Hemoflagellates: Parasites in Blood & Tissue PDF

The Hemoflagellates  The Hemoflagellates Clinically significant group of parasites located in blood and tissue that move by means of flagella Subphylum – Mastigophora Class – Zoomastigophora Blood tissue species – Leishmania tropica – Leishmania braziliensis...

The Hemoflagellates  The Hemoflagellates Clinically significant group of parasites located in blood and tissue that move by means of flagella Subphylum – Mastigophora Class – Zoomastigophora Blood tissue species – Leishmania tropica – Leishmania braziliensis – Leishmania donovani – Trypanosoma brucei gambiense – Trypanosoma brucei rhodesiense – Trypanosoma cruzi  Hemoflagellates Four morphological forms – Amastigote – Promastigote – Epimastigote – Trypomastigote All hemoflagellates undergo these states at some point during their life cycle  Diseases Caused by Hemoflagellates Leishmaniasis: General term used to describe diseases caused by infection with hemoflagellate genus Leishmania Referred to by different names depending on the geographic region in which the infection occurs and specific species involved.  Clinical Signs Include small red papules with intense itching at the infection site; secondary bacterial infections; fever, and diarrhea May also affect kidney and cognitive function, ultimately leading to a comatose state, and death. In some cases, the initial skin lesions spontaneously heal, whereas in others they may remain dormant for months or even years.  Hemoflagellates: Symptoms Small red papule at infection site Intense itching Secondary bacterial infections Fever Diarrhea Kidney dysfunction Cognitive dysfunction Coma Death  Amastigotes Oval shaped Avg size = 5X3 μm Single, large, off-center nucleus Infective stage for the arthropod vector  Promastigotes Avg size = 9-15 μm Long, slender body Large, single nucleus Flagellum extending anteriorly May be seen in human blood samples if collected immediately after transmission  Epimastigote Avg size = 9-15 μm Single, large nucleus located posteriorly Undulating membrane May be seen in human blood samples but typically found in arthropod vectors  Trypomastigote Avg size = 12-35 μm Often curls on itself to form a U or C shape Large single nucleus Full body undulating membrane Flagellum may or may not be present Along with amastigote, form typically found in human specimens (reproduce and are found in peripheral blood) Trypanosome Morphologies in Blood Smears  Transmission and Life Cycle Arthropod vector bite Upon ingestion during a blood meal of an infected human, the amastigotes transform into promastigotes in the fly midgut. These promastigotes multiply and the resulting developed forms eventually migrate into the salivary gland of the fly, where they are ready to be transferred to a new human during a blood meal. Some species are harbored by reservoir vectors such as domestic dogs and rodents Transmission and Life Cycle https://www.cdc.gov/dpdx/leishmaniasis/index.html  Hemoflagellates: Laboratory Diagnosis Blood Lymph node and ulcer aspirations Tissue biopsies Bone marrow Cerebrospinal fluid  Leishmaniasis Primary Distribution: – East and North Africa, Middle East, Southern Europe, Central, South, and East Asia, South America, West Mexico Agent and Vector – transmitted through the bite of female sandflies  Leishmaniasis: Geographic Distribution  Cutaneous Leishmaniasis Pathogen: Leishmania tropica Most New World Cutaneous lesions are ulcers In many cases, healing is spontaneous within months or years of onset In other cases, however, the disease is progressive with visceral manifestations or spreading skin lesions  Cutaneous Leishmaniasis Cutaneous leishmaniasis is characterized by single or multiple lesions; 40% of cases affect the ear and surrounding cartilage Typically progress from papules to nodules to non-ulcerated dry plaques or ulcers (with raised indurated border and central depression) that usually are painless unless secondarily infected Low-grade fever, regional lymphadenopathy and/or lymphangitis, and lesion pruritis (itching) or pain may be present  Cutaneous Leishmaniasis: Treatment Pentavalent antimonials, such as sodium stibogluconate (Pentosam), are considered the drug of choice for treating infections Amphotericin B and liposomal amphotericin B (Ambisome) have also proven to be effective.  Cutaneous Leishmaniasis: Prevention and Control Personal protection (clothing, repellents, screens) Prompt treatment of infected ulcers Control of sandfly and reservoir host (rodent and domestic dog) populations  Side Note: A number of troops who participated in the Gulf War were stationed in Saudi Arabia and neighboring areas known to be endemic for L. tropica. It is estimated that there are approximately 16,000 cases of leishmaniasis reported in Saudi Arabia every year. Following the war, a number of veterans, as well as members of their families, began to experience vague symptoms, including joint and muscle pains (arthralgias and myalgias, respectively), headaches, bleeding gums, hair loss, and intestinal disorders. Although a skin test (the Montenegro skin test) for leishmaniasis has been developed, patients in active disease will test negative. There is still a great deal of concern that undiagnosed patients may actually have leishmaniasis and are unknowingly spreading the disease.  Mucocutaneous Leishmaniasis Pathogen: Leishmania braziliensis Pathologic condition resulting from New World Cutaneous Leishmaniasis Results from direct extension or hematogenous or lymphatic metastasis to the nasal or oral mucosa In most cases, naso-oropharyngeal symptoms appear several years after resolution of the primary lesion(s), but may also appear while the primary lesions are still present  Mucocutaneous Leishmaniasis Large ulcers in the oral or nasal mucosa areas (mucocutaneous) develop after the initial invasion of the reticuloendothelial cells. There may be large cutaneous lesions, mucosal lesions, or a combination of both; cutaneous lesions sometimes heal on their own. In extreme cases of mucosal infection/lesions, if left untreated, may result in the eventual destruction of the nasal septum. Lips, nose, and surrounding soft tissues may also be affected in these infections. Edema and secondary bacterial infections, combined with numerous mucosal lesions, may cause disfigurement of the patient's face. Death is usually attributed to a secondary bacterial infection. Mucocutaneous Leishmaniasis: Signs and Symptoms Chronic nasal symptoms, especially of the anterior nasal septum (leading to development of the characteristic "tapir nose") and progressing to extensive naso- oropharyngeal destruction Secondary bacterial (or fungal) infections and associated problems are common Mucocutaneous Leishmaniasis: Diagnosis Presence of cardinal signs, positive history, and geographic risk lead to suspicion of mucocutaneous leishmaniasis Diagnosis is difficult because amastigotes are scarce in the usual sources (scrapings, tissue aspirates, biopsy) Culture and serologic tests are usually necessary  Mucocutaneous Leishmaniasis: Treatment The most widely used anti-leishmanial agent for the treatment of mucocutaneous leishmaniasis is with antimony compounds. – May lead to severe adverse effects – Some species are resistant Other treatments include liposomal amphotericin B injections and other antifungal drugs that are administered orally such as fluconazole (Diflucan), ketoconazole (Nizoral) and itraconazole (Sporonox). Mucocutaneous Leishmaniasis: Prevention and Control Personal protection (clothing, repellents, screens) Prompt treatment of infected ulcers Control of sandfly and reservoir host (rodent and domestic dog) populations  Leishmaniasia donovani Complex Comprises l. dononvani chagasi, l. dononvani donovani, and l. dononvani infantum Very similar in presentation, diagnosis and treatment Different sandfly species responsible for spreading each one  Leishmaniasia donovani Complex: Reservoir Hosts l. dononvani chagasi – Dogs, cats, foxes l. dononvani donovani – Dogs (China) l. dononvani infantum – Dogs, foxes, jackals, porcupines  Visceral Leishmaniasis Most severe form of leishmaniasis Also known as kala azar Irregular bouts of fever Substantial weight loss Swelling of the spleen and liver Anemia (occasionally serious) If left untreated, the fatality rate in developing countries can be as high as 100% within 2 years.  Visceral Leishmaniasis: Signs and Symptoms Cardinal Systemic signs: symptoms include gradual onset fever that Prolonged feverand falls twice/day, often rises Splenomegaly Fatigue Anemia Leukopenia Weight loss Hypergammaglobulinemia Dizziness Cutaneous nodule may appear Cough at the site of the bite within several Diarrhea days of inoculation If present, the nodule remains, but in most cases, no other symptoms are present for at least several months  Visceral Leishmaniasis: Signs and Symptoms Cont’d Splenomegaly (hard, non-tender) Hepatomegaly (to a lesser extent) Generalized lymphadenopathy Hyperpigmented skin of the forehead, abdomen, hands, and feet in light-skinned persons Skin lesions in dark-skinned persons Bleeding (petechiae, epistaxis, bleeding gums) Jaundice Onset may also be acute, with the above manifestations appearing a few weeks after infection  Diagnosis For Leishmania, the amastigote is the primary diagnostic form; For Trypanosoma, the trypomastigote is the primary diagnostic form, with the exception of Trypanosoma cruzi, in which amastigotes may also be found  Summary The morphological forms of hemoflagellates are amastigote, promastigote, epimastigote, and trypomastigote Hemoflagellates typically infect hosts via arthropod vectors Laboratory diagnosis includes analysis of blood, lymph node and ulcer aspirations, tissue biopsies, bone marrow, and cerebrospinal fluid