DD 02-28-14 11am-Noon Introduction to Parasites - Holmes Flashcards
Parasite defn.
an organism which lives upon or within another living organism at whose expense it obtains some advantage
Parasitology’s concern
= pathogenic protozoa (unicellular eukaryotes) & metazoa (multicellular eukaryotes)
Includes:
- helminths (worms)
- arthropods (insects)
Life Cycles of human parasites
Complex life cycles
- some involve development in one or more additional host species (definitive host + intermediate hosts)
Definitive host of a parasite
= the species in which the parasite undergoes sexual replication
Intermediate host of a parasite
= other species besides the definitive host, in which asexual replication occurs
Important factors in parasite’s life cycle
Ability of parasites to infect specific tissues (tropism)
Geographic occurrence of parasitic diseases
- often restricted by availability of host species
Protozoan vs. Worm parasites
Most protozoan parasites can replicate and increase their numbers in humans.
In contrast, many worms undergo development but do not replicate in humans
- worm burden in humans reflects intensity of their exposure to infection
Parasites & the Immune system
- Many parasites evade or subvert the protective immune responses of their hosts
- Damage to host tissues is often result of host immune responses
- Diseases caused by many parasites become clinically apparent when the number of parasites (the parasite burden) is high or when infection persists for long periods of time.
- Development of effective vaccines against major human parasitic diseases has been difficult & remains an important goal for world health
Selective toxicity in parasitic disease
- B/c parasitic diseases are caused by EUKARYOTIC pathogens, the biological bases for selective toxicity of anti-parasite drugs are quite different from anti-bacterial & anti-viral drugs
Dx of parasitic disease
- often made by direct examination of parasites in specimens or biopsy materials collected directly from patients
- Generally morphological criteria are much more helpful in parasitic disease than viral/bacterial disease
- Immunological tests (detection of specific Ags & Abs) & molecular diagnostic tests (for specific nucleic acid sequences) are sometimes helpful
Helminth groups causing human disease
- Roundworms/Nematodes
- Flatworms/Trematodes/Flukes
- Tapeworms/Cestodes
Roundworms/Nematodes - examples
Ascaris Pinworms Whipworms Hookworms Strongyloides Echinococcus Trichinella Filarial worms
Flatworms/Trematodes/Flukes - examples
Schistosomes
Lung fluke
Tapeworms/Cestodes - examples
beef tapeworm
pork tapeworm
fish tapeworm
Protozoan groups that are human parasites
- Amebas
- Flagellates
- Ciliates (Balantidium coli)
- Sporozoa
- Microsporidia
Amebas - example
Entamoeba histolytica
Flagellates - examples
Giardia
Trichomonas
Trypanosoma
Leishmania
Ciliates - example
Balantidium coli
Sporozoa - examples
Cryptosporidium
Cyclospora
Plasmodium
Toxoplasma
Microsporidia - examples
Enterocytozoon
Septata
Schistosomiasis - paradigm of helminthic infection - Transmission, Basic course
- transmitted to humans by exposure to contaminated fresh water
- -> causes acute manifestations & progresses to chronic disease affecting intestinal or urinary system
Epidemiology of Schistosomiasis
- affect ~200-300 million people a year globally
- causes 200,000 deaths per year globally
- 2nd only to malaria among parasitic diseases
Among infected people, - 120 million are symptomatic
- 20 million have severe disease
- 85% live in sub-Saharan Africa
Schistosomes
= trematodes/flatworms
- 3 species are widely distributed & cause most human infections
- 2 species have more restircted distribution
- Schistosomiasis in the US is only seen in immigrants or travelers
3 species of Schistosomes with wide distribution
Schistosoma mansoni
S. japonicum
S. haematobium
Schistosoma mansoni - location
primarily in Africa, South America and the Middle East
S. japonicum - location
primarily in China, the Philippines and Indonesia
S. haematobium - location
primarily in Africa and the Middle East
2 species of Schistosomes with restricted geographic distribution
Schistoma intercalatum (West Africa) Schistoma mekongi (Southeast Asia)
Life Cycle of Schistosomes
Complex life cycle
Eggs shed in feces/urine of infected humans
- -> hatch in fresh water
- -> release miracidia, which infect snails
Sporocysts develop in the snails
- -> free-swimming cercaria are released
- -> can penetrate human skin to initiate infection
Cercaria lose their tails & develop into schistosomulae in tissues of human host.
Schistosomulae gain access to circulation
- -> migrate to portal blood
- -> mature into adult worms
Adult worms migrate to mesenteric veins or venous plexus of bladder (depending on species)
–> mating –> eggs
Eggs produced circulate in venous blood to the liver & are also released into intestine or urinary bladder, depending on the anatomic location of adult worms.
–> Release of eggs into environment perpetuates infection cycle
(see pic in notes)
Schistosomes that migrate to & mate in the mesenteric vein
S. mansoni
S. japonicum
S. intercalatum
S. mekongi
–> eggs produces are released into intestines (or circulate to liver)
Schistosomes that migrate to & mate in the venous plexus of the bladder
primarily S. haematobium
–> eggs produces are released into urinary bladder (or circulate to liver)
Cercarial invasion into the skin
can cause dermatitis (swimmers itch) within 2-3 days
Acute phase of schistosomiasis
- aka Katayama fever
= a serum-sickness like illness - occurs 4-8 weeks after skin invasion
= occurs coincident w/ worm maturation & onset of oviposition - often accompanied by lymphadenopathy & hepatosplenomegaly
chronic stage of schistosomiasis
- involves granulamatous & fibrotic changes in liver or bladder (site depending on species)
= consequences of host rxns to deposited eggs
–> leads to formation of infiltrates containing large numbers of eosinophils & eventually to scarring
Severity of Schistosomiasis & Symptoms
Light infestations = may be asymptomatic Heavier infestations = often symptoms such as... For intestinal schistosomiasis: - diarrhea - abdominal pain - ascites For urinary schistosomiasis: - bloody urine (hematuria) - bladder cancer
Dx of Schistosomiasis
- microscopic examination of stool or urine for schistosome eggs w/ characteristic sizes & shapes
- detection of similar schistosome eggs in tissue biopsies
Major strategies for controlling schistosomiasis:
Public health education
- avoid contact w/ infected water
- build wells & latrines to provide potable water
- avoid contamination of environmental water sources
Molluscicides & environmentasl modification to control snail intermediate
Mass treatment of populations w/ anti-schistosome drugs (such as praziquantel, etc.),
Research on diagnostic tests, improved therapeutics, & vaccines for schistosomiasis
Even in regions where control of schistosomiasis has been effective, parasite has not been eliminated & transmission continues, albeit at lower frequency
Malaria as an important paradigm of protozoan infection - Overview
= the most important parasitic disease
- 4 species of protozoa in genus Plasmodium cause malaria in humans
Malaria - Epidemiology
- affects > 1 billion people a year
- causes 1-3 million deaths/year
- eliminated from US, Canada, Europe, Russia (except imported cases)
- Global malaria & resistance to anti-malarial drugs are still major problems
Four species of protozoa causing malaria in humans
Plasmodium genus
- P. vivax
- P. ovale
- P. malariae
- P. falciparum
Plasmodium vivax
widely distributed, from tropical to temperate zones
Plasmodium falciparum
- causes most of the malaria deaths
- primarily in tropics / subtropics
Life cycle of malaria parasites - Asexual Phase of Development
Infected mosquitos bite humans & inject sporozoites into the blood
After primary replication in liver…
- -> merozoites are released into blood
- -> infect erythrocytes
- -> undergo additional asexual replication
Gametes (macro- & micro-gametocytes) are
formed in some infected erythrocytes.
Asexual phase of development for malaria parasites occurs in…
- aka schizogony
- occurs in humans
Dormant phase of malaria in humans
- Sporozoites of all malaria parasites can infect liver cells & replicate
- BUT only P. vivax & P. ovale can establish a dormant hepatic phase w/ non-dividing
forms called hypnozoites that can initiate late relapses.
Life cycle of malaria parasites - Sexual Phase of Development
- aka sporogony
- occurs in infected mosquito
- Gametes fuse in intestine to form zygotes.
- Development of parasite in mosquitoes eventually leads to production of sporozoites in salivary gland.
- Introduction of sporozoites into susceptible human by bite of an infected mosquito initiates a repetition of the life cycle of the parasite.
Acquire immune response to malarial parasites
- Acquired immune responses that help to control the development of malaria parasites in humans are also shown.
Symptoms of malaria – associated with…
- primarily associated w/ rupture of infected RBCS & release of merozoites
P. falciparum – malaria pathogenesis
- invades erythrocytes of all ages & can therefore achieve highest parasitemia & mortality
P. vivax & P. ovale – malaria pathogenesis
- invade only young erythrocytes
P. malariae – malaria pathogenesis
- invades only old erythrocytes
Untreated patients with malaria & periodicity
Process often becomes synchronized
Fever paroxysms may have regular periodicity
- 48 hr for benign tertian malaria caused by P. vivax or P. ovale
- 72 hr. for quartan malaria caused by P. malariae
- 36-48 hr. for malignant tertian malaria caused by P. falciparum
Anemia in malaria
May be disproportionate to parasitemia
Results from…
- RBC lysis
- RBC phagocytosis by stimulated reticuloendothelial system
- RBC sequestration in enlarged spleen
- Depressed bone marrow function
Hemolysis can be extreme, resulting in hemoglobinuria (blackwater fever)
Physical examination findings in malaria patient
- jaundice
- hypotension
- tachycardia
- fever
- hepatosplenomegaly
P. falciparum infections – symptoms & mechanism
- vasodilation causes hypotension & inadequate blood supply to vital organs
- P. falciparum-infected RBCs bind to microvascular endothelium, which is especially significant in cerebral malaria (up to 50% mortality)
Malarial death - major cause in adults
- Multi-organ failure
With P. malariae infections – symptoms & mechanism
- immune complex deposition leading to glomerulonephritis is common
Immunity to malarial infection
- pt mounts immune response that makes subseqent episodes of symptomatic disease less severe
- Both B & T cell responses are involved
- W/in a few weeks of infection, stage specific anti-plasmodium antibodies are produced
- Natural immunity is short-lived
- Continual re-infection is required to maintain it
- People returning to endemic areas following long absence may thus be quite susceptible to re-infection
Diagnosis of malaria
- Usually by detection of asexual forms of parasites in stained thick or thin blood films
- Morphological features of intracellular parasites & infected erythrocytes are used to differentiate the 4 species from each other & from other protozoan that also can replicate in erythrocytes
- Rapid monoclonal Ab-based tests for the PfHRP2 antigen or for Plasmodium LDH antigens are also useful in diagnosis of P. falciparum infections
Splenic enlargement in malaria
- common in apparently healthy individuals w/ repeated infections
- often used to estimate prevalence of malaria in populations in endemic areas
Malaria & Selection of traits
- widespread & lethal nature of malaria has apparently selected for traits that protect against plasmodia but are otherwise undesirable
Includes:
- sickle cell anemia
- thalassemias
- glucose-6-phosphate dehydrogenase deficiency
Malaria & HbS (Sickle Cell)
- Parasites do not appear to thrive in Hb S associated w/ sickle cell disease, nor in certain other abnormal Hgb’s
Thalassemia & Malaria
- In thalassemia, there is increased production of fetal hemoglobin
- -> retards maturation of P. falciparum
G6PD deficiency & Malaria
- the oxidative stress may inhibit parasite growth
HLA-B53 & Malaria
- associated w/ recovery from falciparum malaria
- very common in West Africa
Prevention of malaria
- Minimize mosquito contact in endemic areas
- Efforts at mosquito control & malaria eradication during 1950’s & 1960’s by using DDT & drugs were eventually frustrated by concurrent appearance of DDT-resistant mosquitoes, cessation of DDT use due to its environmental effects, & development of drug resistant plasmodia
- Array of drugs for prophylaxis & treatment
- Extensive efforts to develop effective vaccines against various forms of malaria
