•  Amebiasis

  • Paromomycin sulfate (Humatin):

    • Overview:

      •  Classification: aminoglycoside-- related to neomycin, streptomycin, and kanamycin (Kantrex)

      •  Luminal amebicide (no significant absorption from the gastrointestinal tract)

      •  Direct and indirect gametocidal activity (indirect secondary to bowel bacteria inhibition)

    • Clinical Uses:

      •  Monotherapy: alternative for asymptomatic amebiasis

      •  For mild/moderate disease: paromomycin (Humatin) in combination with tissue amebicide, e.g. metronidazole (Flagyl)

    • Pharmacokinetics:

      •  Minimal absorption/small amount absorbed slowly excreted by glomerular filtration

    •  Cautions:

      •  In patients with renal insufficiency-- toxic levels may be achieved

      •  Prolonged use at non-therapeutic levels can cause bacterial/yeast superinfections.

• Leishmania

  • Overview:-Leishmaniasis

    • Characteristics-of idea diseases (cutaneous, visceral, mucocutaneous) caused by protozoal parasites classified in the genus Leishmania.

  • Causal Agents:

    •  "Leishmaniasis is an infection caused by obligate intracellular protozoa transmitted by sandflies, belonging to the genus Leishmania.  

      • Several species are found in different geographical areas and cause different clinical manifestations. 

      • While the taxonomy is still not definitive, a generally accepted classification recognizes 12 species. 

      • These include a L. donovani complex with 3 species (L. donovani, L. infantum, L. chagasi); a L. mexicana complex with 2 species (L. mexicana and L. amazonensis); L. tropica; L. major; L. aethiopica; and a group of the subgenus Viannia with 4 species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana. 

      • The different species are morphologically undistinguishable, but can be differentiated on the basis of their isoenzymes, antigens, and nucleic acids composition."

    • Life Cycle

      • "Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. 

      • The sandflies  become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes.

        • In the sandfly, the parasites differentiate into promastigotes that multiply and mature. 

        • A minimum of 7 days are required before infective promastigotes are present

        • The promastigotes block the insect's pharynx and hypostome, and are regurgitated by the sandfly during a subsequent blood meal. 

        • Promastigotes that reach the puncture wound and are phagocytized by macrophages transform into amastigotes and multiply, thus closing the life cycle. 

        • Multiplication is by  binary fission, and no sexual stage has been identified."

  • Clinical Characteristics:Leishmaniasis

    •   "Human leishmanial infections can result in 3 main forms of disease. 

      • The factors determining the form of disease include leishmanial species, geographic location, and immune response of the host.  

      • Cutaneous leishmaniasis is characterized by one or more cutaneous lesions on areas where sandflies have fed.  

      • Ulcerative lesions appear that resolve spontaneously over a period of weeks to months, but can recur. 

      • Mucosal leishmaniasis is caused principally by members of the subgenus Viannia and is found in Central and South America.  This form of leishmaniasis results in nasopharyngeal lesions that can be severe. 

      • Visceral leishmaniasis (kala-azar) is caused primarily by the L. donovani complex and to a lesser extent by L. tropica in the Old World, and by L. amazonensis in the New World. 

        • Its clinical manifestations include fever, hepatosplenomegaly, weakness and progressive emaciation which can result in death if untreated.  Some patients develop post kala azar dermal leishmaniasis. 

        • Visceral leishmaniasis is becoming an important opportunistic infection in areas where it coexists with HIV."- CDC: http://www.dpd.cdc.gov/DPDx/HTML/Leishmaniasis.htm

  • Laboratory Diagnosis:leishmaniasis

    • "Specific diagnosis is based on microscopic examination of Giemsa stained smears of tissue scrapings or aspirates, or biopsy material, for the presence of amastigotes." CDC

    • Microscopy

  • Pharmacological Management: Leishmaniasis

    • Drug of choice --sodium antimony gluconate (Sodium stibogluconate (Pentostam))

      • Preferred Route of Administration -- IV for large volumes

      • Side effects develop with drug accumulation

        • Most common:  Gastrointestinal symptoms, fever, rash.

        • Uncommon: cardiac, renal, liver damage; hemolytic anemia

    • Alternative drugs:

      • Pentamidine (Pentam)

      • Amphotericin B (Fungizone, Amphotec) (may be associated with severe side effects)

Primary Reference: Goldsmith, R. S., Antiprotozoal Drugs in Basic and Clinical Pharmacology (Katzung, B. G., ed) Appleton-Lange, 1998, p. 838-861.