176: Leishmaniasis and Other Protozoan Infections

Question 1

What are the four human diseases caused by Leishmania?

Answer 1

1. Localized cutaneous leishmaniasis
2. Diffuse cutaneous leishmaniasis
3. Mucocutaneous leishmaniasis
4. Visceral leishmaniasis

Question 2

These New World LCL pathogens only cause cutaneous disease.

Answer 2

L. mexicana and L. guyanensis.

Question 3

What are the main reservoir hosts for Leishmania?

Answer 3

1. Great gerbil
2. Fat sand rat
3. Meriones spp.
4. Other rodents
5. Dogs
6. Opossums
7. Sloths

Question 4

What factors contribute to the increasing relevance of humans as reservoir hosts for Leishmania?

Answer 4

1. Human settlements in close proximity to forests
2. Restrictions in the diversity of mammals available for sand fly feeding

Question 5

Describe the life cycle of Leishmania parasites, including the transition between promastigote and amastigote forms.

Answer 5

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.

Question 6

What are the major differences between anthroponotic and zoonotic leishmaniasis?

Answer 6

Anthroponotic leishmaniasis involves humans as primary reservoir hosts, while zoonotic leishmaniasis is transmitted from wild and domestic animals to humans.

Question 7

How does the immunologic status of the host affect the disease caused by Leishmania species?

Answer 7

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.

Question 8

What are the primary methods used for diagnosing leishmaniasis?

Answer 8

Diagnosis of leishmaniasis is performed through:
1. Organism isolation
2. Serology
3. Species identification by isoenzyme analysis and new molecular techniques

Question 9

What is the annual global incidence of leishmaniasis cases?

Answer 9

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.

Question 10

What are the neglected tropical diseases associated with leishmaniasis?

Answer 10

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

Question 11

Which countries report the highest cases of cutaneous leishmaniasis?

Answer 11

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.

Question 12

What is the role of HIV in the context of leishmaniasis?

Answer 12

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.

Question 13

What are the characteristics of the amastigote form of Leishmania?

Answer 13

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.

Question 14

What are the three genera of phlebotomine sand flies involved in leishmaniasis transmission?

Answer 14

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.

Question 15

What are the challenges in treating leishmaniasis?

Answer 15

Challenges in treating leishmaniasis include:
- Often difficult treatment options
- Limited availability of effective therapies
- Development of resistance to existing treatments
- Lack of prophylactic vaccines.

Question 16

What is the role of serology in the diagnosis of leishmaniasis?

Answer 16

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.

Question 17

How does the size of phlebotomine sand flies relate to their role as vectors?

Answer 17

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.

Question 18

What is the impact of globalization on the distribution of phlebotomine sand flies?

Answer 18

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.

Question 19

What are the potential outcomes of co-infection with HIV and Leishmania?

Answer 19

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.

Question 20

What are the cardinal manifestations of visceral leishmaniasis?

Answer 20

• Persistent, high, undulating fever
• Leucopenia
• Splenomegaly
• Anemia
• Hypergammaglobulinemia

Question 21

Enumerate the important protozoan infections for humans, stating their mode of transmission, pathogen, disease and main organ involved.

Answer 21

Question 22

What are the main treatment options currently available for leishmaniasis?

Answer 22

Main treatment options for leishmaniasis include:
- Systemic therapy with antimonials
- Other treatments under investigation
- No effective prophylactic vaccine currently exists.

Question 23

What are the epidemiological regions where cutaneous leishmaniasis is most prevalent?

Answer 23

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.

Question 24

What is the role of observation in the management of leishmaniasis?

Answer 24

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.

Question 25

What are the potential consequences of untreated leishmaniasis?

Answer 25

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.

Question 26

What are the causative Leishmania species for different Leishmaniasis disease forms?

Answer 26

Question 27

What factors influence the pathogenesis of leishmaniasis?

Answer 27

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.

Question 28

How do Th1 and Th2 responses affect leishmaniasis outcomes?

Answer 28

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.

Question 29

What is the clinical spectrum of leishmaniasis based on host factors and parasite species?

Answer 29

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.

Question 30

Enumerate the local therapies against cutaneous leishmaniasis.

Answer 30

Question 31

Explain the role of sand fly saliva in the pathogenesis of leishmaniasis.

Answer 31

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.

Question 32

How does the immune response differ in localized cutaneous leishmaniasis (LCL), diffuse cutaneous leishmaniasis (DCL), and mucocutaneous leishmaniasis (MCL)?

Answer 32

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.

Question 33

This New World LCL pathogen is associated with persistent lesions and are often associated with lymphadenopathy.

Answer 33

L. braziliensis.

Question 34

LCL is considered chronic if the disease lasts for how long?

Answer 34

More than 1 year.

Question 35

It is the anergic rare form of CL.

Answer 35

DCL or pseudolepromatous leishmaniasis.

Question 36

T or F: Disseminated CL is described as >10 pleomorphic lesions in noncontiguous areas of the body.

Answer 36

True.

Question 37

What are the known pathogens of leishmaniasis recidivans?

Answer 37

- L. tropica (mostly) - L. braziliensis - L. amazonensis - L. panamensis - L. guyanensis

Question 38

It is causes Uta, Andean cutaneous form of leishmaniasis, which affects exposed areas in children.

Answer 38

L. braziliensis.

Question 39

How does sand fly behavior influence disease transmission?

Answer 39

Sand flies are crepuscular or nocturnal, rest in dark, humid places, and prefer outdoor feeding, limiting control through house spraying.

Question 40

It causes the atypical nodular form of New World CL and is common in Honduras and Nicaragua and among immunosuppressed patients.

Answer 40

Leishmania donovani chagasi.

Question 41

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.

Answer 41

Kala-azar

Question 42

This sign pertains to trichomegaly found in patients with VL.

Answer 42

Pitalugo sign.

Question 43

This is predictive of development of Post-Kala-Azar Dermal Leishmaniasis among VL patients.

Answer 43

High IL-10 blood concentration.

Question 44

What are the clinical presentations of leishmaniasis based on species?

Answer 44

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.

Question 45

What factors contribute to host susceptibility to leishmaniasis?

Answer 45

Factors include malnutrition, immunosuppression, genetic background, and the presence of regulatory T cells and Th17 cells.

Question 46

What is the role of humoral immunity in leishmaniasis?

Answer 46

Humoral immunity is involved in parasite opsonization but does not significantly determine the course of infection.

Question 47

What are the implications of the Montenegro skin test in leishmaniasis diagnosis?

Answer 47

The Montenegro skin test assesses delayed-type hypersensitivity to leishmanial antigens, indicating previous exposure and an effective Th1 immune response.

Question 48

What is the hallmark feature of LCL in histology?

Answer 48

Numerous extracellular and intracellular (within histiocytes) amastigotes a.k.a. Leishman-Donovan bodies.

Question 49

Organisms of leishmaniasis are highlighted by what stains in histology?

Answer 49

Wright and Feulgen.

Question 50

What is the geographic distribution of Leishmania species?

Answer 50

Question 51

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?

Answer 51

L. tropica.

Question 52

What is the mode of transmission for Trypanosoma brucei?

Answer 52

Trypanosoma brucei is transmitted through insect bites and causes African trypanosomiasis (sleeping sickness).

Question 53

What is the primary vector for L. (L.) major?

Answer 53

L. (L.) major is transmitted by the Phlebotomus sand fly.

Question 54

What is the primary vector for L. (L.) braziliensis?

Answer 54

L. (L.) braziliensis is transmitted by the Lutzomyia sand fly.

Question 55

A patient undergoing treatment for acute LCL presents with diffuse asymptomatic and symmetric papular eruption. What is the next step?

Answer 55

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.

Question 56

How do you take a biopsy specimen for CL?

Answer 56

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

Question 57

What is the significance of the promastigote stage in Leishmania?

Answer 57

The promastigote stage is the infective form injected into the human host, initiating infection.

Question 58

What are the main clinical manifestations of visceral leishmaniasis?

Answer 58

Visceral leishmaniasis primarily manifests as fever, weight loss, splenomegaly, and hepatomegaly.

Question 59

How do leishmaniasis pathogens stain on Giemsa?

Answer 59

Parasite: nonmetachromatically. Kinetoplast: bright red.

Question 60

What are the differential diagnoses for cutaneous and visceral leishmaniasis?

Answer 60

Question 61

What is the life cycle of Giardia lamblia?

Answer 61

Question 62

What are the systemic drugs available against leishmaniasis, their dosing regimen, mechanism of action and adverse events?

Answer 62

Question 63

What are the systemic treatment recommendations for leishmaniasis for specific old and new world pathogens?

Answer 63

Question 64

How does the presence of multiple Leishmania species affect treatment options?

Answer 64

It complicates treatment due to varying drug resistance patterns and clinical presentations.

Question 65

What are the potential consequences of untreated visceral leishmaniasis?

Answer 65

It can lead to severe complications, including organ failure and death.

Question 66

What preventive measures can reduce the risk of Leishmania transmission?

Answer 66

Preventive measures include vector control, use of insect repellent, public education, and surveillance.

Question 67

Describe the histology of DCL.

Answer 67

A diffuse infiltrate composed of vacuolated macrophages with numerous intracellular and extracellular amastigotes.

Question 68

What are treatment options against African Trypanosomiasis?

Answer 68

Question 69

What are the spectrum of cutaneous lesions seen in acquired toxoplasmosis in immunocompetent persons?

Answer 69

Question 70

Describe early lesions of LCL. What do you call homogenous eosinophilic immunoglobulin material seen inside the cytoplasm?

Answer 70

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.

Question 71

What is the gold standard for diagnosis of leishmaniasis?

Answer 71

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.

Question 72

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.

Answer 72

PCR.

Question 73

How can public health initiatives address the socio-economic factors contributing to leishmaniasis transmission?

Answer 73

Public health initiatives can improve housing conditions, enhance access to healthcare, and implement community education programs on prevention strategies.

Question 74

This is currently considered to be the gold standard for Leishmaniasis specification.

Answer 74

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.

Question 75

What factors influence the choice of treatment for leishmaniasis?

Answer 75

Factors include species of Leishmania, clinical form of the disease, patient's health status, and local drug resistance patterns.

Question 76

This is the mainstay of systemic treatment for leishmaniasis.

Answer 76

Sodium stibugluconate and meglumine antimonate.

Question 77

What are the characteristics of Localized Cutaneous Leishmaniasis (LCL)?

Answer 77

LCL accounts for 50% to 75% of cases, is the mildest form, starts as erythematous papules, and has a characteristic 'volcanic' nodulo-ulcerative morphology.

Question 78

What are the major complications associated with Localized Cutaneous Leishmaniasis?

Answer 78

Major complications include secondary bacterial infection, permanent scarring, disfigurement, social stigma, and increased risk of mucocutaneous and visceral dissemination.

Question 79

What is the most common presentation of New World LCL?

Answer 79

Isolated ulcers in exposed areas.

Question 80

What are the 2 major types of Old World LCL?

Answer 80

- Moist type: L. major - Dry type: L. tropica

Question 81

What is Leishmaniasis recidivans?

Answer 81

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.

Question 82

The pathogen of an Old World LCL which presents as multiple moist ulcerations resembling furuncles with lymphadenopathy.

Answer 82

L. major.

Question 83

The pathogen of an Old World LCL which presents as few lesions mainly on the face, without lymph node involvement.

Answer 83

L. tropica.

Question 84

What are the key features of diffuse cutaneous leishmaniasis (DCL)?

Answer 84

DCL presents as nonulcerated, parasite-laden nodules on exposed areas, often leading to leonine facies.

Question 85

What are the clinical features of New World cutaneous leishmaniasis caused by L. mexicana?

Answer 85

L. mexicana causes chiclero ulcer, presenting as isolated ulcers in exposed areas, often healing within 3 months.

Question 86

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?

Answer 86

L. infantum.

Question 87

What are the major clinical features of leishmaniasis caused by L. aethiopica?

Answer 87

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%.

Question 88

What are the major clinical features of leishmaniasis caused by L. mexicana?

Answer 88

L. mexicana causes New World cutaneous leishmaniasis with isolated ulcers and chiclero ulcer, a chronic mutilating infection of the ear pinna of forest workers.