1

Blood & Tissue Protozoa

Lange Chapter 52

Faculty: AGUAZIM SAMUEL, M.D.Faculty: AGUAZIM SAMUEL, M.D.

2

The medically important organisms: 

The sporozoans: Plasmodium and Toxoplasma

  The flagellates: Trypanosoma and

Leishmania  

Trypanosoa Trypanosoa speciesspecies

Vertebrate Vertebrate hosthost

vectorvector diseasedisease EpidemioloEpidemiologygy

T.bruci bruciT.bruci bruci Horses, pigs, Horses, pigs, cattle, cattle, rodentsrodents

Glossina spp.Glossina spp. NaganaNagana Tropical AfricaTropical Africa

T.bruci T.bruci gambiensegambiense

Human, Human, monkeys, monkeys, dogs,pigs,etc.dogs,pigs,etc...

Glossina spp.Glossina spp. Sleeping Sleeping siknesssikness

West AfricaWest Africa

T.bruci T.bruci rhodesienserhodesiense

Human,pigs.Human,pigs. Glossina spp.Glossina spp. Sleeping Sleeping siknesssikness

East AfricaEast Africa

T.crusiT.crusi Human, Human, domestic & domestic & wild animal.wild animal.

Reduviid Reduviid bugs bugs ((Triatoma Triatoma rhodniusrhodnius))

Chagas’ Chagas’

diseasedisease South AmericaSouth America

T.evansiT.evansi Horses, dogs.Horses, dogs. Tabanus spp.Tabanus spp. SurraSurra India, Africa, India, Africa, Australia, Australia, South and South and central central AmericaAmerica

Diseases caused by Trypanosoma spp. parasite

5

Trypanosoma cruzi (American Trypansomiasis) 

Disease: Chagas’ disease (American trypanosomiasis)

Characteristics: Blood and tissue protozoan.

Life cycle:

1. Trypomastigotes in blood of reservoir host2. Ingested by reduviid bug ( kissing bug or cone bug)3. Form epimastigotes 4. Form trypomastigotes in the gut.

6 Riduvid bug, the vector of American trypanosomiasis

cone-nose or kissing bug

7

Trypanosoma cruzi

• When the bug bites, it defecates and feces containing trypomastigotes contaminate the wound.

• Organisms enter the blood and form amastigotes within cells; these then become trypomastigotes.

• Transmission: Transmitted by reduviid bugs. Humans and many animals are reservoirs. Occurs in rural Latin America.

• Pathogenesis: Amastigotes kill cells, especially cardiac muscle

Pathogenesis (Acute)

Acute phase Starts 1 week after infection Fever, lymph node

enlargement, unilateral swelling of the eyelids (Romana’s sign), acute myocarditis, damaged muscle cells and edema.

Pathogenesis (Chronic)

Chronic Phases: Starts 2 months after initial

infection. Indeterminate form: 60-70% of

people with Chagas. Completely free of cardiac, gastrointestinal and neurological symptoms but 2-5% of patients convert to cardiac or digestive forms each year (reason not clear).

Cardiac manifestation

Cardiac form: 30-40% of people with

Chagas. Induces arrhythmia, cardiac failure, thromboembolism, atrioventricular fibrillation, ventricular hypertrophy

Gastrointestinal manifestation Digestive form:

10% of people. Megaoesophagus 3%, megacolon and may be associated with cardiac form. Difficulty in swallowing, regurgitation, aspiration may cause pneumonia and death. Chronic constipation, fecal compacting causes perforation of the colon.

12

Trypanosoma cruziLaboratory Diagnosis: •Trypomastigotes visible in blood•But bone marrow biopsy, culture in vitro, or serologic tests may be required.

Clinical findings: facial edema (Ramana’s sign) nodule (chagoma) near the the bite. Complications include megacolon and enlarged heart. DEATH FROM CHRONIC CHAGAS DZ IS USUALLY DUE TO CARDIAC ARRHYTHMIAS AND FAILURE

13

Trypanosoma cruzi, trypomastigote form, in a blood smear (Giemsa stain) CDC

Chagoma: raised, non-purulent erythematous

plaque surrounded by hard edema

14

15

Romana's sign: unilateral conjunctivitis and orbital edema

16

Trypanosoma cruzi

Treatment: Nifurtimox and benznidazole  for acute disease. No effective drug for chronic disease. Prevention: Protection from bite. Insect control. 

17

Trypanosoma Disease: Sleeping sickness (African trypanosomiasis)

•Trypanosomiasis is a systemic disease caused by the parasite Trypanosoma brucei.

• East African trypanosomiasis: T. rhodesiense

• West African trypanosomiasis: T. gambiense.

• It is transmitted by the bite of the tsetse fly, a gray-brown insect about the size of a honeybee.

18

Trypanosoma (African Sleeping Sickness)Characteristics: Blood and tissue protozoan.

Life cycle: 1. Trypomastigotes in blood of human or animal

reservoir, are ingested by tsetse fly.3. They differentiate in the gut to form epimastigotes 4. Metacyclic trypomastigotes formed in salivary glands. 5. When fly bites, trypomastigotes enter the blood. 6. Repeated variation of surface antigen occurs, which

allows the organism to evade the immune response. Recurrent Fever.

19

MOT: metacyclic trypomastigote

20

Tsetse fly. The vector of African trypanosomiasis

21

Trypanosoma (African Sleeping Sickness)

Transmission: Transmitted by tsetse flies.

Pathogenesis: Trypomastigotes infect brain, causing encephalitis.

Laboratory Diagnosis:

Trypomastigotes visible in blood in early stages and in cerebrospinal fluid in late stages.

Serologic tests useful.

22 Blood smear from a patient (a U.S. traveler) with Trypanosoma

METACYCLIC TRYPOMASTIGOTE

Pathogenesis (2 stages) Stage 1: Haemolymphatic

stage (ACUTE) Most patients do not notice this

stage of infection. Small papule from bite may develop

exciting local inflammation. When trypomastigotes enter the

haemo-lymphatic system to multiply,clinical symptoms include:

Fever, headache and joint pain Winterbottom’s sign: swelling of

lymph nodes at the posterior neck region.

Stage 2: Meningoencephaltic stage (CHRONIC)

Sleeping sickness stage because trypanosomes have crossed the blood-brain barrier

Personality changes, headaches and withdrawal from the environment.

Simple tasks become harder to accomplish as individual experience nocturnal insomnia and daytime lethargy, apathy and ultimately succumb to secondary infections such as pneumonia.

25

Trypanosoma African Sleeping Sickness

Clinical Finding: Important!!! Indurated skin ulcer (trypanosomal chancre) at the site of

fly bite Fever for 1 wk./ no fever 2 wks./fever again Enlargement of the glands of the posterior cervical region

(Winterbottom's sign) Neurological complications can occur as a result of

infection. Wasting and skin damage caused as a result of the intense

itching which can accompany late-stage disease. Coma

26The leg of a teenage girl who has sleeping sickness, showing the chancre at the site of the tsetse fly bite

Parasitemia

2-3 WEEKS after the bitefevermalaise, lassitudeinsomnia, headachelymphadenopathy and edema

Kerandel's sign : painful sensitivity of palms and ulnar region to pressure

Febrile episodes: few months- Rhodesian diseaseseveral years - Gambian disease

27

28

Very characteristic of Gambian disease is visible enlargement of the glands of the posterior cervical region (Winterbottom's sign)

CNS Stage changes in character and personality lack of interest and disinclination to work avoidance of acquaintances morose and melancholic attitude alternating with

exaltation mental retardation and lethargy low and tremulous speech tremors of tongue and limbs slow and shuffling gait altered reflexes males become impotent

29

Neuropathology of Human African Trypanosomiasis Acute hemorrhagic leucoencephalopathy

30

Why do they call it sleeping sickness?

31

DAYTIME SOMNOLENCENIGHTTIME INSOMNIA

Ziggy’s Micro class

DOC: 1. Pentamidine–inhibiting dihydrofolate

reductase enzyme, interfering with aerobic glycolysis

2. Suramin – trypanocidal; inhibiting parasitic enzymes ,growth factors

3. Melarsoprol – CNS; trypanocidal, inhibiting parasitic glycolysis ; late disease

32

PREVENTION Protection against the fly bite, using netting and

protective clothing. Clearing forest around villages Irradiation of male flies technique Chemical sprays( insecticides)

33

LEISHMANIASIS

IntroductionIntroduction

In the Middle East L. major and L. tropica are the most common species

• L. major causes skin infection• L. tropica causes skin and visceral infection and rarely

causes mucocutaneous infection

About 1.5 million new cases of cutaneous leishmaniasis in the world each year

500,000 new cases of visceral leishmaniasis estimated to occur each year also

20 cases of cutaneous leishmaniasis from L. major/ L tropica and twelve cases of visceral infection caused by L. tropica were reported in soldiers from Desert Storm

Endemic Areas for LeishmaniasisEndemic Areas for Leishmaniasis

BMJ 2003;326:378

Leishmaniasis in the Middle EastLeishmaniasis in the Middle East 90% of cutaneous leishmaniasis occurs in Afghanistan, Iran, Saudi Arabia,

Syria, Brazil and Peru• 8,779 cases were reported in Iraq in 1992• Sore is commonly called the Baghdad boil• At least 20 cases of cutaneous leishmaniasis were reported in

Americans from Desert Storm 90% of all visceral leishmaniasis occurs in Bangladesh, Brazil, India, and the

Sudan• 2893 cases were reported in Iraq in 2001• 12 visceral leish cases were reported in Americans in Desert Storm

90% of mucocutaneous leishmaniasis occurs in Bolivia, Brazil and Peru• Rarely associated with L tropica which is found in Middle East

LEISHMANIASIS:

Leishmania 2nd largest parasitic killer in the world

L. donovani: visceral leishmaniasis (Kala-azar, black disease, dumdum fever)

L. tropica: cutaneous leishmaniasis (oriental sore, Delhi ulcer, Aleppo, Delhi or Baghdad boil)

L. braziliensis: mucocutaneous leishmaniasis (espundia, Uta, chiclero ulcer)

39

LEISHMANIASIS

prevalent world wide south east Asia Indo-Pakistan Mediterranean north and central Africa south and central America

40

MOT: bite of Sandfly (Phlebotomus)aka sandflea, no-see-um, no-see-em, noseeum, sand gnats, chitras, punkie, or punky

41

42

Infective form: promastigoteIntracellular form: amastigote

43

Leishmania donovani Disease: Kala-azar

45

Leishmania donovaniCharacteristics: Blood and tissue protozoan Life cycle: 1. Human macrophages containing amastigotes are ingested

by sandfly.2. Amastigotes differentiate in fly gut to promastigotes3. Migrate to pharynx which can be transmitted during next

bite. 4. When fly bites, promastigotes enter blood and engulfed by

macrophages and form amastigotes. 5. These can infect other reticuloendothelial cells, especially

in spleen and liver.

46

Leishmania donovani

Transmission:

•Transmitted by sandflies.

• Animal reservoir (chiefly dogs, small carnivores, and rodents) in Africa, Middle East, and parts of China.

•Human reservoir in India. 

47

Leishmania donovani

Pathogenesis: Amastigotes kill reticuloendothelial cells, especially in liver, spleen, and bone marrow. Laboratory Diagnosis:• Amastigotes visible in bone marrow smear

• Serologic tests useful.

• Skin test indicates prior infection.

48

Leishmania donovani

Clinical Finding: Severe muscle wasting. visceral leishmaniasis develop a noticeable thickening,

stiffening and darkening of the eyelashes and eyebrows Jaundice Enlarged spleen and liver Skin ulcer

49

Profile view of a teenage boy suffering from visceral leishmaniasis(dumdum fever). The boy exhibits splenomegaly, distended abdomen and severe muscle wasting. CDC

50

Many children suffering from visceral leishmaniasis develop a noticeable thickening, stiffening and darkening of the eyelashes and eyebrows

A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.

52 Jaundiced hands of a visceral leishmaniasis patient

Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.

54Skin ulcer due to leishmaniasis, hand of Central American adult. CDC

Cutaneous leishmaniasis (Oriental sore, Delhi ulcer, Baghdad boil)

L. tropica multiplies locally encrusted ulcer with

satellite papules disfiguring scar

55

Cutaneous LeishmaniasisCutaneous Leishmaniasis Most common form Characterized by one or more sores, papules or

nodules on the skin Sores can change in size and appearance over time Often described as looking somewhat like a volcano

with a raised edge and central crater Sores are usually painless but can become painful if

secondarily infected Swollen lymph nodes may be present near the sores

(under the arm if the sores are on the arm or hand…)

Cutaneous LeishmaniasisCutaneous Leishmaniasis Most sores develop within a few weeks of the sandfly bite,

however they can appear up to months later

Skin sores of cutaneous leishmaniasis can heal on their own, but this can take months or even years

Sores can leave significant scars and be disfiguring if they occur on the face

If infection is from L. tropica it can spread to contiguous mucous membranes (upper lip to nose)

Cutaneous leishmaniasis of the face. 

A cutaneous leishmaniasis lesion on the arm.

60

Scar on skin of upper leg representing healed lesion of leishmaniasis CDC

61Girl with diffuse cutaneous leishmaniasis of the face which is responding to treatment

Mucocutaneous LeishmaniasisL. braziliensis

67

begins with a papule at the bite site, but then metastatic lesions form, usuallyat the mucocutaneous junction of the nose andmouth. Disfiguring granulomatous, ulcerating lesions destroy nasal cartilage but not adjacent hone. These lesions heal slowly, if at all. Death can occur from secondary infection.

Treatment and Prevention

DOC: Sodium stibogluconate-potent inhibitor of parasitic enzymes ,enhancer of cytokines

Amphotericin B: resistant strains

PREVENTION Protection from sandflies using netting,

protective clothing and insect repellents and insecticide spraying.

69

The Highest form of Deception is to Think or Believe….Everybody is Doing It!!!!!!

General Bison 70