MIDTERM: LEISHMANIA Flashcards
Leishmania spp. 4 MAIN COMPLEXES
o Leishmania braziliensis complex
o Leishmania donovani complex
o Leishmania mexicana complex
o Leishmania tropica complex
Leishmania braziliensis complex
o Leishmania braziliensis
o Leishmania panamensis
o Leishmania peruviana
o Leishmania guyanensis
Leishmania donovani Complex
o Leishmania donovani
o Leishmania infantum
o Leishmania chagasi
Leishmania mexicana Complex
o Leishmania mexicana
o Leishmania amazonensis
o Leishmania venezuelensis
o Leishmania pifanoi
o Leishmania garnhami
Leishmania tropica Complex
o Leishmania aethiopica
o Leishmania major
o Leishmania tropica
Old world Leishmania:
- L. tropica (Asia and Eastern)
- L. aethiopica (Africa)
- L. major
New world Leishmania:
L. Mexicana
L. amazonensis
L. guyanensis
L. braziliensis
L. chagasi
Causative agent of LEISHMANIASIS
Leishmania spp.
a general term used to describe diseases caused by the hemoflagellate genus Leishmania (a diploid protozoa)
Leishmaniasis
4 categories of Leishmaniasis:
▪ Cutaneous leishmaniasis (CL)
▪ Diffuse cutaneous leishmaniasis (DCL)
▪ Mucocutaneous leishmaniasis (MCL)
▪ Visceral leishmaniasis (VL)
vectors of Leishmania spp.
Sandflies of genus (female)
vectors of old world Leishmania spp.
Phlebotomus
vectors of new world Leishmania spp.
Lutzomyia
Primary reservoir:
o Dogs (urban)
o Rodents (urban and rural)
Mode of transmission:
o Congenitally
o Bite of sandfly
o Through blood transfusion
o Contamination of bite wounds
o Direct contact with contaminated
specimens
The immune response of the host against
the infection depends on:
▪ Leishmania-specific Th1-type CD4+ T-cells
▪ Macrophages
▪ Cytokines
However, other factors such as _________, ___________ and _______________may affect the outcome of infection
genetics, nutritional status, environmental factors
Symptoms manifested by leishmaniasis is often
compared to?
LEPROSY
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
studied the “Delhi boil” in India
A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)
Cunningham (1885)
properly identified the intracellular parasites
A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)
Leishman (1903)
o later identified Leishmania braziliensis
A. Cunningham (1885)
B. Henrique Aragao (1922)
C. Gaspar Viana (1911)
D. Leishman (1903)
Gaspar Viana (1911)
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)
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
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)
