Case Report

1. Case Report Time:2006.1.23 Site:臨床病理科簡報室 Speaker:I2 楊秀謙

2. Brief History • A 25 y/o nurse had recently returned to the United States from a stay in Brazil(巴西), where she had worked at a clinic treating rural patients. • Symptoms: fever, anorexia, weight loss, shortness of breath, myalgia. • Visit her primary care doctor. • P.E: a thin woman, a slightly enlarged liver and spleen, lymphadenopathy (+),upper and lower eyelid edema in R’t eye, along with conjunctivitis. • EKG: abnormalities of the P, T waves and the QRS complex, cardiomegaly(+)

3. Case Report • Thick and thin blood smears were ordered and were stained by the Giemsa method. • Microscopic examination : a few flagellated spindle-shaped protozoan parasites (some assuming a C shape) with undulating membranes. • Diagnosis: An infection with a blood parasite

4. Case Report

5. QUESTIONS • What is the name of this patient's illness? Which blood protozoan parasite iscausing the infection? • How is this infection transmitted? • Why is the vector for this protozoan known as the "kissing bug"? • Describe the life cycle of this parasite. • What is the name of the lesion that may develop at the site of inoculation ofthe parasite? What is the name given to the unilateral edema of the eye in this disease? • Which methods are available to diagnosis this infection? • How does this parasite differ from other parasites in the same genus? • How is this infection treated? • This infection may be acquired during blood transfusion. List other protozoanparasitic infections that may be transmitted during blood transfusions. • Explain the cardiac abnormalities found in this patient. Which othercomplication may occur?

6. LYMPHADENOPATHY • Analysis of lymphadenopathy : > 2/3 p’ts →nonspecific causes or URI (viral or bacterial), <1% : malignancy. • 186 of 220 patients (84%) evaluation of lymphadenopathy →“benign” diagnosis. • 34 patients (16%) : malignancy (lymphoma or metastatic adenocarcinoma). • 186 p’ts: 63% (112) : nonspecific or reactive etiology (no causative agent found) • The remainder: most commonly infectious mononucleosis, toxoplasmosis, or tuberculosis.

7. Clinical Assessment • Extent of lymphadenopathy: localized or generalized, size, texture, nodal tenderness, signs of inflammation over the node, skin lesions, splenomegaly. • Adult, cervical adenopathy, Hx of smoke→ ENT exam. • Localized, regional adenopathy: involvement of a single anatomic area. • Generalized adenopathy : involvement > 3 noncontiguous lymph node areas. • Generalized lymphadenopathy : nonmalignant disorders → infectious mononucleosis(EBV, CMV), toxoplasmosis, AIDS, viral infections, SLE, MCTD. →ALL, CLL, malignant lymphomas →generalized in adults.

8. TABLE 54-1 Diseases Associated with Lymphadenopathy

9. Toxoplasmosis • Toxoplasma gondii • Found throughout the world(more than 60 million people in USA) • Very few have symptoms→ keeps the parasite from causing illness. • Pregnant women and individuals with compromised immune systems→serious health problems.

10. Toxoplasmosis • Fever • Sore throat • Sore muscles and tiredness • Swollen glands in the neck, armpits or groin • Temporary blurred vision or loss of vision • Most people who are infected do not show any signs of the disease. • Persons who are pregnant or are experiencing a suppressed immune system due to AIDS, cancer or following organ transplants are at higher risk for illness.

11. Toxoplasmosis • P.E: • Toxoplasmosis cannot be diagnosed on clinical grounds alone because it may mimic a variety of other diseases. • No clinical features are pathognomonic for toxoplasmosis. • Lymphadenopathy is the most common finding.

12. Leishmaniasis • Spread by the bite of infected sand flies. • Cutaneous leishmaniasis →skin sores(one or more cutaneous lesions →sandflies have fed ) painless or painful. • Visceral leishmaniasis →internal organs of the body (spleen, liver, bone marrow)

13. Leishmaniasis • Cutaneous leishmaniasis: • Skin sores • Raised edge sores - like a volcano with a central crater • Scabs • Swollen glands or underarm glands • Visceral leishmaniasis: • Fever • Weight loss • Enlarged spleen or liver(usually spleen > liver) • Swollen glands • Bone marrow symptoms • WBC, RBC, PLT ↓

14. Leishmaniasis • Some patients develop post kala-azar dermal leishmaniasis. • Visceral leishmaniasis →opportunistic infection →HIV(+) • Laboratory Diagnosis:Examination of Giemsa-stained slides of the relevant tissue is still the technique most commonly used to detect the parasite.

15. Trypanosomiasis • Each individual may experience symptoms differently. • Symptoms: within one to four weeks of infection →initially nonspecific ( fever, skin lesions, rash, edema, or swollen lymph nodes on the back of the neck) →meningoencephalitis • personality change • weight loss, loss of concentration • irritability • progressive confusion, slurred speech, seizures, difficulty walking and talking • sleeping for long periods of the day, insomnia at night • Untreated→death (within several weeks to month)

16. Trypanosomiasis • Acute stage: 1 percent of cases The first sign: chagoma (swelling and thickening of the skin near the site of infection), redness, enlarged lymph nodes nearby. →Romaña's sign– a person's eye on one side of the face swells, usually at the bite wound or where feces were deposited or accidentally rubbed into the eye. • Other symptoms: fatigue, fever, enlarged liver or spleen, swollen lymph glands, rash, loss of appetite, diarrhea, and vomiting. • In infants and in very young children →brain damage→ death. • In general, a person's symptoms last from 4 to 8 weeks and then they go away, even without treatment.

17. Trypanosomiasis • Indeterminate stage: 8 to 10 wks after infection → last for many years → not have symptoms • Chronic stage→ serious symptoms : Enlarged heart, altered heart rate or rhythm, heart failure, cardiac arrest Enlargement or perforation of the esophagus or large bowel →swallowing difficulties, severe constipation.

18. Filariasis • Not feel any symptoms until after the adult worms die. • Not life threatening →permanently damage lymph system and kidneys. • Lymph system does not work right→fluid collects → swelling in the arms, the vulva, breasts, legs, the genital area → lymphedema (swell to several times its normal size) • Difficult for your body to fight germs and infections. • More bacterial infections in skin and lymph system → hardening and thickening of the skin → elephantiasis

19. Filariasis • Acquire early in childhood →take years to manifest itself. • May be no clinical symptoms→ outwardly healthy(hidden lymphatic pathology and kidney damage ) • The asymptomatic form of infection →the presence in the blood of thousands or millions of larval parasites (microfilariae) and adult worms located in the lymphatic system. • The worst symptoms →appear in adults(M > F). • M(10-50%) →genital damage: hydrocoele (fluid-filled balloon-like enlargement of the sacs around the testes) and elephantiasis of the penis and scrotum.

20. Chagas disease (American trypanosomiasis) • A human tropical parasitic disease • Americas, particularly in South America. P • Pathogenic agent : flagellate protozoan: Trypanosoma cruzi hematophagous insects of the subfamily Triatominae (Family Reduviidae). • Numerous common names varying by country: assassin bug, benchuca, vinchuca, kissing bug, chipo, barbeiro, et cetera. • The most common insect species belong to the genera Triatoma, Rhodnius, and Panstrongylus. • Other forms of transmission : ingestion of food contaminated with parasites, blood transfusion, fetal transmission • Trypanosoma cruzi is a member of the same genus as the infectious agent of African sleeping sickness, but its clinical manifestations, geographical distribution, life cycle and insect vectors are quite different.

21. Infection cycle of Trypanosoma cruzi, the pathogen of Chagas disease 無鞭毛體 錐鞭毛體 側鞭毛體 CDC-DPD

22. Chagas disease • Acute stage: 1 percent of cases The first sign: chagoma (swelling and thickening of the skin near the site of infection), redness, enlarged lymph nodes nearby. →Romaña's sign– a person's eye on one side of the face swells, usually at the bite wound or where feces were deposited or accidentally rubbed into the eye. • Other symptoms: fatigue, fever, enlarged liver or spleen, swollen lymph glands, rash, loss of appetite, diarrhea, and vomiting. • In infants and in very young children →brain damage→ death. • In general, a person's symptoms last from 4 to 8 weeks and then they go away, even without treatment.

23. Chagas disease • Indeterminate stage: 8 to 10 wks after infection → last for many years → not have symptoms • Chronic stage → cardiomyopathy: the most serious manifestation Enlarged heart, altered heart rate or rhythm, heart failure, cardiac arrest Enlargement or perforation of the esophagus or large bowel →swallowing difficulties, severe constipation.

24. Adult Rhodnius prolixus taking a blood meal through human skin. The insect transmits the parasites which cause Chagas disease in feces that they deposit near the site of their bite.Scratching or rubbing by the person bitten can transfer the parasites into the body via the wound or other sites such as the eye. Trypanosoma cruzi in thin blood film (Leishmans stain) showing developing tryptomastigotes that have a free flagellum.

25. Photomicrograph of Trypanosoma cruzi parasites (Chagas disease pathogen). US Federal Government public domain image (CDC).

26. Different stages of triatomine insects, the vectors of Chagas disease. Acute Chagas Disease in a young child. The eye sign of Romana is present. This is frequently seen in acute cases and is presumed to mark the point of entry of the parasite.

27. Laboratory diagnosis • Microscopic examination: a) fresh anticoagulated blood, or its buffy coat, for motile parasites b) thin and thick blood smears stained with Giemsa, for visualization of parasites; it can be confused with the 50% longer Trypanosoma rangeli, which has not shown any pathogenity in humans yet. • Isolation a) inoculation into mice b) culture in specialized media (e.g. NNN, LIT) c) xenodiagnosis, where uninfected Reduviidae bugs are fed on the patient's blood, and their gut contents examined for parasites 4 weeks later. • Immunodiagnostic tests: Complement fixation, indirect hemagglutination, IFA, RIA, ELISA, PCR(most promising)

28. Treatment • Medication : only effective when given during the acute stage • The drugs of choice are azole or nitroderivatives such as benznidazole or nifurtimox, but resistance to these drugs has already been reported. • These agents: very toxic many adverse effects • Use of oxidosqualene cyclase inhibitors and cysteine protease inhibitors : cure experimental infections in animals.

29. Treatment • Chronic stage→manage the clinical manifestations of the disease: Drugs and heart pacemaker for chronic heart failure and arryhthmias Surgery for megaintestine • The disease per se is not curable in this phase. Chronic heart disease caused now a common reason for heart transplantation surgery. → After operation, survival rates can be significantly improved by using lower dosages of the immunosuppressant drug cyclosporine. • Direct stem cell therapy of the heart muscle using bone marrow cell transplantation →dramatically reduce risks of heart failure in Chagas patients. • Patients have also been shown to benefit from the strict prevention of reinfection, though the reason for this is not yet clearly understood.

30. Parasitic infections which may be transmitted during blood transfusions • Malaria • Babesiosis • Toxoplasmosis • Chagas’ Disease

31. THANKS FOR YOUR ATTENTION!

32. Chagas disease The Fight for Recognition: Chagas’ Disease Meets Controversy Anna Moorhouse, Science JournalistEnglish and Cell and Molecular Biology, Simon Fraser University

33. Questions？