Parasitic Infections: Clinical Manifestations, Diagnosis and Treatment Part II

1. Parasitic Infections:Clinical Manifestations, Diagnosis and TreatmentPart II Lennox K. Archibald, MD, PhD, FRCP, DTM&H Hospital Epidemiologist University of Florida

2. Case 1 A 24-year-old white male army officer Referred to the VA ID clinic with a 3-month history of a lesion on his right leg, developing approximately 2 weeks after returning from Iraq Recent travel history: 1 month in Kuwait and 2 months traveling between Kuwait and Iraq Recalled being bitten numerous times by small flying insects and other nasty “bugs”

3. Case 1 Physical examination essentially normal except for: Non-tender (20 × 15 mm) scaly erythematous plaque with a moist central erosion of the left popliteal area. There was no lymphadenopathy and no mucosal lesions were noted

7. Leishmaniasis Tropical areas where phlebotomine sandfly is common: South America, India, Bangladesh, Middle East, East Africa Sandfly introduces flagellated promastigote into human ? ingested by macrophages ? develops into nonflagellated amastigote

8. Leishmaniasis: Clinical Manifestations 3 forms: visceral, cutaneous, mucosal A single species can produce more than one syndrome, and each syndrome is caused by multiple different species Visceral (kala azar) Species most prevalent in different places L. donovani – India L. infantum – Mid East L. chagasi – Latin America L. amazonensis -- Brazil

11. Leishmaniasis Cutaneous Most common among farmers, settlers, troops and tourists in Mid East (L. major and tropica), Central and South America (L. mexicana, braziliensis, amazonensis, and panamensis) L. mexicana reported in Texas Visceral (kala azar) Anemia, leukopenia, thrombocytopenia, hypergammaglobulinemia common

12. Visceral Leishmaniasis Dissemination of amastigotes throughout the reticulendothelial system of the body Spleen Bone marrow Lymph nodes Opportunistic infection in AIDS patients Ineffective humeral response

13. Hepatosplenomegaly

14. Splenic aspirate Most satisfactory method Spleen must be at least 3cm below LCM Aspirate stained with Giemsa

15. Leishmaniasis: treatment Only drug approved in US is Amphotericin B Treatment of cutaneous disease depends on anatomic location Many spontaneously heal and do not require treatment

16. Remember.. The factors determining the form of leishmaniasis: Leishmanial species Geographic location Immune response of the host

17. Case 2 6-yr-old boy recently arrived from Brazil Swelling around the eye Conjunctivitis Fever Enlarged lymph nodes Hepatosplenomegaly Had stayed in a hotel—adobe style with thatched roof

19. Blood smear

20. Reduviid bug(assassin bug)

21. Chagas disease: Clinical manifestations Local edema is followed by fever, malaise, anorexia More rarely: myocarditis, encephalitis Years later: chronic Chagas Disease (10-30%) Heart: primary target Cardiomyopathy associated with CHF, emboli, arrythmias GI tract: mega-esophagus, megacolon

22. Chagas disease: Diagnosis and treatment Acute disease is diagnosed by seeing trypomastigotes on peripheral blood smear Chronic disease is diagnosed by ELISA detecting IgG antibody to T. cruzi Treatment slows the progression of heart disease

23. Chagas Disease Public health implications in the US Chronic Cardiomyopathy Megaesophagus Megacolon Blood transfusion Transplant Solid organ Musculoskeletal allograft tissue

24. Case 3 6-year-old son of seasonal farm worker. His father notes that he always wares shoes Presents with cough and fever, wheeze CXR reveals a lobar pneumonia Admitted for initial therapy After 2 days of antibiotics, with good defervescence, a worm is found in his bed Stool exam reveals …

26. Ascaris lumbricoides Roundworm most commonly found in humans Asia, Africa, Latin America (100% of population harbor parasite) Adults: white/creamy/pink Largest of intestinal nematodes (females: 20-35 cm; males 15-30 cm) Females lay up to 200,000 eggs /day

27. Epidemiology Indiscriminate defecation: seeds soil with eggs Children become infected by ingesting soil or putting soiled items in the mouth The eggs contaminate unwashed vegetables and water supplies Eggs can be carried by cockroaches, flies, wind, and even on money

28. Ascaris lumbricoides 1 million infected in U.S. Common: coastal regions/Appalachia Eggs ingested, usually toddlers playing in contaminated soil China: nightsoil May mimic TB

29. Ascaris lumbricoides In GI tract, few symptoms in light infections Nausea Vomiting Obstruction of small bowel or common bile duct. Pulmonary: symptoms due to migration Alveoli (verminous pneumonia)—cough, fever wheeze, dyspnea, X-ray changes, eosinophilia

30. Effects of Adult Ascaris Worms Depends on worm load Effects Mechanical: obstruction, volvulus, intussusception, appendicitis, obstructive jaundice, liver abscesses, pancreatitis, asphyxia Toxic and Metabolic Malnutrition (complex)

31. Ascaris lumbricoidesDiagnosis Characteristic eggs on direct smear examination If treating mixed infections, treat Ascaris first Mebendazole Pyrantel Control: Periodic mass treatment of children, health education, environmental sanitation

33. Case 4 11-year-old female Doing poorly in school Not sleeping well Anorectic Complains of itching in rectal region throughout the day A Scotch-tape test reveals…

37. Enterobius (Pinworm) 18 million infections in U.S. Incidence higher in whites Preschool and elementary school most often Mostly asymptomatic Nocturnal anal pruritis cardinal feature due to migration and eggs May have insomnia, possible emotional symptoms DS-eggs or adults on perineum {scotch tape} Mebendazole 100 mg. Repeat in 2 weeks.

38. 69-year-old male was admitted to VA Hospital Far East Prisoner of War (FEPOW) COPD--steroids for 3 years 2-month history of nausea, vomiting and anorexia 25 pounds weight loss

39. On the day of admission… Fever, confusion, and not able to get out of bed---transported to the hospital Initial blood work: Elevated WBC Raised eosinophil count 4 times normal Underwent UGI endoscopy Duodenal biopsy obtained

41. Strongyloides: Crucial Aspects of Life Cycle Infection acquired through penetration of intact skin Infection may persist for many years via autoinfection In immunocompromised patients, there is risk of dissemination or hyperinfection Hyperinfection syndrome

42. Disseminated Strongyloidiasis High mortality?75% Penetration of gut wall by infective larvae Gut organisms carried on the surface of larvae results in polymicrobial sepsis, meningitis Larvae disseminate into all parts of body: CNS, lungs, bladder, peritoneum

43. Summary—Clinical Findings Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?) Gl symptoms in about two-thirds: Abdominal pain Bloating Diarrhea Constipation Wheezing, SOB, hemoptysis

44. Summary—Clinical Findings Skin rash or pruritis in ~ one-third Larva currens (racing larva) Intensely pruritic Linear or serpiginous urticaria with flare that moves 5-15 cm/hr Usually buttocks, groin, and trunk In dissemination, diffuse petechiae and purpura

45. Larva currens

46. Summary-Clinical Findings Eosinophilia 60-95% Less if on steroids

47. Case 6 8-yr-old schoolgirl visiting the U.S. from Malaysia 1 week history of epigastric pain, flatulence, anorexia, bloody diarrhea No eosinophilia noted Clinical diagnosis of amoebic dysentery made However, microscopy of stool prep…

49. Trichuris trichiura (Whipworm) Common in Southeast U.S. Frequently coexists with ascaris Entirely intraluminal life cycle—eggs are ingested Frequently asymptomatic Severe infections: diarrhea, abdominal pain and tenesmus Rectal prolapse in children DS-eggs in stool Mebendazole 100 mg bid x 3 days

53. Case 7 A 34 yr-old woman from Saudi Arabia Radiation and cyclophosphamide, adriamycin, vincristine and prednisone for diffuse large B cell lymphoma of the neck. Mild eosinophilia (AEC=500) at the time of diagnosis 4 months after initiation of chemo, c/o intermittent diffuse abdominal pain, bloating, constipation and occasional rectal bleeding. Absolute eosinophil count: 1000

54. Case 7 No evidence of lymphoma found on re-staging Completed chemo, was deemed to be in complete remission, but had persistence of GI complaints. Upper endoscopy was unrevealing. Colonoscopy and biopsy revealed granulomatous inflammation, prominent eosinophilic infiltrate, surrounding a collection of eggs.

57. Case 7 The patient was treated with praziquantel and did not have relapse of symptoms at 2-year follow-up AEC=250

58. Schistosomiasis: Epidemiology and life cycle Cercariae in fresh water penetrate human skin. Cercariae mature to schistosomulae, which enter the bloodstream, liver and lung. Mature worms migrate to the venous system of the small intestine (S. japonicum), large intestine (S. mansoni) or bladder venous plexus (S. haematobium).

59. Schistosomiasis: Epidemiology and life cycle Worms release eggs for many years into stool or urine, resulting in fresh water contamination. Freshwater snails are infected by miracidia and are necessary for the production of cercariae and human infection. S. mansoni South America, Caribbean, Africa, Mid East S. japonicum China and Philippines S. haematobium Africa, Mid East

61. Schistosomiasis: Clinical manifestations Three stages of disease, corresponding to life cycle within human hosts Swimmer’s itch Within 24 hours of cercariae penetration Serum sickness syndrome (Katayama fever) 4 to 8 weeks later when worms mature and release eggs Fever, headache, cough, chills, sweating, lymphadenopathy, hepatosplenomegaly ? usually resolves spontaneously Elevated IgE and eosinophils Most common with S. japonicum

62. Schistosomiasis: Chronic Disease Results from granulomatous reaction to egg deposition in intestine, liver, bladder, lungs (less common) and CNS (less common) S. mansoni & S. japonicum: Chronic diarrhea, abdominal pain, blood loss, portal hypertension, hepatosplenomegaly, pulmonary hypertension Eosinophilia is common Liver function tests are usually normal S. haematobium: hematuria, bladder obstruction, hydronephrosis, recurrent UTIs, bladder cancer

63. Chronic Schistosomiasis Granulomatous reaction to egg deposition in intestine, liver, bladder, lungs S. mansoni, japonicum Chronic diarrhea, abdominal pain, blood loss, portal hypertension, hepatosplenomegaly, pulmonary hypertension Eosinophilia is common Liver function tests are usually normal S. Haematobium Hematuria, bladder obstruction, hydronephrosis, recurrent UTIs, bladder cancer

66. Schistosomiasis: Diagnosis and Treatment Detection of characteristic eggs in stool, urine or tissue biopsy is diagnostic Urine is best between 12N and 2Pm, passed through 10 µm filter to concentrate eggs Antibody tests are available, but limited by sensitivity, specificity Praziquantel is the drug of choice

69. Summary Tissue Protozoa Leishmaniasis - sand fly, discrete nonhealing skin lesions, and visceral disease - kala azar Trypanosoma cruzi - Chaga’s disease Nematodes Ascaris Trichuris (whip worm) Enterobius (pin worm) Strongyloides Hookworm (read about)

70. Summary Tissue and Blood Helminths Schistosomiasis - intestinal and bladder Trichinella, Cystiscercosis & Echinococcocus (read about) Visceral & cutaneous larval migrans (read about) Filariasis (read about) Wucheria bancrofti and Brugia Malayi Dirfilaria imitus, dog heartworm

71. This is just the beginning of a great adventure in infectious diseases Sine qua non: history and physical examination

72. Thank you Lennox K. Archibald, MD, PhD, FRCP lka1@ufl.edu