parasitic protozoa

A heterotroph is an organism that cannot produce its own food, instead taking nutrition from other sources of organic carbon, mainly plant or animal matter.

Apicomplexa, Flagellates, Amoebae

Malaria, Sleeping sickness, Toxoplasmosis, Chagas, Leishmaniosis, Amoebiosis

guarantees quick adaptation to new conditions/ host responses/ environmental challenges

Important parasitic Eugglenozoae are Trypanosoma and Leishmania

by longitudinal division

by pinocytosis

An amastigote is a protist cell that does not have visible external flagella or cilia. The term is used mainly to describe an intracellular phase in the life cycle of trypanosomes that replicate. It is also called the leishmanial stage since in Leishmania it is the form the parasite takes in the vertebrate host but occurs in all trypanosome genera.

(a) Trypomastigote (flagellum runs forward along surface: wave-like movements)

(b) Epimastigote

(c) Promastigote

(d) Amastigote

chagas disease

transmitted via reduviid bugs: Triatoma, Panstrongylus, Rhodnius

Trypanosomes enter the human host via a wound caused by the bite

Triatomine infection occurs via ingestion of bloodstream trypomastigotes during the blood meal. a) After ingestion, they transform into epimastigotes in the insect midgut. b) T. cruzi epimastigotes multiply and then c) migrate to the rectum where they differentiate into infective and nonreplicative metacyclic trypomastigotes.

T. cruzi is transmitted during blood meal, but via feces

• invade mononuclear phagocytes, cardiac muscle cells or neuroglia cells

• transform into amastigote stage (2µm)

• reproduce by fission

• swelling at the site of bite (2-3 weeks)

• preference for thin skin (head region/face, mouth) => kissing bug; Romana’s sign

• fever, respiratory symptoms

• swollen lymph nodes

• brain inflammation & myocarditis

Proliferative (acute) infection: limited by host immune response in 60% of all cases.

Cave: 40% of all cases develop chronic infection, persist over years, develop the typical Chagase disease-like symptoms

at least two serological tests based on different principles must be performed to detect anti-T. cruzi IgG antibodies, such as indirect immunofluorescence, hemagglutination, and enzyme-linked immunosorbent assay (ELISA) Cave: check blood transfusion!

- only symptomatic supportive treatment is performed in CD chronic phase

in acute phase: benznidazole and nifurtimox, are effective in the acute cases, in congenital cases, and in reactivation due to immunosuppression

- biventricular heart failure

- peripheral oedema, hepatomegaly

- ascites

- systemic and pulmonary embolisms

Sand fly

(A) After a sand fly takes its first infected blood meal (BM1), amastigotes are released into a blood bolus confined by a peritrophic matrix (PM). Amastigotes differentiate into procyclic promastigotes, a sluggishly dividing form that gives rise to nectomonad promastigotes (NPs). NPs exit a disintegrating PM and anchor to the midgut epithelium. NPs differentiate to leptomonad promastigotes (LPs). LPs divide efficiently, establishing the midgut infection. A few haptomonad promastigotes (HPs), whose origin remains uncertain, attach to the chitinous stomodeal valve (SV).

(B) The infected sand fly takes BM2, promoting LP multiplication. LPs differentiate into infectious nondividing metacyclic promastigotes (MPs).

(C) The sand fly takes another blood meal (BM3), egesting MPs into the host (transmission). Fresh blood causes MPs to differentiate into rapidly dividing retroleptomonad promastigotes (RPs). RPs represent the majority of midgut parasites over the next 3 days. RPs and residual LPs differentiate to metacyclic promastigotes, amplifying sand fly infectiousness

Anthroponosis refers to pathogens sourced from humans and can include human to non-human animal transmission but also human to human transmission.

= Reverse zoonosis

• a reservoir can be defined as one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population. (target = humans for L.)

• Populations in a reservoir may be the same or a different species as the target and may include vector species.

• As long as a reservoir constitutes a maintenance community and all populations within the maintenance community are directly or indirectly connected to each other, the size of the reservoir has no upper limit.

Athropode host

Vertebrate host

skin, viscera, ear cartilage

• Surface protease GP63 of the promastigotes binds and activates complement component C3

• C3 is cleaved into C3b and C3bi cleaved (unusual)

• Macrophages recognize with complement receptors the complement fragment and phagocytize the leishmania

=> elicits only weak activation of host immunity

Macrophages

acidic pH, lytic enzymes, oxidative effectors

They …

• delay the fusion of parasitophorous vacuole with lysosomes

• inhibit of phagolysosomal proteases by proton pump

• delay of host cell apoptosis (macrophage apoptosis)

• suppress toxic oxygen and nitrogen products example: superoxide dismutase of Leishmania degrades O2- to H2O2, which is then degraded by Leishmania catalase

• modulate macrophage cytokine production: IL-10 induction

• inhibit antigen presentation and T-cell stimulation (e.g. suppression of MHCII)

Neutrophils are a type of white blood cell (leukocytes)

The humoral immune response involves mainly B cells and takes place in blood and lymph.

• Activated B cells produce antibodies to a particular antigen.

• Memory B cells remain in the body after the immune response is over and provide immunity to pathogens bearing the antigen.

- L. have evolved ways to sustain a chronic infection (by manipulating the immune system/ hiding inside human cells in which antibodies can’t easily find and kill them).

- need for a T-cell response : T cells that can recognize and kill infected cells.

- but, a T-cell response is difficult to induce in humans.

- and, T cells are much tougher to study and measure than are antibodies

• Producing genetically engineered parasites that can infect, but dont grow well in humans (protection should be cross-species)

• Researchers produced a dermotropic live attenuated centrin gene deleted Leishmania major (LmCen−/−) vaccine (Centrin is a calcium binding protein and essential in the duplication of centrosomes)

• Currently: phase I safety trial in the United States planned to start next year

• practiced in middle East (bedouin people): pus from active lesions was also inoculated by excoriation of the recipient’s arm or thigh

• Initial clinical studies with L. major promastigotes in Iran, Israel, Uzbekistan, former USSR => divers outcomes depending on parasite survival/infectivity, side effects: cutaneous infection symptoms

• Later discovery => Th1 cells that produce IFN-γ, which is necessary for activation of macrophages and the production of nitric oxide (NO), the key effector molecule for destroying intracellular amastigotes