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Definition
Major neglected disorder of poverty
– 5% of world population infected (~500 million) – Endemic in 100+ nations
• Killsonemillionannually
– Disproportionate impact on children
– 90% of malaria-related deaths in Sub-Saharan Africa
• Grouped with HIV and TB as the major killers of mankind
• Tremendous social, political, and economic impact |
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Definition
• Several species of the genus Plasmodium • Obligate intracellular pathogens
• Mosquito vector: female Anopheles spp.
• Medieval Italian, mala-aria = “bad air”
– “Roman fever,” associated with swamps and night air
• Humans are only reservoir |
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Definition
• Plasmodium falciparum
– Malignant, high parasitemia, CNS disease
• Plasmodium vivax – Latent course
• Plasmodium ovale – Latent course
• Plasmodium malariae – Chronic persistent |
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| Malaria types of infections |
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Definition
• P.falciparuminfectionisamedicalemergency • Complications of infection
– All species: anemia, hypoglycemia, splenomegaly, splenic rupture
– P. falciparum: cerebral malaria, blackwater fever (massive hemolysis and hemoglobinuria)
– P. vivax: splenic rupture
– P. malariae: immune complex disease, nephrotic syndrome, and renal failure |
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| Malaria what happens in the host |
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Definition
• Invasionoferythroidcells
– P. falciparum invades all erythroid cells
– P. vivax and P. ovale invade only reticulocytes – P. malariae invades only mature erythrocytes
• Merozoite receptors on red cell membrane – Duffy antigen receptor for P. vivax
– Several receptors for P. falciparum
• Innate resistance
– Duffy negative individuals resistant to P. vivax – Individuals with sickle cell anemia/trait
• Immunity to recurrent disease – Not sterile
– Found in individuals who have resided in endemic area for more than five years |
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Definition
made by examination of blood smear
– The Plasmodium species can be identified by various properties of the smear (parasite morphology, percentage of red blood cells infected, presence or absence of gametocytes, schizonts, ring forms, etc.) |
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| This is just some examples of various blood cell forms. You can see these various ring forms in these red blood cells. Here's one with schizonts and gametocytes in it. So this is exactly how the lab-- you do a thing called a thick and thin smear. The thick smear is done to identify the presence of malaria in the red blood cell. The thin smear is done to determine what specific malarial cell-- what parasite it is. |
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This is the life cycle. The thing I want to point out with the life cycle, mainly focus on the human side, over on this side. There are two portions to this. There's the liver stage, which is the exoerythrocytic stage. And there's the erythrocyte stage or human blood stage.
Liver cells can become infected. They continue to grow and multiply. Eventually, they form together and they form the schizont inside the liver cell. The schizont is going to rupture and it's going to cause release of all these malarial cells into the liver, which is going to get into the bloodstream.
We also have this cycle through these various ring forms, and trophozoites, and gametocytes in the blood. The problem is, treatment-wise, if you only treat the red cell stage, you kill all the parasites that are in the red blood cells, but you don't kill the liver stage, eventually these schizonts are going to rupture, release more malarial parasites into the blood. And you're going to get reinfected all over again. It's this release of these cells from the liver that cause the cyclic fevers that we see in patients. |
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Definition
• Digestion of hemoglobin
– Parasite enzymatically digests hemoglobin for nutrient substrates, resulting in diminished Hgb available for gas transport
• RBC lysis and sequestration result in progressive anemia
• Cytokine release (TNF, IFN-γ, and IL-1) further suppresses RBC production, stimulates inappropriate NO, and promotes endothelial dysfunction
• Diffuse endothelial activation and inflammatory states may promote diffuse coagulation (DIC) and capillary leak syndrome (SIRS)
• Sequestration and endothelial cyto-adherence result in progressive capillary bed occlusion, promoting end-organ dysfunction, splenomegaly, and thrombocytopenia
• Hepatocytesbecomedysfunctional,ladenwith pigments and cellular debris, resulting in eventual cholestatic liver dysfunction with metabolic and synthetic impairment
• Renalinjuryastubulesandcapillarytuftsbecome occluded, ischemic, and injured with free hemoglobin
• Chronicspleniccongestionandfibrosismayleadto splenic rupture (especially P. vivax)
• Metabolic disturbance |
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| Now, these are the fever spikes that we typically see with these various species. Vivax and ovale follow the same type of fever spike. You can see, like every couple of days, there's a fever spike. With Plasmodium malarie, you can see there's a fever spike like every three days. Falciparum basically causes continuous fever. It doesn't really follow a pattern. |
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| Different ways to diagnose malaria |
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Definition
• InfectederythrocytesonthickandthinGiemsa- stained blood smears
• Identificationisbasedon
– Shape and size of asexual parasites
– Shape and size of micro- and macrogametocytes – Modifications of infected RBCs
– Developmental stages in peripheral blood
– Presence of dots or clefts on RBCs
• PCR diagnosis, speciation, and determination of resistance pattern |
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Definition
• Sickle cell Hb results in premature RBC lysis and polymerization results in nutrient deprivation.
– HbS and C traits are protective against malaria • Duffyantigen(-)commoninAfrica,resistantto
P. vivax.
• α+-thalassemia protective by unclear mechanisms |
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| steps if suspicion of malaria |
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Definition
| perform thick and thin blood films and read in <12 hr is pos calculate parasite density, if neg repeat every 12 to 24 hr for 48 to 72 hr. severe malaria treat w intravenous quinidine plus tetracycline and doxycycline and or clindamycin. if uncomplicated malaria p.ovale/p. vivax treat w chloroquine. p. vivax treat w alovaquone-proguanil. if p. falciparum- chloroquine or oral quinine plus tetracycline and or doxycycline and or clindamycin |
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Definition
• Tick-borne malaria like illness
• Mainly infects cattle
• First human case in U.S. in 1969
• May have been the cause of the plague upon the cattle in the story of Moses and the Pharaoh.
• Babesia species – divergens: cattle – bovis: cattle
– equi: horses
– canis: dogs
– microti: mice
• Main cause in United States |
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Definition
• Endemic areas in United States
– Northeastern and northwestern United States – Particularly Long Island and Nantucket
• Occurs in Europe and Asia
• Vector is Ixodidae ticks
– Same ticks as Lyme disease
• White-footed mouse is the main reservoir
• May be transmitted in utero |
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| Here's its lifecycle. Once again, I don't expect you to memorize this. But I want you to notice again in humans there's a trophozoite phase and a merozoite phase in humans. |
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| Babesia Clinical Findings |
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Definition
• Acuteinfectionresemblesmalaria
– Series of severe chills, followed by fever, sweating, and profound prostration
• Presentwithfeverandfatigue
• Onexamenlargedliverandspleen,butlymph nodes are normal
– Relative bradycardia
• Labs:
– Decreased haptoglobin
– Anemia with increased reticulocytes – Decreased platelets are common |
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Definition
• Exam of Giemsa-stained thin and thick smears
– Resemble ring forms of
falciparum
• Indirect immunofluorescent titer for B. microti
– Active infection IgM titers >1:64.
– IgG titers >32 prior infection. |
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Definition
Asymptomatic – No treatment
Ill patients
– Atovaquone 750 mg BID plus azithromycin 500−100 mg day one then 250−1000 mg per day OR
– Clindamycin 600 mg TID or 300−600 mg QID plus quinine 650 mg TID (standard treatment)
– Treat for 7−10 days |
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Definition
• Platyhelminths (flatworms) – Trematodes (flukes)
– Cestodes (tapeworms)
• Nematodes (roundworms)
• Annelids (segmented roundworms)
– Leeches are the only ones of medical importance |
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Definition
• Leaf-shaped flatworms of various size
• Two anterior (oral) suckers and one ventral sucker
• Most are hermaphroditic
– Schistosomes are not
• All trematode life cycles include molluscan hosts
• Blood flukes
– Schistosoma mansoni
– Schistosoma japonicum
– Schistosoma haematobium
• Liver flukes
• Intestinal flukes
• Lung flukes |
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Definition
• 250 million people infected by these blood flukes annually
– Over one million die
• Three species that infect humans
– Schistosoma mansoni
• Seen in Africa, Middle East, South America,
Caribbean
– Schistosoma japonicum
• Seen in Japan
– Schistosoma haematobium
• Seen in Africa, especially Nile River valley |
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| The life cycle. Once again, don't expect you to memorize this in detail, but I want you to understand that you have this form that has to go in like snails. There's these sporocytes in snails. Then they are actually released by the snail. They become free-swimming, and that's how we get them. |
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| Intravascular Locations of schistosomiasis different species |
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Definition
• S. mansoni
– Inferior mesenteric venules
• S. japonicum
– Superior mesenteric venules
• S. haematobium
– Venules of the bladder |
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Term
| schistosome Adults live encopula |
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Definition
| The smaller, more slender female finds a mate and slips into the males gynecophoric canal to live out her life, literally, inside of the male. This life style is called living “encopula.” |
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| schistosoma and immunology |
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Definition
– Immune response to adult schistosomes are not generated because they absorb human antigens
– Hundreds to thousands of eggs produced daily • Half are released in feces or urine
• Half remain in the body – These may elicit inflammatory responses including delayed- type hypersensitivity and granuloma formation |
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Term
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Definition
• Areroundorovalwith appendages
• S.haematobium
– Spiny with a terminal
location
• S.mansoni
– Spiny with a lateral location
• S.japonicum
– Small, round with a lateral location |
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Definition
| S. mansoni, lateral spine |
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Definition
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Definition
| S. haematobium, terminal spine |
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Definition
– From cercariae that don’t completely penetrate the skin and die
– Swimmer’s itch, schistosomiasis |
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| Acute schistosomiasis infection |
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Definition
– Occurs 4−6 weeks after heavy primary infection
– Due to release of egg antigen • Antigen-antibody reaction
– Resembles serum sickness
• Have immune complex disposition, tissue damage resulting from action of complement and neutrophils
– Disease lasts for weeks with significant mortality |
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| Chronic schistosomiasis (gastrointestinal) |
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Definition
– Due to S. mansoni and S. japonicum
– Granulomatous responses to eggs (Th1)
– Mild mucohemorrhagic diarrhea initially
– Granulomatous hepatosplenomegaly
– Periportal fibrosis leads to portal hypertension, intractable ascites, and esophageal varices
– Intestinal polyposis leads to protein-losing enteropathy |
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| Chronic schistosomiasis (urinary tract) |
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Definition
– S. haematobium
– Dysuria, terminal hematuria initially
– Obstructive uropathy with pyelonephritis, gram-negative rod bacteremia leads to renal failure
– Chronic bacteriuria
– Bladder cancer |
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| Diagnosis/Treatment of schistosomiasis |
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Definition
• Detect eggs in the urine and feces
• Treatment
– Praziquantel |
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Definition
– Largest and most disgusting of intestinal parasites
– Long, ribbonlike helminths with no body cavity
– Adult divided into:
• Scolex (head)
• Neck and strobila (segmented body) |
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Definition
| – Attachment organ with sucking discs and hooklets in cestodes/tapeworms |
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Definition
-in cestodes/tapeworms
– Composed of proglottids (generated at neck)
– Self-contained, hermaphroditic reproductive units
– Older proglottids proceed posteriorly
– Male and female gonads mature and affect fertilization
– Gravid proglottid ruptures or disintegrates, releasing eggs |
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Definition
– Diphyllobothrium latum
– Taenia saginata
– Taenia solium |
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| Extraintestinal tapeworms |
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Definition
| – Echinococcus granulosus |
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Definition
• Caused by the cestode Diphyllobothrium latum
• Found primarily in temperate, subarctic regions
(Scandinavia, Russia, Japan, North America, Chile)
• Largest human tapeworm (to 25 meters)
• Reservoirs
– Domestic and wild animals are reservoirs
• Disease properties
– Usually no symptoms
– Megaloblastic anemia (worm utilizes vitamin B12)
• Diagnosis
– Detection of operculated eggs in feces |
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| hwo do humans get infected by tapeworms |
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Definition
| ingesting raw or undercooked infected meat |
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Definition
• Caused by the cestode Taenia saginata • Worldwide distribution
• Human is only definitive host
• Intermediatehostiscow
• Disease properties
– Dull, colicky abdominal pain – Symptoms usually mild
• Diagnosis
– Detection of eggs and/or proglottids in feces |
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Definition
• Caused by the cestode Taenia solium
• Found in Mexico, Latin America, Africa, Asia
• Human may be both definitive host and intermediate host
• Life cycle same as that of Taenia saginata – Except pig is usual intermediate host
• Disease properties – Tapeworm infection
• Same as for T. saginata infection
– Cysticercosis
• Central nervous system disease
• Seizures, focal deficits, hydrocephalus (ventricular cysts) • Ocular disease
• Diagnosis
– Detection of eggs and/or proglottids in feces
– Eggs of T. solium and T. saginata are indistinguishable
– Proglottids differ |
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Definition
As I said, this is the life cycle. The interesting thing here that I want to point out is the human two accidental intermediate host here. So human one here is the definitive host. It has the adult tapeworm, passes it off, the eggs in the stool. And then the ingestion of this Taenia solium eggs by fecal contamination, this is where you get the secondary infection. And these cysticerca develop in the brain, skeletal muscle, and in the eyes.
So we kind of get-- another human kind of gets in the pathway. Instead of passing this on to the pig and going through the life cycle again, we kind of get in the middle of this as an intermediate host. |
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Definition
• Usually proglottids and eggs passed in feces
• If eggs (eaten by human or carried to stomach by reverse peristalsis), mature and hatch
– Human may serve as intermediate host
• Larvae carried to tissues develop into cysticerci
• Cysts may develop in a variety of body tissues (especially brain and striated muscle) |
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