176: Leishmaniasis and Other Protozoan Infections Flashcards
What are the four human diseases caused by Leishmania?
- Localized cutaneous leishmaniasis
- Diffuse cutaneous leishmaniasis
- Mucocutaneous leishmaniasis
- Visceral leishmaniasis
These New World LCL pathogens only cause cutaneous disease.
L. mexicana and L. guyanensis.
What are the main reservoir hosts for Leishmania?
- Great gerbil
- Fat sand rat
- Meriones spp.
- Other rodents
- Dogs
- Opossums
- Sloths
What factors contribute to the increasing relevance of humans as reservoir hosts for Leishmania?
- Human settlements in close proximity to forests
- Restrictions in the diversity of mammals available for sand fly feeding
Describe the life cycle of Leishmania parasites, including the transition between promastigote and amastigote forms.
Leishmania parasites exist in two forms: promastigote and amastigote. In the gut of the sand fly or in culture, they are in the promastigote form, which is spindle-shaped and motile with a single anterior flagellum. Upon transmission to the host, they transform into the amastigote form, which is oval, nonmotile, and intracellular. Amastigotes are ingested by macrophages and neutrophil granulocytes, where they multiply by binary fission. When infected macrophages rupture, amastigotes are released and transform back into promastigotes in the sand fly’s stomach, eventually becoming infective metacyclic promastigotes in the fly’s salivary glands.
What are the major differences between anthroponotic and zoonotic leishmaniasis?
Anthroponotic leishmaniasis involves humans as primary reservoir hosts, while zoonotic leishmaniasis is transmitted from wild and domestic animals to humans.
How does the immunologic status of the host affect the disease caused by Leishmania species?
The disease caused by Leishmania species depends mainly on the interaction between the specific Leishmania species and the immunologic status of the host, influencing the severity and type of leishmaniasis that develops.
What are the primary methods used for diagnosing leishmaniasis?
Diagnosis of leishmaniasis is performed through:
1. Organism isolation
2. Serology
3. Species identification by isoenzyme analysis and new molecular techniques
What is the annual global incidence of leishmaniasis cases?
Annually, approximately 1.6 million new cases of leishmaniasis are reported, with around 200,000 to 400,000 cases being visceral leishmaniasis and 700,000 to 1.2 million cases being cutaneous leishmaniasis.
What are the neglected tropical diseases associated with leishmaniasis?
Neglected tropical diseases associated with leishmaniasis include:
- Poverty-associated infectious diseases
- Primarily prevalent in subtropical and tropical regions
- Characterized by little public interest and research activity
- High morbidity and mortality rates
- No safe and long-lasting therapies
Which countries report the highest cases of cutaneous leishmaniasis?
The ten countries with the highest case counts of cutaneous leishmaniasis are:
1. Afghanistan
2. Algeria
3. Brazil
4. Colombia
5. Costa Rica
6. Ethiopia
7. Iran
8. Peru
9. Sudan
10. Syria
These countries account for 70% to 75% of all CL cases.
What is the role of HIV in the context of leishmaniasis?
HIV-infected individuals have longer periods of parasitemia, which can lead to humans becoming reservoirs for the Leishmania parasite. This has resulted in an increased rate of leishmaniasis cases in regions with high numbers of HIV/Leishmania co-infected patients, particularly in Southern Europe.
What are the characteristics of the amastigote form of Leishmania?
The amastigote form of Leishmania is characterized by:
- Obligate intracellular, oval shape
- Size ranging from 2 to 6 μm
- A relatively large basophilic nucleus
- A smaller rod-shaped kinetoplast at the base of the lost flagellum.
What are the three genera of phlebotomine sand flies involved in leishmaniasis transmission?
The three genera of phlebotomine sand flies involved in leishmaniasis transmission are:
1. Phlebotomus (Old World)
2. Lutzomyia (New World)
3. Psychodopygus (New World)
Approximately 70 species are implicated as vectors.
What are the challenges in treating leishmaniasis?
Challenges in treating leishmaniasis include:
- Often difficult treatment options
- Limited availability of effective therapies
- Development of resistance to existing treatments
- Lack of prophylactic vaccines.
What is the role of serology in the diagnosis of leishmaniasis?
Serology plays a crucial role in the diagnosis of leishmaniasis by detecting antibodies against Leishmania species, helping to confirm infection and differentiate between various forms of the disease.
How does the size of phlebotomine sand flies relate to their role as vectors?
Phlebotomine sand flies are small (<3 mm), which allows them to easily access hosts for feeding. Their size and feeding behavior contribute to their effectiveness as vectors for transmitting Leishmania parasites.
What is the impact of globalization on the distribution of phlebotomine sand flies?
Globalization has led to the spread of phlebotomine sand flies into new regions, including northern Europe, due to changes in climate and human activities, increasing the risk of leishmaniasis transmission in these areas.
What are the potential outcomes of co-infection with HIV and Leishmania?
Co-infection with HIV and Leishmania can lead to:
- Increased severity of leishmaniasis
- Prolonged parasitemia in HIV-infected individuals
- Higher rates of leishmaniasis cases in regions with high HIV prevalence.
What are the cardinal manifestations of visceral leishmaniasis?
- Persistent, high, undulating fever
- Leucopenia
- Splenomegaly
- Anemia
- Hypergammaglobulinemia
Enumerate the important protozoan infections for humans, stating their mode of transmission, pathogen, disease and main organ involved.
What are the main treatment options currently available for leishmaniasis?
Main treatment options for leishmaniasis include:
- Systemic therapy with antimonials
- Other treatments under investigation
- No effective prophylactic vaccine currently exists.
What are the epidemiological regions where cutaneous leishmaniasis is most prevalent?
Cutaneous leishmaniasis is most prevalent in three epidemiological regions:
1. The Americas
2. The Mediterranean basin
3. Western Asia from the Middle East to Central Asia.
What is the role of observation in the management of leishmaniasis?
Observation is a management strategy for leishmaniasis, particularly in cases where the disease is self-limiting or when the clinical presentation is mild, allowing for monitoring without immediate intervention.
What are the potential consequences of untreated leishmaniasis?
Untreated leishmaniasis can lead to severe complications, including:
- Chronic skin lesions in cutaneous leishmaniasis
- Systemic involvement and organ damage in visceral leishmaniasis
- Increased risk of secondary infections and mortality.
What are the causative Leishmania species for different Leishmaniasis disease forms?
What factors influence the pathogenesis of leishmaniasis?
The pathogenesis of leishmaniasis is influenced by numerous parasite-related and host-related factors, including:
Parasite-related factors:
- Sand fly saliva, which contains vasodilators and immunomodulators.
- Variations in Leishmania species affecting immune response (Th1 vs Th2).
- Promastigote virulence factors like lipophosphoglycan and gp63.
Host-related factors:
- Malnutrition and immunosuppression.
- Genetic background of the host.
- The balance of Th1 and Th2 immune responses, which determines the course of the disease.
How do Th1 and Th2 responses affect leishmaniasis outcomes?
The balance between Th1 and Th2 responses significantly affects the outcomes of leishmaniasis:
1. Th1 Response:
- Produces interferon-γ and nitric oxide.
- Leads to a leishmanicidal state in macrophages.
- Associated with self-healing localized cutaneous leishmaniasis (LCL).
- Positive Montenegro skin test indicates delayed-type hypersensitivity.
2. Th2 Response:
- Associated with progressive disease such as diffuse cutaneous leishmaniasis (DCL).
- Characterized by anergy to leishmanial antigens and negative Montenegro skin test.
- Contributes to disease susceptibility through regulatory T cells and Th17 cells producing interleukin-17A.
What is the clinical spectrum of leishmaniasis based on host factors and parasite species?
The clinical spectrum of leishmaniasis varies based on host factors and parasite species:
- Cutaneous Leishmaniasis (CL): Primarily presents in most cases.
- Mucocutaneous Leishmaniasis (MCL): Tends to occur with certain species that spread across mucosal membranes.
- Visceral Leishmaniasis (VL): Some species can spread into visceral organs.
- Cryptic Infections: May also occur, depending on the host’s immune status and other factors.
Enumerate the local therapies against cutaneous leishmaniasis.
Explain the role of sand fly saliva in the pathogenesis of leishmaniasis.
Sand fly saliva contains vasodilators, anticoagulants, and immunomodulators, which increase the inoculum size and lesion diameter in previously unexposed individuals. Intraspecific variations in sand fly saliva can affect the clinical outcome by shifting adaptive immunity from a Th1 to a Th2 immune response.
How does the immune response differ in localized cutaneous leishmaniasis (LCL), diffuse cutaneous leishmaniasis (DCL), and mucocutaneous leishmaniasis (MCL)?
In LCL, T-cell immunity is intact, leading to a dominant Th1 response and self-healing lesions. In DCL, there is defective T-cell immunity with a dominant Th2 response, resulting in progressive disease. In MCL, both Th1 and Th2 responses are present, with a slight predominance of Th2 immunity, leading to persistent disease.
This New World LCL pathogen is associated with persistent lesions and are often associated with lymphadenopathy.
L. braziliensis.
LCL is considered chronic if the disease lasts for how long?
More than 1 year.
It is the anergic rare form of CL.
DCL or pseudolepromatous leishmaniasis.
T or F: Disseminated CL is described as >10 pleomorphic lesions in noncontiguous areas of the body.
True.
What are the known pathogens of leishmaniasis recidivans?
- L. tropica (mostly)
- L. braziliensis
- L. amazonensis
- L. panamensis
- L. guyanensis
It is causes Uta, Andean cutaneous form of leishmaniasis, which affects exposed areas in children.
L. braziliensis.
How does sand fly behavior influence disease transmission?
Sand flies are crepuscular or nocturnal, rest in dark, humid places, and prefer outdoor feeding, limiting control through house spraying.
It causes the atypical nodular form of New World CL and is common in Honduras and Nicaragua and among immunosuppressed patients.
Leishmania donovani chagasi.
These are the ashy hyperpigmented patches on the temple, around the mouth, on the abdomen, hands and feet that develop later in the course of VL.
Kala-azar
This sign pertains to trichomegaly found in patients with VL.
Pitalugo sign.
This is predictive of development of Post-Kala-Azar Dermal Leishmaniasis among VL patients.
High IL-10 blood concentration.
What are the clinical presentations of leishmaniasis based on species?
Cutaneous leishmaniasis is primarily caused by L. major and L. tropica, mucocutaneous leishmaniasis by L. braziliensis, and visceral leishmaniasis by L. donovani and L. infantum.
What factors contribute to host susceptibility to leishmaniasis?
Factors include malnutrition, immunosuppression, genetic background, and the presence of regulatory T cells and Th17 cells.
What is the role of humoral immunity in leishmaniasis?
Humoral immunity is involved in parasite opsonization but does not significantly determine the course of infection.
What are the implications of the Montenegro skin test in leishmaniasis diagnosis?
The Montenegro skin test assesses delayed-type hypersensitivity to leishmanial antigens, indicating previous exposure and an effective Th1 immune response.
What is the hallmark feature of LCL in histology?
Numerous extracellular and intracellular (within histiocytes) amastigotes a.k.a. Leishman-Donovan bodies.
Organisms of leishmaniasis are highlighted by what stains in histology?
Wright and Feulgen.
What is the geographic distribution of Leishmania species?
Viscerotropic leishmaniasis does not manifest with classic signs of VL with no involvement of the skin. Culture is positive from bone marrow aspirates and it has good response to antimonials. This is caused by?
L. tropica.
What is the mode of transmission for Trypanosoma brucei?
Trypanosoma brucei is transmitted through insect bites and causes African trypanosomiasis (sleeping sickness).
What is the primary vector for L. (L.) major?
L. (L.) major is transmitted by the Phlebotomus sand fly.
What is the primary vector for L. (L.) braziliensis?
L. (L.) braziliensis is transmitted by the Lutzomyia sand fly.
A patient undergoing treatment for acute LCL presents with diffuse asymptomatic and symmetric papular eruption. What is the next step?
Continue therapy. The patient is experiencing leishmanid, which typically resolves within 8 weeks of its appearance. It can occur in the setting of leishmaniasis recidivans. It is not an indication to withold therapy.
How do you take a biopsy specimen for CL?
Taken from the infiltrated margin, a skin biopsy may be divided into 3 parts:
- one for an impression smear
- one for histologic examination
- one for culture
What is the significance of the promastigote stage in Leishmania?
The promastigote stage is the infective form injected into the human host, initiating infection.
What are the main clinical manifestations of visceral leishmaniasis?
Visceral leishmaniasis primarily manifests as fever, weight loss, splenomegaly, and hepatomegaly.
How do leishmaniasis pathogens stain on Giemsa?
Parasite: nonmetachromatically.
Kinetoplast: bright red.
What are the differential diagnoses for cutaneous and visceral leishmaniasis?
What is the life cycle of Giardia lamblia?
What are the systemic drugs available against leishmaniasis, their dosing regimen, mechanism of action and adverse events?
What are the systemic treatment recommendations for leishmaniasis for specific old and new world pathogens?
How does the presence of multiple Leishmania species affect treatment options?
It complicates treatment due to varying drug resistance patterns and clinical presentations.
What are the potential consequences of untreated visceral leishmaniasis?
It can lead to severe complications, including organ failure and death.
What preventive measures can reduce the risk of Leishmania transmission?
Preventive measures include vector control, use of insect repellent, public education, and surveillance.
Describe the histology of DCL.
A diffuse infiltrate composed of vacuolated macrophages with numerous intracellular and extracellular amastigotes.
What are treatment options against African Trypanosomiasis?
What are the spectrum of cutaneous lesions seen in acquired toxoplasmosis in immunocompetent persons?
Describe early lesions of LCL. What do you call homogenous eosinophilic immunoglobulin material seen inside the cytoplasm?
Dense and diffuse mixed inflammatort cell infiltrate composed predominantly of histiocytes, scattered multinucleated giant cells, lymphocuytes and plasma cells. Structures referred to are called Russell bodies.
What is the gold standard for diagnosis of leishmaniasis?
Culture (at room temperature) by means of a biphasic medium such as Novy-MacNeal-Nicolle or chick embryo medium. It has a sensitivity of approximately 50% and is performed using aspirates, scraping or bresh skin biopsies.
This diagnostic technique is useful and offers superior specificity and sensitivity in the diagnosis of CL, MCL, VL especially in cases where organisms are scarce.
PCR.
How can public health initiatives address the socio-economic factors contributing to leishmaniasis transmission?
Public health initiatives can improve housing conditions, enhance access to healthcare, and implement community education programs on prevention strategies.
This is currently considered to be the gold standard for Leishmaniasis specification.
PCR + isoenzyme analysis. The latter consists of enzyme electrophoresis of cultured promastigotes and is based on the fact that morphologically similar promastigotes of different species have different enzyme profiles. It is lengthy and costly.
What factors influence the choice of treatment for leishmaniasis?
Factors include species of Leishmania, clinical form of the disease, patient’s health status, and local drug resistance patterns.
This is the mainstay of systemic treatment for leishmaniasis.
Sodium stibugluconate and meglumine antimonate.
What are the characteristics of Localized Cutaneous Leishmaniasis (LCL)?
LCL accounts for 50% to 75% of cases, is the mildest form, starts as erythematous papules, and has a characteristic ‘volcanic’ nodulo-ulcerative morphology.
What are the major complications associated with Localized Cutaneous Leishmaniasis?
Major complications include secondary bacterial infection, permanent scarring, disfigurement, social stigma, and increased risk of mucocutaneous and visceral dissemination.
What is the most common presentation of New World LCL?
Isolated ulcers in exposed areas.
What are the 2 major types of Old World LCL?
- Moist type: L. major
- Dry type: L. tropica
What is Leishmaniasis recidivans?
Leishmaniasis recidivans is a rare chronic form characterized by erythematous scaly papules with an apple jelly appearance at the border of a healed CL lesion, and may reactivate dormant infections years after resolution.
The pathogen of an Old World LCL which presents as multiple moist ulcerations resembling furuncles with lymphadenopathy.
L. major.
The pathogen of an Old World LCL which presents as few lesions mainly on the face, without lymph node involvement.
L. tropica.
What are the key features of diffuse cutaneous leishmaniasis (DCL)?
DCL presents as nonulcerated, parasite-laden nodules on exposed areas, often leading to leonine facies.
What are the clinical features of New World cutaneous leishmaniasis caused by L. mexicana?
L. mexicana causes chiclero ulcer, presenting as isolated ulcers in exposed areas, often healing within 3 months.
The pathogen of an Old World LCL which is the causative agent of Mediterranean VL in children and presents as a self-limited skin disease in adults with rare ulceration?
L. infantum.
What are the major clinical features of leishmaniasis caused by L. aethiopica?
L. aethiopica causes Old World cutaneous leishmaniasis with dry-type lesions, often on the face (same with L. tropica) but carries a higher risk of eloving into DCL in up to 20%.
What are the major clinical features of leishmaniasis caused by L. mexicana?
L. mexicana causes New World cutaneous leishmaniasis with isolated ulcers and chiclero ulcer, a chronic mutilating infection of the ear pinna of forest workers.
