Week 10 Flashcards
Protozoa
eukaryotic, unicellular organisms composed of nucleus / nuclei and cytoplasm, generally colourless and motile, no chlorophyll, no cell wall, no fruiting bodies
genetic material (DNA) carried on well-defined chromosomes
within membrane-bound nucleus
cytoplasm differentiated into:
− outer layer - ectoplasm - in gel state of colloid
− inner layer - endoplasm - in sol state of colloid (bears
nucleus, mitochondria, Golgi bodies)
bodies of protozoa covered by trilaminar unit membrane
locomotion (if accomplished) carried out by special
ectoplasmic organelles
4 classes of protozoa contain important parasites of humans:
− Rhizopodea - amoebae (locomote by means of
pseudopodia)
− Zoomastigophorea - flagellates (locomote by flagella)
− Ciliatea - ciliates (locomote by cilia)
− Sporozoasidea (lack definite organelles of locomotion)
parasitic protozoa reproduce by asexual process - fission
some (sporozoans) have sexual and asexual reproduction
Groups of Protozoan Parasites
- Amoebozoa (Sarcodina) – amoeboid motion. Entamoeba histolytica which causes amoebic dysentery
- Flagellates (Mastigophora) – flagella. Trypanosomes which cause
African sleeping sickness and Leishmania which cause skin disease - Sporozoa (Apicomplexans) – non motile. Plasmodium falciparum
which causes malaria - Ciliophora – cilia. Balantidium coli which causes intestinal dysentery
Leishmaniasis
Leishmaniasis is caused by a protozoa parasite from >20 Leishmania sp.
It is transmitted to humans by the bite of infected female phlebotomine
sandflies
>90 sandfly species are known to transmit
Leishmania parasites
Approx 70 animal species, including humans, are natural reservoir hosts of Leishmania parasites
There are 3 main forms of the disease:
Cutaneous leishmaniasis (CL) or oriental sore, bush yaws is the most
common form of leishmaniasis and causes skin lesions, mainly ulcers, on exposed parts of the body e.g. face, arms, legs, leaving permanent scars and causing disability. An estimated 1 million new cases of CL occur each year worldwide. > 60% of new cases occur in: Afghanistan, Algeria, Brazil,
Colombia, Iran and Syria.
Visceral leishmaniasis (VL) or kala azar is fatal if left untreated.
Characterized by irregular bouts of fever, weight loss, splenomegaly,
hepatomegaly, anaemia. Highly endemic in the Indian subcontinent and East Africa. An estimated 300,000 new cases of VL occur each year worldwide. >90% of new cases occur in: Bangladesh, Brazil, Ethiopia, India, South
Sudan and Sudan.
Mucocutaneous leishmaniasis (MCL) or espundia leads to partial or total destruction of mucous membranes of the nose, mouth and throat cavities. Almost 90% of mucocutaneous leishmaniasis cases occurs in:
Bolivia, Brazil and Peru.
Transmission Leishmaniasis
Phlebotomine sandflies can become infected when taking a blood meal from a reservoir host
Hosts include infected humans, rodents, and dogs
Most cases of leishmaniases are zoonotic (transmitted to humans via the sandfly from animals), and humans become infected only when accidentally exposed to the natural transmission cycle.
Some cases are anthroponotic (human to human via the sandfly).
Leishmaniasis reproduction cycle
1 Sandfly takes a blood meal (injects promastigote into skin)
2 Promastigotes are phagocytized by macrophages or other types of mononuclear phagocytic cells
3 Promastigotes turn into amastigotes
4 Amastigotes multiply in cells of various tissues and infect other cells
5 Sandfly takes a blood meal (ingests macrophages infected with amastigotes)
6 Ingestion of parasitized cell
7 Amastigotes transform into promastigotes stage in the gut
8 Divide in the gut and migrate to proboscis
cycle repeats
2-4 in human stage
other stages in sandfly
Treatment of Leishmania
A major drug used to treat for leishmaniasis is Sodium
stibogluconate, a pentavalent antimony developed in 1930. Exact
mechanism of action is unknown but it may inhibit parasite
glycolysis or fatty acid beta-oxidation.
Amphotericin B is used to treat visceral forms unresponsive to
pentavalent antimony alone, or in cases resistant to sodium
stibogluconate.
A more recently-developed drug is miltefosine. This is a
membrane signaling pathway inhibitor. Can be taken orally and is
effective against visceral leishmaniasis
Epidemiology of Malaria
Malaria is caused by a Sporozoan
Genus: Plasmodium
Malaria is a life-threatening disease caused by Plasmodiumparasites
transmitted to people through the bites of infected mosquitoes
Plasmodium sp. infect and destroy erythrocytes with disease symptoms that include fever, headache, vomiting. The characteristic “paroxysm” (fever and chill) occurs when parasites are released periodically from erythrocytes
Death occurs by anaemia, clogged capillaries, cerebral malaria, pulmonary oedema, or kidney failure
According to the latest estimates released by the WHO in December 2014, there were approx 198 million cases of malaria and an estimated 584,000 deaths in 2013 with most deaths occurring in children living in Africa
Increased malaria prevention and control measures are reducing the malaria burden in many places
Malaria mortality rates have fallen by 47% globally since 2000, and by 54% in the WHO African Region
There are four parasite species that cause malaria in humans:
* Plasmodium falciparum
* Plasmodium vivax
* Plasmodium malariae
* Plasmodium ovale.
Transmission Malaria
Sporozoites are injected into human host with mosquito saliva when the mosquito takes its blood meal
An infective bite contains between 5-200 sporozoites
Infected mosquitoes have increased feeding rates
Quinine
The medicine from the bark is
known as the antimalarial,
quinine, which was one of the first
drugs available for the treatment
of malaria
Commonly used anti-malarial drugs
Artemisinin - derived from Chinese herb Artemisia annua - effective against
Cholaquine-resistant strains - induces oxidative stress. Has neurological side effects
Atovaquone/proguanil (Malarone) - blocks the parasitic electron ransport
chain/inhibits dihydrofolate reductase halting deoxythymidilate synthesis. Side effects include nausea, vomiting, headaches, mouth ulcers
Doxycycline - side effects include photosensitivity, yeast infections
Chloraquine - interferes with with haemozoin formation in lysosomes forming a freeheme-chloroquine complex that is highly toxic to the parasite. Side effects include blurred vision, nausea
Melfloquine (Lariam) - acts as a blood schizonticide. Can induce vivid dreams,
anxiety, nausea, dizziness psychosis
Malaria vaccine
Difficulties in developing a vaccine
- Four different species of Plasmodium cause malaria
- The parasite changes through several life stages, presenting a different subset of molecules for the immune system to combat at each stage
- The parasite has evolved strategies that allow it to hide from and misdirect the human immune system
(RTS,S) is a vaccine that acts against Plasmodium falciparum, the deadliest malaria parasite globally and the most prevalent in Africa.
Malaria Life cycle
1 Transmission of sporozoite into human trough bite by mosquito
2 Sporozoite enters liver cell and Exoerythrocytic stage begins (formation of Schizont and merozoites)
3 Infection of RBCs
4 Erythrocytic stage (Merozoites infect and reproduce in RBCs
5 Production of gametes
6 Transmission by bite from mosquitos, maturation of gametes within mosquito
7 fertilization then growth then development of sporozoites and then release of them
Cycle then repeats
Schizogony (One of two stages of Mosquito life cycle)
Sporogony (other stage)
schizogony
asexual phase
in humans as intermediate host
sporogony
sexual phase
in female anopheline mosquitoes as definitive host
Clinical significance Plasmodium
patient asymptomatic week or more after mosquito’s bite
(during preerythrocytic cycle in liver)
when erythrocytic cycle synchronised, rupture of RBCs,
release of merozoites, and malarial metabolites precipitate
paroxysms
typical paroxysm involves:
− prodromal period (brief, influenzalike)
− cold stage (shaking chill lasting 1 to 2 hours)
− fever stage (remittent fever quickly reaching 41oC to 42oC with warm and dry skin)
− terminal sweating stage (drop in body temperature to normal)
Plasmodium falciparum paroxysms
− chill stage less pronounced
− fever stage more prolonged and intensified
− sweating stage usually absent
Characteristic features of malaria
anaemia
− microcytic, hypochromic type
− caused by: direct RBC lysis
spleenic removal of infected and uninfected RBCs decreased incorporation of iron into haeme
increased fragility of RBCs
decreased RBC production from bone marrow
pigmentation of certain organs
− due to phagocytosis of malaria pigment
− constantly increases with age of infection
hypertrophy of liver and spleen
− due to congestion and increase in macrophage elements
other symptoms
− anorexia, nausea, vomiting
− diarrhoea, headache, lethargy
capillary occlusions
− characteristic in Plasmodium falciparum infection
− most serious in brain, leading to cerebral malaria (fatal if
untreated)
− often accompanied by hyperpyrexia, convulsion, coma,
acute renal and cardiac failure
