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Misfolded proteins, neural degeneration, dementia, myoclonus, CNS deficits
- Prions - Creutzfeldt-Jakob disease (CJD)
- Rapidly progressing dementia - death within 1 year.
- Misfolded proteins enter CNS cells and induce abnormal folding of normal proteins which leads to spongioform cortex (holes in tissues). Can come from corneal transplants.
- Gait abnormalities
Mad cow disease England 1980s, very rare, symptoms develop at younger age (< 30 years old)
Prions - variant Creutzfeldt-Jakob disease (vCJD)
Giant intestinal roundworm, mechanical activities (penetrate through intestine after being swallowed - oral-fecal route, travel to liver then to heart and lungs), early symptoms are pulmonary (cough/wheezing), later GI (cramps/abdominal pain due to obstruction with heavy worm loads). Diagnosis by stool examination, treat with albendazole, mebendazole, or ivermectin
- Parasite - Ascaris lumbricoides
- Have cuticle, lays lots of eggs in patient's feces.
- Can cough, vomit worms up, they can also come out nose or mouth or anus.
Watery diarrhea - in immunocompromised can cause substantial electrolyte and fluid loss; chlorine resistant - acquired through contaminated water, most common recreational waterborne illness. Healthy people - illness is self-limiting, lasts ~ 2 weeks, Otherwise treat the AIDS with antiretroviral therapy
Parasite - Cryptosporidium parvum
Watery diarrhea, N&V, abdominal pain. Food (berries) or water contamination, long incubation period. Treat with TMP-SMX.
- Parasite - Cyclospora cayetanensis
- low number needed to infect, disrupts small intestine epithelium - watery diarrhea.
Can be asymptomatic, usually Amebic colitis (dysentery-inflammation of the colon); ingested cysts hatch out trophozoites that produce ulcers on the surface of the intestines - bloody/mucus diarrhea. Symptoms can mimic appendicitis. Can cause abscesses in liver and then right lung. Treat with metronidazole.
- Parasite - Entamoeba histolytica
- Flask shaped ulcers on large intestines.
Pinworm, perianal pruritus, scotch tape test. Usually in children. Treat with albendazole or mebendazole. Most common helminthic (roundworm) infection in US. Fecal-oral. Treat with albendazole.
- Parasite - Enterobius vermicularis
- Lives in large intestine, female comes out anus to lays eggs.
Water borne, malabsorptive diarrhea, intermittent flatulence/belching. Treat with metronidazole, or during pregnancy use paromomycin.
- Parasite - Giardia lamblia (intestinalis)
- multiples rapidly
- in Giardia - parasite covers over the villi so they can't absorb - get steatorrhea
- reduction in area of absorptive intestinal epithelium.
Barefoot spread - travel through blood and lungs, ascend respiratory tract, are swallowed and then feed in small intestines, anemia (iron deficiency) and lethargy. Rash at site of larval entry. Ova in stool. Treat with albendazole or mebendazole.
Parasites - hookworms (e.g., genus Necator and Ancylostoma)
Barefoot spread - travel through blood and lungs, ascend respiratory tract, are swallowed and then feed in small intestines, can auto infect - Larva currens (creeping infection). Larvae in stool. Treat with ivermectin.
- Parasite - Strongyloides stercoralis
- A type of round worm commonly called "threadworm"
- Ivermectin targets Cl- channels, causes hyperpolarization which leads to nerve and muscle dysfunction.
- creeping infection
- specific to Strongyloides stercoralis
- Results from autoinfection, eruption begins in the perianal region and rapidly spreads, causing intense pruritus. Can persist for decades because of this.
- Autoinfection can be internal (larvae convert within intestine and immediately re-enter bowel wall), or external (larvae passed in stool re-enter through skin of buttocks and thighs)
Infected meats (raw/undercooked), scolex and proglottids. Can pass motile segments. Treat with praziquantel.
- Parasites - tapeworms (e.g., Taenia saginata)
- Praziquantel binds to tape worm, creates calcium channel influx, which then causes muscle contraction and paralysis and then tegument disruption.
The knoblike anterior end of a tapeworm, having suckers or hooklike parts that in the adult stage serve as organs of attachment to the host.
a sexual segment of an adult tapeworm, containing both male and female reproductive organs. Each mature segment is shed and produces additional tapeworms.
Reticular and elementary bodies, very common, treat with azithromycin, cell-mediated immunity to clear infection. Vertical infection leads to neonatal conjunctivitis and pneumonia. PID, epididymitis, lymphogranuloma venereum, reactive arthritis. Treat with azithromycin or doxycycline.
- Chlamydia trachomatis
- Most common cause of STDs in US
- Uncomplicated - azithromycin/doxycycline
- PID, epididymitis, lymphogranuloma venereum - doxycycline
- Treatment is presumed when gonorrhea is present.
Seen in Chlamydia trachomatis, (LGV) is a sexually transmitted systemic disease (STD) caused by a parasitic organism closely related to certain types of bacteria. It affects the lymph nodes and rectal area, as well as the genitals, in humans. The name comes from two Latin words that mean a swelling of granulation tissue in the lymph nodes resulting from sexual intercourse. Granulation tissue is tissue that forms during wound or ulcer healing that has a rough or lumpy surface.
Causes bacterial vaginosis, clue cells on microscopic evaluation. Alteration of natural vaginal flora, reduced lactobacilli. Can be caused by antibiotic use. Fishy, gray discharge and itching. Treat with oral or topical metronidazole or topical clindamycin.
- Gardnerella vaginalis
- Forms biofilms
- pH > 4.5
Gram + rod, can be taken in by raw food (dairy, vegetables, meats), can survive and grow at refrigeration temperatures. Generally controlled by cell-mediated immunity, immunocompromised, neonates, and elderly at high risk. Can cross placenta from infected mother causing abortion or early infant death. Blood culture and CSF inspection. Treat with IV ampicillin + gentamicin (synergistic)
- Listeria monocytogenes
- Lightly contaminated foods can become heavily contaminated during refrigeration so avoid soft cheeses (unpasteurized), hot dogs, deli meats, smoked seafoods, raw milk (unpasteurized)
- Neonatal meningitis
Environmental mycobacterium (soil/water), only in severely immunocompromised people. Pulmonary infection is similar to TB. Not contagious from person to person. Treat with clarithromycin or azithromycin, rifampin, ethambutol.
- Mycobacterium avium-intracellulare complex
- Type IV hypersensitivity
Gram - diplococcus, lots of pus, dysuria, untreated can cause sterility in both males and females. Vertical transmission can infect neonate's eyes. PID, inflammation of the Skene ducts and Bartholin glands in women. Septic arthritis - knees. Epididymitis in men. Drug resistance is increasing. Treat with 3rd generation cephalosporin - ceftriaxone plus azithromycin or doxycycline
UTIs, urease production and stones. Normal fecal flora, present in soil and water. Infection due to disruption of normal flora by antibiotic therapy. Treat with sulfa drugs.
urease hydrolyzes urea, leading to the formation of struvite (Mg ammonium phosphate) stones - seen in Proteus infections
Gram + coccus, UTI in younger, sexually active women. Treat with cephalosporin, augmentin, fluoroquinolones.
Gram + coccus, 40% of women have it, newborn at risk for meningitis with early rupture of amniotic sac/long delivery, so screen late in pregnancy and treat if present with penicillin.
- Streptococcus agalactiae (group B strep)
- The “group B” refers to the Lancefield antigen.
- Neonatal sepsis with in first 5 days, meningitis in first 10-60 days, with high mortality if not treated.
Spirochete, treat with penicillin, nonspecific titers decrease with treatment, specific titers persist. Primary: PAINLESS chancre. Secondary: rash including hands and feet, condyloma lata, alopecia areata, lymphadenopathy. Tertiary: Gumma, neuro(symptoms), thoracic aneurysm, blindness. Vertical transmission also.
- Treponema pallidum (neurosyphilis in tertiary form)
- "Great imitator" - rash and disease can present in many different ways.
- Argyll-Robertson pupil (prostitute pupil) accommodates but doesn't react.
- Congential manifestations - Hutchinson teeth (notches), Saddle-nose deformity, ToRCH syndrome = deaf
Found in tertiary stage of syphilis. Soft, destructive, inflammatory masses that are typically localized but may diffusely infiltrate an organ or tissue; they grow and heal slowly and leave scars
- Haemophilus ducreyi
- "you do cry with ducreyi"
- Without treatment chancre healing can damage or scar the genitals.
- Not on exam - just to show there are painful chancres in comparison with the painless chancre of syphilis
Immunocompromised, congenital infections, transplants. Similar to infectious mononucleosis infection (atypical lymphocytes) but lacks severe pharyngitis. Retinitis. Vertical transmission may cause abortion, stillbirth, or postnatal death. Treat with ganciclovir, foscarnet
- Cytomegalovirus (CMV) - A Herpesvirus
- Congenital - ToRCH syndrome - Microcephaly, sensorineural hearing loss, TTP, petechiae, hepatosplenomegaly, mental and motor dysfunction.
- CMV retinitis - scrambled eggs/ketchup or pizza pie appearance on fundoscopy (hemorrhage with soft exudates) when CD4 < 50.
- Owl's eye appearance on tissue biopsy.
Reduced CD4 count (symptomatic at CD4 < 350), impaired cell-mediated immunity, increased risk of infections. Diagnosis by antibody, nucleic acid, or antigen testing.
mild German measles, potentially teratogenic in fetus, vaccine available. Respiratory droplets for transmission, less contagious than measles, lifelong immunity after natural infection. Rash is less extensive than in measles. Supportive care only.
- Rubella - vaccine is MMR (live virus)
- ToRCH syndrome - congenital syndrome, sensorineural deafness, cataracts, TTP, MR, heart defects.
- Rash lasts ~ 3 days.
Thrush, skin folds, gets worse with HIV. Altered flora from antibiotic use. KOH test. Vaginal candidiasis.
Immunocompromised, particular situation in diabetics with rhinocerebral mucormycosis (breath in spores, get nasal --> brain infection), these fungi are helped by decreased PMN function and by the ketone body environment of DM1 (ketoacidosis). Treat by controlling underlying conditions, amphotericin B, surgical debridement. Also caused in patients taking iron-chelating drug deferoxamine, treat by stopping that med.
Mucor and Rhizopus species
HIV-associated, opportunistic, need alveolar macrophages to clear it, presents as interstitial pneumonia, ground glass appearance. Treat with sulfa drugs, TMP-SMX. Does not cause disease in immunocompetent patients.
Pneumocystis jiroveci (carinii) - the fungus that acts like a protozoan
Lots of neutrophils in discharge, trophozoites only as they swim around, direct microscopic examination of secretions. Mostly asymptomatic in men, copious, yellow-green, frothy vaginal discharge in women. Strawberry cervix. KOH whiff test - fishy odor. Treat both partners with metronidazole.
Parasite - Trichomonas vaginalis
Tick borne rickettsia, human granulocytic anaplasmosis, treat with doxycycline, fever as it infects a number of WBCs. No rash. Targets neutrophils.
- Anaplasma phagocytophilium
- Same tick as Lyme and Babesiosus
Lyme disease, deer tick, spirochetes that take some time to transmit, treat with doxycycline, primary site of infection with erythema migrans, can continue to arthritis, heart block, and neurological symptoms (focal signs like cranial nerve palsies, cognitive effects) Can mimic RA findings.
a disease that begins as small papules that spread peripherally, characterized by a raised, red margin and clearing in the center. It may mark the site of a tick bite and is a diagnostic sign of Lyme disease. Also called bullseye rash.
Q fever (FUO), rickettsia, livestock wastes, can be inhaled. No rash. Specimens are hazardous - lab should be notified, very contagious. Treat with doxycycline.
- Coxiella burnetii
- Q is for Query - what the ...!?
Tick borne rickettsia, human monocytic ehrlichiosis, treat with doxycycline, fever as it infects a number of WBCs. No rash. Lone star tick.
Tularemia, multiple mammal reservoirs, few bacteria needed to infect, several vectors like ticks and deer flies. Primary presentation with local ulcerative lesion, regional lymphadenopathy. Treat with streptomycin. Can be infected by inhalation, tick bite, ingestion of contaminated food/water, direct contact with infected tissues or material. Notify lab - very contagious!
- Francisella tularensis
- (mowed over the rabbit den in Martha's Vineyard)
Rickettsia, Rocky Mountain Spotted Fever, endothelial invasion - rash from extremities to trunk. Treat promptly with doxycycline, can be fatal but easily curable.
- Rickettsia rickettsii
- "black measles" because of rash
- Red maculopapular rash FIRST on wrists/ankles then spreading centrally (usually sparing face)
- May develop coma, encephalitis, and multiorgan failure.
- Doxycycline treatment even in children, hepatotoxicity be damned!!
Bubonic plague, with prairie dog and rat reservoirs, flea bite spread, battle at lymph nodes, get bubo. Treat with aminoglycosides
- Yersinia pestis
- can progress to DIC (extensive purpura - "black death") and gangrene. Death from pneumonia or meningitis. Organism looks like a "safety pin"
- large, infected lymph node
- an enlarged and inflamed lymph node, particularly in the axilla or groin, due to such infections as plague, syphilis, gonorrhea, lymphogranuloma venereum, and tuberculosis
Aedes mosquito, tropical regions, breakbone fever, can have hemorrhagic outcome if had one strain and then infected with another
- Biphasic fever, biphasic rash, then hemorrhagic fever stages
- Tourniquet test - purpura from pressure of tourniquet placed on the arm.
- Manage with volume support, Acetaminophen (not NSAIDs to reduce bleeding)
All body fluids infectious, as the virus generates a high count with a longer incubation; so not infectious until symptomatic
Rodent droppings inhaled when sweeping, so aerosolized and get a severe pneumonia pattern
- Hantavirus (Hemorrhagic Fever)
- Southwest US, affects young, healthy adults (esp male)
- Fever, chills, severe myalgias (back and legs), then N/V/D, HA and weakness.
- Supportive ICU admission.
Transmitted by bite/saliva, further from CNS is a better prognosis - wash wound to lessen saliva transmission. Treat with both immune globulin and active immunization - PEP
- Not by rodents.
- Raccoons, bats, skunks, foxes, wolves. Vaccination of domestic animals.
- Pain, paresthesias, itching, then hydrophobia, laryngospasm, numbness, paralysis. Rage, foaming at the mouth. Respiratory phase is muscle paralysis leading to death.
- Negri bodies in brain tissue (hippocampus)
- PEP - Rabies vaccine (HDCV) with rabies immune globulin to wound and IM
Older adults more vulnerable, arbovirus (mosquito spread)
- West Nile Virus
- Flavivirus, transmitted by a mosquito and can cause mild illness as well as severe, sometimes fatal encephalitis and meningitis. Birds are reservoirs - large numbers of birds (crows) died when first outbreak occurred.
- Late summer and early fall.
- Flu like symptoms, headache, fatigue, malaise, N/V, stiff neck, mental status changes.
- Intense supportive treatment only.
- ar-bo = arthropod-borne
- any one of more than 300 viruses transmitted by the saliva of insects. The majority of human infections are asymptomatic, but symptomatic infections can be characterized by fever, rash, and bleeding into the viscera or skin. Some lead to encephalitis with fatality or permanent neurologic damage. Vertebrate infection occurs when a contaminated arthropod takes a blood meal. Dengue, yellow fever, and equine encephalitis are three common arboviral infections. Treatment is symptomatic for all arbovirus infections. Vaccines have been developed to prevent infection from some arboviruses. Also called arthropod-borne virus. arboviral adj.
"American Malaria", tick borne, asplenic patients cannot clear the infected red cells. Fever, hemolytic anemia, and jaundice. Higher risk in elderly and AIDS patients. Treat with atovaquone plus azithromycin.
- Protozoa Babesia microti Babesiosis
- Northeast US.
- Same tick as Lyme and Ehrlichiosis (Anaplasma phagocytophilium)
Contaminated water with freshwater snail stage, penetration of skin with cercarial stage, adults set up house and lay eggs for decades, with granulomatous response to try to clear the eggs. Watery diarrhea from intestinal mucosal ulcerations. Treat with praziquantel. Children more susceptible to infection than adults in endemic areas - suggests possibility of acquired immunity.
- Flukes (trematodes), particularly Schistosoma species
- Eosinophilic response to eggs can lead to bladder cancer or cirrhosis depending on species and where eggs are lodged
The parasitic larva of a trematode worm, having a tail that disappears in the adult stage. Seen in flukes (trematodes), particularly Schistosoma species.
Sandfly spread, flagellate that can penetrate into different areas of body, requires CDC-type meds to clear, liposomal amphotericin B. Supportive measures also.
The ameba goes up the nose to cause fatal meningitis; Symptoms begin with alteration of smell and taste within 1-2 weeks. Death within another 10 days usually due to cerebral herniation. Try to treat with amphotericin B, azithromycin, miltefosine.
Malaria, with (_____) species most deadly. Life cycle of sporozoite from mosquito getting into bloodstream and initially settling in the liver, with subsequent eruption of merozoites to infect RBCs, once in RBCs feeding stages of trophozoites, then multiply as schizonts, then released as merozoites again. Some end up as gametocytes and get sucked up by mosquito, where they "mate" to form oocytes and then release sporozoites again. Need prophylaxis and mosquito avoidance.
- Protozoa Plasmodium falciparum <-- most deadly
- and other Plasmodium species (vivax)
- Anopheles mosquito
- Sickle cell trait and thalassemia trait are protective against Malaria.
- Cyclical fevers as RBCs burst.
- Treat with Chloroquine, quinidine
Cat poop handling, pregnant women and immunocompromised at risk. Vertical transmission can produce retinochoroiditis, seizures, and intellectual disability. Treat with pyrimethamine plus sulfadiazine. Prevention by washing hands thoroughly after handling raw meat, soil, or cat litter.
- Toxoplasma gondii
- Most common brain pathogen in AIDS patients
- Ring enhancing lesion
- Congenital - ToRCH Syndrome - TTP, hepatosplenomegaly, hearing loss, mental retardation.
Chagas disease (topical regions) from reduviid bugs (not bedbugs); hard to clear trypanosomes in peripheral blood. Symptoms begin with a skin lesion or unilateral periorbital edema, then fever, malaise, generalized lymphadenopathy, and hepatosplenomegaly. Years later can develop fibrosis around heart (cardiomyopathy) from nerve cell ganglia destruction; and gut (megacolon). Treat with nifurtimox or benznidazole, also supportive care for heart failure, heart block, arrhythmia, esophageal stricture.
Protozoa Trypanosoma cruzi
- a member of the family Reduviidae. Called also cone-nose bug, assassin bug or kissing bug. One of the triatoma species is involved in the transmission of chagas' disease.
- As commonly used, any bug that acts as a vector for Chagas disease, so named because they often bite on the face. It is a cone-nosed haematophagous insect with various hosts in the tropics and subtropics; it measures 1-4 cm and is ‘autumn-colored’; its bite elicits papules, painful urticaria, haemorrhagic bulla, occasionally angiooedema, anaphylactoid reaction, and shock; it is also the vector for trypanosoma—Chaga’s disease—causing inflammation, atrophy and fibrosis of Auerbach’s plexus ganglion cells, resulting in acquired megacolon
- Later presentation in Chagas disease. Abnormal massive dilation of the colon that may be congenital, toxic, or acquired.
- Intraluminal overgrowth of microorganisms
Oral fecal transmission, shellfish/oysters, spiking fevers, vaccine available. Self limiting. Exposure to contaminated water during international travel.
- Hepatitis A
- IgM HAV Ab positive during acute infection
- IgG HAV Ab positive with IgM negative with past exposure.
- Strong adaptive response (both cell-mediated and humoral) subsequent immunity once cleared.
DNA Virus, vaccine available. Acute infection - supportive care, Chronic - alpha-interferon2b, lamivudine, adefovir. Reverse transcriptase inhibitors. Sexual, vertical, and parenteral transmission.
HBV - HBsAg
Actual virus is the Dane particle – round things, there are also surface antigens (HBsAg) that are filaments (cheese doodles). The Dane particle is what reproduces and sheds bits that turn into the filaments (HBsAg). Once a person is infected the viral load increases (more Dane particles) and then there is a window period before HBsAb increases enough to be protective. Not only does there need to be enough HBsAb to act on the Dane particles but enough to also act on the HBsAg in the filament form because they work like a distractor (chaff) and could prevent the HBsAb from getting to the Dane particles (to neutralize or allow triggering of complement or have antibody-dependent cell-mediated cytotoxicity). The HBsAb and HBsAg titrate each other in the window period as part of the effort to clear the infection (during the window period both HBsAg and HBsAb are negative). Once HBsAb is positive and HBsAg is negative the individual has immunity and can no longer be infected with HBV (this also means they are no longer contagious).
Chronic HBV infection
- Chronic HBV infection is when HBsAg is positive longer than 6 months and/or HBsAb is not developed within 6 months.
- Positive HBV DNA indicates chronic infection with active replication in the liver.
- antigen-antibody complexes may cause Type III hypersensitivity reactions in skin/joints/kidneys
- Liver damage is from cell mediated immunity of the cytotoxic T lymphocytes trying to clear the infection.
Vaccination provides the HBsAb required to be protective against exposure to HBV/HBsAg. This effectively makes a “memory” and provides immunity so that if the patient comes in contact with HBsAg it is immediately destroyed.
HBV and HDV
HDV is defective and needs HBV to cause a co-infection/superimposed infection because it needs HBV for envelopment. When infected with both HBV and HVD, hepatitis is more severe, with a faster progression to cirrhosis. Vaccination against HBV is also protective against HDV in that HDV will never have HBV to help “activate” it.
Parenteral transmission, usually IVDU (much more than sexual), can also transmit vertically, or get from blood transfusions before 1992. Treat with ribavirin + pegylated interferon. Sofosbuvir ($$$$) is a new treatment that could put viral load to zero (~remission).
- Hepatitis C
- Error-prone RNA polymerase allows for antigenic drift so there is a population of varying virus which makes it harder to treat and leads to long-term, chronic infections.
- 80% of infected individuals will go on to chronic disease.
Co-infection with HBV (superinfection)
- Hepatitis D
- With vaccine against Hepatitis B or post exposure immunity to Hepatitis B, Hepatitis D is completely harmless.
Oral fecal transmission, self limiting but can be fatal in pregnancy (esp 3rd trimester).
- Hepatitis E
- Vaccine developed in China but not available globally.
- More prevalent outside of US.