Leishmania/Leishmaniasis

General Characteristics

Leishmania spp.

• Structure: 
  • Unicellular Unicellular Cell Types: Eukaryotic versus Prokaryotic, 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 4.8 million
• 20–30,000 deaths per year
• Geographic areas affected:
  • Old World leishmaniasis:
    • Species found in Africa, Asia ASIA Spinal Cord Injuries, 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 Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli 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. Skin: Structure and Functions.

In humans:

• Promastigotes: 
  • Are phagocytosed by macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation 
  • Lose the flagella Flagella A whiplike motility appendage present on the surface cells. Prokaryote flagella are composed of a protein called flagellin. Bacteria can have a single flagellum, a tuft at one pole, or multiple flagella covering the entire surface. In eukaryotes, flagella are threadlike protoplasmic extensions used to propel flagellates and sperm. Flagella have the same basic structure as cilia but are longer in proportion to the cell bearing them and present in much smaller numbers. Helicobacter and form amastigotes
• Amastigotes multiply within the phagolysosome Phagolysosome Chédiak-Higashi Syndrome, 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 Suppression Defense Mechanisms 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: Histology
• 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 Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions) leading to macrophage release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of toxic nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs, 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: Anatomy, 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: Anatomy, bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, and lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy

Clinical Presentation

Cutaneous leishmaniasis (CL)

• Causative strains:
  • L. tropica
  • L. mexicana
  • L. major
• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: weeks to months
• Spectrum of cutaneous disease:
  • Localized CL: 
    • Most common 
    • A single or multiple painless, pink papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes(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 Scar Dermatologic Examination after months
  • Leishmaniasis recidivans (LR):
    • Associated with L. tropica
    • Papules develop around the scar Scar Dermatologic Examination 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 Ulceration Corneal Abrasions, Erosion, and Ulcers  
    • 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. Skin: Structure and Functions, leading to nodules or plaques.
    • Affects the face and extensor limb surfaces, even the entire body 
    • At-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a defect in the cell-mediated immune response ( biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma shows minimal lymphocytic reaction).

Mucocutaneous leishmaniasis

• Causative strains: 
  • L. braziliensis
  • L. panamensis
  • L. peruviana
• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus 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 Perineum The body region lying between the genital area and the anus on the surface of the trunk, and to the shallow compartment lying deep to this area that is inferior to the pelvic diaphragm. The surface area is between the vulva and the anus in the female, and between the scrotum and the anus in the male. Vagina, Vulva, and Pelvic Floor: Anatomy).
  • May completely destroy the nasal septum Nasal septum The partition separating the two nasal cavities in the midplane. It is formed by the septal nasal cartilage, parts of skull bones, and membranous parts. Nose Anatomy (External & Internal)
  • Presents with mucosal secretions, deformities, and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

Visceral leishmaniasis (VL)

• Causative strains:
  • L. donovani
  • L. infantum
• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus 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: Anatomy, 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: Anatomy, lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis. 
  • Systemic symptoms:
    • 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, rigor, and chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
    • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • 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. Skin: Structure and Functions hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi
  • 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 Hepatosplenomegaly Cytomegalovirus)
  • 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 and Types resulting from splenic sequestration Splenic sequestration Severe Congenital Neutropenia or bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis suppression Suppression Defense Mechanisms)
  • Petechial rash Rash Rocky Mountain Spotted Fever 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 Pancytopenia Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. Aplastic Anemia from bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis 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 Hypoalbuminemia A condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria). Nephrotic Syndrome in Children)
  • 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. Skin: Structure and Functions 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. Skin: Structure and Functions and oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis

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. Skin: Structure and Functions lesion aspirate, scraping, or biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Mucocutaneous leishmaniasis: mucosal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, dental scrapings
  • VL: aspirates from bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, 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: Anatomy, lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, 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: Anatomy
• 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 Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles, cytoplasm, and rod-shaped kinetoplast)
  • Culture of tissue aspirates (results in 1–3 weeks)
  • Molecular testing (requires specialized laboratories): polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR))
  • 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. Skin: Structure and Functions 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. Skin: Structure and Functions test):
    • Injection of killed promastigotes; ≥ 5-mm induration Induration Dermatologic Examination is positive
    • Use in CL (except diffuse form)
    • Positive test: present or past (resolved) infection
    • Negative in immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, active VL (becomes positive after treatment) 
    • Not available in the United States

Additional tests for VL

• Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus 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: Types and Functions:
  • Enzyme-linked immunosorbent assay ( ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus)
  • 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: Types and Functions to a recombinant antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination rK39 (39 amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids in the kinesin Kinesin A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kda) and two light (62 kda) chains. The Cell: Cytosol and Cytoskeleton 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 Relapse Relapsing Fever 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: Histology
• 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 Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship) resolve spontaneously.
• Treatment accelerates healing, and decreases scarring Scarring Inflammation and superinfection.
• Local treatment recommended in:
  • Persistent or spreading lesions
  • Lesions in the face or hands
• Local treatment options:
  • Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma 
  • Local heat Heat Inflammation therapy
  • Intralesional pentavalent antimonial drugs
  • Topical paromomycin Paromomycin An aminoglycoside antibacterial and antiprotozoal agent produced by species of streptomyces. Amebicides
• Systemic treatment recommended in:
  • DCL, LR
  • Large lesion (≥ 5 cm) 
  • Multiple (> 4) cutaneous lesions
  • Subcutaneous nodules
  • Immunosuppressed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Liposomal Amphotericin B Polyenes
  • Pentavalent antimonial drugs ( sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia stibogluconate, meglumine antimoniate)
  • Pentamidine

Mucocutaneous leishmaniasis

• Pentavalent antimonial drugs (with pentoxifylline Pentoxifylline A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. Phosphodiesterase Inhibitors)
• Liposomal amphotericin B Liposomal Amphotericin B Polyenes
• Miltefosine

VL

• Liposomal amphotericin B Liposomal Amphotericin B Polyenes (preferred in the Americas and Europe)
• Pentavalent antimonial drugs
• Miltefosine
• Treat HIV HIV Anti-HIV Drugs, if present, when tolerated by patient.
• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: mortality Mortality All deaths reported in a given population. Measures of Health Status 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 Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus 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. Skin: Structure and Functions.

Comparison of Flagellated Protozoa

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. Skin: Structure and Functions 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 Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, 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: Anatomy, 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: Anatomy, and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Pulmonary illness, though, is a more common manifestation. Urine and serum antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination 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 Erythematous Nodules Hidradenitis Suppurativa also can occur. Blood count may show leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus and eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome. 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 leprae Mycobacterium leprae A species of gram-positive, aerobic bacteria that causes leprosy in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side. Mycobacterium, often presents with similar cutaneous manifestations that cause scarring Scarring Inflammation 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. Skin: Structure and Functions and peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology. So, 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 often causes severe disfigurement with  neuropathy Neuropathy Leprosy, differentiating 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 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 (SCC): central ulcerations may be confused with large 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 (SCC). Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma 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 Cutaneous nocardiosis Nocardia/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. Skin: Structure and Functions with erythematous, nodular lesion(s) along lymphatic channels Channels The Cell: Cell Membrane). 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. Plasmodium/Malaria: mosquito-borne infectious disease caused by single-celled micro-organisms of the Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs 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. Plasmodium/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 Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever 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 Types 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 Peripheral Blood Smear Anemia: Overview and Types (which identifies the infecting parasite) aid in diagnosis.