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Define UTI
=microbial invasion of any tissue of the urinary tract -extends from renal cortex -> urethral meatus -UTI you have sx (dysuria=painful urination, etc) -Asymptomatic bacteriuria= colonization of urinary tract in absence of sx (more than 10^5 colonies per ml urine) -facultative organisms of fecal origin are most common causes of UTIs
Define pyelonephritis
=inflammation and infection of the kidney -presents w/fever, chills, and flank pain -sx of lower urinary tract infection might be present -notable for systemic sx (fever, chills) vs cystitis no systemic sx
Define cystitis
=inflammation and infection limited to bladder and lower urinary tract -presents with dysuria, frequency, and uregency
Define urethritis
=presents w/pain, burning and discharge from urethra -consider STDs
What bacteria accounts for more than 90% of UTIs in pts with normal anatomic structures?
Who is at risk for UTIs caused by proteus mirabilis?
1. young boys 2. patients with stones
Young sexually active women are at risk for UTIs caused by what 2 bacteria?
1. E. coli 2. Staph saprophyticus
Name 3 types of bacteria/fungi that can cause UTIs in diabetics w/poor control.
1. Klebsiella 2. Group B strep 3. Candida
Pseudomonas is most likely to cause UTIs in what type of pts?
=pts treated w/antibiotics
Staph aureus causes UTIs in what types of pts?
=patients with underlying disease
What type of infection is the most common nosocomial infection
=UTIs -predispose pt to sepsis and shock
Name 2 modes of developing UTIs
1. Ascending infection -most common (over 90%) -usu preceded by periurethral or introital colonization -E.coli, other enterobacteriaceae, proteus, staph saprophyticus, enterococci, candida 2. Hematogenous infection after bacteremia -staph aueus, cryptococcus neoformans, coccidiodes immitis
Name 7 virulence factors of E.coli that are important for it to infect the urinary tract
1. K1 capsule -nephritogenic strains have this antiphagocytic capsule 2. Type 1 fimbriae -enable colonization urinary tract -mannose sensitive 3. Type 2 fimbriae -colonize upper urinary tract 4. Hemolysin 5. flagella 6. LPS 7. Aerobactin =siderophore which allows acquisition
What is the most important virulence factor for bacteria that cause UTIs?
=adherence factors -pili that mediate attachment 1. type 1 pili (mannose sensitive) 2. P pili 3. others
What is the major virulence factor for Proteus mirabilis to cause UTIs?
=urease -increases pH of urine from 7 to 9 -if pt w/UTI has alkaline urine -> think proteus -predisposes to struvite stone formation b/c alkaline urine promotes precipitation of phosphate, carbonate and magnesium -proteus can actually hide in stones and stones become permanent source of bacteria that make it hard to clear the infection
What is the most important virulence factor to enable Klebsiella to cause UTIs
-causes UTIs in poorly controlled diabetics -large capsule (made when glucose present)
What is the most important host defense to prevent UTIs?
=normal urinary flow
Name some mechanical factors predisposing host to UTIs.
1. Short urethras -explain why females get more UTIs 2. any obstruction to urine flow -BPH, neurogenic bladder, stones, strictures 3. Foreskin in males 4. Reflux 5. Urinary tract manipulation/mucosal injury -catheters
Name some different types of host factors that predispose to UTIs
1. Mechanical/anatomic factors 2. Genetic factors 3. Hormonal factors 4. behavioral factors 5. immunologic/tissue factors
Name some genetic factors associated with predisposition to develop UTIs
=variations in antigens express on vaginal epithelial cells (ex increased density of Rs for bacteria to adhere to) 1. HLA type 2. P blood group phenotype 3. ABO nonsecretor status
How does progesterone affect the urinary tract system
=hormonal factor that can predispose to UTIs -progesterone dilates the upper collecting system -> makes it easier for organisms to reach the kidneys -also decreases peristalsis -increased progesterone levels during pregnancy
Why is the kidney an immunologic desert?
-b/c complement and PMNs do not work in the medulla of the kidney -predisposes to developing UTIs
Name some host behaviors that predispose to UTIs.
1. sexual intercourse 2. anal sex 3. diaphragm/spermicide -changes vaginal flora 4. voiding practices 5. condom/foley catheters -breaking normal mechanical barriers
Name some host factors that help prevent the development of UTIs.
1. Normal urine flow -most impt 2. urine osmolality, acid pH 3. mucosal integrity and bactericidal activity 4. inhibitors of adherence -tamm-Horsfall protein -bladder mucopolysaccharide -secretory IgA 5. prostatic secretions 6. low vaginal pH
What is the fxn of the Tamm-Hosfall protein?
=protein that everyone secretes as part of host defense against UTIs -acts as mimick Rs for bacteria -bacteria bind to this protein instead of bindins to your cells -you urinate the bound bacteria out
What are diagnostic criteria for a UTI?
1. Pyuria (=WBCs in urine) AND 2. Bacteriuria -usu more than 10^5 colonies per ml urine -cystitis only need 10^2 colonies/ml urine
What sign indicates kidney involvement in a UTI?
=white blood cell casts in the urine
Name some complications of untreated UTIs
1. Sepsis 2. low birth wt infants/premature labor 3. progressive renal parenchymal loss/renal scarring 4. renal calculi 5. perinephric/renal abscesses 6. prostatitis
How do we treat UTIs?
1. Relieve obstruction/correct the correctable 2. Antibiotics that concentrate in the urine -septa -quinolones -cephalosporins -impt to tx UTIs in pregnant women 3. Duration of therapy depends on level of UTI -cystitis: 3-5 days antiobiotics -pyelonephritis: 2 weeks
What is the infective agent that causes malaria?
=parasite protozoan Plasmodium -5 species can cause: 1. P. falciparum 2. P. vivax 3. P. ovale 4. P. malariae 5. P. knowlesi -found only in Indonesia
Define Plasmodium falciparum
=protozoan parasite -can cause malaria -causes most deadly and serious infections -infects all ages of RBCS -> higher parasitemia -mature trophozites and schizonts are sequestered in microvascular system -> tissue ischemia -widespread drug resistance to chloroquine and Fansidar
Which Plasmodium causes most deadly and severe malaria infections?
=Plasmodium falciparum
Define Plasmodium vivax
=type of protozoan parasite -can cause malaria -usu does NOT cause life-threatening infections -infects only reticulocytes -produces hypnozoites that are latent in the liver -relapses can occur up to 5 yrs after infection -plasmodium vivax uses duffy R to get into RBCS -> duffy neg individual NOT infected -emerging resistance in chlorquine in Indonesia
Name 2 Plasmodium that only infect reticulocytes
-reticulocytes=immature RBCs 1. P. vivax 2. P. ovale
Name 2 Plasmodium species that are hypnozoites
hypnozoites=able to remain latent in liver and infect later 1. P. vivax 2. P. ovale
What's the major difference between Plasmodium ovale and Plasmodium vivax
Plasmodium vivax -uses Duffy blood R to enter RBCs -can't infect Duffy negative individuals Plasmodium ovale -similar to vivax in life cycle, appearance tx, clinical presentation and tx -but it CAN infect Duffy blood group negative individuals
Define Plasmodium malariae
=protozoan parasite -can cause malaria -does NOT cause life-threatening infections -causes low grade parasitemia that can persist for over 40 yrs -can cause glomerulonephritis -infects mature RBCs -uncommon
How many people in malaria endemic regions are symptomatic?
-about 20% of infected individuals -asymptomatic parasitemic individuals may be impt resevoirs for continued transmission
Which species of Plasmodium undergoes antigenic variation to cause persistent infection
=Plasmodium falciparum
Who is more likely at risk for serious malaria infections/complications in malaria endemic regions
1. children -most likely to die -sx: fever, irritability, poor feeding, vomiting, diarrhea, convulsions 2. pregnant women -Plasmodium able to infect the placenta -congenital malaria -women with multiple pregnancies less likely to have severe malaria infection (b/c humoral immunity against PfEMP1)
True or false: prophylaxis against malaria is guaranteed to prevent malaria infection
-false -malaria is most common imported acute febrile illness in US
Describe the life cycle of Plasmodium parasites
-life cycle occurs in 2 stages 1. Asexual (schizogony stage) -human liver and RBCs 2. Sexual (sporogony) stage -occurs in Anopheles mosquito 1. Bite of female anopheles mosquito inoculates sporozoites 2. Sporozoites infect hepatocyte -> prolif into merozoites 3. Merozoites rupture from hepatocytes and invade RBCs 4. asexual cycle merozoites develop into trophozoites (feeding stages) -> then turn into schizonts 5. sexual cycle develop into gametocytes -> sexual cycle completed in mosquito
What is the vector for malaria infections?
=female Anopheles mosquito -bites occur between dusk and dawn -during a bite female anopheles mosquito inoculates sporozoites
Define trophozoites
=feeding stage of Plasmodium in infected RBCs -eat hemoglobin -parasite has to sequester the heme group away from body of parasite (othersie it gets oxidized) -parasite polymerizes heme into crystal form (pigment seen on RBCs) -antimalarial drugs like chlorquine prevent polymerization of heme -mature trophozoites turn into schizonts -> release more merozoites that can infect more RBCs
Which type of parasite uses the Duffy blood group antigen as a receptor to infect RBCs?
=Plasmodium vivax -so plasmodium vivax can't infect Duffy blood group negative individuals -West Africans have evolved NOT to have Duffy Ag on RBCs
What forms of Plasmodium are peripherally sequestered?
=mature trophozoites and schizonts of P. falciparum -adhere to postcapillary endothelium in various organs (brain, heart, mesentery, lungs, kidney, placenta) to cause complications of malaria infection
How do you diagnose malaria?
1. Look for parasite-infected RBCs with thick or thin Giemsa stained blood smears 2. Level of parasitemia should be quantified 3. It is important to differentiate the species of Plasmodium because early tx is critical and depends on species
Which species of Plasmodium is most resistant to chlorquine?
=Plasmodium falciprum
Describe the unique features of Plasmodium falciparum in peripheral blood
-causes most serious malarial infection -infects all ages of RBCs -no RBC pigment -Can see multiple rings in 1 RBC -no mature trophozoite form -no schizonts -gametocytes are banana shaped
Describe the unique features of plasmodium vivax on peripheral blood
-infects reticulocytes -has RBC pigment -ringed trophozoite form has single thick ring -mature trophozoite form present in amoeboid forms -schizonts present -gametocytes are round, filled cells
True or false: cyclic fever is pathognomonic for malaria
-false! -there is no pathognomonic malaria sx or sign -cyclic fevers are atypical -usu see intermittent, irregular fevers
Describe the classic presentation of malaria
-Periodic fever paroxysms are composed of 4 stages 1. prodrome -malaise, myalgias, viral like syndrome 2. Cold stage -shaking chills 3. Hot stage -sudden fever that lasts for hrs -tachycardia, hypotension, headache, nausea, abdominal pain, delirium 4. Sweating stage -diaphoresis, resolution of fever, severe fatigue, sleep
Name the 4 classic sx of malaria
1. anemia 2. jaundice 3. splenomegaly 4. fever
Describe the lab findings of malaria.
1. Plasmodium parasites in RBCs on peripheral blood smear 2. Chem panel -elevated BUN/Cr -hyponatriemia, hypoglycemia -evidence of hemolysis 3. Urinalysis -presence of protein and bilirubin 4. CBC -anemia, thrombocytopenia, infected RBCs, reticulocytosis
True or false: all species of Plasmodium can cause anemia, dehydration, electrolyte abnormalities, and acute splenic rupture
Name some complications of malaria
1. Anemia, dehydration, electrolyte abnormalities, acute splenic rupture -can be caused by all species of Plasmodium that cause malaria 2. Severe anemia 3. Coma 4. Respiratory distress 5. renal failure 6. seizures and other neurological problems
What Ag allows for Plasmodium falciparum to cause microvascular disease?
=PfEMP1 -allows for cytoadherence to endothelial cells -> microvascular sequestration in brain, kidney, lungs -also provides antigenic variation -concentrated in knobs Plasmodium falciparum puts up on infected RBCs
Nonspecific signs of malaria include all of the following except: a. fever b. malaise c. renal failure d. watery diarrhea e. headache
=renal failure -results from microvascular sequestration, hypovolemia, and hemolysis
Describe cerebral malaria
-usu manifests as: 1. impaired consciousness 2. +/- seizures 3. fatal if untreated 4. can rapidly progress to coma and death 5. Even with tx, 15% of kids and 20% of adults die 6. Some who survive may have persistent neurologic abnormalities
Describe immunity to malaria
1. There is no complete immunity 2. immunity is species specific 3. immunity involves both antibodies and cell-mediated -both develop after repeated infection 4. immunity fardes w/in weeks-months after eradication of organism or leaving the endemic region 5. severe complications are more common in non-immune persons
Name some genetic conditions that have been selected for because the improve survival against malaria infection
1. Sickle cell trait 2. Lack of Duffy blood group 3. G6PD deficiency 4. Thalassemias 5. SE Asian ovalocytosis
Where is drug resistant Plasmodium falciparum found?
-every country where P. falciparum found EXCEPT 1. Dominican Republic 2. Haiti 3. Central America North of Panama canal 4. Egypt 5. Most countries of middle east
How long should people travelers take malarial chemoprophylaxis?
1.1-2 weeks before travel to endemic areas 2. during travel to malaria endemic areas 3. 4 weeks after leaving malaria endemic areas
Name some drugs used for malarial chemoprophylaxis
1. chlorquine 2. mefloquine 3. primaquine
Which anti-malarial medication can precipitate severe hemolytic anemia individuals w/G6PD deficiency
How does Primaquine work?
=anti-malarial medication -tissue schizonticide (kills the parasite forms in the liver) -prevents relapses of P. vivax and P. ovale -can precipitate severe hemolytic anemia in individuals with G6PD def
How does Chlorquine work?
=anti-malarial medication -kills blood forms of Plasmodium -significant resistance w/P. falciparum
What is the drug of choice w/severe malarial infections?
When does malaria transmission occur?
-between dusk and down -this is why bed nets are advised
Describe Babesiosis
=apicomplexan parasite -has superficial resemblance to Plasmodium -endemic worldwide -doesn't need to polymerize heme (won't see pigment in RBCs vs Plasmodium) -disease acquired through tick bite -infection often asymptomatic -fulminant disease seen in immunocompromised -clinical symptomatic infection may look like malaria
True or false: chlorquine can be used to treat babesiosis infections.
-false! -chlorquine doesn't work b/c no polymerization of heme (vs Plasmodium)
Define apicoplast
=modified organelle found in Plasmodium -2nd place where there is independent DNA replication and protein synthesis -some anti-malarial drugs like tetracycline are able to target this as well as parasite itself
True or false: protozoan populations expand in a host b/c they reproduce asexually
True or false: the severity of disease in a protozoan infections depends on the infecting dose.
-false -it does NOT depend on infecting dose -can get full blown infection w/ingestion of just a few parasites
Which intestinal protozoan is an apicomplexan and has a sexual phase in its life cycle?
=Cryptosporidium parvum
What is the resevoir of Eneamoeba histolytica?
=intestinal protozoa -human resevoir ONLY -fecal-oral transmission
Who is at greatest risk of Entamoeba histolytica infections?
-Worldwide distribution -highest incidence in developing countries -people at greatest risk 1. male homosexuals 2. travelers to developing countries 3. recent immigrants from developing countries 4. instiutionalized populations
Is Entamoeba histolytica an intestinal protoza or a helminth?
=intestinal protozoa
Name 3 intestinal protozoan species
1. Entamoeba histolytica 2. Giardia lamblia 3. Cryptosporidium -all have fecal to oral transmission -Giardia and crypto tend to be more water-borne -Entamoeba tends to be more food born -all 3 can be sexually transmitted
What's the difference between Entamoeba histolytica and Entamoeba dispar
=intestinal protozoa that are morphologically indistinguishable -histolytica is pathogenic and dispar is nonpathogenic Differences 1. E. dispar is killed by complement 2. E. dispar can have up to 8 nuclei in cyst form
Describe the life cycle of Entamoeba histolytica
=pathogenic intestinal protozoa 1. Mature cysts passed in feces 2. Cysts ingested (by fecal contamination of food, water, hands) 3. Excystation in SI -trophozoites get out of cysts 4. Trophozoites migrate to large intestine 5. Trophozoites multiply by binary fission, form new cysts and get passed in feces
What is the main form of Entamoeba histolytica that gets transmitted to infect new hosts?
=cysts -passed in feces -resistant to environmental degradation (H20, Cl-); can survive days to weeks -mature cysts ingested, then inside new host trophozoites come out of cyst, multiply, and make new cysts -cyst wall contains chitin -can be killed by: 1. heat 2. removed by filtration -mature cysts have 4 nuclei -cysts spherical and often w/halo
Name 3 clinical syndromes associated with Entamoeba histolytica
1. Asymptomatic infection -most people 2. Amebic dystery -acute colitis or fulminant colitis -bloody diarrhea, abdominal pain -due to trophozoites invading intestinal mucosa 3. Extraintestinal amebiasis -distant abscesses, esp in: 1. liver 2. lungs 3. cutaneous lesions
True or false: all people with Entamoeba histolytica will have invasive disease
-false -it can cause invasive disease, but most have a non-invasive, asymptomatic infection where they pass cysts in their stools -vs E. dispar never causes invasive disease
Which intestinal protozoa can ingest RBCs in its trophozoite form?
=Entamoeba histolytica -RBC ingestion pathognomic -RBC ingestion can be used to distinguish between E. histolytica and nonpathogenic E. dispar -motile, feeding stage in colon -anaerobic -can be killed w/metronidazole -can lyse tissue, cause invasive disease (severe bloody diarrhea, extraintestinal abscesses in liver, lungs) -can't survive in the environment
How is amoebiasis diagnosed?
1. should be considered in cases of protracted diarrhea or dystery 2. Rule out other causes -bacterial diarrhea -inflammatory bowel disease 3. Serology -seen w/invasive amebiasis and abscesses -Ab produced is NOT protective 4. Look for cysts in stool -usu need 3 stool samples 5. Ask about travel hx
Describe amebic dysentery
=invasive disease caused by Entamoeba histolytica -Sx: 1. severe bloody diarrhea 2. abdominal pain 3. flasked shaped ulcers on sigmoidoscopy -ulcers may cause 2nd bacterial infections 4. fever 5. wt loss Dx with serology, 3 stools positive for cysts
Which intestinal protozoa likes to cause liver abscesses?
=Entamoeba histolytica -Sx: 1. liver tenderness 2. hepatomegaly 3. fever 4. +/- diarrhea, wt loss (amoebiasis) -trophozoites migrate to liver via portal vein -dx by serology -tx with metronidazole
Which intestinal protozoa has a high incidence in day care centers?
=Giardia lamblia -high rate of person-person transmission
How is at increased risk of Giardia lamblia infection?
=intestinal protozoa -endemic and epidemic disease -worldwide distribution -Groups at risk: 1.male homosexuals 2. kids in daycare 3. food handlers 4. institutionalized pts 5. travelers to endemic areas 6. hikers and campers who don't purify their water
A hiker comes in complaining of 2 days of abdominal pain, diarrhea, bloating, flatulence with malordorous stools. He went camping over the weekend in the Rockies and drank water from a stream when thrisy. He most likely has____________.
=Girardia lamblia -intestinal protozoa -most infections are asymptomatic (40-60%)
Which intestinal protoza has resevoir in humans, beavers, muskrats, dogs?
=Giardia lamblia -fecal-oral route -cysts get into people by ingestion of contaminated water, food -high rate of person-person transmission
Describe the life cycle of Giardia lambia
1. Ingestion of cysts in contaminated water 2. Excystation of trophozoites in SI -1 cyst -> 2 trophozoites 3. Multiply by binary fission in small bowel 4. Encystation 5. Passed in stool
Describe the morphologic features of Giardia lamblia
=intestinal protozoa Cyst -oval; 4 nuclei -infective form -gives rise to 2 trophozoites Trophozoite -8 flagella -ventral disk (adherence to intestinal mucosa) -no mitochondria -looks like it has 2 eyes
How are Giardia lamblia and Entamoeba histolytica similar? Different?
Similar 1. Intestinal protozoa 2. Infective form is cysts 3. Trophozoite has no mitochondria 4. Can tx w/metronidazole Different 1. Trophozoite morphology 2. Giardia trophozoite in SI, Entamoeba trophozoite in colon
How does Giardia lamblia attach to the small intestine epithelial cells?
-via ventral disk -interdigitates w/intestinal epithelium
True or false: people can be reinfected with the same Giardia lamblia parasite
-true -b/c Giardia lamblia can undergo antigenic variation -> allows it to evade immune system
Name 5 clinical syndrome associated w/Giardia lamblia infection
=intestinal protozoa 1. Asymptomatic infection 2. Partial villous atrophy -severe infection 3. Protracted diarrhea and or steatorrhea -can have flatulence, malodorous stools 4. Malabsorption syndrome -steatorrhea, dissaccharide def, B12 mal 5. Lactase deficiency -severe disease -may persist after tx
Which of the following immune disorders is associated with increased risk of symptomatic infection of Giardia lamblia a. hypogammaglobulinemia 2. selective IgA def 3. HIV (decreased CD4 T cells)
How do you diagnose Giardia lamblia infecton?
-stool sample positive for cysts -detect organism using Ag
Which intestinal parasite can cause life threatening infections in immunodeficient patients?
Describe the life cycle of Cryptosporidium parvum
=intestinal protozoa -fecal oral transmission 1. Oocysts ingested by host by drinking contaminated water 2. Excystation 3. Fuse to intestinal villi but ONLY invade brush border 4. undergo both asexual and sexual multiplication 5. Sexual multiplication generates new oocysts and passed in feces
Which intestinal protozoa fuses to brush border of intestinal epithelial cells but does NOT invade further?
=Cryptosporidium parvum -Giardia=non-invasive -Entamoeba histolytica =invasive (can migrate to liver, etc)
Which intestinal protozoan is acid fast?
=Cryptosporidium parvum -can also be stained w/auramine
Name 2 clinical syndromes associated with Cryptosporidium parvum
1. Immunocompetent host -self-limited, mild disease -watery diarrhea, anorexia, wt loss 2. Immunodeficient host -severe protracted diarrhea -can be fatal in AIDs pts
How do you diagnose and tx Cryptosporidium infection?
=intestinal protozoa Dx 1. Oocyst in stool -stain w/acid fast, auramine Tx: 1. Nitazoxanide -good for kids -not useful for HIV/AIDs pts
Define protozoa
=single celled eukaryotic organisms -can undergo asexual reproduction -severity of disease NOT related to infecting dose of organism (b/c it can expand in host) -can be parasites of humans -2 impt phyla 1. Arcomastigophora =amoeboid and flagellated protozoans -motile 2. Apicomplexan =intracellular parsites -nonmotile
Describe the group characteristics of Apicomplexans. Name 5 impt species
=phyla of parasitic protozoa -all intracellular parasites -all nonmotile -at apex of cells, have special complex of organelles that allows them to penetrate host cells -life cycles w/both sexual AND asexual reproductoin -Members 1. Toxoplasma 2. Plasmodium 3. Cryptosporidium 4. Cyclospora 5. Babesia
Name some members of the phyla sarcomastigophora
-parasites =amoeboid or flagellated protzoa -motile 1. Giardia 2. Trichomonas vaginalis 3. Trypanosoma 3. Leishmania 4. Entamoeba histolytica
The infective agent of African sleeping sickness is ______.
=Trypanosoma brucei -protozoan -2 subspecies, found in 2 diff regions of Africa 1. T. brucei rhodesiense -East Africa 2. T. brucei gambiense -West Africa
How is African Sleeping sickness transmitted?
-vector=tsete fly -infective agent=T. brucei rhodesiense and T. bruci gambiense
Define African Sleeping sickness
=caused by parasite protozoa Trypanosoma brucei rhodesiense and gambiense -waves of parasitemia -untxed results in: 1. CNS involvement 2. death -Rhodesiense causes more rapid and fatal disease -transmitted by Tsete fly
What is the infective agent of Chagas disease?
=Trypanosoma cruzi -parasitic motile protozoa -trasmitted by Reduviid bug (kissing bug) -3 disease phases
How is Trypanosoma cruzi transmitted?
-parasitic protozoa that causes Chagas disease in South America -transmitted by bit of Reduviid bug (kissing bug) -infected bug carrying Trypanosoma cruzi bites then defecates on skin -tryp rubbed into bite, mouth,eyes
Describe the 3 stages of Chagas disease
-cause=Trypanosoma cruzi 1. Acute -Romana's sign: acute swelling near one eye -fatigue, fever, wt loss -4-8 wks sx -only 1% infected show acute sx 2. Intermediate phase -no sx -organisms proliferating in mphages (heart, GI) 3. Chronic phase -10-20 yrs later -1/3 of infected pts -enlarged heart, heart failure, cardiac arrest -megaesophagus, megacolon -> difficulty swallowing food, constipation
How do we treat Chagas disease?
-no vaccines -tx acute infections with: 1. nifurtimox 2. benznidazole -chronic infections 1. supportive measures 2. sx relief
Define Leishmania
=intracellular protozoan parasites -live in phagolysosome of mphages -transmitted by bit of sand fly -can cause: 1. cutaneous leishmaniasis 2. mucocutaneous leishmaniasis 3. visceral leishmaniasis -organism disseminates in blood -infects reticuloendothelial organs -disease severity depends on species and geographic distribution -some species able to grow at body temp (ex. L. donovani) others not (species that cause cutaneous Leishmaniasis)
Where is the infecting organism causing mucocutaneous leishmaniasis come from?
=Leishmania braziliensis -found in rural Central and South America -can cause disfiguring lesions of oronasopharyngeal mucosa
What is the vector for Babesia
=causes malaria-like illness that can be endemic to US -vector=tick -looks like plasmodium infection but no schizonts are produced -most infections asx -life cycle occurs exclusively in RBCs
Define cyclospora
=parasitic protozoa -can cause watery diarrhea that can be severe, long, and relapsing -seen in tropical and subtropical locations -cause of food-borne epidemics in US -oocysts can be stained acid-fast -Tx: 1. Trimethoprim-sulf combo
Define helminths
=worms -can be parasitic -group characteristics 1. multicellular 2. complex metamorphoses 3. migrate w/in host 4. do NOT multiply in human host -infecting dose correlates w/severity of disease -2 types: 1. Playhemlenthes (flatworms) 2. Nematoda (roundworms)
Define Platyhelminthes
=flat worms -can be parasitic -group characteristics 1. dorsoventrally flattened 2. no body cavity 3. usu lack skeletal, circulatory and respiratory systems -can be divided into: 1. Cestoda (tape worms) 2. Trematoda (flukes)
Name 4 types of tape worms that can cause human disease
=subclass of flatworms -parasitic 1. Taenia saginata 2. Taenia solium 3. Diphyllobothrium latum 4. Echinococcus
Name 6 types of flukes that can cause disease in humans
=subclass of flatworms -parasitic -Blood flukes 1. Schistosoma mansoni 2. Schistosoma japonicum 3. Schistosoma haematobium Tissue Flukes 1. Fasciola hepatica 2. Clonorchis (Opisthorchis) 3. Paragonimus westermani
What is the resevoir of Trichinella spiralis?
=parasitic roundworm =domestic pigs -host usu infected by ingesting raw or undercooked meat containing viable larvae
Define Trichinella spiralis
=parasitic roundworm -resevoir: pigs -infection: ingest undercooked meat w/viable larvae in it -larvae develop into adults in intestine -female worms shed larvae into blood and lymphatics -larvae can encyst in muscle cells -various clinical syndromes are associated
Describe the clinical syndromes associated with Trichinella spiralis
=round worm; infection via ingesting undercooked meat w/larvae in it 1. Asymptomatic infections 2. Intestinal invasion -diarrhea, vomiting, abd pain -larval migration into muscles -> fever, splinter hemorrhages, eosinophilia, rash, facial edema 3. Life threatening complications -myocarditis, pneumonitis, CNS infection -no specific tx -early mmebendazole can help reduce # of larvae
Describe Dracunculus medinesis (Guinea worm)
=round worm -found in rural Africa -ingestion of water contaminated w/larvae -once ingested penetrate stomach and intestinal wall, get into abd cavity and retroperitoneal space -> mature into adults -> mate -> females migrate toward skin surface -1 yr after infection female causes skin blister on leg -> when skin comes in contact with H20 -> release eggs -No specific tx -best is to worm control (slowly pulling out worm as it emerges and prevent from releasing larvae into water)
Where do filarial worms like to live?
=lymphatics and subcutaneous tissues -roundworms -8 infective types -Bite of infected insect transmits larve of worms to new host -the can migrate, develop in adults, live for years -infect new arthropods when they bite
Name 2 species that can cause lymphatic filariasis
=elephantiasis -parasitic roundworms 1. Wuchereria bancrofti -found in tropical regions worldwide 2. Brugia malai -found in Asia -most infections are asymptomatic -can cause lymphedema and elephantiasis
Define onchocerca volvulus
=round warm parasite -found in Africa, Latin America, Middle East -vector: black fly -live in nodules in subcutaneous tissues -can cause eye infections that lead to blindness -ivermectin (antihelminth agent) is given yearly in endemic areas to prevent infections causing blindness
Helminths are unable to undergo direct replication w/in definitive host EXCEPT _________.
=strongyloides -so infecting dose correlates w/severity of disease -but tx of helminth infections are difficult b/c antibiotics inhibiting macromolecular synthesis are NOT effective
True or false: helminths are able to elicit protective immunity only after many years/decades of exposure
-true -immunity is usu only partial
Are helminth infections more likely to cause morbidity or mortality?
-morbidity -infections associated w/chronic sequelade from persistent infection and accumulation of parasites -longterm infections can exacerbate nutrition -disease may result from host's immune response attempt to control parasites that causes more damage -disease severity related to worm burden
True or false: helminth infections are often associated w/eosinophilia
How do infections with microparasites differ from infections with macroparasites
Microparasites -infections can persist via antigenic variation and divergence Macroparasites -antigenic variation is very slow -so host factors most impt in immunity
True or false: host acquisition of immunity to helminth infection is age-dependent
-true -often comes after years even decades of exposure -immunity is only partial -can also have concomitant immunity =where pt has established worm load but host is protected against newly invading larvae
Name 3 factors accounting for differences in heavy vs light helminth infections:
1. differences in exposure 2. susceptibility to infection (based mostly on host factors) 3. ability to mount effective immunological responses
Name 3 impt strategies for helminths to resist host defenses
1. Avoid initial induction of damaging host response -helminths take up host Ags to make them look less foreign -interfere w/host Ag processing 2. Neutralize parts of the immune system -Ig cleaving proteases -interfere w/complement -interfere w/specific T cells subsets 3. Short acting -thick coats of helminths -antioxidant enzymes to counteract oxdiative burst
Describe the group characteristics of platyhelminthes
=flat worms 1. Hermaphrodites -Except: schistosomes 2. Severity of disease related to worm burden 3. 2 main subtypes -trematodes (flukes) -cestodes (tapeworms)
What is the difference between blood flukes and tissue flukes?
=type of flatworms (platyhelminthes) -blood flukes 1. blood flukes= snail host and human host 2. tissue flukes =have a snail host, a second host, and a human host
Name 3 impt species of Schistosoma
=helminths; platyhelminthes (flat worms); trematodes; blood flukes 1. S. mansoni 2. S. japonicum 3. S. haematobium
Describe the life cycle of schistosomes
=blood flukes; flatworms 1. Eggs released in feces or urine 2. Eggs hatch -> miracidia swim and get into snails (intermediate host) and develop in snails 3. get released into fresh water and penetrate skin of human host 4. Migrate through tissues and reside in veins 5. females lay eggs that are moved toward intestine and ureters, get excreted in feces and urine
Describe Schistosoma japonicum
=blood fluke; flat work Characteristics: 1. Likes to reside in superior mesenteric veins draining SI 2. Eggs excreted in feces 3. Endemic to SE Asia 4. Similar life cycle and clinical syndromes as S.. mansoni 5. Can cause cerebral sx (ex convulsions) 6. Tx: praziquantel
Which blood fluke produces so many eggs that they get deposited in ectopic sites, including the brain?
=Schistosoma japonicum -can cause cerebral sx including convulsions
Describe Schistosoma masoni
=blood fluke; flatworm Characteristics: 1. Likes to reside in superior mesenteric veins draining large intestine 2. Eggs passed in feces 3. Similar life cycle and clinical syndromes as S. japonicum 4. Endemic to Central Africa, Egypt, South America, Caribbean 5. Adults mate in host and make eggs 6. Can have both acute and chronic presentations 7. Tx: praiquantel
Describe the clinical syndromes associated w/ Schistosoma mansoni
=same as S. japonicum (w/out cerebral sx) Acute 1. Katayama fever Chronic -pathology due to EGGS 2. Pressinusoidal egg granulomas 3. Symmer's pipe stem periportal fibrosis 4. portal HTN 5. Chronic infection can lead to growth retardation tx: praziquantel
A pt returns from his safari to Africa with fever, anorexia, abdominal pain, and lymphadenopathy. His travel history is notable only for falling in a river during a canoe trip. You suspect ________________.
=Schistomiasis -Acute form=Katayama fever -seen often in travelers to endemic areas (Central Africa, Egypt, South America, Caribbean) -S. mansoni lives in fresh water w/snail as intermediate host -Dx: eggs in feces -tx: praziquantel
Describe Schistosoma haematobium
=blood fluke; flat worm Characteristics: 1. Resides in venous plexus of bladder; renal veins 2. Eggs passed in urine 3. Endemic to Middle East, Africa (Nile Delta) 4. Eggs cause pathology -induce formation of granulomas in liver 5. Tx: Praziquantel 6. Infection linked to risk of squamous cell carcinoma of bladder
A patient presents with hematuria after a trip to Egypt. His travel hx is notable for swimming in the Nile Delta races. You suspect _________.
=Schistosoma haematobium -blood fluke; flatworm 1. Endemic to Nile river delta 2. Pathology can include fibrosis and calcification of the bladder, dilation of ureters 3. Linked to risk of squamous cell carcinoma of the bladder 4. Tx: praziquantel
Name 4 clinical syndromes associated with Schistosomiasis
1. Cercarial dermatitis -avian schistosomes 2. Acute schistosomiasis -high fevers -eosinophilia -serology helpful to dx 3. Uncomplicated established infection -hepatomegaly, hematuria 4. Late disease -portal HTN, variceal bleeding -seen w. S. mansoni, S. japonicum -can see cerebral sx with S. japonicum
Describe Clonorchis sinensis
=Tissue fluke; flatworm =Chinese liver fluke Characteristics 1. Endemic in Asia (China, Korea, Taiwan, Vietnam) 2. 3 hosts (snail, carp, humans) 3. Resevoirs= dogs and cats 4. Humans get it by eating raw or undercooked fish 4. Eggs hatch in intestine, larvae migrate to bile duct, produced eggs pass in stool 5. Can cause inflammation and obstruction -> abd pain, diarrhea, nausea 6. Dx: eggs in stool 7. Praziquantel
Chronic infection with Clonorchis sinensis predisposes to ____________.
=cholangiocarcinoma of the liver -due to chronic inflammation/obstruction caused by Clonorchis living in bile duct =tissue fluke/flat worm
How do people get Clonorchis sinesis?
=through ingesting undercooked, salted, picked, or smoked freshwater fish -carp is an intermediate host -endemic in Asia (China, Korea, Taiwan, Vietnam)
Which parasitic infection predisposes to recurrent cholangitis?
=Clonorchis sinesis =tissue/liver fluke; flatworm -recurrent sx b/c of bile stasis -Other associated clinical syndromes: 1. Asymptomatic infection 2. Acute infection -anorexia and abd pain 3. Cholangiocarcinoma of liver/biliary tree -rare cancer
Paragonimus westernmani is a blood fluke or a tissue fluke?
=tissue fluke/lung fluke; flat worm Characteristics: 1. Endemic to Far East 2. 3 hosts (snail, crab, humans) 3. Domestic and wild animals can be resevoirs 3.Chronic disease can present as pulmonary disease that initially resembles pulm disease (ex TB) 4. Dx eggs from sputum or feces 5. Tx: Praziquantel
If you ingested infected crab while on vacation in the Far East have diarrhea, abdominal pain, fever, cough, you may have __________.
=infection w/ paragonimus westermani -tissue fluke/lung fluke -organism migrates from GI tract to lungs -Chronic infection presents as pulm disease (look like TB) -Dx: eggs in sputum or feces -Tx: Praziquantel
The infective form of Paragonimus westernmani is called ___________.
=metacercariae -tissue/lung fluke; flat worm
Is Fasciola hepatica a blood fluke or a liver fluke?
=sheep liver fluke/flatworm Characteristics: 1. Encysts on watercress 2. Fluke migrates to liver and resides in bile duct -migration associated with fever, RUQ pain, eosinophilia 4. Chronic infection associated with biliary obstruction 5. Dx: eggs in feces
How do humans get infected with Fasciola hepatica?
=tissue fluke -by eating watercress containing metacercariae (infective form) -sheep and cattle can also be infected this way -after ingestion -> excystation -> migrate to liver (sx associated w/ migration) -> reside in biliary duct
Define definitive host
=the host inhabited by the adult form of the parasite -if there is sexual reproduction, it occurs in this host, and eggs are produced -vs intermediary host: host inhabited by larval form of parasite -Humans are both intermediary AND definitive host for Taenia solium
Taenia solium is a ________ while Taenia saginata is a ________.
T. solium -pork tapeworm T. saginata -beef tapeworm
What parasite causes Cysticercosis?
=Taenia solium =pork tapeworm Characteri Characteristics: 1. Endemic in Mexico, Latin America, Eastern Europe, Africa, Asia 2. Humans can be definitive or intermediary host 3. Cysticercosis caused by ingested of eggs -> larvae hatch -> penetrate intestinal wall -> get into blood stream -> travel to tissues where they encyst (muscle, brain) 4. Sx depend on number and location of cysts 5. Neurocysticercosis associated w/vomiting, headache, visual changes, seizures -cysts in brain
True or false: humans are both definitive and intermediary host for Taenia saginata
-false -definitive hosts ONLY -T. solium is both definitive and intermediary
Describe Taenia saginata
=beef tapeworm/flatworm Characteristics 1. Definitive host only 2. larvae acquired by eating infected meat 3. Attach to SI by scolex 4. Release eggs that are passed in feces -eggs can survive in environment for a long time
Where do Taenia solium and Taenia saginata live in human hosts?
=intestines -attach by scolex (head w/ hooks) -Produce proglottids (segments); once mature/gravid are released from intestine into feces -eggs contained w/in proglottids
Name some sx associated with neurocystercicosis
=associated w/Taenia solium (pork tape worm) 1. Adult onset seizures 2. Severe headaches 3. Median incubation is 35 yrs Dx 1. Characteristic CT scan -cysts have inflammatory response "ring enhancers" -cysts can later be calcified 2. serology
True or false: Taenia saginata and Taenia solium can be distinguished by their eggs
Diphyllobothrium latum is a ___________.
=fish tapeworm/flat worm Characteristics: 1. largest human tapeworm 2. Can live in hosts up to 25 yrs 3. Infection via ingestion of raw or undercooked freshwater fish 3. disease usu asymptomatic but can cause pernicious anemia (release a chemical that interferes w/Vit B12 absorption) 4. Segments (proglottids) and eggs pass in feces 5. Reside in intestine
Who is at risk for infection with Diphyllobothrium latum?
=people who ingest raw or undercooked freshwater fish (perch, trout, walleyed pike) -Endemic in: 1. Great Lakes 2. Scandinavia 3. Western Europe 4. Japan 5. South America
Define proglottids? Who has them?
=segments Characteristic of: 1. Taenia solium and Taenia saginata 2. Diphyllobothrium latum
Echinococcus granulosus is a _________.
=dog tapeworm; flat worm Characteristics: 1. Found worldwide, esp in sheepherding areas 2. Humans are intermediate hosts -acquire by ingesting eggs 3. Larvae hatch and migrate and form cysts in multiple tissues (esp liver) 4. Asymptomatic infections until enlargment of cysts causes obstruction (ex jaundice) 5. Tx: surgical removal of cysts (breaking them open can cause anaphylaxis) 6. Proglottids are passed in feces 7. Sx depend on how big cysts are 8. Dx by characteristic xray and serology
Describe the group characteristics of Nematodes
=round worms 1. Multicellular 2. unsegmented 3. Have separate sexes 4. Have 4 larval molds 5. Severity of disease depends on worm load (b/c most can NOT multiply w/in host) -Exception: Strongyloides
Name a feature of strongyloides that make it unique compared to other roundworms
1. Can multiply w/in host
Define Loeffler's syndrome
Characterized by: 1. Transient pulmonary infiltrates 2. peripheral eosinophilia Caused by worms that migrate through the lungs
Who is most likely to have an infection with Enterobius vermicularis?
=pinworm; round worm =kids!
What parasite causes perianal pruritis, esp seen in kids?
=Enterobus vermicularis (pinworm) Characteristics: 1. roundworm 2. Seen wordlwide 3. Humans are only hosts 4. Fecal/oral transmission 5. Dx: scotch tape test to check for eggs in perianal region 6. most infections are asymptomatic 7. Remain infective for about 20 days 8. Rare ectopic disease -appendictis -salpingitis
True or false: itching areas infected with pinworm can cause reinfection
-true -perianal itching common when infection is symptomatic -itching can also cause excoriation, bacterial infection -self-infection can also occur by transferring eggs on hands that scratch perianal region to mouth
Describe the life cycle of enterobius vermicularis
=pinworm 1. eggs deposited on perianal folds 2. eggs transferred to mouth by hands that scratched perianal region 3. larvae hatch in SI, mature into adults and live in colon (takes 1 month) 4. females come outside anus at night to deposit eggs 5. eggs become infective in 4-6 hrs
What parasite can cause rectal prolapse following chronic bloody diarrhea in kids?
=Trichuris trichiura (whipworm)
Describe Trichuris trichiura
=Whipworm; round worm Characteristic: 1. Fecal/oral transmission 2. found worldwide, esp tropical climates 3. Can live for years in large intestine 4. Dx by finding eggs in feces (look lemon shaped) 5. Most infections asymptomatic but can cause rectal prolapse in heavy infection 6. Eggs passed in feces, develop in soil, ingestion of soil-contaminated food, hands transmits infection
Which parasite can actively swim in your intestine?
=Ascaris lumbricoides -does NOT attach to intestinal mucoas
Name 2 helminths that eggs get into soil and can survive in soil for a long time
1. Ascaris lumbricoides 2. Trichuris trichura b/c eggs mature in soil -> NO autoinfection
Describe Ascaris lumbricoides
=round worm Characteristics 1. Worldwide distribution -esp subtropical and tropical 2. Eggs passed in feces, mature in soil, ingestion leads to infection 3. Can migrate through tissue to lung and cause eosinophilia 4. Larvae in lungs can be cough up and swallowed 5. Obstruction in major serious complication of infection 7. Dx: eggs in stool 8. can be zoonosis 9. Tx: mebendiazole + piperazine 10. Adult worms live in SI and actively swim!
Name 3 phases of infection with Ascaris lumbricoides
=round worm -peak prev in children 1. Tissue phase -larvae migrating -liver sinusoids: degenerate larvae in granulomas -lung: hypersensitivity response w/eosinophils 2. Intestinal phase -little pathology 3. Migratory phase -can end up in wrong spot -> cause obstruction Tx: mebendazole + peperazine
Name 2 hook worms
=nematodes (roundworms) 1. Necator americanus 2. Ancylostoma duodenale
What is the geographic distribution of hook worms
Includes: 1. Necator americanus 2. Ancylostoma duodenale -can be found in: 1. Africa 2. Asia 3. Americas -N. americanus can be acquired in SE USA
What is the most common sx of a hookworm infection?
=anemia -caused by blood loss at site of intestinal attachment
The filariform larvae is the infectious form of ___________.
=hookworms 1. Necator americanus 2. Ancylostoma duodenale
How do you get a hookworm infection?
1. Eggs passed in feces 2. Larvae hatch in soil -> develop into infective form (filariform) 3. Larvae penetrate host of skin 4. Larvae carried in venous circulation to hear and lungs 5. larvae mature into adults in intestine, attach, and cause blood loss -> anemia (they suck your blood!) Tx: 1. Mebendazole 2. iron replacement
What parasite in associated with anemia and "ground itch" (dermal pruritis)
=hookworms -dermal itching is at site of penetration by the infective filariform larvae -can also see pulm sx as larve travel through venous circulation into lungs (but finally reside in intestines)
Describe the life cycle of Strongyloides stercoralis
-very complex b/c 2 generations 1. free living 2. parasitic -infective larvae penetrate skin to cause infection -rapid life cycle -capable of autoinfection and reinfection of host -infection can last a long time (ex 40 yrs)
What parasite is diagnosed by finding larvae in the feces?
=Strongyloides stercoralis Other dx: 1. eosinophilia (except in disseminated disease) 2. serology
Describe infection with Strongyloides stercoralis
=round worm 1. Infections can be asymptomatic 2. Can cause GI sx (abd pain, diarrhea) 3. Can cause pulm sx as migrate through lungs 4. b/c autoinfection, infections can last for up to 40 years 5. Hyperinfection in immunosuppressed can be fatal -steroids or chemo can cause rapid dissemination -abd pain, distension, shock, pulm and neurologic complications, septicemia tx: Ivermectin
What parasite in found specifically in Pacific fish (like cod, haddock, herring, salmon)
=Anisakis species -roundworm -larvae infect the fish -humans infected by eating undercooked fish or sushi -prevention by heating or freezing fish -fish penetrate gastric and intestinal mucosa -sx: acute, severe epigastric pain (can vomit the worm out) -worms may need to be removed surgically
Describe the life cycle of Anisakis species.
=type of roundworm found in 80% of Pacific fish -can reside in marine mammals stomach mucosa-> eggs pass in stool -eggs hatch, molt into larvae -larvae infect crustaceans -larvae transferred fish to fish by predation -humans infected y eating raw or undercooked infected marine fish
What parasite is the second most common cause of infectious blindness?
=Onchoceriacis -vector: black fly -can get itchy skin nodules from bite -larvae migrate into eye
Name 2 structural components common to viruses
1. nucleic acid -RNA or DNA 2. Protein coat (capsid) -protects nucleic acid -in non-enveloped virus it mediates attachment to and penetration of host cells
Describe the metabolic needs of a virus
=obligate intracellular parasites that infect host cells, multiply and spread -they lack: 1. ability to make ATP 2. structural components to synthesize DNA, RNA, proteins -they do NOT divide by cell division but synthesize components separately and then assemble them
Which tend to be more stable in the environment: non-enveloped viruses or enveloped viruses?
=non-enveloped viruses (not surrounded by lipid bilayer derived from host cell membrane) -enveloped virus more susceptible to desiccation, detergents, alcohols, proteolytic enzymes
Define virion
=infectious virus particle -capable of existing freely outside a host cell -cannot replicate extracellularly
Contrast structural protein vs nonstructural protein for viruses
Structural protein =viral protein that is part of the virion Nonstructural protein =viral protein NOT incorporated into virion -usu fxn to: 1. aid virus replication 2. help counteract host defenses
What must all viruses synthesize in order to replicate?
=messenger RNA
What is an example of a virus with a broad host range? A narrow host range?
Broad host range -can infect lots of cell types and tissues in many diff species 1. Herpes simplex virus Narrow Host range 1. Human Papillomavirus
Define tissue tropism
=cells that a virus readily infects
What determines host range and tissue tropism?
=whether a given species and tissue within a given species have specific receptors that a given virus uses for attachment and entry into the host cell -if cell lacks those specific receptors, it cannot be infected by that virus
Define portal of entry
=location of first cells infected by a virus (where it enters the body) -initial sx may be at portal of entry (ex. HSV) or a distal site (ex Varicella Zoster virus)
Define cytopathic effects
=the distinctive morphology of cells infected by a given virus -different viruses will produce different CPE
True or false: viral replication will take place in all cells susceptible to infection.
-false -infections can be productive, restrictive, abortive, or latent (replication is not guaranteed) Susceptible cells=those that express Rs that allow virus to attach and invade
Contrast permissive vs nonpermissive cells in viral infections
Permissive cells =cells in which virus can produce progeny -if permissive, there will be productive infection (production of progeny) Nonpermissive cells =cells virus can infect, but in which virus can NOT produce progeny
Define abortive viral infection
=virus is able to enter susceptible cells but no viral progeny are produced -2 major reasons: 1. Cells are nonpermissive -allow some but not all viral genes to be expressed 2. virus is defective and doesn't have all the genes it needs
Define enhancer elements
=regulatory DNA or RNA sequences in a viral genome that bind specific txn factors thus regulating rate of txn of nearby viral genes
Define restrictive viral infection
=when a susceptible cell will only allow progeny to be produced transiently -this means virus must wait until right cell conditions in order to have successful progeny production
Define latent viral infection
=persistence of viral genomes, but NOT infectious virions in host cell -but NO destruction of infected cell -viral genome can be integrated into host genome -latent cells retain potential to produce infectious virus
Describe the 4 major steps in viral invasion and replication
1. Attachment 2. Penetration and uncoating of virus 3. Replication, txn, and translation 4. Assembly of virions and release
Name 2 ways a virus can enter a host cell once it has attached to it.
1. R mediated endocytosis -both enveloped and non-enveloped viruses -vesicle -> fuses with endosome -> acidification w/in endosome stimulates uncoating of virus 2. Fusion -of host cell membrane with virus -virus must be able to fuse at neutral pH
What is the requirement of a virus to enter a cell by fusion?
-it must be able to fuse at neutral pH -characteristic of fusion virus 1. multinucleated giant cells 2. syncytia
State the fxns of immediate, early, and late gene products for viruses.
Immediate gene products -regulate expression of other genes Early gene products -involved directly in replication of viral genome Late gene products -occur after DNA replication -structural proteins of virion
All DNA viruses undergo replication in the nucleus EXCEPT _________.
All RNA viruses undergo replication in the cytoplasm EXCEPT ____________.
What's the difference between positive sense and negative sense RNA viruses?
Positive sense RNA virus -can be used as direct template for txn Negative sense RNA virus -must carry RNA dependent RNA polymerase or transcriptase into host cell
True or false: release of an enveloped virus by budding from an infected host cell damages the membrane and kills the host cell
-false -it does NOT have to do this
Describe Polio virus
= -Genetic material= single stranded positive sense RNA virus -Capsid: icosahedral -No envelope -Replication in cytoplasm -humans are only natural hosts -transmission by ingestion
How does polio virus enter susceptible cells?
-receptor-mediated endocytosis -RNA uncoated in cytoplasm -genome translated as one long polypetide -> cleaved into smaller proteins by viral protease -RNA dependent RNA polymerase used to make negative sense (complementary) RNA strand -> this is used to make more positive strands -nucleic acids assembled into capsids -host cell lyse -> release virions
True or false: polio virus 1 can get into mice or chickens
-false -b/c polio virus uses a R that is only present on cells of primate origin (humans, chimps)
What type of cell surface protein does Polio virus 1 attach to?
=membrane of Immunoglobulin (Ig) superfamily -found only on primate cells
Describe the cytopathic effects of polio virus 1
Early changes 1. cells shrink and round up -> small breaks in monolayer Later 1. infected cells detach from surface -> monolayer destroyed
Do polio viruses use a hit and run strategy?
-yes -this means they enter host, cause infection/disease, and are completely cleared from body by host immunity -to maintain the virus a large population of susceptible (non-immune) persons is required
Name 5 host factor affecting susceptibility to viral infections
1. Genetic factors 2. Age 3. Immune responses -humoral -cell mediated 4. Normal barriers -skin -resp epithelium -gastric acid 5. Other host defenses -interferon -recognition by toll like Rs
Name some factors that alter the nature of exposure to viruses
1. Travel 2. Human invasion of a new territory (ex clearing of the rain forest) 3. Blood transfusion 4. IV drug abuse 5. Organ allografts 6. Cancer chemo 7. Altered sexual practices 8. SES changes -delayed exposure
True or false: virion stability is the sole determinant of pathogenicity
-false -there are a ton of viral determinants related to how virus interacts with infected host cells, replication, sensitivity to various host immune defenses
Describe the group characteristics of Picornaviruses
1. Non-enveloped 2. Icosahedral capsid 3. Positive sense single stranded RNA genome -strand is like mRNA 4. cytoplasmic replication
Name some types of Picornaviruses
1. Rhinoviruses 2. Enteroviruses 3. Hepatovirus (Hepatitis A) 4. Cardioviruses
Name 4 types of Enteroviruses
=picornaviruses (+ ss RNA viruses) 1. Coxsackie viruses A and B 2. Echoviruses 3. Polioviruses 4. Unclassified enteroviruses
Describe the characteristics of adenovirus
1. Double stranded linear DNA virus 2. non-enveloped 3. Icosahedral capsid -made up of hexons, pentons, and fibers 4. Group specific Ag (hexon, penton) and type specifc Ag (fiber) 5. Replication and virion assembly occur in the nucleus 6. 51 known serotypes
Where does viral replication take place for adenovirus?
-in the nucleus
Neutralizing antibodies can be made against what adenovirus Ag(s)?
1. hexon 2. fiber
How does adenovirus attach to its host?
-using fibers on the icosahedral capsid -it uses CAR as a receptor
How is adenovirus transmitted?
1. aerosol 2. close contact 3. fecal oral 4. opthalmic instruments
What is the cytopathic effect of an adenovirus infection?
1. grape-like clustering of cells 2. basophilic inclusion bodies 3. Host cells are lysed and virion is released
Describe the genome of adenovirus
-3 main groups of genes: 1. For viral replication -usu transcribed early 2. For host cell replication -block host translation -block host mRNA transport out of nucleus 3. For interaction with host organism -for immune evasion -Gene expression in 2 phases 1. Early -proteins used for DNA replication -primer, DNA polymerase, DNA binding protein 2. Late -capside subunits and other structural proteins
What types of cells are adenovirus able to chronically infect?
=lymphoid cells -able to persist in these cells for long time -can cause latent infection
Name some diseases caused by adenovirus
1. Acute respiratory tract infections 2. conjunctivitis 3. hemorrhagic cystitis 4. gastroenteritis
What does the Ea1 gene of adenovirus encode?
=first RNA transcribe -codes for 2 proteins w/ several fxns including 1. Turning on other early genes and late genes 2. Binding to RB gene product -inhibits activation of IFN response elements
What does the E1b gene of adenovirus encode for?
-it encodes a protein that blocks host mRNA transport to cytoplasm -binds p53 gene product -> prevents apoptosis of host cell -also protects cell from lysis by TNF
What does the E2 gene of adenovirus encode?
=DNA replication proteins including: 1. DNA polymerase 2. pTp 3. 72 kD binding protein
Which adenovirus gene encodes for a protein that forms a complex w/MHC Class I?
=E3 -this causes MHC class I to stay in the ER -> virus escapes immune surveillance -also protects cell from lysis by TNF alpha
What is the fxn of the VA genes of adenovirus?
=small RNAs that don't get translater -bind ds RNA kinase and inactivate -> preventing shut down of translation so viral mRNAs can finished being translated
What virus causes pharyngoconjunctival fever?
=adenovirus -causes this in childrend -AKA summer camp illness, swimming pool conjunctivitis =conjunctivitis +/- pharyngitis, rhinitis, cervical adenitis, temperature up to 38 degree C
Name 5 diseases adenovirus can cause in kids.
1. colds 2. pharyngoconjunctival fever 3. hemorrhagic cystitis 4. diarrhea 5. Intussusception 6. Intestinal block
What virus causes epidemic keratoconjunctivitis?
=adenovirus -adults -insidious onset -bilateral, preauricular adenopathy -keratitis (affects cornea, eye pain and impaired vision) starts as conjunctivitis wanes -can last months
True or false: half of adenovirus illness do not show clinical illness
-true -accounts for a large percent (5%) of infections in infancy and childhood
Name 3 diseases adenovirus can cause in immunocompromised
1. Pneumonia w/ dissemination 2. UTI 3. Meningoencephalitis
How do you diagnose an adenovirus infection?
1. clinical suspicion 2. can isolate virus from clinical specimens 3. Enzyme immunoassay -Ab to hexon epitope 4. Restriction enzyme analysis
True or false: tx of adenovirus infection requires immediate tx.
-false -usu no tx is necessary b/c infections tend to be self-limited
What are some potential uses of adenovirus as a vector?
1. Can be used as a vector to kill tumor cells 2. Vector for gene therapy -b/c broad tropism for cells 3. Vector for HIV vaccine -but vaccine found NOT to be protective and made people more susceptible to infection adenovirus has fallen out of favor as a vector
True or false: adenovirus causes cancer in humans.
-false (prob) -no direct evidence that it causes cancer in humans -evidence that it causes cancer in mice -carcinogenic potential comes from its ability to block apoptosis of host cells
Variola, Monkeypox, cowpox, vaccinia, orf virus, and molluscum contagiosum are all part of what family of viruses?
=Poxviridae -these are all capable of causing disease in humans
What virus is responsible for smallpox?
=Variola -only host is humans -can only transmit person to person by airborn droplets (requires close contact with infected person) -no carrier state -rare transmission by: 1. airborne 2. fomites (ex blankets)
What virus causes a zoonotic infection with a rash similar to smallpox?
=monkeypox -also see severe swelling of lymph nodes -transmission and mortality lower with monkeypox vs smallpox -last outbreak acquired from infected prairie dogs
What type of Poxviridae was used in the original smallpox vaccine by Jenner?
=coxpox -caused localized disease to the hands of milkmaids
Which Poxviridae is currently used in the smallpox vaccine?
Which Poxviridae causes infection spread by direct skin-to-skin contact?
=Molluscum contagiosum -causes chronic localized infection -flesh colored, dome shaped papules on the skin -STD -diagnosis made on appearance
Name 5 factors that allowed smallpox to be eradicated
1. Humans are only host -no animal resevoirs 2. Variola does NOT remain latent in host and immunity is lifelong 3. Cases of variola are easy to identify and isolate b/c there are NO asymptomatic infections 4. The vaccine is stable and easily transported 5. Time, money, effort invested
True or false: there are asymptomatic variola infections
=false -no asymptomatic smallpox infections
Describe the group characteristics of Poxviridae
1. Double stranded linear DNA virus 2. enveloped 3. large and brick shaped 4. core of nucleoprotein 5. ends of genomes are direct terminal repeats that form hairpin loops 6. replication and virion assembly in cytoplasm
What is the only DNA virus to replicate and carry out virion assembly in the cytoplasm?
=Poxviruses -carries pretty much everything it needs except for ribosomes
Describe a smallpox infection
=caused by Variola -spread by inhalation -multiplies locally w/in mphages -spreads to bloodstream through mphages getting into circulation -multiplies in lympoid tissue -virus localized to dermal blood vessels-> endothelial swelling and infection of epidermal cells -intraepidermal vesicles form on skin -> can leave scarring (pox marks)
Name 3 sequelae for survivors of smallpox
1. Pox marks -face is NOT spared 2. Blindness 3. limb deformities
All of the following are involved in the immune response to smallpox EXCEPT: a. cytotoxic T cells b. neutralizing Ab c. macrophages d. production of interferon
-macrophages -these get infected with the virus, then spread it to the bloodstream by getting in the circulation
What disease can be easily confused with smallpox on PEX? What are the differences
=chickenpox 1. no prodromal phase (or very mild) 2. skin lesions appear in crops -skin lesions look like they're at different stages 3. Skin lesions more centrally located (truncal distribution)
Describe the clinical features of smallpox
1. Acute onset of fever 101 or higher 2. Rash develops following fever 3. Rash characterized by: -lesions all of same stage -centrifugal distribution (see all over, including limbs, face) -skin lesions develop over 7-10 days, become pustular and later form scabs as fluid is resorbed -scabs are STILL infectious! -incubation may be up to 2 weeks before onset of sx
What substance can be used to kill enveloped viruses?
=chloroform -lipid solvent -but not effective against non-enveloped viruses
Describe the group characteristics of rhinoviruses.
=positive single stranded RNA viruses -type of Picornavirus 1. inactivated by acid pH 2. optimum growth at 33 3. resistant to inactivation at 50 -used to distinguish rhinovirus from enterovirus 4. 120 different serotypes 5. Use ICAM-1 R to enter host cell
What is the most common cause of the common cold?
=rhinovirus! -Peak incidence: 1. Spring 2. early fall -Transmitted by aerosols or fomites -infection induces high levels of IFN -optimal growth at same temp as your nasal mucosa
What does the body produce to help deal with rhinovirus infection?
1. IgA -block binding of virion to cell R -protection fades w/time 2.IFN -production induced by infection
How does rhinovirus enter host cells?
Describe the group characteristics of enteroviruses
=positive, single stranded RNA viruses -Picornaviruses -Stable at: 1. pH 3 2. room temp -sensitive to inactivation at 50 degrees celsius -4 subgroups 1. Poliovirus 1,2,3 2. Echoviruses 3. Coxsackie viruses A, B 4. Unspecified virus
When is the peak incidence of enterovirus infections?
-late summer -> early fall
Describe enterovirus infections
1. fecal-oral transmission 2. Most can cause aseptic meningitis 3. Rash is common manifestation of infection 4. immunity is type specific (4 diff subtypes-echo, polio, coxsackie, unspecified)
What is a cause of aseptic meningitis?
=aseptic meningits= resembles bacterial meningitis but no bacterial growth in CSF cultures -cause: enteroviruses -fever, stiff neck, CSF pleocytosis
Define Echoviruses
=subtype of enteroviruses= positive single stranded RNA virus -Infections: 1. aseptic meningiti 2. rashes 3. generalized infections: newborns 4. Boston exanthema -fever followed by roseola-rash -Echovirus 16 5. 29 diff serotypes
Name the 4 major subtypes of enterovirus
=positive single stranded RNA virus; Picornaviruses 1. Echovirus 2. Poliovirus 3. Coxsackie virus 4. Unspecified enterovirus
Which Coxsackie virus readily grows in primate cell culture?
-Coxsackie B virus -Coxsackie A does NOT
Which Coxsackie virus attacks SKM in mice to cause myositis and flaccid paralysis?
=Coxsackie A virus -Coxsackie B causes encephalitis -> spastic paralysis
Herpangina is characterized by sore throat, ulcers in throat, and fever. What is the cause?
=Coxsackie virus A
Name 4 diseases caused by Coxsackie virus A
=positive single strand RNA virus 1. Herpangina (fever, sore throat, mouth sores in kids) 2. Hand-Foot-and Mouth disease 3. Paralytic disease (flaccid) 4. Acute hemorrhagic conjunctivitis Note: Coxsackie A does NOT cause myocarditis (but B does!)
Pleurodynia is characterized by intense paroxysmal pain of lower chest or abdomen. What is the cause?
=Coxsackie virus B -single stranded RNA enterovirus -uncommon complication of Coxsackie B infection -paroxysmal pain caused by myositis of intercostal/abd muscles -can be associated with fever, malaise, headaches -usu follows asx or brief upper resp or GI infection
Name 3 diseases caused by Coxsackie virus B.
1. Pleurodynia -paroxysmal pain to lower chest, abdomen 2. Myocarditis - inflammation w/pain, friction rub, ECG changes 3. Generalized disease of newborn (high mortality)
What causes acute hemorrhagic conjunctivitis?
=enterovirus 70 -usu in epidemics
True or false: humans are the only natural host for poliovirus
-true -also other primates -range is limited to these species b/c they are the only ones with the R needed for cell entry
How does poliovirus get into host cells?
=via R mediated endocytosis -all 3 polioviruses use same R
Where does replication of the poliovirus occur in host cells?
-in the cytoplasm
How is the viral genome of poliovirus expressed?
=whole genomic strand is translated as 1 big mRNA -> 1 big protein -protein gets cleaved into smaller viral proteins via proteases
Name 2 proteins used for viral replication and virion assembly that poliovirus makes itself
1. RNA polymerase -catalyzes synthesis of new DNA 2. viral protease -cleaves viral polyprotein into smaller proteins
Name 4 clinical syndromes caused by poliovirus
1. asymptomatic -95% of infections 2. abortive infection 3. aseptic meningitis 4. paralytic polio
How does poliovirus infect humans?
1. virus gets ingested (enterovirus) 2. infects mucosa of SI and replicates 3. spreads to Peyer's patches -> mesenteric lymph nodes -> blood -> primary viremia 4. spreads to extraneural sites (liver, spleen, BM, lymph nodes) 4. If neutralizing Ab produced -> clear infection and get asx infection -if immune responses delayed, get viral shedding into bloodstream -> secondary viremia -> sx
What prevents/terminates poliovirus viremia?
=neutralizing Ab -in 95% cases, these are sufficient to deal with the infection before it becomes asymptomatic
Define abortive polio
-when secondary viremia and sx disappear in a day or 2 -develops due to delay of immune responses (neutralizing Ab) -sx: 1. Acute flue-like illness 2. fever, headache, vomiting, diarrhea, sore throat 3. resp. infection 4. gastroenteritis
True or false: the aseptic meningitis caused by poliovirus tends to be chronic
-false -tends to be self-limited w/poliovirus
Define paralytic polio
=disease caused by poliovirus (enterovirus) -less than 0.1% of infected people -involves motor neurons of SC, medulla, cortex -> kills infected MN -> muscle paralysis -neurophagia (dying neurons being phagocytosed) -CNS infection achieved by spread of virus in the blood -1/200 will have permanent paralysis -legs most common site affected -bulbar polio (5-10% of paralytic) -> MN in medulla are affected -> can be fatal if resp muscles affected
True or false: neutralizing Ab in circulation will prevent developing paralytic polio
-true -viremia is required for paralytic disease to develop
How long is poliovirus shedding in infected people?
1. Pharynx 3-4 weeks 2. Feces 5-6 weeks
How is poliovirus transmitted?
1. Fecal oral -can be through fomites 2. respiratory transmission also possible
When is the peak incidence for poliovirus infection?
-summer-early fall
True or false: one enterovirus in the gut can interfere with the ability of another enterovirus to infect
-true -this is basis of live attenuated vaccine
What factor increases risk of infected person developing paralytic polio?
-age of person -greater age at time of primary infection, greater chance of developing paralytic polio
How do you diagnose polio?
1. Virus isolation 2. Seroconversion =rising Ab titer
Name 4 countries endemic for poliovirus
1. Nigeria 2. India 3. Pakistan 4. Afghanistan
Name 2 types of polio vaccines
1. Salk -inactivated -favored vaccine 2. Sabin -live attenuated -can be given orally -risk of vaccine-induced paralytic disease (outweigh benefits)
What type of immunity does the sabin vaccine induce? The salk vaccine?
Sabin =live attenuated polio vaccine -induces GI tract immunity as well as systemic immunity -affected pts can still shed -infection by non-polio enteroviruses can interfere w/vaccine Salk =killed polio vaccine -induces humoral immunity -no GI immunity -requires injection, booster doses -more exensive b/c need a large amt of virus to vaccinate -no interference from wild type non-polio enteroviruses -no shedding of virus
Who is at risk of paralytic induced disease with the sabin vaccine
=live attenuated vaccine 1. Immunocompromised -worry about them b/c increased risk of paralytic disease if vaccinenated with live attenuated or if contact of recently vaccinated person
Describe the group characteristics of papovaviruses
1. small, circular, double stranded DNA viruses 2. non-enveloped 3. Icosahedral capsid 4. histones for DNA w/in capsid 5. Replication in host cell NUCLEUS 6. chronic and persistent infections in their natural hosts
Name the 2 major groups of papovaviruses
1. Papillomaviruses -HPV 1-HPV100 -papilloma viruses of other animal species 2. Polyomaviruses -JC and BK viruses -SV40 -Papillomaviruses of many other animal species
Define papillomaviruses
=type of papovaviruses 1. small, circular, ds DNA viruses 2. more than 100 distinct HPV 3. have narrow host range and are associated with specific syndromes 4. Specific HPV are associated w/different wart morphologies and locations
When are 2 papillomaviruses considered to be different?
=if their genomes have less than 50% DNA sequence homology under stringent DNA-DNA hybridization conditions
True or false: all human warts are produced by a single HPV
-false -specific HPVs are associated with different wart morphologies and different locations
When does an HPV virus display its genus specific epitope?
-only when virus is denatured -all HPV have SAME genus specific epitope -this is the basis of a diagnostic tests for HPV -group specific Ab are made against denatured virus -intact virus -> host makes type specific Ab to virus
Describe the genome of Papillomaviruses
=small, circular double stranded DNA -have histones within capsid -7 early genes, 2 late genes all on same DNA strand -replication in the nucleus -uses RNA splicing -exists as episome in nucleus of infected cell (can be either free or integrated into host genome)
Define episome
=genetic element that can exist in 2 states in host: 1. Either free and separate from host genome 2. Integrated into host chromosome Examples: 1. Papillomaviruses
Name the impt early genes for HPV
1. E2 -modulates viral txn -suppresses E5, E6, E7 2. E5 3. E6 4. E7 E5, E6, E7 influence transformation of infection to cancer
What types of cells does HPV like to infect?
=terminal differentiating squamous epithelial cells (keratinocytes) -b/c of this requirement,can't grow HPV in tissue culture -however, viral DNA gets into basal cells
What causes recurrent HPV infections
=viral DNA present in normal looking basal epithelial cells -if only wart is removed -> reccurent disease -ONLY early HPV genes expressed in basal cells
What is the hallmark cytopathogenic effect of HPV?
=koilocyte =squamous epithelial cell w/shrunken, pyknotic nucleus sitting in middle of large vacuole
How can HPV cause cancer?
=viral genome gets integrated into host genome in a way that disrupts E2 gene -E2 normally acts to suppress E5, E6, E7 -loss of E2 fxn -> no get action of E5, E6, E7 -E6 binds to host p53 -> accelerated degredation -> apoptosis inhibited -E7 inactivates host RB -> cell begins DNA synthesis and mitosis
True or false: the types of HPV most common to cause genital warts are also most likely to cause cancer
HPV 16, HPV 18, HPV 31, HPV 45 are most likely to cause___________.
=cervical cancer
HPV 6 and HPV 11 are most likely to cause __________.
=genital warts
True or false: all cervical cancer is caused by HPV.
-false -can get cervical cancer without HPV from mutations in RB or p53
What does E6 of HPV do?
-normally supressed by E2 -when viral genome integrated into host genome -> E2 disrupted -> E6 uncontrolled -E6 combines with host p53 and accelerates its degredation -> inhibit apoptosis
What does E7 of HPV do?
-E7 normally suppressed by E2 -integration of viral genome into host genome disrupts E2 -> E7 no longer suppresed -E7 binds to RB and inactivates it -> cell stimulated to begin DNA synthesis and mitosis
How is HPV transmitted?
1. Direct contact -STD 2. Indirect contact -cut on your foot and comes in contact with virus on floor
Describe the HPV vaccine
=papilloma-like particles that are empty shells of virus proteins (NO DNA) -vaccine stimulates production of protective antibodies -targets HPV types 16 and 18 (most causes of cervical, anal, genital cancer) -also targets HPV 6 and 11 (cause genital warts)
Name 5 clinical syndromes caused by HPV
1. Cervical cancer 2. benign squamous epithelial tumors or warts 3. laryngeal papillomatosis 4. epidermodysplasia verruciformis 5. Condyloma acuminatum
Laryngeal papillomatosis is caused by ___________
=HPV -children infected as they pass through birth canal -warts develop in laryngeal area -> may cause obstruction -tx w/surgical removal -tend to recur even after removed
Epidermodysplasia verruciformis is caused by ____________.
=HPV -autosomal recessive condition -extensive chronic cutaneous infection wiht HPV -1/3 develop malignant carcinomas on sun-exposed skin -esp HPV 5 and HPV 8
Condyloma acuminatum is caused by ___________.
=HPV =genital warts -most common STD viral disease -caused by: 1. HPV 6 2. HPV 11 -most infections asymptomatic and transient
Define Polyomaviruses
=type of papovaviruses 1. small, circular ds DNA viruses 2. resistant to formalin and heat inactivation 3. Do NOT cause tumors in natural hosts 4. Includes: -JC virus -BK virus
Name some differences between the genomes of papillomaviruses and polyomaviruses
=both are types of papovaviruses 1. Size of genome -papillomavirus is bigger 2. Location of early and late genes -Papillomavirus: early and late genes on same DNA strand -Polyomavirus: early genes on 1 DNA strand, late genes on other
When does polyaviruses cause productive infections? Abortive infections?
Productive infections 1. in tissue culture in cells from natural hosts Abortive infections 1. in cells of other related species -but may transform cells
What causes Progressive Multifocal Leukoencephalopathy?
=JC virus -subacute, progresive, demyelinating disease in pts with impaired cellular immunity -sx include dementia, ataxia, visual field defects, weakness of extremities, speech problems -coma and death w/in 6 months -primary infection during childhood or adulthood -reactivated latent infection in immunocompromised states
Who gets Progressive multifocal leukoencephalopathy?
=people in immunocompromised states 1. AIDs 2. Organ transplant 3. pregnancy -usu due to reactivation of latent JC virus infection (polyomavirus)
What kinds of cells does JC virus infect to cause PML?
1. oligodendrocytes 2. astrocytes JC virus replicates best in primary human fetal glial cells
JC virus is a __________.
=polyomavirus -small, circular, ds DNA genome virus -caues progressive multifocal leukoencephalopathy (demyelinating disease in immunocompromised pts) -JC infection is ubiquitous
How does JC virus cause PML?
1. Infection usu sometime in childhood or adults 2. JC virus infects and establishes latency in kidney -virus can be shed in the urine 3. JC virus reactivates during immunocompromised state (AIDs, organ transplant, pregnancy) and infects oligodendrocytes and transforms astrocytes 4. progressive neural degeneration with coma and death within 6 months of onset of sx
How are SV40 virus, JC virus, BK virus alike? How are they different?
Alike 1. All are polyomaviruses (circular ds DNA viruses) -70% genome homology Different 1. enhancer elements
True or false: BK virus causes disease in humans with normal immune systems
-false -disease usu due to reactivation of latent infections in immunocompromised states 1. AIDs 2. pregnancy 3. organ transplants
Name some types of cells BK virus can replicate in.
1. human embryonic kidney cells 2. fetal fibroblasts 3. fetal brain cells 4. newborn urinary epithelial cells
How does BK virus cause infection?
-can cause nephritis 1. primary infection in kids and adults 2. BKV infects and establishes latency in kidney -virus shed in urine 3. reactivation of latent BKV during immunocompromised states (AIDs, organ transplant, pregnancy)
How are BK virus and JC virus alike? Different?
Alike 1. both are polyomaviruses 2. both establish latent infections in kidney 3. both can be shed in urine 4. disease usu due to reactivation of latent infections in immunocompromised Different 1. JC virus has more narrow tropism (BKV can infect more cell types) 2. BKV infection in kids occurs at a younger age
Influezna virus is a ___________.
Define influenza virus
1. orthomyxovirus 2. enveloped 3. helical capsid 4. have surface glycoprotein spikes 5. segmented (8), single strand negative RNA genome
What do negative sense RNA viruses need to replicate in host?
=RNA dependent RNA polymerase (transcriptase) -this enzyme makes RNA from RNA -virus must carry its own b/c host cells don't have these enzymes
Name the 4 impt antigens of the influenza virus
1. Nuceloprotein -main structural protein 2. Matrix proteins 3. Hemagglutinin HA 4. Neuraminidase
What is the fxn of the matrix proteins of influenza virus
=2 proteins that are alternatively splice 1. M1 -membrane protein for budding and assembly 2. M2 -forms pH activated ion channel that is impt for viral uncoating -targeted by: 1. amantadine 2. rimantadine
True or false: antibodies against the NP and M1 Ag of influenza virus are protective
-false -they can be used to dx -these antibodies are type specific to the influenza virus
What is the fxn of hemagluttinin for influenza virus?
-mediates attachment and entry into host cells -uses sialic acid as a R -HA able to change antigenic structure to evade immune system -HA must be cleaved to be infectious
Amantadine and Rimantadine target what component of influenza virus?
=M2 protein -form pH activated ion channels that are impt in viral uncoating
True or false: hemagluttinin must be cleaved in order for influenza virus to be infectious
-true -without cleavage, HA can attach to host cell but virus can't enter
What is the most impt factor for immunity against influenza virus?
=antibody against hemagglutinin -antibody to neuramidase also confers protection
What is the fxn of neuramidase for the influenza virus?
=allow the release of virus from host cell -hydrolyzes of sialic acid residues off baby viruses so they don't form 1 big ball -can also hydrolyze mucoproteins in nasal secretions -Ab to NA can be protective
How does influenza virus get into cells?
=pH dependent endocytosis -as pH in endosome drops -> viral membrane fuses w/membrane of endosome -> nucleocapsid released into cytoplasm
Where does influenza virus replicate?
=nucleus -influenza and measles are the ONLY RNA viruses that replicate in nucleus -it steals 5' caps from host mRNA
How is influenza virus classified?
-3 types (A, B, C) that are serologically and genotypically distinctive
What are some unique features of influenza virus A?
1. has both subtypes of HA and NA -influenza virus A must by further subtyped based on HA and NA 2. has animal reservoirs 3. can undergo antigenic shift -can lead to pandemics and epidemics
What does influenza virus do to try to evade immune response?
=alter antigenic of HA and NA -allows influenza to continue to infect people even w/acquired immunity -can do this by: 1. Antigenic drift -A, B, C 2. Antigenic shift -A ONLY
Define antigenic drift
=alter structure of proteins that are main antigens of a pathogen so it can evade immune system Influenza virus 1. antigenic drift in hemagluttinin and neuramidase -due to missense mutations causing minor changes w/out changing fxn -influenza A, B, C 2. Antigenic shift -introduce new RNA segments acquired from reassortment or from transmission of virus directly from animal resevoir -> humans -influenza A ONLY
True or false: antigenic shift can result in pandemics on infection
-true -seen with influenza virus A
Which type of influenza causes the most severe infection?
-influenza A
Describe the outbreak of Avian flu in 1997
-due to influenza A (H5N1) -virus transmitted from chickens -> humans -no epidemic b/c virus could not spread easily from person -> person
Describe the spread of influenza A virus H5N1. In what countries has it been seen? What types of animals?
Outbreaks in poultry 1. Asia 2. Europe 3. Near East 4. Africa Human infections 1. Thailand 2. Vietman 3. Cambodia 4. China 5. Indonesia 6. Turkey 7. Iraq Species 1. Poultry (chicken, etc) 2. pigs 3. domestic cats 4. tigers
What is preventing a epidermic of influenza virus A H5N1?
-poor person-person transmission -most human infections have been in people with direct contact with infected poultry Could get person -> person transmission if outbreak of avian flu cases during same time as a human influenza outbreak -coinfection of host with both viruses could allow for reassortment that result in H5N1 acquiring new genes to enable human -> human transmission
When is peak influenza season
=winter months -every year influenza occurs in distinct outbreaks of varying degrees -influenced by virulence of virus (including antigenic shift, transmission, ability to cause disease w/sx), host susceptibility
Describe influenza A outbreak
1. Time course -abrupt onset, peak 2-3 weeks, outbreak last 2-3 months 2. Early sign is acute increase in febrile illness in kids, then adults 3. attack rate usu 10-20% (50% in pandemics)
True or false: influenza B outbreaks usu cause less severe disease but can still be lethal.
Describe influenza (the disease)
=acute febrile illness caused by influenza virus -usu self-limited -mortality associated with complications of infections 1. pneumonia 2. bronchitis 3. sinus/ear infections -sx: fever, headache, sore throat, cough, nasal discharge, malaise, myalgias
How is influenza virus transmitted?
-airborne -infects: 1. mucosal cells 2. resp epithelial cells
What is the fxn of antibodies for influenza infection? Cell mediated immunity?
Antibodies -produced during 2nd week infection -protect against new infections Cell mediated -clearance and recovery from infection
Who is at risk for serious complications of influenza viral infection?
1. people over 65 yrs 2. people over 50 yrs 3. people w/chronic medical conditions (COPD, diabetes, heart or lung disease) 4. very young children 5. pregnant women
What test can be used to diagnose influenza? Is this done in everyone
-tests to confirm not done in everyone -Tests 1. PCR 2. direct fluorescent antibody 3. enzyme immunoassay 4. can use hemagluttinin inhibition as retrospective test
Name 4 antiviral drugs that can be used to tx influenza
1. Amantadine -influenza A only 2. Rimantadine -influenza A only 3. Zanamivir -neuraminidase inhibitor -A and B 4. oseltamivir -A and B -neuraminidase inhibitor
Define paramyxoviruses
1. non-segmented, single-stranded RNA genome 2. enveloped w/surface glycoprotein spikes 3. helical capsid 4. Replication in cytoplasm -EXCEPT measles virus
Where do paramyxoviruses get their envelope from?
=host cytoplasmic membrane
What is the characteristic cytopathic effect of paramyxoviruses?
1. syncytia =multinucleated giant cells -large aggregates of intact nuclei and extensive cytoplasmic masses -formed by fusion of host cells 2. eosinophillic cytoplasmic inclusion bodies -also see nuclear inclusion bodies w/measles virus
What do paramyxoviruses need to fuse w/host cytoplasmic membrane?
=proteolytic cleavage of viral glycoprotein -done by host protease
Define Nipah virus and Hendra virus
=animal paramyxoviruses 1. capable of jumping species and causing severe, fatal disease in humans 2. Natural resevoir is bats 3. Humans get infection by close contact w/ infected domestic animals 4. no person-person spread 5. Hendra virus: respir illness (severe flu-like) Nipah viurs: encephalitis in SE Asia, Australia
The Genus Rubulavirus includes ___________.
=mumps virus
How are parainfluenza virus and mumps virus transmitted?
-person to person via respiratory secretions
What are the fxns of the HN and F glycoproteins of parainfluenza and mumps viruses?
HN -binds the R -acts as both hemaglutinin and neuramidase F -mediates fusion of virus with host cell
Influenza virus, parainfluenza virus, and mumps virus all use the ________ receptor to get into host cells
=sialic acid R
Croup is caused by __________.
=parainfluenza types 1,2, 3 -acute febrile illness in children -involves upper and lower respiratory tracrt -sx: fever, stridor, hoarseness, cough -usu ages 3 months-3 yrs
Name 3 clinical syndromes caused by parainfluenza virus
1. Croup 2. bronchiolitis 3. lower respr infections -infants
Define Mumps virus
=paramyxovirus; genus rubulavirus -attacks: 1. partoid gland, pancreas, gonads 2. usu present w/ fever and salivary gland enlargement 3. Can also cause: -deafness -orchitis (inflamm of testis) -meningitis
All members of the genus morbillivirus cause _________.
=type of paramyxovirus= (-)ss RNA virus =CNS disease -members 1 measles 2. canine distemper 3. rinderpest
How is measles transmitted?
=person-person spread via respiratory secretions -true for other infections caused by genus morbillivirus
What are the fxns of the 2 glycoproteins used by the measles virus?
=paramyxovirus; genus morbillivirus =(-) ssRNA virus 1. H -binds R (CD46, CD150) and performs hemagluttinin activity 2. F -mediates fusion of virus into host cell -gets cleaved -no neuraminidase activity -sialic acid NOT the receptor -inclusion bodies can be seen in cytoplasm AND nucleus
Name some diseases caused by genus morbillivirus
=measles virus et al -(-) ss RNA virus 1. measles (rubeola) 2. acute post infection encephalitis 3. pneumonia 4. atypical measles 5. subacute sclerosing panencephalitis 6. modified measles
Describe measles infection
=caused by measles virus (genus morbillivirus) -infection via resp secretions -infects nasal mucosa -> lymph nodes -> viremia -sx: rash (morbilliform exanthem that moves from face -> trunk), conjunctivitis, dry cough, fever -no specific tx -give Vit A to reduce morbidity and mortality -can get lifelong immunity from: 1. natural infection 2. vaccine
Define measles virus
=paramyxovirus; genus morbillivirus - (-) ssRNA virus Characteristics: 1. causes measles 2. no antigenic variation 3. no animal resevoirs 4. lifelong immunity from: -natural infection -vaccine
What is the most common cause of death due to measles in developed countries?
=acute post infection encephalitis
What was the cause of atypical measles?
=formalin inactivated vaccine -> no Ab formed to F glycoportein so if acquired wild-type measles it could get infection -associated with severe and prolonged measles (high fever, edema of extremities, pulm infiltrates)
What causes subacute sclerosing panencephalitis?
=measles virus -rare complication of natural measles infection -usu around 7 years after original infection -death 6-12 months after onset -caused by restricted measles virus replication in the brain
Respiratory Syncytial virus is a __________ virus of genus _________.
-paramyxovirus, genus pneumovirus -2 major groups (A, B) -transmission by fomites -causes: 1. respiratory tract infections -infants, young children 2. pneumonia and bronchiolitis -children < 1 yr 3. Colds -adults -immunity is incomplete (can get respeat infections)
Name the 2 glycoproteins for respiratory synctial virus
=paramyxovirus, genus pneumovirus - (-) ssRNA virus -Glycoproteins 1. G -binds R and mediates attachment 2. F -mediates fusion with host cell
What is the most common cause of pediatric nosocomial infections?
=respiratory synctial virus -paramyxovirus; genus penumovirus - (-) ssRNA virus
How does Ivermectin work?
=antiparasitic drug -broad spectrum antiparasitic agen -agonist of GABA R -> inhibition of motor neurons in nemotodes and arthropods -> paralysis of parasite -does NOT cause paralysis in mammals b/c can't cross BBB
Name 2 uses of Ivermectin
1. Strongyloides intestinal form 2. Onchocerca volvulus -txs larval form that can cause blindness
True or false: while members of the herpesvirus rarely cause disease in their natural host, the can cause severe disease when they infect other host species
Describe the group characteristics of herpesvirus
1. Linear double stranded DNA genome 2. Large complex viruses -genome encodes lots of enzymes 3. enveloped 4. icosahedral capsid 5. Tegument in between capsid and envelope 6. genome consists of UL and US regions bounded by inverted repeats 7. Replication and assembly in nucleus 8. No common family antigens 9. capable of establishing latency in host
How is the herpesvirus family classifed
-3 groups based on biologic properties +/- DNA homology 1. Alpha viruses -HSV-1, HSV-2, VZV 2. Beta viruses -CMV, Roseolaviruses (HHV-6, HHV-7) 3. Gamma viruses -EBV, HHV-8
Herpes Simplex Virus (HSV-1, HSV-2) and Varicella-Zoster virus are: a. alpha herpseviruses b. beta herpesviruses c. gamma herpesviruses
=alpha viruses Characteristics: 1. Broad host range 2. short replication cycle 3. latent infection in sensory neurons 4. CPE= eosinophilic intranuclear inclusion bodies and multinucleated giant cells
CMV, Roseolaviruses (HHV-6, HHV-7) are: a. alpha herpesviruses b. beta herpesviruses c. gamma herpesviruses
=beta viruses Features: 1. Restricted host range 2. long replication cycle 3. slowly progresive infections 4. CPE= cell enlargement (cytomegalia) 5. Latent infections in secretory glands, reticuloendothelial cells, kidney
EBV and HHV-8 are: a. alpha herpesviruses b. beta herpesviruses c. gamma herpesviruses
=gamma herpesviruses Features: 1. restricted host range 2. replicate in lymphoblastoid cells in vitro 3. Latency in lymphoid tissues, esp B and T lymphocytes 4. Can cause either latent or lytic infection in B or T lymphocytes
Where do alpha herpesviruses establish latent infections?
=sensory neurons Includes: 1. Herpes simplex virus 2. Varicella zoster
Which herpesvirus has a CPE of multinucleated giant cells w/eosinophilic nuclear inclusions?
=alpha herpesvirus 1. herpes simplex virus 2. varicella zoster virus
Define tegument
=amorphous protein region in between capsid and envelope -seen in herpes viruses
Name 3 proteins found in the tegument of herpes simplex virus
1. alpha TIF (VP16) -transactivator of alpha genes 2. viral host shutoff protein -promotes degredation host mRNAs 3. Phosphoprotein -allows viral DNA to circularize
Define Herpes Simplex virus
=alpha herpesvirus Features: 1. Linear, ds DNA virus 2. enveloped w/ glycoprotein spikes -envelope from nuclear membrane, Golgi, 3. Icosahedral capsid w/central hole 4. Broad host range
Describe the viral genome of herpes simplex virus
1. Large genome 2. linear ds DNA 3. genome circularizes when virus uncoats -remains in circular form for replication 4. 80 open reading frames 5. inverted repeats 6. contains UL (unique long) and US (unique short) sequences
What is the significance of having both US and UL gene sequences flanked by inverted repeats in the herpes simplex virus genome?
-allows production of 4 isomers of the virus -usu produced in equimolar amts
What is the fate of infection cells during a herpes simplex productive infection? Reactivated latent infection?
Productive -cells are killed Latent/reactivated -primary site is sensory neurons -they are not killed
Define Herpes simiae
=Herpes B virus -monkey equivalent of human herpes simplex -humans acquire by monkey bite -causes meningoencephalitis w/95% mortality rate
Where does primary herpes virus infection occur?
-at portal of entry -HSV has short incubation period -80-90% of primary infections are asymptomatic -so one can be infected and not know it, and then spread the virus to others
Name some factors that can lead to reactivation of herpes simplex infection
1. fever 2. sunlight 3. menses 4. stress
True or false: 80-90% of primary infections and most latency reactivations of Herpes simplex virus are asymptomatic
HSV infection can be diagnosed by a ________ smear.
=Tzanck -look for CPE of Herpes simplex (multinucleated giant cells) -positive Tzanck smear also for varicella zoster
Name some host defenses against herpes simplex virus
1. cornified epithelium 2. NK cells 3. cellular immunity (T cells) -impaired T lymphocytes -> more severe infection
How does herpes simplex virus infect a host cell?
1. gB and gC (glycoproteins on envelope surface of HSV) bind heparin sulfate on host cell 2. gD binds to another R on host cell 3. Fusion of viral envelope w/ host cell membrane -at neutral pH 4. HSV nucleocapside gets into nucleus via nuclear pores
Name the 3 types of genes within the herpes simplex viral genome
1. alpha genes -immediate early genes 2. beta genes -early genes -not expressed when alpha proteins absent 3. gamma genes -late genes Note: do NOT confuse this with 3 subfamilies of herpesvirida (alpha, beta, and gamma) -HSV is an alpha herpesvirus BUT contains alpha,beta, and gamma genes
What transcribes the alpha genes of herpes simplex virus?
=immediate early genes -txn by HOST cell RNA POL II -They are transactivated by alpha TIF (=VP16 in the tegument of herpes virus) -all alpha genes have regulatory fxns
Name the 4 alpha genes of herpes simplex virus
=immediate early genes Features: 1. regulatory fxns 2. transactivated by alpha TIF (VP16) 3. transcribed by HOST cell RNA POL II Includes: 1. ICP0 2. ICP4 3. ICP27 4. ICP47
ICP0, ICP4, ICP27, ICP47 are genes belonging to __________.
=herpes simplex virus -alpha (immediate early genes) -play a regulatory fxn
What is the fxn of ICP0 (encoded by alpha gene of HSV)?
=transactivates promotoers -enhances fxn of ICP4
What is the fxn of ICP4 (alpha gene of HSV)?
-required for expression of many late genes -activity enhanced by ICP0
What is the fxn of ICP27 (encoded by alpha gene of HSV)?
-regulates many HSV genes -required for transition between beta and gamma gene expression
What is the fxn of ICP47 (encoded by alpha gene of HSV)?
-blocks presentation of HSV peptides by MHC I -> prevents recognition and lysis of HSV infected cells
Define beta genes of HSV
=early genes Features: 1. encode proteins used in viral replication 2. beta genes NOT expressed in absence of alpha proteins 3. transcribed by cellular RNA POL II
Define the gamma genes of HSV
=late genes Includes: 1. Alpha TIF (VP16) -transactivates alpha genes 2. envelope glycoproteins 3. capsid proteins -gamma genes are made at 2 diff times
True or false: the viral life cycle of varicella is similar to herpes simplex virus
-true -both are alpha herpesviruses
Where does HSV get its envelope from?
=host cell's nuclear membrane
Define latency
=absence of infectious virus but presence of cells with capacity to produce it
How does HSV establish latent infection?
1. Latent infection established in sensory neuron 2. HSV enters at axon and travels up to cell body of sensory neuron 3. during latency no production of viral mRNA or viral proteins 4. reactivation triggered by an outside factor (mechanism unknown) -LAT is impt (antisense RNA)
True or false: reactivation of latent HSV leads to more circumscribed, shorter disease than primary infection
-true -this is b/c of pre-existing humoral and cellular immunity against HSV
Define LAT of HSV
=latency associated transcript -anti-sense RNA -partially overlaps with alpha-0 gene -found in large amts in latently reactivated cells -not sure how it works
True or false: prior infection with HSV-1 provides partial immunity against HSV-2 infection
-true -these 2 herpes simplex viruses are closely related -very similar genomes
Most oral herpes is caused by _______ while most genital herpes is caused by____________.
oral herpes=HSV-1 -also reactivates from latency more frequently than oral herpes caused by HSV-2 genital herpes=HSV-2 -also more frequently reactivates from latency than genital herpes caused by HSV-1
How is herpes simplex virus 1 acquired? HSV-2?
HSV-1 -contact with infected oral secretions HSV-2 -sexual contact with infected genital secretions
What causes acute gingivostomatitis?
=HSV-1 -symptomatic HSV-1 infection in children -sx: -vesicles, painful ulcers, overgrowth of oral anaerobes b/c decreased swallowing -in adults can cause clinical syndrome similar to sore throat from Group A strep
Define herpes labialis
=typical manifestation of reactivation of ORAL herpes -asymtomatic shedding of HSV in saliva
Define Herpetic Whitlow
=infection of a finger with HSV -acquired usu by autoinoculation (thumb sucking, etc)
True or false: HSV can cause keratoconjunctivitis that can cause blindness
-true -corneal inflammation and scarring from keratitis can lead to blidness
Define Herpes encephalitis
=caused by HSV -sporadic necrotizing encephalitis -70% mortality w/out tx -presentations: 1. aseptic meningitis w/fever 2. severe, rapidly progressive w/impaired consciousness 3. Adults -HSV1 neonates -HSV2 4. Likes to infect temporal lobes
Define herpes gladiatorum
=skin infection caused by HSV -seen in wrestlers -spread by direct contact w/person who is shedding the virus
Describe signs and sx of genital herpes
1. genital sores 2. flu-like sx -fever, swollen glands 3. most infections are asymptomatic and usu first infection is associated with most severe disease
What are the complications of genital herpes?
1. painful, recurrent sores 2. severe infections in immunocompromised 3. fatal infections in babies
Name 5 key differences between varicella zoster virus and herpes simplex virus
1. Number of serotypes 2. % GC content -can tell you how similar 2 viruses are 3. Narrow host range 4. no cell free virus found in tissue culture 5. less sensitive to acyclovir
Name some key differences between varcella zoster virus infections and herpes simplex virus infections
1. VZV causes only 1 disease (chickenpox) while HSV causes lots of different diseases 2. VZV lesions found at distant target organs while HSV at site of entry 3. VZV has longer incubation period than HSV 4. VZV is transmitted by resp droplets vs HSV by direct contact 5. Most VZV infections are symptomatic while most HSV infections are asymptomatic 6. Most people are seropositive for VZV while less than 50% are seropositive for HSV
Chickenpox is caused by __________.
=varicella zoster virus -alpha herpesvirus -NOT to be confused with smallpox (both cause skin lesions that can look alike but there are key differences)
Name some diseases caused by Herpes simplex virus
1. Gingivostomatitis 2. Pharyngotonsillitis 3. Keratoconjunctivitis 4. Herpetic Whitlow -infected finger 5. Cutaneous herpes 6. Genital herpes 7. Herpes proctitis -anal and rectum infection 8. Herpes simplex meningitis 9. Herpes simplex encephalitis
Shingles is the recurrent infection caused by reactivation of _____________.
=varicella zoster virus Features: 1. dermatomal (causing many lesions in single dermatome) 2. infection has long prodrome w/severe pain 3. latent infection in sensory neurons in sensory ganglia 4. postherpetic neuralgia is common 5. low frequency of sx recurrence (approx once per lifetime in immunocompetent persons) 6. no asymptomatic virus shedding 7. reactivation associated w/increase in antibody titer 8. risk of recurrence increases with age
True or false: chickenpox infections in adult are generally benign
-false! -can result in severe life threatening infections and death
Name some differences between varicella zoster virus and herpes simplex virus latent infections
1. only 1 VZV recurrent infection (shingles) but lots for HSV 2. VZV causes many lesions in single dermatome (HSV less lesions in single dermatome) 3. VZV has long severe prodrome (HSV shorter and mild) 4. Post herpetic neuraligia is common with VZV but rare with HSV 5. HSV has higher frequency of recurrence (VZV usu only 1 recurrence per lifetime) 6. Most HSV recurrent infections NOT symptomatic while all shingles are 7. VZV no asymptomatic virus shedding 8. 95% shingles get increase in antibody titer (vs few for HSV)
Define postherpetic neuralgia
=pain that continues after shingles outbreak (ie after rash and blisters of shingles heal) -pain usu limited to area where shingles outbreak occured -postherpetic neuralgia is common with varicella zoster virus but rare with HSV recurrent infections -Sx: sharp, jabbing pain or burning deep pain; sensitivity to touch and temp, headaches, itching and numbness
Who should get the varicella virus vaccine?
-all healthy children over age of 12 months -live attenuated VZV virus -vaccine-immunity can wane over time so can get mild breakthrough infection
What is required for acyclovir to be an effective tx of chickenpox?
=must be given w/in 24 hrs of onset of chickenpox rash -good for: 1. persons w/chronic skin or lung disease 2. anyone otherwise healthy older than 13 years of age 3. pts getting steroid therapy
True or false: acyclovir can prevent postherpetic neuralgia
-false -it can decrease it -acyclovir can also decrease new lesions, shedding, and duration of pain
HHV-6 and HHV-7 exhibit tropism for what type of cells?
=CD-4 T lymphocytes -beta human herpes viruses -cause exanthem subitum (Roseola infantum)
What causes Roseola infantum (exanthem subitum)?
=Human herpes virus-6 and 7 (HHV6,7) -Most children infected by 2 yrs of age -Sx: 1. fever 2. maculopapular rash -resolves uneventfully in few hrs-days -80-100% of adults are seropositive for HHV6 -HHV-6 is shed in saliva
Define HHV-8
=gamma human herpesvirus Features: 1. Genome similar to EBV 2. More likely to cause disease in immunocompromised pts -associated w/ Kaposi's sarcoma -body cavity lymphomas
Owl eye inclusions are characteristic of __________.
=CMV -beta herpesvirus -CPE of herpes virus is cytomegalia (cell enlargement)
Where do CMV and HHV6, HHV7 establish latent infections?
=beta herpesviruses Sites of latent infections 1. secretory glands 2. reticuloendothelial cells 3. kidney
Define CMV
=cytomegalovirus=beta herpesvirus Features: 1. linear, ds DNA virus 2. enveloped w/glycoprotein spikes 3. icosahedral capsid 4. tegument in between envelope and capsid 5. replication in nucleus 6. productive infection results in cell death
Name some cells in vivo that CMV likes to infect
=beta herpes virus; linear ds DNA virus 1. monocytes 2. macrophages 3. PMNs 4. endothelial cells 5. sinusoidal lining cells
True or false: viral protein synthesis is required for alpha genes of herpesviruses to be transcribed
Who is at increased risk of acquiring CMV infection?
-daycare workers -CMV is ubiquitous -while most people have been infected with CMV by age 40, risk is to pregnant daycare workers who have NOT been previously infected -there are risks of CMV infection to unborn child
CMV is transmitted by all of the following EXCEPT: a. body secretions b. sexual contact c. organ transplant d. transplacental e. all of the above
=all of the above -most people only infected w/1 strain of CMV, but immunocompromised can be infected w/more than 1 strain
Who is at high risk of severe consequences of CMV infection?
1. unborn children -congenital CMV infection 2. immunocompromised -transplant pts -AIDs -can get: pneumonia, retinitis, colitis, esophagitis, encephalitis
Name 4 clinical syndromes caused by CMV
1. Asymptomatic infection -most infections acquired after birth UNLESS immunocompromised 2. Mononucleosis-like syndrome 3. disease in immunocompromised -pneumonia, retinitis, colitis, esophagitis, encephalitis -AIDs pts more likely to get CMV retinitis, encephalitis -transplant pts more likely to get interstitial pneumonitis 4. Congenital CMV infections -in unborn children
What is the most common cause of heterophile negative mononucleosis?
=CMV -can cause mono-like illness -sx: 1. fever 2. mild hepatitis 3. sometimes: lymphadenopathy, splenomegaly, pharyngitis
Describe congenital CMV infection
=CMV in unborn children when mom gets first CMV infection while pregnant -happens in 1-3% of women -usu no sequelae for most children -infants can be asymptomatic at birth but have later complications (MR, hearing loss) -can get generalized infection -presentation of generalized infection can range from hepatosplenomegaly to fatal illness -> if survive 80-90% have complications (MR, hearing loss, vision impairment)
What is the most common way to diagnose CMV infection?
=PCR Other tests: 1. culture virus (1-3 weeks) 2. ELISA 3. Shell vial technique -lots of false negatives 4. CMV antigen detection -look for antigens on leukocytes in infected person
Name 3 drugs used to tx CMV
1. Ganciclovir -needs to be phosphorylated by viral kinase before drug is active 2. Foscarnet 3. Cidofovir -all these drugs act on DNA polymerase of CMV
How does CMV evade the immune system?
1. CMV downregulate MHC class I -retains MHC I in ER -viral proteins help transport heavy chains of MHC I for degredation -also blocks assembly 2. CMV down regulates MHC II 3. CMV infection depresses non-CMV specific cell mediated immunity
What is impt for recovery from CMV infection?
=cell-mediated immunity -both CD4 and CD8 cells -IgM and IgG are also increased during CMV infection
Define EBV
=epstein barr virus; gamma herpesvirus Features: 1. linear, ds DNA genome 2. Envelope w/glycoprotein spikes 3. icosahedral capsule 4. Tegument in between capsid and envelope 5. Replication in nucleus 6. 2 strains but no difference in clinical disease 7. Latency established in some B lymphocytes 8. EBV can immortalize some lymphoid cells
How does EBV get into host cells?
1. EBV glycoprotein 350 binds to CD21 on B cell 2. gH, gL, and gp42 are glycoproteins required for EBV to penetrate host cell membrane -gp42 binds HLA-Dr
Who is NOT at risk for an EBV infection? Why?
=X-linked agammaglobulinemia -b/c they lack mature B cells
Where does EBV like to establish latency?
=some B lymphocytes
Describe the gene expression of EBV during latency
-can express at least 10 genes, including: 1. EBER1, 2 (=RNAs) 2. EBNa 1,2,3A-C, LP (nuclear proteins) 3. LMP 1, 2A, 2B (membrane proteins) -different genes expressed in different latent conditions -most have impt regulatory fxns
Name 3 latent EBV infections
1. Type 1 -associated w/Burkitt's lymphoma -expressed: EBER-1 and 2, EBNA-1 2. Type 2 latency -associated w/nasal pharyngeal carcinoma -EBER-1 and 2, LMP are expressed 3. Type 3 -associated with non-cancerous cells -at least 10 different genes expressed
What are the fxns of EBNA-3B and EBNA-3C proteins of EBV?
=proteins expressed during latent EBV infections 1. upregulate expression of selective B cell proteins -> B cell proliferation 2. inhibit upregulation of LMP-2
What are the fxns of BARF-1 and BCRF-1 proteins of EBV?
=proteins expressed during latent EBV infection 1. block ability of interferon to inhibit growth of EBV transformed cells
What are the fxns of BHRF-1 and LMP-1 proteins of EBV?
=proteins expressed during latent infection 1. inhibit apoptosis
How many people have antibodies to EBV by adulthood?
How is EBV transmitted?
1. Through saliva 2. Virus can persist oropharynx up to 18 months after infectious mono
Name 5 clinical syndromes associated with EBV
1. Asymptomatic infection/minor upper resp infection -common in infants and young children, 2. Infectious mononucleosis 3. EBV infection in X-linked lymphoprolifeve disease 4. EBV associated malignancies -Burkitt's lymphoma -Nasopharyngeal carcinoma -Hodgkin's disease 5. EBV associated infections in AIDs pt -oral hairy leukoplakia -lymphoid interstitial pneumonitis -non-Hodgkin's lymphoma
What causes infectious mononucleosis?
=EBV -Sx: -fever, lymphadenopathy, pharyngitis, splenomegaly +/- rash, jaundice, hepatomegaly
Name some complications of infectious mononucleosis
-caused by EBV 1. Splenic rupture 2. hepatitis 3. cardiac and pulm problems
Describe EBV infections in pts with X-linked lymphoproliferative disease
1. Can die from EBV infections 2. If survive EBV infection, can develop B cell lymphoma -genetic defect causes impaired normal B cell, T cell interactions -> unregulated growth of EBV-infected cells
Name 3 malignancies associated with EBV.
1. Burkitt's lymphoma 2. nasopharyngeal carcinoma 3. Hodgkin's disease
Hodgkin's disease is associated with ________.
=EBV -in Africa, 90% of Burkitt's lymphoma is caused by EBV -tumor usu presents in jaw -in US, most present with abdominal tumors, only 20% associated with EBV -c-myc expression in EBV infected cells results in increased tumorigenicity of cells
Oral hairy leukoplakia is associated with ______ infection in _______ pts.
EBV infection in AIDs pts
What is the differential diagnosis of atypical lymphocytes?
-atypical lymphs have more cytoplasm (larger) and more nuceoli; =activated, uninfected T lymphocytes 1. EBV 2. toxoplasmosis 3. rubella 4. viral hepatitis 5. mumps 6. drug rxns
How do you diagnose an EBV infection?
1. Heterophile test -monospot -85-90% of pts w/acute EBV infection produce heterophile antibodies that peak 2-3 weeks after onset -antibodies can persist for 2-9 months -NOT EBV specific Ab 2. EBV specific antibodies 3. atypical lymphs on peripheral blood smear
Name 3 100% positive EBV specific antibodies
Against viral capsid Ag 1. IgM VCA 2. IgG VCA EBV nuclear Ag 3. (EBNA)
What is most important for clearance of EBV infection?
=cell-mediated immunity -antibodies also impt -EBV depresses non-EBV specific cell mediated immunity -> reversed normal CD4/CD8 ratio
Koplik's spots refer to ____________.
=the morbilliform rash of measles -moves from face to trunk
Name 3 common upper respiratory infections
1. common cold 2. pharyngitis 3. laryngitis
The sx of nasal obstruction and discharge, sneezing, +/- sore throat, +/- cough but usu WITHOUT fever describes ___________.
=common cold
The sx of sore throat, +/- cervical adenopathy, +/- ulceration, +/- conjunctivitis best describes __________.
=pharyngitis -Can be: 1. dominant complaint 2. can occur with fever 3. may be part of common cold or influenza syndrome Causes: 1. bacterial 2. viral
The sx of hoarseness and loss of speaking voice best describe ________.
=laryngitis -viral illness -should be distinguished from epiglottitis in kids (caused by H. influenza)
The sx of hoarseness, barking cough, dyspnea, and inspiratory stridor often in a young child best describe ____________.
=croup =acute laryngotracheobronchitis
What's the difference between bronchitis, bronchiolitis, pneumonia/pneumonitis?
=which part of the lung or airways is affect 1. Bronchitis -large airways -can be viral or bacterial -if bacterial -> purulent sputum 2. Bronchiolitis -bronchioles affected -usu viral -can get wheezing from obstruction of small airways 3. Pneumonia/pneumonitis -infection of the pulmonary parenchyma
Define the influenzal syndrome
=abrupt onset of fever, headache, severe myalgias, malaise, and prostration -Followed by cough, nasal obstuction, sore throat -can get bacterial illness as a consequence of vial influenza syndrome
True or false: in regards to respiratory infections, the same etiologic agent can cause different syndromes in different hosts and different syndromes in the same host over time.
What is the most common cause of the common col?
True or false: rhinovirus infection causes a lot of destruction to the epithelium of the nasal cavity
-false -it does little damage -it has optimal tempt for replication in nasal passages and large airways
Define coronavirus
=ss (+) RNA virus Features: 1. enveloped 2. replication in cytoplasm 3. 2nd most common cause of common cold 4. 2 antigenically distinct strains 5. S protein forms petal like surface projections
Which virus has an S protein that forms petal like projections?
Define SARS
=Severe acute respiratory syndrome -caused by Urbani SARS associated virus (newly discovered coronavirus) -originated in Guangdong Province in China, spread to Hong Kong, elsewhere -Sx 1. Fever 2. Respiratory Sx 3. Travel to Hong Kong or close contact w/someone who did -many people needed to be hospitalized and those who died died of fulminant pneumonia -95% of people sympomatic if infected w/in 10 days of exposure -no effective tx known
What causes SARS?
=Urbani SARS associated virus -new strain of coronavirus but antigenically distinct from others -CPE= multinucleated giant synctial cells in tissue -prob came from animal resevoir (palm civet)
What disease does coronavirus mostly cause?
=common cold -Urbani strain causes SARS
_______ is a major cuase of lower respiratory tract infection in neonates and young children
=respiratory synctial virus -paramyxovirus; ss (-) RNA enveloped virus -nosocomial infections are common -yearly outbreaks in winter -mortality usu in young children with underlying disease
True or false: RSV has a low secondary attack rate
-false! -high secondary attack rate -since peds nosocomial infection, many healthcare workers get it and get a common cold but spread the virus to other babies and young children
True or false: maternal IgG is protective against RSV infection in neonates
-false -this is the most common cause of pneumonia in neonates
Name 3 complications of RSV infection
1. Respiratory failure 2. otitis 3. reactive airway disease -this is a common peds nosocomial infection and can cause sig mortality (usu in kids with underlying disease)
Aerosolized ribavirin can be used to tx ___________.
=RSV infection
Define human metapneumovirus
=subtype of paramyxovirus -discovered in Netherlands -Can cause: 1. Pneumonia/bronchitis -young children 2. common colds -older children and adults -almost all kids in Netherlands have antibodies to this -tx is supportive
Which respiratory infecting virus is a major cause of ARDS?
Which virus causes swimming pool conjunctivitis?
True or false: the CF antibodies of adenovirus are crossreactive for different serotypes
What virus has a CPE of grapelike clusters?
True or false: all parasites have a true nucleus
-true -b/c both protozoa and helminths are eukaryotes
True or false: almost all people infected with poliovirus develop paralytic polio
-false -95% of infections are asymptomatic -only 0.1% of infected people develop poliomyelitis -paralysis is permanent in 1/200 developing poliomyelitis
True or false: protozoan infections are associated with eosinophilia
-false -only helminth infections associated with eosinophilia
How do we tell the difference between Entamoeba histolytica and Entamoeba dispar
-impt b/c E. histolytica causes invasive disease while E. dispar does NOT (it stays in the intestine) =E. histolytica ingests RBCs is the distinguishing characteristic
True or false: E. histolytica can cause abscesses
-true -esp in liver, but also in brain, lung, skin
Where does Giardia cause it's pathology
=intestinal protozoa -causes pathology in small intestine -vs. Entamoeba histolytica, causes pathology in colon
Name 3 viruses that can cause chronic hepatitis
1. Hep B virus 2. Hep C virus 3. Hep D virus
Define Hepatitis A virus
=ss (+) RNA virus Features: 1. member of the picornavirus family 2. nonenveloped, icosahedral capside 3. only 1 serotype 4. similar replication cycle to poliovirus 5. causes little CPE 6. does NOT replicate well in tissue culture 7. fecal-oral tansmission 8. more physically stable than other enteroviruses 9. Causes acute but NOT chronic hepatitis
How is hepatitis A virus transmitted?
=fecal oral tranmission via 1. close personal contact (household, sexual, kids at daycare) 2. contaminated food and water 3. parenteral transmission -IV drug users, transfusion -rare -Everyone is at risk for Hep A infection -Improving SES conditions is reducing # of adults that are seropositive -in developing countries most infections occur early in childhood
True or false: Hep A virus causes both acute and chronic hepatitis
Describe infection caused by Hep A virus
=only causes acute hepatitis Features 1. Disease less severe in kids, kids usu NOT jaundiced 2. 30 day incubation period 3. Rates of jaundice w/infection increase with age (if over 14 yrs 70-80% become jaundiced) 4. Dx by serology 5. almost everyone recovers from Hep A -tx is supportive care, recover in 6-8 weeks 6. survivors have lifelong immunity 7. rare complications: fulminant hepatitis, choestatic hepatitis
How can we prevent hepatitis A infections?
1. avoid exposure 2. vaccine -very effective b/c only 1 serotype of Hep A and isolates so only minor genetic variation
Define Hepatitis B virus
=ds, partially circular DNA virus Features: 1.member f the Hepadnaviridae family 2. enveloped, icosahedral capsid 3. causes both acute and chronic hepatitis infections 4. viral DNA can be integrated into host genome in chronic infections 6. humans are a natural host 7. major Ag is HBsAg (a surface Ag)
Define Dane particle
=42 nm diameter infectious Hep B virion Contains: 1. Central core surrounded by a layer of HbsAg 2. Core= HBcAg + viral DNA + DNA polymerase + additional protein -core made in nucleus of host cell and gets coat in cytoplasm
Define HBsAg
=surface capsid protein of Hep B virus Features: 1. produced in excess during viral replication 2. Found on both Dane particles (infectious virions) and noninfectious other particles 3. present in bloodstream during acute disease, carrier state
How is Hepatitis B virus transmitted?
1. percutaneous exposure 2. sexual exposure 3. mother-child Hep B can cuase both acute and chronic hepatitis
Describe the Hepatitis B infection
=both acute and chronic infections 1. Prodrome -immune complex formation -> sx (rash, arthritis, glomerulonephritis) 2. avg incubation 60-90 days 3. 30-50% get jaundice if over 5 yrs 4. Dx by serology 5. Infected neonates, infants more likely to develop chronic hepatitis 6. Tx: supportive care, drugs (dipoxil, alpha interferon, lamivudine)
Who gets chronic Hep B infections?
1. > 90% of neonates infected with Hep B 2. 80% of perinantal pts with hep B 3. 50% infants with hep B 4. only 5-10% of adults with Hep B
Name some complications of chronic Hep B infection.
1. Increased risk of hepatocellular carcinoma 2. Cirrhosis 3. Premature death from chronic liver disease
What's the risk of hepatocellular carcinoma with Hep B infection?
=15% of carrier develop it -the younger a pt with chronic infection acquires infection, the higher the risk of hepatocellular carcinoma
How do we prevent Hep B infection?
1. avoid 2. passive immunization with high titer HBV immune globulin 3. vaccine against HBsAg subunit 4. Screen women during pregnancy for Hep B infection, then give baby hep B immune globulin after birth to prevent chronic infection
True or false: dx of chronic Hep B infection can be made by detection of serum antibodies against the HBsAg
-false -antibodies not detectable for chronic infection (only for acute)
Define chronic hepatitis B
=chronic liver disease due to persistent infection with Hep B virus Features: 1. persistent hepatocyte necrosis 2.hepatic inflammation 3. can be divided into HBeAg positive and HBeAg negative forms
Define asymptomatic HBV carrier state
=they have persistent HBsAg in bloodstream but NO evidence of hepatocyte necrosis or inflammation
Define resolved Hepatitis B
=previous HBV infection of liver without significant evidence of persistent HBV infection -usu seropositive for: 1. anti-HBs 2. anti-HBc
Define acute exacerbation of chronic Hep B
-increase serum levels of liver enzymes (SGOT) to more than 10x normal and more than 2x baseline -could be due to Hep D superinfection
Define reactivation of Hepatitis B
=reappearance of active hepatocyte necrosis and inflammation in a person who was: 1. asymptomatic carrier 2. had previously resolved Hep B
True or false: antibodies against 1 strain of Hep B virus will protect you against all strains
-true -if successfully vaccinated against Hep B, you will also be vaccinated against Hep D
What is required for Hep D infection?
=infection with Hep B -you if you're vaccinated against Hep B, you'll be immune to Hep D as well
Define Hepatitis D virus
=defective, ss (-) RNA virus Features: 1. only 1 serotype 2. requires help of Hep B to replicate (Hep B infection required for hep D infection) 3. genome similar to plant viruses 4. can cause both acute and chronic hepatitis 5. can get acute coinfection of Hep B and D (can be severe) or superinfection of Hep D in chronic HBV carrier
How is hepatitis D virus transmitted?
1. Percutaneous transmission 2. sexual transmission 3. rare perinatal transmission
Why do we worry about Hep D superinfections?
-b/c 70-80% of pts with superinfection of hep D (were previously chronic carriers of Hep B infection) will go on to develop chronic liver disease and cirrhosis
Define Hepatitis C virus
= ss (+) RNA virus Features: 1. member of the family Flaviviridae 2. enveloped, icosahedral capsid 3. replicates in cytoplasm 4. does NOT grow in tissue culture 5. humans are natural hosts 6. can cause both acute and chronic hepatitis
Which hepatitis virus is major cause of post-transfusion hepatitis?
=hep C -rates of acquiring from properly screened blood are small
How is Hepatitis C virus transmitted?
1. Percutaneous -IV drug use -clotting factors -transfusion from infected donor -contaminated equipment -needlestick (HCW hazard) 2. Perinatal 3. sexual
True or false: healthcare workers who get a needlestick from a Hep C infected person are likely to develop Hep C
-false -transmission very inefficient b/c low concentration in blood of chronic hep C carriers -risk is 1.8% -more likely to get Hep B as a healthcare worker than Hep C
Is there a difference in outcome for neonates infected perinatally with Hep B vs Hep C?
-yes - >90% of babies infected with Hep B go onto develop chronic hep B -infected babies with Hep C tend to do well and severe hepatitis is rare -transmission of hep C at birth is about 6% and rate of transmission is higher with HIV coinfection
Describe hepatitis C infection
=can cause both acute and chronic infections Features: 1. acute infections tend to be mild 2. avg incubation period about 6-7 weeks 3. chronic infection occurs in 60-85% -many of these can be asymptomatic 4.cirrhosis can occur in 5-20% of pts with chronic infections 5. diagnosis by serology 6. course of disease is variable and influenced by certain factors 7. increased risk of liver cancer (1-4% per yr) 8. Tx: interferon, ribavirin (response varies by genotype)
Name 5 factors the promote the progression/severity of chronic Hepatitis C
1. increased EtOH 2. age > 40 yrs at time of infection 3. HIV coinfection 4. Male 5. other coinfections (HBV) A slow progression of disease (30 yrs) is associated with young age at infection, female
True or false: response to tx in Hep C varies by genotype of the virus
-true -genotypes II and III respond better than genotype I
Define Hepatitis virus E
=ss (+) RNA virus Features: 1. used to be member of Caliciviridae but now own family (HEV-like viruses) 2. nonenveloped, icosahedral capsid 3. does NOT replicate in tissue culture 4. humans are natural hosts
Which Hepatitis virus is often linked to drinking fecally contaminated water?
=hep E -minimal person-person transmission
Describe infection by Hepatitis E virus
=causes acute infection ONLY Features: 1. avg incubation 40 days 2. dx by serology 3. High fatality rate in pregnant women (esp if in 3rd trimester) 4. tx: supportive care 5. old people that get Hep E tend to get sicker 6. prevention: be careful what you eat and drink in endemic regions

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