Leishmania/Leishmaniasis

Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The disease is endemic to Asia, the Middle East, Africa, the Mediterranean, and South and Central America. Clinical presentation varies, dependent on the pathogenicity of the species and the host’s immune response. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Management is based on the clinical severity and patient’s immune status. Some cutaneous lesions spontaneously resolve or require local therapy. Systemic treatment (amphotericin B), however, is needed for VL.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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General Characteristics

Leishmania spp.

  • Structure: 
    • Unicellular, with slender body and polar flagellum (depending on form)
    • Species morphologically similar, with differing molecular features
  • 2 forms:
    • Promastigote: extracellular flagellate organism in the phlebotomine sandfly 
    • Amastigote: obligate intracellular non-flagellate ovoid organism in human or animal host
  • Associated diseases:
    • Cutaneous leishmaniasis (CL), also called:
      • Oriental sore
      • Chiclero ulcer
      • Baghdad boil
    • Mucocutaneous or mucosal leishmaniasis (also called espundia)
    • Visceral leishmaniasis (VL; also called kala-azar or “black fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever”)

Clinically relevant species

  • Leishmania donovani (L. donovani), L. infantum (VL)
  • L. tropica, L. major (Old World CL)
  • L. mexicana (New World CL)
  • L. braziliensis, L. panamensis, and L. peruviana (mucocutaneous leishmaniasis)

Epidemiology

  • Global prevalence: 4.8 million
  • 20–30,000 deaths per year
  • Geographic areas affected:
    • Old World leishmaniasis:
      • Species found in Africa, Asia, and Europe
      • Associated with cutaneous or visceral disease
    • New World leishmaniasis:
      • Species found in the Americas (predominantly Central and South America)
      • Associated with cutaneous, mucocutaneous, and visceral disease

Pathogenesis

Reservoirs and transmission

  • Reservoirs: mammals (e.g., dogs, rodents, and foxes)
  • Transmission: 
    • Bite of an infected sandfly (vector):
      • Anthroponotic (from infected humans to healthy humans)
      • Zoonotic (from infected animal reservoir to healthy humans) 
    • Human-to-human transmission can also occur via shared infected needles.

Pathophysiology

In the sandfly:

  • Nocturnal sandflies acquire amastigotes from a zoonotic host.
  • In the gut, the amastigotes develop into flagellated promastigotes and replicate.
  • Promastigotes eventually migrate into the proboscis.
  • When the sandfly bites a human, the promastigotes are then injected into the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin.

In humans:

  • Promastigotes: 
    • Are phagocytosed by macrophages 
    • Lose the flagella and form amastigotes
  • Amastigotes multiply within the phagolysosome, seen in smears as a distinctive form: Leishman-Donovan bodies.
  • Evasion and survival facilitated by:
    • Surface lipophosphoglycan (↓ complement attachment, ↑ complement inactivation)
    • Membrane acid phosphatase: ↓ macrophage oxidative burst and lysosomal enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Suppression of CD4+ T helper lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes
  • Multiplying amastigotes lead to cell rupture:
    • Spreading the organisms to other cells
    • Allowing the organism to be possibly taken up by a feeding sandfly

Disease process

  • Depends on the pathogenicity of the species and the host’s immune response
  • Localized CL:
    • Species elicit adequate cellular immune response (CD4+ T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells) leading to macrophage release of toxic nitric oxide, reducing the parasites.
    • Disease leads to eventual spontaneous cure with lesions disappearing.
  • Mucocutaneous or mucosal leishmaniasis:
    • Cutaneous sequence similar to CL, but followed by secondary lesions after weeks to months
    • Tissue destruction noted especially in nasopharyngeal structures
  • VL:
    • Other strains fail to elicit a cellular immune response, resulting in disseminated infection.
    • Spread from bloodstream to reticuloendothelial cells: liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, and lymph nodes
Leishmaniasis life cycle

The life cycle of the parasites from the genus Leishmania, the cause of the disease leishmaniasis:

On the left side (start at the bottom): Sandfly acquires amastigotes from an infected mammal. Amastigotes transform into extracellular promastigotes that multiply in the midgut. Eventually, the promastigotes migrate to the sandfly proboscis, ready to be transferred to a host when the sandfly bites.
On the right side (start at the top): Promastigotes are transferred to mammals, and are phagocytosed by macrophages. In the cell, promastigotes transform into amastigotes and multiply. Affected cell ruptures and amastigotes spread to infect other cells.

Image: “Leishmaniasis life cycle diagram” by Mariana Ruiz Villarreal. License: Public Domain

Clinical Presentation

Cutaneous leishmaniasis (CL)

  • Causative strains:
    • L. tropica
    • L. mexicana
    • L. major
  • Incubation period: weeks to months
  • Spectrum of cutaneous disease:
    • Localized CL: 
      • Most common 
      • A single or multiple painless, pink papule(s) at the site of the bite 
      • Affects exposed areas
      • Lesions enlarge and ulcerate centrally, covered with a hyperkeratotic eschar or white fibrinous material.
      • Can have satellite lesions
      • Often heals with a depigmented scar after months
    • Leishmaniasis recidivans (LR):
      • Associated with L. tropica
      • Papules develop around the scar of a healed primary lesion. 
      • Can appear following trauma in the same healed lesion many years after 
    • Diffuse CL (DCL):
      • A localized lesion develops, but no ulceration  
      • Amastigotes spread to other areas of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, leading to nodules or plaques.
      • Affects the face and extensor limb surfaces, even the entire body 
      • At-risk patients have a defect in the cell-mediated immune response (biopsy shows minimal lymphocytic reaction).

Mucocutaneous leishmaniasis

  • Causative strains: 
    • L. braziliensis
    • L. panamensis
    • L. peruviana
  • Incubation period: weeks
  • Signs and symptoms:
    • Lesions can be single or multiple.
    • Destructive painful mucosal lesions affect the nasopharyngeal and palatine mucosal tissues (occasionally, the perineum).
    • May completely destroy the nasal septum
    • Presents with mucosal secretions, deformities, and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain

Visceral leishmaniasis (VL)

  • Causative strains:
    • L. donovani
    • L. infantum
  • Incubation period: 2–6 months (but can reach up to 24 months)
  • Signs and symptoms:
    • Spread occurs from the initial lesion to reticuloendothelial cells including the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, lymph nodes, and bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow
    • Systemic symptoms:
      • Fever, rigor, and chills
      • Anorexia
      • Weight loss
    • Skin hyperpigmentation
    • Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
    • Abdominal discomfort (secondary to hepatosplenomegaly)
    • Pallor (secondary to anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview resulting from splenic sequestration or bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow suppression)
    • Petechial rash and bleeding (from thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia and/or pancytopenia from bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow dysfunction)
    • In advanced disease: ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema (from hypoalbuminemia)
    • Post-Kala-Azar dermal leishmaniasis (PKDL):
      • In India, Sudan, and other East African countries, some develop skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions during VL or after treatment of VL. 
      • Presents with hypopigmented macules, papules, or nodules; possible infiltration of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and oral mucosa

Diagnosis

General diagnostic tools

  • Relies on history (including travel) and clinical findings
  • Specimens:
    • CL: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesion aspirate, scraping, or biopsy
    • Mucocutaneous leishmaniasis: mucosal biopsy, dental scrapings
    • VL: aspirates from bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, lymph nodes, or spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen
  • Tests:
    • Histopathologic examination of the specimen:
      • Use of Giemsa’s, Leishman’s, or Wright’s stains
      • Visualization of amastigotes or Leishman-Donovan bodies (round organisms with nucleus, cytoplasm, and rod-shaped kinetoplast)
    • Culture of tissue aspirates (results in 1–3 weeks)
    • Molecular testing (requires specialized laboratories): polymerase chain reaction (PCR)
    • Skin test (Montenegro skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin test):
      • Injection of killed promastigotes; ≥ 5-mm induration is positive
      • Use in CL (except diffuse form)
      • Positive test: present or past (resolved) infection
      • Negative in immunosuppressed patients, active VL (becomes positive after treatment) 
      • Not available in the United States

Additional tests for VL

  • Serology or detection of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins:
    • Enzyme-linked immunosorbent assay (ELISA)
    • Indirect immunofluorescent antibody test (IFAT)
  • Rapid immunochromatographic test:
    • Detects antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to a recombinant antigen rK39 (39 amino acids in the kinesin region of L. infantum)
    • Used in the field (result noted in 15 minutes)
    • Fingerprick blood or serum
    • Positive for years, so not used for detection of relapse or cure
  • Complete blood count: ↓ white blood cell, hemoglobin, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets
  • Abnormal liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests

Management

Cutaneous leishmaniasis

  • Most uncomplicated lesions (small (< 1-cm), single lesion in immunocompetent patients) resolve spontaneously.
  • Treatment accelerates healing, and decreases scarring and superinfection.
  • Local treatment recommended in:
    • Persistent or spreading lesions
    • Lesions in the face or hands
  • Local treatment options:
    • Cryotherapy 
    • Local heat therapy
    • Intralesional pentavalent antimonial drugs
    • Topical paromomycin
  • Systemic treatment recommended in:
    • DCL, LR
    • Large lesion (≥ 5 cm) 
    • Multiple (> 4) cutaneous lesions
    • Subcutaneous nodules
    • Immunosuppressed patients with CL
    • Failed local therapy
  • Systemic treatment options:
    • Miltefosine
    • Azoles Azoles Azoles are a widely used class of antifungal medications inhibiting the production of ergosterol, a critical component in the fungal cell membrane. The 2 primary subclasses of azoles are the imidazoles, older agents typically only used for topical applications, and the triazoles, newer agents with a wide spectrum of uses. Azoles
    • Amphotericin deoxycholate
    • Liposomal amphotericin B
    • Pentavalent antimonial drugs (sodium stibogluconate, meglumine antimoniate)
    • Pentamidine

Mucocutaneous leishmaniasis

  • Pentavalent antimonial drugs (with pentoxifylline)
  • Liposomal amphotericin B
  • Miltefosine

VL

  • Liposomal amphotericin B (preferred in the Americas and Europe)
  • Pentavalent antimonial drugs
  • Miltefosine
  • Treat HIV, if present, when tolerated by patient.
  • Prognosis: mortality rate of 75%–90% without treatment

Prevention

  • Reduce sandfly burden by spraying living/sleeping areas with insecticide.
  • Minimize exposure to sandflies:
    • Reduce outdoor time from dawn to dusk.
    • Use insecticide-treated bed nets.
    • Apply insect repellent to exposed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin.

Comparison of Flagellated Protozoa

Table: Comparison of clinically relevant flagellated protozoa
Giardia Leishmania Trypanosoma Trichomonas
Characteristics
  • 4 pairs of flagella
  • Ovoid shape
  • Adhesive disc
  • Anaerobe
  • Antigenic variation
  • Single, polar flagellum
  • Slender, elongated body
  • Single, polar flagellum
  • Undulating membrane
  • Thin, irregularly shaped
  • Antigenic variation
  • 5 flagella
  • Undulating membrane
  • Ovoid shape
  • Facultative anaerobe
Forms
  • Cyst
  • Trophozoite
  • Promastigote
  • Amastigote
  • Trypomastigote
  • Amastigote
  • Epimastigote
  • Trophozoite
  • No cyst form
Transmission
  • Waterborne
  • Fecal-oral
  • Vector (sandfly)
  • Human to human
  • Zoonotic (rodents, dogs, foxes)
  • Vector (tsetse fly, kissing bug)
  • Blood transfusion
Sexually transmitted
Clinical Giardiasis Giardiasis Giardiasis is caused by Giardia lamblia (G. lamblia), a flagellated protozoan that can infect the intestinal tract. The hallmark symptom of giardiasis is foul-smelling steatorrhea. Patients who develop chronic infections may experience weight loss, failure to thrive, and vitamin deficiencies as a result of malabsorption. Giardia/Giardiasis Leishmaniasis
  • African sleeping sickness
  • Chagas disease Chagas disease Chagas disease is an infection caused by the American trypanosome Trypanosoma cruzi. This parasitic protozoan is transmitted in the feces of reduviid bugs in South and Central America. Acute infection may present with inflammation at the inoculation site (chagoma), fever, and lymphadenopathy. Untreated, chronic infection can progress to severe complications. Trypanosoma cruzi/Chagas disease
Trichomoniasis
Diagnosis
  • ELISA
  • DFA
  • NAAT
  • Stool microscopy
  • Blood smear
  • Biopsy
  • PCR
  • Leishmanin skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin test
  • Antibody titers
  • Blood smear
  • Antibody titers
  • Xenodiagnosis
  • Microscopy of vaginal secretions
  • NAAT
  • Urine or urethral swab culture
Treatment
  • Metronidazole
  • Tinidazole
  • Nitazoxanide
Depends on the clinical syndrome:
  • Amphotericin B
  • Pentavalent antimonials
  • Miltefosine
Depends on the clinical disease:
  • Suramin
  • Pentamidine
  • Melarsoprol
  • Eflornithine
  • Nifurtimox
  • Benznidazole
  • Metronidazole
  • Tinidazole
Prevention
  • Handwashing
  • Water treatment
  • Insecticide
  • Insect repellent
  • Protective clothing
  • Insecticides
  • Insect repellent
  • Bed nets
  • Protective clothing
  • Treatment of sex partners
  • Condoms

ELISA: enzyme-linked immunosorbent assay

DFA: direct immunofluorescence assay

NAAT: nucleic acid amplification assay

PCR: polymerase chain reaction

Differential Diagnosis

  • Histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis: a fungal infection that can present with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions (nodules, ulcers, plaques). Histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis also spreads hematogenously to lymph nodes, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, and bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow in immunocompromised patients. Pulmonary illness, though, is a more common manifestation. Urine and serum antigen assays, and culture with travel history can help differentiate the causative agent. 
  • Coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis: a fungal infection principally manifesting with pulmonary symptoms. Painful erythematous nodules also can occur. Blood count may show leukocytosis and eosinophilia. History and serologic testing point to the diagnosis.
  • Leprosy Leprosy Leprosy, also known as Hansen's disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy: a disease caused by Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium leprae, often presents with similar cutaneous manifestations that cause scarring and deformities. Leprosy Leprosy Leprosy, also known as Hansen's disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy affects the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and peripheral nerves. So, leprosy often causes severe disfigurement with neuropathy, differentiating leprosy from leishmaniasis. 
  • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma: central ulcerations may be confused with large squamous cell carcinoma. Biopsy and travel history are helpful in distinguishing the cutaneous lesions. 
  • Sporotrichosis: infection caused by Sporothrix schenckii. Lymphocutaneous infection is the most common form and presents like cutaneous nocardiosis (inoculation of soil through skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin with erythematous, nodular lesion(s) along lymphatic channels). Culture of aspirated material helps distinguish the organisms.
  • Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria: mosquito-borne infectious disease caused by single-celled micro-organisms of the Plasmodium group. Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and chills in intervals, with anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly among other findings that are similar to VL. History and peripheral blood smear (which identifies the infecting parasite) aid in diagnosis.

References

  1. Aronson, N. (2020). Cutaneous leishmaniasis: Clinical manifestation and diagnosis. UpToDate, Retrieved December 11, 2020, from https://www.uptodate.com/contents/cutaneous-leishmaniasis-clinical-manifestations-and-diagnosis
  2. Aronson, N. (2020). Cutaneous leishmaniasis: Treatment. UpToDate, Retrieved December 11, 2020, from https://www.uptodate.com/contents/cutaneous-leishmaniasis-treatment
  3. Bern, C. (2019). Visceral leishmaniasis: Epidemiology and control. UpToDate, Retrieved December 11, 2020, from https://www.uptodate.com/contents/visceral-leishmaniasis-epidemiology-and-control
  4. Bern, C. (2020). Visceral leishmaniasis: Treatment. UpToDate, Retrieved December 11, 2020, from https://www.uptodate.com/contents/visceral-leishmaniasis-treatment 
  5. Ryan, K.J.(Ed.), (2017). Sarcomastigophora the flagellates. Sherris Medical Microbiology, 7e. McGraw-Hill.
  6. Riedel, S., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2019). Jawetz, Melnick & Adelberg’s Medical microbiology (pp. 733-734). New York: McGraw-Hill Education.
  7. Sundar, S. (2018). Leishmaniasis. Jameson J, & Fauci A.S., & Kasper D.L., & Hauser S.L., & Longo D.L., & Loscalzo J (Eds.),  Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill. 
  8. Stark, C., & Vidyashankar, C. (2020) Leishmaniasis. Medscape. Retrieved 27 Dec 2020, from https://emedicine.medscape.com/article/220298-overview

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