Andrews’ Chapter 20 pgs 526-547

1. Andrews’ Chapter 20pgs 526-547 JoAnne M. LaRow, D.O. December 9, 2003

2. Phylum Protozoa • One-celled organisms • Divided into classes according to nature of locomotion • Class Sarcodina move by temporary projections of cytoplasm (pseudopods) • Class Mastigophora by means of one or more flagella • Class Ciliata by short, hair-like projections of cytoplasm (cilia) • Class Sporozoa with no special organs of locomotion

3. Class Sarcondina • Best known organism in class: ameba • Entamoeba histolytica is ameba of medical significance • Amebiasis cutis begins as deep abscesses that rupture • These form ulcerations with distinct, raised, cordlike edges and an erythematous halo approx. 20 cm wide • Base is covered with necrotic tissue and hemopurulent, glairy, pus-containing amebae

4. Multiple large ulcers • Extensive tissue destruction • Resembles pyoderma gangrenosum

5. Amebiasis Cutis • Lesions may occur on trunk, abdomen, external genitalia, buttocks, or perineum • Abdominal lesions may arise from hepatic abscesses • All ages are at risk • Intestinal amebiasis, with bloody diarrhea and hepatic abscesses, may be present • Chronic urticaria may be sole manifestation of early amebiasis • Organism may be found at base of lesion by direct smear or shave bx

6. Histology-Amebiasis • Necrotic ulceration with many lymphocytes, neutrophils, plasma cells, and eosinophils • E. histolytica is found in tissue, within blood and lymph vessels • Organisms measures 50-60 microns in diameter • Has a basophilic cytoplasm, a single eccentric nucleus with a central karyosome

7. Diagnosis Amebiasis • Organism is frequently demonstrable in fresh material from base of ulcer • Indirect hemagglutination test results remain elevated for yrs after initial invasive disease onset • Whereas, results of gel diffusion precipitation tests and counterimmunoelectrophoresis become neg at 6 months • This property can be used to test for recurrent or active disease in persons coming from endemic areas

8. Tx-Amebiasis • Recommended is Metronidazole 750 mg orally TID for 10 days, followed by iodoquinol 652 mg TID for 20 days • Surgical drainage for abscesses

9. Class Mastigophora • Organisms are known as flagellates • Many have undulating membrane with flagella along crest

10. Trichomoniasis • Trichomonas vulvovaginitis is a common cause of vaginal pruritis with burning and frothy leukorrhea • Vaginal mucosa appears bright red from inflammation and may be mottled with pseudomebranous patches • Males may harbor organism and develop urethritis and prostatitis, and occasionally balanoposthitis • Neonates may acquire infection during passage through birth canal, but require tx only if symptomatic or if colonization lasts more than 4 weeks • However, as this is otherwise nearly exclusively a sexually transmitted disorder, trichomonas vulvovaginitis in a child should make one suspect sexual abuse

11. Trichomonas • Tx Metronidazole 2.0 g in single oral dose TOC • Alternatively, 500 mg twice daily for 7 days may be given • Warn pts not to drink alcohol for 24 hrs after last dose because disulfiram type of effects of this med • Male sex partners should be tx • Metronidazole is contraindicated in pregnant women-use clotrimazole intravaginally

12. Colorless pyriform flagellate 5-15 microns long • Demonstrated in smears from affected areas • DIF is sensitive and specific

13. Leishmaniasis

14. Leishmaniasis • Three forms: • A.) cutaneous form restricted to skin • B.) mucocutaneous form affects both skin and mucosal surfaces • C.) visceral leishmaniasis that affects organs of reticulo-endothelial system

15. Leishmaniasis • Cutaneous leishmaniasis, American mucocutaneous leishmaniasis, and visceral leishmaniasis (kala-azar), which includes infantile leishmaniasis and post-kala-azar dermal leishmaniasis, are all caused by morphologically and culturally indistinguishable protozoa of the family Trypanosomidae, called Leishmania

16. Cutaneous Leishmaniasis • Several types of lesions • All tend to occur on exposed parts as all are transmitted by the sandfly

17. Pathogenesis • Organisms are obligate intracellular parasites existing in two forms: promastigote and amastigote • In gut organisms multiply as extracellular flagellated promastigotes • Following migration to the proboscis, parasites are inoculated (in promastigote form) via sandfly bite • These transform into amastigotes within cells of the reticuloendothial system in host- be it human, rodent or canine

18. Life Cycle

19. Old World Leishmaniasis • Limited to the skin • Called Baghdad boil, oriental sore, leishmaniasis tropica, birskra button, Delhi boil, Aleppo boil, Kandahar sore, & Lahore sore • May present in two ways: moist or rural type, a slow growing, indurated, livid, indolent papule which enlarges in a few months to form an ulcer as much as 5 cm in diameter • Spontaneous healing takes place within 6 months, leaving a characteristic scar • Contracted from rodent reservoirs such as gerbils via the sand fly as vector • Short incubation period-1-4 weeks

22. Bagdad boil of 5 months’ duration

23. Old World Leishmaniasis • Dry or urban type • Has a longer incubation period (2-8 months or longer) • Develops more slowly, and heals more slowly than the rural type

24. Leishmaniasis Recidivans • Rarely, after initial or “mother “ lesion heals, there may appear at the borders of healed areas a few soft red papules covered with scales and having the “apple jelly” characteristics of lupus vulgaris • These spread peripherally on an erythematous base and are called lupoid type • Aka leishmaniasis recidivans • Occurs most commonly with urban type caused by L. tropica

26. New World Leishmaniasis • Subtypes present of purely cutaneous involvement are uta, pain bois, and bay sore or chiclero ulcer • Primary papule may become nodular, verrucous, furuncular, or ulcerated, with an infiltrated red border • Subcutaneous peripheral nodules, which eventually ulcerate, may signal extension of disease • A sporotrichoid pattern may occur with lymphadenopathy, and nodes may rarely yield organisms • Recidivans lesions are unusual in New World form of disease

27. American cutaneous leishmaniasis • Lesion of localized cutaneous leishmaniasis presenting as an indurated nodule with an ulcerated crateriform center

28. Cutaneous leishmaniasis • A well circumscribed ulcerated lesion on the face of a child

29. Cutaneous leishmaniasis • Multiple ulcerated lesions on the legs of a rural worker

30. Circular scars at previous sites of cutaneous leishmaniasis • Often only sign of a previous infection

31. Chiclero Ulcer • In Yucatan and Guatemala, a subtype of New World disease exists: the chiclero ulcer • Most frequently site of infection is the ear • Lesions ulcerate and occur most frequently in workers who harvest chicle for chewing gum in the forests, where there is high humidity • This form is a more chronic ulcer that may persist for yrs, destroying ear cartilage and leading to deformity • Etiologic agent is L. mexicana and the vector, a sandfly, Lutzomyia flaviscutellatta

33. Uta • Uta is a term used by Peruvians for leishmaniasis occurring in mountainous territory at elevations of 1200 to 1800 meters above seas level • Ulcerating lesions are found on exposed sites, and mucosal lesions do not occur

34. Disseminated Cutaneous Leishmaniasis • May be seen in New and Old World disease • Multiple nonulcerated papules and plaques • Chiefly on exposed surfaces • Caused by several subspecies of L. mexicana • L. aethiopica be etiology in Ethiopia and Kenya • Begins with a single ulcer, nodule, or plaque • Satellite lesions may develop & cover entire body • Disease is progressive and tx ineffective • Characterized by anergy to organism • Montenegro rxn is negative

35. Disseminated cutaneous leishmaniasis

36. Epidemiology • Cutaneous leishmaniasis is endemic in Asia Minor & to a lesser extent in many countries around the Mediterranean Sea • Iran and Saudi Arabia have a high occurrence rate • Purely cutaneous lesions are found in Central and South America & 9 pts who acquired their disease in Texas have been reported • Children are affected most often, since immunity is acquired from initial infection • Deliberate inoculation on thigh is sometimes practiced so that scarring on face- a frequent site for Oriental sore-may be avoided

37. Pathogenesis • Organism has an alternate life in vertebrate and an insect host • Man and other mammals such as dogs and rodents are the natural reservoir hosts • Host vectors are Phlebotomus sandflies in Old World type and Phlebotomus perniciosus & Lutzomyia sandflies for the New World cutaneous leishmaniasis • After insect has fed on blood, the flagellates (leptomonas, promastigote) develop in gut in 8-20 days, after which migration occurs into the mouth parts; from here transmission into humans occurs by a bite • In humans, flagella are lost and a leishmanial form (amastigote) is assumed

38. Histopathology • Typical features of an ulcer: heavy infiltrate of histiocytes, lymphocytes, and a polymorphonuclear leukocytes • Numerous organisms are present ( mostly in histiocytes), which are nonencapsulated and contain a nucleus and a paranucleus • Wright’s, Giemsa, and monoclonal antibody staining may be helpful in identifying the organisms • Parasitized histiocytes form tuberculoid granulomas in dermis • Pseudoepitheliomatous hyperplasia may occur in edges of ulcer

39. Localized cutaneous leishmaniasis: a diffuse infiltrate extends into the subcutis • Epidermis is ulcerated

40. Mixed cell infiltrate with many plasma cells and neutrophils but with histiocytes predominating • Organisms are seen within the histocytes

41. Diagnosis (cont’d) • More sophisticated tests to diagnose and classify subspecies involve detection of monoclonal antibodies with immunoperoxidase, radiolabeling, or fluorescenation, DNA probes, DNA buoyancy, restriction-endonuclease fragment patterns of kenetoplast DNA, restriction-frequent length polymorphisms of unclear DNA, and isoenzyme electrophoresis

42. Montenegro skin test • Uses leishmanial antigen to induce a cell-mediated response • Can be used as a diagnostic method • Cannot distinguish between past & present infections • Skin tests can be false-neg in anergic pts with disseminated infections

43. Diagnosis • Demonstration of organism in smears • Parasites can be cultured from tissue fluid • A hypodermic needle is inserted into normal skin and to edge of ulcer base • Needle is rotated to work loose some material and serum, which is then aspirated • Culture on Nicolle-Novy-MacNeal (NNN) medium at 22 degrees- 35 degrees C • Leishmanin intradermal test may be helpful in nonendemic areas (Leishman-Montenegro-Donovan) • It becomes positive 3 months after infection

44. Treatment • Spontaneous healing occurs, usually within 12-18 months, shorter for Old World disease • Rationale for tx an ordinarily self-limited infection include avoiding disfiguring scars in exposed areas, avoiding secondary infection; controlling disease in the population; and failure of spontaneous healing; in diffuse cutaneous and recidivans types, disease may persist for 20-40 yrs if untreated

45. Tx (cont’d) • In areas which localized cutaneous leishmaniasis is not complicated by recidive or sporotrichoid forms or mucocutaneous disease, tx with topicals: Paromycin sulfate 15% plus methylbenzethonium chloride 12% • Ketoconazole cream under occlusion, • Cryotherapy, local heat, and laser ablation, or with intralesional sodium stibogluconate antimony or emetine hydrochloride, may be effective and safe • Perilesional injections of interferon-gamma have also been reported to be effective but are expensive

46. Tx (cont’d) • In pts who are immunocompromised or who acquire disease in areas where mucocutaneous disease may occur, systemic therapy is recommended • Many alternatives reported effective • Sodium antimony gluconate (sodium stibogluconate) solution given IV or IM-20mg/kg/day in two divided doses for 28 days • Repeated courses may be given • Antimony n-methyl glutamine (Glucantime) is used more often in Central and South America because of its local availability • Ketaconazole (600mg/day for 28 days), itraconazole, dapsone, rifampin, and allopurinol

47. Tx (cont’d) • Some of these have not been subjected to control trials, as is true of most topical treatments • Recidive and disseminated cutaneous types may require prolonged courses or adjuvant interferon therapy • Amphotericin B may be used in antimony-resistant disease • Control depends on success of anti-fly measures taken by health authorities

48. Mucocutaneous Leishmaniasis (Leishmaniasis Americana, Espundia) • Infection occurs at site of fly bite • Initially a destructive ulcer • Secondary lesions on the mucosa occur at the same time or sometime during the next 5 yrs • Earliest mucosal lesion is hyperemia of nasal septum with subsequent ulceration • Ulceration progresses to invade septum and later paranasal fossae • Perforation of septum eventually takes place • Nose remains unchanged externally, despite internal destruction

49. Clinical Features • Initially only dry crust is observed, or a bright red infiltration or vegetation on nasal septum • Symptoms are obstruction and small hemorrhages • Despite mutilation and destruction it never involves nasal bones • When septum is destroyed, nasal bridge and tip of nose collapse, giving an appearance of a parrot beak, camel nose, or tapir nose • Four of the great chronic infections (syphilis, tuberculosis, leprosy, and leishmaniasis) have a predilection for the nose • Ulcer may extend to lips and continue to advance to pharynx, attacking soft palate, uvula, tonsils, gingiva, tongue

50. Leishmaniasis americana (mucocutaneous)