as the VISCERAL FORM of the disease o due to side-effects and the development of drug resistance, pentamidine use has been limited.

PENTAMIDINE

shows efficacy for the cutaneous form of leishmaniasis

TOPICAL PAROMOMYCIN

drug of choice for treating visceral leishmaniasis

Liposomal amphotericin B (Ambisome)

effective treatment for infections with L. donovani complex

Sodium stibogluconate (Pentosam)