Diseases naturally transmitted between vertebrae animals and humans by contact, ingestion of contaminated water, or thru arthropod vectors (tick MCC). Risk factors: agricultural workers, animal processing workers, outdoorsmen, pet owners, vets, immunocompromised.
General viral illness vs tick-borne illness: consider in flu-like syndrome with either thrombocytopenia, elevated LFTs, or hyponatremia.
Tick Removal: apply viscous lidocaine to kill the tick and anesthetize the bite. Then use tweezers and pull upward from the closest point to the skin that the tick has attached to. Avoid crushing body. Then clean the surface of the skin off with disinfectant.
Rocky Mountain Spotted Fever
Caused by Rickettsia rickettsii. Vector is dermacentor tick. Peak between April and September. Most severe tick disease; mortality 5-10%. Around mid-Atlantic region: North Carolina, South Carolina, Tennessee, Oklahoma, Arkansas.
Clinical Features: fever, headache, myalgias, malaise; also get lymphadenopathy, nausea/vomiting, hepatosplenomegaly, conjunctivitis, renal failure, respiratory failure. Rash occurs 2-4 days after fever – blanching erythematous rash that becomes petechial later. Begins usually on hands,feet,wrists,ankles that then spreads centripetally.
Testing/Treatment: IgG/IgM antibodies not present in acute phase. Nonspecific neutropenia, thrombocytopenia, elevated LFTs, hyponatremia. Tx with doxycycline 100mg BID x 5-10d both for adults and children (recommended by AAP and CDC – insignificant teeth staining with one abx course)
Bug: Borrelia burgdorferi (spirochete), Vector: Ixodes scapularis (black legs). Endemic areas: Northeast and Wisconsin/Minnesota
Clinical Features: Stage I (days to week, typically 7 days after bite): fever (should be low grade), myalgias, athritis, headache, sometimes RUQ tenderness. Can have elevated transaminases. 90% will have classic rash: erythema migrains. Erythematous macular/papular rash with central clearing, though do not necessarily have to have central clearing. Stage II (weeks to months): neurologic abnormalities – bilateral Bell’s palsy, meningitis/encephalitis, peripheral neuropathies. Cardiac abnormalities as well – various AV blocks, myocarditis. Later late stage has migrating oligoarthritis usually in larger joints such as knee. Post-treatment Lyme disease syndrome: aches/pains, cognitive problems – difficulty thinking, stuttering. Can occur even after correct treatment.
Testing/Treatment: Clinical suspicion. Tests are basically pointless in the ED, except for possible Stage II or later disease. Two Tier system: Do ELISA (checks for antibodies, very sensitive) first, then if positive, do Western Blot (checks for antigens) of either IgM (earlier) or IgG (later). PCR, urine all useless. Adults, non-pregnant, non-lactating, kids > 8yo: Doxycycline 100mg BID x 3 weeks. Allergy or other populations: Amoxicillin 500mg TID x 3 weeks (kids 30mg/kg/day), PCN, cefuroxime, azithromycin. Stage II usually needs longer course.
Prophylaxis: NEJM 2001: 3.2% of placebo group got Lyme vs 0.4% of treated group. 1 in 33 chance of getting Lyme disease with tick bite in endemic area. CDC recommendations for prophylaxis: tick on for > 36 hrs, ixodes tick, endemic area, < 72 hrs since bite. Chance of getting Lyme disease with time of exposure: 0% at 24 hrs, 12% at 48hrs, 79% at 72hrs, 94% at 96hrs. Doxycycline 200mg x 1 only. No studies have shown benefit with amoxicillin. Unable to give in kids < 8.
Bug: Ehrilicia genus. Vector: lonestar tick, Amblyomma americanum. Usually from white-tailed deer in southeast US.
Clinical Features: begin 10-14d after bite. Fever, headache, malaise, N/V, diarrhea, abdominal pain, arthralgias. Can develop severe renal failure, respiratory failure, encephalitis. Labs: leukocytopenia, thrombocytopenia, elevated LFTs.
Testing/Treatment: Diagnosis clinical, though can watch for rise in antibodies from acute to chronic phase. Tx with doxycycline for both adults and kids.
Bug: Anaplasma phagocytophilum. Vector: black-legged tick, Ixodes scapularis. Geography: upper mid-Atlantic, north-central states, northern California. Transmission usually in the summer.
Clinical Features: similar to ehrlichiosis or flu: fever, chills, headache, myalgias. Labs: leukocytopenia, thrombocytopenia, elevated LFTs.
Testing/Treatment: clinical diagnosis, again can be confirmed with rise in antibodies over time. Tx with doxycycline.
Tickborne Relapsing Fever
Bug: Borrelia spirochete. Vector: Ornithodoros ticks (soft ticks). Present with rash/eschar which then turns into fever/chills/cephalgia, myalgia, arthralgia, abd pain. Usually have leukocytosis and thrombocytopenia. Diagnosis spirochetes on Wright-Giemsa-stained peripheral smear. Very rare diagnosis. Tx with doxycycline or erythromycin.
Colorado Tick Fever
Bug: Coltivirus. Vector: wood tick, D. andersoni. Only in mountainous regions with elevation > 4000ft. Fever/chills, headache,myalgias, photophobia. May have macular/petechial rash. Have relative leukopenia. Tx supportive.
Bugs: Babesia microti and Babesia equi. Vector: Ixodes tick as well as blood transfusions. Present with fever, chills, malaise, intermittent sweats, myalgias, headache, and hemolytic anemia. Looks like malaria/erlichiosis. Labs: anemia, elevated LFTs, thrombocytopenia, renal failure. 20% will also have Lyme disease. Diagnosis with Giemsa-stain peripheral blood smear. Tx: atovaquone + azithromycin or clindamycin + quinine x 7-10d.
Vector usually mosquito or tick. Usually present with fever, myalgias, malaise; then progresses to headache and decline in mental status. CSF: elevated opening pressure, lymphocytes. Viral culture usually negative. Diagnosis made by serum ELISA.
West Nile Virus: can cause flu-like syndrome or encephalitis. Tx supportive.
Other causes of zoonotic meningitis: brucellosis, listeriosis, plague, salmonellosis, tularemia, leptospirosis, Lyme dx, ehrlichiosis, Q fever, RMSF, psittacosis.
Zoonotic Respiratory Infections
Anthrax: Bacillus anthracis. Usuallly handling animal hides or imported raw wool. Fatal. Causes mediastinitis without alveolar involvement. Presents with flu-like illness that progresses to severe respiratory failure. Can get vaccine if in exposed population. Postexposure prophylaxis: 60d course of abx + 3 dose vaccine.
Brucellosis: ingestion of unpasteurized dairy products. Usually present with URI with cough, hoarseness, wheezing. Peritracheal/hilar lymph nodes, no infiltration on X-ray. Can chronically get granulomas and lymph nodes. Tx: doxycycline + rifampin x 6 weeks.
Psittacosis: parrot fever, parrot disease, ornithosis. Caused by chlamydia psittaci common in birds. Inhalation of bird droppings. Present with flu-like syndrome with nonproductive cough, lobar/interstitial infiltrates on X-ray. Looks like ‘typical’ atypical pneumonia. Tx: doxycycline 100mg BID or tetracycline 500mg QID.
Q fever: rickettsial infection by inhalation, no vector. Common in domesticated farm animals, usually in feedlots. Self-limiting pulmonary syndrome, though can get extra pulmonary symptoms (myo/pericarditis). Tx with doxycycline within 3 days for most effect.
Pasteurellosis: in normal oral flora of cat/dogs. Can cause necrotizing cellulitis, though can get bronchitis/pneumonia. Tx: Augmentin, tetracycline, PCN, cephalosporin.
Melioidosis: Caused by Burkholderia pseudomallei (gram negative saprophytic bacterium). Can be serious, but usually causes pneumonia, sometimes abscesses. Tx doxycycline or bactrim.
Pulmonic Plague: Yersina pestis. Usually in rock squirrels and rodents in the southwest. Vector: rodent flea. Usually get eschar at bite site with a bubo near it. Sepsis/pneumonia can occur next. Highly contagious in pulmonary form. Very fatal without tx. Tx doxycycline or cipro, gentamicin alternative.
Hantavirus: Sin Nombre virus, different vectors, usually deer mouse in southwest US. Usually infected by inhalation of rodent feces or by rodent bite. Worldwide usually present with acute kidney failure with thrombocytopenia, ocular abnormalities, flulike syndrome. In US, presents as flulike syndrome that turns into severe ARDS. High mortality 50-70%. Diagnosis by immunofluorescent or immunoblot assay. Tx supportive, inhalation ribavirin.
Other Zoonotic Infections
Cutaneous Anthrax (woolsorters dx): usually close contact with livestock. Spores deposited into skin, usually arms/legs. Macule that turns into ulcer with multiple vesicles. Turns into eschar in a few weeks and then falls off. Vesicles are contagious. Tx does not help.
Helminths (worms): dogs are source for toxocara canis which causes toxocariasis. Usually subclinical, but can cause fever/cough/rash in children. Tx albendazole/mebendazole. Dipylidiasis (tapeworm): rare, but in children causes diarrhea and pruritus ani. Tx praziquantel or niclosamide.
Toxoplasmosis: can be infected by either ingesting uncooked meat, ingestion of oocytes from cat feces, and transplacentally. 10% infected fetuses have abnormality: retinochoroiditis, hydrocephalus, hepatosplenomegaly, thrombocytopenia. Tx pyrimethamine + sulfadiazine and folinic acid.
Typical foodborne causes: Norwalk-type, astroviruses, rotaviruses, enteric adenoviruses. Usual foods: poultry, leafy vegetables, fruits/nuts.
Staph aureus (usually meats/potato or egg salad, left out pastries), Bacillus cereus, Clostridium botulinum create preformed toxin so symptoms usually rapid with vomiting within 1-6 hrs.
Vibrio (usually water based or shellfish), Shigella, Shiga-toxin producing E.Coli produce toxin after ingestion and usually cause diarrhea (sometimes bloody) with abdominal cramping at 24 hrs. Clostridium prefringens most common toxin induced – usually just diarrhea, vomiting rare.
Typically nausea/vomiting, diarrhea, abdominal cramping. Occasionally fever, dehydration, malaise.
CDC Top 5 pathogens: Norovirus, Salmonella, nontyphoidal, Clostridium perfringens, Campylobacter, Staph Aureus.
Typical gastroenteritis with primarily vomiting: viruses, norovirus, rotavirus, astrovirus, staph aureus, bacillus cereus (fried rice).
Watery nonbloody diarrhea: ETEC (enterotoxigenic E.Coli), Giardia, Vibrio cholerae, Enteric viruses, Cryptosporidium, Cyclospora.
Grossly bloody diarrhea with fever: Shigella (high virulence, seizures in kids), Campylobacter (poultry, MC bacteria), Salmonella (2 MC bacteria, eggs/poultry, dairy, fruit/vegs), ETEC, EHEC (Shiga toxin producing EColi O157:H7, usually grossly bloody diarrhea), Vibrio parahaemolyticus, Yersinia (pork, tofu, shellfish, looks like appendicitis), Entamoeba.
Persistent diarrhea: Parasites such as Giardia (tx w flagyl), Cyclospora (tx w bactrim), Entamoeba (tx w flagyl), Cryptosporidium (supportive).
Neurologic symptoms with disease: Botulism, Scombroid, Ciguatera, tetrodotoxin (puffer fish, toxin still present w cooking – ascending paralysis, dilated pupils, death in 4-6 hrs, usually only lasts a day), toxic mushroom, paralytic shellfish (shellfish, usually w red tide months (months wo r) clams, mussels – numbness, dizziness, myalgias, confusion, memory loss, coma), GBS.
Systemic illnesses: Listeria (cheese, dairy, deli meats, hot dogs), Brucella (raw milk/cheese), Salmonella typhi, S. paratyphi, V. vulnificus, Hepatitis A/E.
Scromboid: due to ingestion of Scombridae fish (tuna, mackerel, bonito, others: maui-mahi, bluefish, herring, sardines). Metallic, peppery taste when eating the fish. Toxin saurine causes by histamine produced. Occurs 30m to 24 hrs after ingestion. Flushing, headache, abd cramping, vomiting, diarrhea. Last 8 hrs. Tx with antihistamines.
Ciguatera: eating reef fish that ingests plankton (dinoflagellate Gamberdiscus toxicus – produces ciguatoxin). Usually with grouper, snapper, amberjack, barracuda (MC). Starts with GI symptoms (N/V/diarrhea) early on, then hypesthesias, paraesthesias, numbness, malaise, generalized weakness, hot/cold reversal, looseness in teeth. Can get hypotension/bradycardia. Neuro symptoms can last months to a year. Supportive tx. Gabapentin/amitripyline controversial. Mannitol found not to be beneficial
Complications: reactive arthritis after Salmonella, Shigella, Campylobacter. Guillain-Barre syndrome can occur 7-21d after Campylobacter. HUS occurs with kids (acute renal failure, hemolytic anemia, thrombocytopenia) with shiga toxin (ETEC, STEC, Campylobacter, Citrobacter, Shigella, Salmonella, Yersinia) and TTP in adults.
Due to ingestion of contact with contaminated water such as swimming pools, hot tubs, spas, naturally occurring water. Pathogens usually due to fecal contamination, though some are indigenous (Pseudomonas aeruginosa, Vibrio, Aeromonas, nontuberculous mycobacterium, Legionella).
Campylobacter – water contaminated with wild bird feces. Ecoli H157 due to farm animal faces contamination.
Vibrio cholera – due to fecal water contamination. Vibrio vulnificus causes life/limb threatening necrotic wound infections (hemorrhagic bullae). Usually in Gulf coast and due to open wounds exposed to seawater. High rate of sepsis and amputation. Mortality 17-24%. Tx with doxycycline + ceftazidime.
Aeromonas – fresh and marine waters, associated with wound infections. Usually cellulitis, though can get necrosis. Rarely diarrhea. Tx w/ cipro BID.
Pseudomonas aeruginosa – in normal hosts, can cause otitis extern and skin infections such as hot-tub folliculitis. Does not usually cause diarrhea in normal hosts. Tx w/ cipro.
Nontuberculous mycobacterium – found in salt/fresh water. Mycobacterium marinum can cause granulomatous skin infection (painful indurated plaque).
Legionella – usually fresh water; infection caused by inhalation of aerosols. Pontiac fever – flu-like illness, lasts 2-5 d, no tx needed. Also legionnaires disease.
Giardia – most common intestinal parasite. Usually surface water with mountain stream, related to beavers. Usually affects backpackers, campers, travelers. Most asymptomatic, but usually causes acute/chronic gastroenteritis.
Cryptosporidium – very common; usually contaminated recreational water. Look for oocytes in stool. Usually self-limited diarrhea, but in immunosuppressed can cause chronic/life-threatening course.
Entamoeba histolytica – intestinal amebiasis. Usually migrants and travelers in the US. Can cause mild diarrhea to dysentery. Can seed to the liver and cause abscess.
Consider stool cultures if patient febrile, bloody diarrhea, severe or protracted diarrhea. Really only need to check for ova/parasites in immunocompromised or prolonged course. Fecal leukocytes (lactoferrin similar, more sensitive though not readily available, present in breast-fed infants) predicts invasive pathogen – stool culture will better sort out bug, though cannot differentiate inflammation from IBD. Stool hemoccult – as good as fecal leukocytes in predicting inflammatory diarrhea and response to therapy. Stool gram stain looks for Campylobacter. Parasites tx with Flagyl 750mg TID x 7-10d. Always think about testing for Cdiff when you are sending stool for other things.
Hydration and supportive care. Without fever and bloody diarrhea, consider anti motility agents (loperamide) for mild-moderate diarrhea. Avoid antimotility with dysentery (fever/bloody diarrhea). No anti motility agents for children. Consider lactobacilli to shorten diarrhea course (NNT). Most bacteria self-resolve.
Consider abx with: fever > 38.5C, severe abd pain, bloody diarrhea, duration > 48 hrs, positive fecal leukocytes/lactoferrin or usually travelers diarrhea. Tx with PO Cipro 500mg BID x 3-5d (can also give 1g Cipro x 1), PO Levafloxacin 500mg qd x 3-5 days, PO Bactrim double strength BID x 3-5d. Consider doxycycline with vibrio cases. Azithromycin 500mg qd x 3-5d for pregnant women,children, pts in areas with fluoroquinolone-resistant campylobacter (Thailand). Always think about EHEC (don’t give abx). Send specific stool study for it and wait/see.
Do not give abx for suspected EColi H7:O157 due to increased risk of HUS (15%) – usually bloody diarrhea, usually don’t have fever – seems impossible to differentiate from inflammatory diarrhea – recommend sending stool cx and wait/see. Abx effect is usually modest at best.
Giardia/Entamoeba: Flagyl; paromomycin for pregnancy. For cryptosporidium, usually self-limited. For HIV, get CD4 > 100 for resolution.
Protozoan infection by female Anopheles mosquito. Carried to liver where they reproduce (amplification stage), then rupture and infect RBCs (erythrocytic stage). 5 types: Plasmodium vivax, ovale, malariae, falciparum, knowlesi.
Regions: Central (Haiti, Honduras) / South America (Guyana, Brazil) , Caribbean, sub-Saharan Africa (MC area of transmission for US citizen coming home, think Nigeria, Ghana, Sierra Leone, Liberia), Indian subcontinent, Southeast Asia, Middle East, Oceania (Papua New Guinea). Top states for reports: New York, California, Maryland, Florida, Texas, New Jersey, Georgia, Virginia.
P. falciparum: most prevalent form in Africa; highest mortality 10-50%. Has resistance to chloroquine (central america and caribbean don’t have resistance), pyrimethamine-sulfadoxine, quinine, mefloquine, doxycycline.
P. vivax: more common in Indian and Central America. Both vivax and oval have dormant hepatic stage that can activate later and cause clinical relapse.
Incubation period 8 days – 1 month. Periodic fevers with flu-like symptoms: headache, chest pain, cough, arthralgias, diarrhea. After several hours of fever, fever goes down and then have diaphoresis and exhaustion. Usually every 48-72 hrs. Paroxysms absent with P.falciparum or partial chemoprophylaxis. Usually no lymphadenopathy. Can have hypoglycemia.
Complications include hemolysis, splenic enlargement or even rupture, glomerulonephritis. Cerebral malaria: coma, delirium, seizures – shows elevated opening pressure, elevated proteins, and some pleocytosis. Most organs can be affected by hypoxia. Blackwater fever (severe hemolysis with hemoglobinuria from P.falciparum = renal failure).
Visualization of parasites on Field or Giemsa-stained thick and thin blood smears (first smear 90% positive, thick smear puts many cells in one view so able to look for parasite in general, thin smears zooms on a few and hopefully able to differentiate the type of malaria). Repeat stain in 2-3 days if negative. Other tests available (PCR, etc) though smear still preferred. Smear able to show viral load as well as determine if from P.falciparum (small rings forms with double-chromatin knobs in RBCs, small amount of trophozoites and schizonts, crescent-shaped gametocyte, parasitemia > 4%). Check smears daily for treatment progress.
Nonspecific labs: anemia, mild neutropenia or thrombocytopenia, elevated LDH, mild liver/renal abnormalities, hyponatremia, hypoglycemia, false positive VDRL.
Severe hospitalized cases (AMS, renal failure, severe anemia, shock, DIC, jaundice, parasitemia > 5%): In the US: IV quinidine (enhanced activity against P.falciparum than quinine). For severe malaria, add on IV artesunate (though recommends discussing with CDC Malaria Hotline). IV artesunate is limited and needs to be used with a second agent due to short half-life and increased resistance as single agent. Quinine/Quinidine can cause hypoglycemia; also causes cinchonism (N/V, headache,tinnitus, dizziness, visual disturbances).
If suspecting P.falciparum with parasitemia > 3%, hospitalization recommended. Treat with quinine and doxycycline (C/I pregnancy, kids) or atovaquone-proguanil (Malarone) (though can treat with chloroquine if absolutely positive the geographic location of P.falciparum is not resistant). Clindamycin or tetracycline can be substituted for doxycycline.
Outpatient tx (though most US pts with malaria usually get admitted): Malarone (atovaquone-proguanil, SE: N/V, oral ulcers, headaches, dizziness, C/I pregnancy, kids <5kg, kidney dysfunction) is >90% effective. Don’t give if it was used as chemoprophylaxis. More effective than mefloquine. Coartem (1:6 fixed dose combo of artemether and lumefantrine, SE: headache, dizziness, severe skin rash rare, QT prolongation) over 3 days effective against P.falciparum. Mefloquine (SE: N/V, cramps, avoid in pregnancy/kids, if also taking quinidine) is effective against chloroquine-resistant P.falciparum. Don’t use if used as chemoprophylaxis or in area with resistance. More severe neuropsychiatric reactions. Chloroquine (SE: N/V, pruritus, hypotension with IV, can cause retinitis chronically) is tx for P.vivax, P.ovale, P.malariae. It does not tx dormant stage in liver with P.vivax or P.ovale so will need to add on primaquine (don’t give to G6PD pts – can cause massive hemolysis, SE: N/V, diarrhea, cramps, C/I pregnancy as well) so relapses don’t occur.
After dark, stay in well screened areas, use mosquito nets preferably with insecticides on them. Pyrethrum-containing insect sprays work well. Insect repellants: use DEET containing ones – only need to be at most 35%.
CDC Malaria Map Application – Shows countries that are susceptible and resistance patterns with prophylaxis recommendations.
Chloroquine-sensitive P.falciparum region: Chloroquine 300mg base qweekly + 4 weeks after exposure; Hydroxychloroquine 300mg base qweekly + 4 weeks after exposure. Second-line: Doxcycline 100mg daily + 4 weeks after exposure as well. Malarone 250mg/100mg qday + 1 week after exposure.
Chloroquine-resistance P.falciparum region: Malarone qday x 1 week after exposure; Mefloquine 228mg base qweek + 4 weeks, Doxycycline 100mg + 4 weeks. Second-line: Primaquine 30mg qd + 1 week.
Multiple-drug resistance P.falciparum region: Doxycycline or Malarone. Second-line: Primaquine.
Dogs account for < 5% cases where controlled, whereas they account for >90% causes in other parts of the world. Other animals: foxes, skunks, mongooses, bats. For US, most cases (not human infection, just diagnosed rabies in the wildlife) were with raccoons (36.6%), bats (27.2%), skunks (20.4%), foxes (6.7%), and other animals including coyotes, opossums, otters, bobcats, rodents and lagomorphs (rabbits, hares, picas).
Animal bites not causing rabies: squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, domesticated rabbits, other small rodents. Nonbite exposures very rarely cause rabies. Dogs/cats with two vaccines will never get rabies from exposure. Have been cases with aerosolized virus in bat caves.
Most human infections are associated with bats (80%, specifically the silver-haired bat) with most other cases related to dog bites from other countries. Highest risk for transmission with multiple bites around the face.
No great test for confirmation. Negri bodies on autopsy. Most reliable test: nuchal skin biopsy with immunofluorescent rabies antibody staining. If did not receive vaccine or IG, serum rabies antibodies confirms diagnosis.
Tetanus does not have altered mental status. Rabies does.
Basically is an encephalitis. Incubation period 20-90 days (though some documented much earlier and much later).
Prodromal period: fever, sore throat, chills, malaise, anorexia, headache, nausea. Sometimes get early limp pain, limb weakness, paresthesia at exposure site.
Acute neurologic phase: Two forms: furious and paralytic. Furious: 80% of patients, hyperactivity, disorientation, hallucinations, bizarre behavior. Sympathetic surge. 50% have hydrophobia in which they get pharynx/larynx/diaphragm spasm with drinking fluid. Aerophobia occurs with pharyngeal spasm triggered by feeling draft of wind. Paralytic: paralysis primarily in the bitten extremity, though can have diffuse or symmetric paralysis as well.
Coma usually occurs within 10 days of onset of symptoms. Death occurs due to seizures/respiratory dysfunction. Only 6 people have survived with all but one receiving pre or post exposure prophylaxis.
Clean (soap/water) the wound immediately. Found in animal experiments that simple cleaning reduced risk of rabies.
Patients suspected of having rabies should have contact isolation and healthcare workers wear masks/eye protection (though no healthcare associated transmission documented).
No treatment for patient with rabies. One case report of ketamine, versed, ribavirin, and amantadine (‘Milwaukee protocol’) saved patient’s life (NEJM, 2005).
Pre-Exposure: For people at risk for possible rabies exposure. Primary vaccinations given IM HDCV (Human diploid cell vaccine) or PCECV (purified chick embryo cell vaccine) 1.0mL on days 0, 7, 21 and 28. Still will need treatment after possible rabies exposure, though much less treatment. Wont need immune globulin. Vaccine given to people who work in rabies labs, vets, animal-control, wildlife, spelunkers. Serology testing in the higher risk individuals and booster given if antibody titer below normal range. If exposed after this, only need vaccine on day 0 and day 3 with no HRIG.
Post-Exposure: If animal exposure with bite/salivary exposure, if cat/dog and can be captured, then it will be quarantined for 10 days and released if normal behavior at that time. No prophylaxis at all. If the cat/dog can not be captured, check epidemiological data for area and if low risk, no prophylaxis. If unavailable or higher risk, give vaccine + HRIG. If animal is other carnivore or bat/raccoon, bobcat, fox, cow, if can be captured and quarantined, it will be sacrificed and sent to lab and patient given vaccine. If results negative for rabies, no HRIG. If animal can not be captured, patient receives HRIG and vaccine. It states consider post-exposure prophylaxis for persons who were in the same room as a bat and who might be unaware that a bite or direct contact had occurred. Contact public heath officials if unsure of therapy. Treatment: 1 dose of HRIG 20 IU/kg (as much can be injected in wound and then distal site) and 4 doses (0,3,7,14) of rabies vaccine over 14 days. Give first doses within 24 hrs. Vaccine must be injected IM into the deltoid.
References / Resources
Uncommon in the US; mostly in California, Texas, Florida (very low prevalence in high altitudes) in older patients with inadequate immunity. 11% mortality, more likely in the elderly.
Most cases related to acute wound or puncture wound; did not seek medical care or did not receive tetanus when seeking care.
Clostridium tetani, gram positive anaerobic rod. Creates indestructible spores that germinate into its toxin-producing form. Two toxins: tetanolysin which increases bacteria production and tetanospasmin, which is the neurotoxin.
Prevents release of glycine and GABA from presynaptic nerve terminals. Loss of inhibition. No person-to-person transmission.
Muscular rigidity, muscular contractions, increased sympathetic system. Incubation period is 1 day to 1 month. Looks like strychnine poisoning. Other considerations: dystonic reaction, hypocalcemia, malignant neuroleptic syndrome, serotonin syndrome, rabies.
Generalized tetanus: 80% of pts. Initially present with lock jaw (masseter muscles). Descends to neck, chest, extremities. Risus sardonicus (sardonic smile/grin). Tonic muscle contractions and convulsive spasms occur. Opisthotonus – body bent concave forward, resting on head and heels. Extension of lower extremities. No change in mental status though. Conscious until contraction of respiratory muscles. After first week, more sympathetic response occurs with tachycardia, elevated BP, sweating, increased urination. Can last for months before nerve regrow. Complications: rhabdo, long-bone fractures. Aspiration pneumonia found in 50-70% of autopsies.
Neonatal tetanus: Due to unsterile treatment of umbilical stump, poorly immunized mother. Usually occurs in second week of life. Weak, irritable, unable to suck.
Cephalic tetanus: Usually related to facial injuries and involves cranial nerves. Usually seventh (facial) nerve involved.
Local tetanus: Just localized tetanus near wound; can progress to generalized.
Clinical diagnosis. Not really a good test. Wound cultures can grow the bug, but doesn’t mean you have tetanus. Serum antitoxin titers > 0.1 are protective, though there have been cases with normal levels. Consider checking urine strychnine to rule out strychnine poisoning.
Usually ICU admission for respiratory monitoring. If intubated, may need to do neuromuscular blockade.
Human tetanus immunoglobulin (TIG) knocks out the circulating toxin, though does not neutralize the toxin already in the nerves. Helps reduce mortality. 3000-6000 units IM with some injected into wound. Do this before cleaning the wound bc toxin can be released during handling.
Antibiotics: Metronidazole usually given, but doesn’t really help. Don’t give PCN (centrally acting GABA antagonist).
Muscle relaxation: Usually benzos, though only give water-soluble midazolum (versed) due to propylene glycol solution in lorazepam or diazepam.
Magnesium sulfate can help reduce sympathetic. Labetolol probably preferred B-blocker due to both alpha/beta activity. Consider morphine or clonidine as well.
When diagnosed with tetanus, should receive tetanus toxoid IM at presentation, then at 6 weeks and 6 months. Disease dose not create immunity.
TdaP (Tetanus-diptheria-acellular pertussis / Adacel) booster every 10 years in adults > 19yo. Td vaccination is 3-shot series starting at 2 months.
Wound Management: If unsure of previous 3-dose series, give TIG. If minor wound with low contamination, booster given if last booster was > 10 years. If contaminated wound, may need booster if last booster was > 5 years.
References / Resources
Mitral valve MC valve. Then aortic > tricupsid > pulmonic. Occurs due to either cardiac structural abnormality (congenital or acquired) or other risk factor (IVDA, indwelling catheter, poor dental hygiene, HIV). Other RF: renal disease, DM, lower SES, age > 60, male.
Native valves: MC structural abnormality: mitral valve prolapse. Others: bicuspid aortic valve, aortic stenosis, rheumatic heart disease (leading cause in developing world). IVDA: usually tricuspid valve or right sided heart valves. Increased rate of reoccurrence. Risk 2-5% every year. Cocaine in particular increases risk. Staph aureus MCC (30% in non-IVDA, >50% in IVDA), then strep (non-viridans and viridans) and enterococci. IVDA can also have gram-negative bacilli.
Prosthetic valves: no difference in mechanical vs bioprosthetic. Early valve endocarditis in first 60 days after surgery (higher mortality, usually coag neg staph) vs late valve endocarditis (usually staph aureus). Staph epidermis MCC; Aspergillus and Candida also involved.
Fever > 38C in 90% overall, >98% in IVDA. Other nonspecific symptoms: N/V, fatigue, malaise.
Regurgitation murmur: reported in > 85% of cases. 70% have acute or progressive CHF.
Embolization (22-50%): stroke (MCA distribution MC), retinal artery embolism (monocular blindness), pulmonary emboli, splenic / renal infarction (microscopic hematuria seen in 50% due to glumerulonephritis), mesenteric ischemia, acute limb ischemia.
Skin findings: Osler nodes (small, tender subq nodules on pads of fingers or toes), Janeway lesions (painless hemorrhagic plaques on palms or soles), petechiae, splinter or sublingual hemorrhages.
Roth Spots – retinal hemorrhages: pale with red halo.
If suspicious, will have to admit for culture, echocardiogram, and clinical observation. No clinical prediction rules.
Duke Criteria: Two major or 1 major + 3 minor or 5 minor. MDCalc Link.
Major: Positive blood culture (Strep bovid, Viridans, HACEK (H.aphrophilus, Actinobacillus, Cardiobacterium, Eikenlla, Kingella) ; Staph aureus/enterococci without other source; Coxiella burnetti or anti phase I immunoglobulin G antibody >1:800); Positive echocardiogram (intracardiac mass on valve or supporting structure; abscess; new partial dehiscence of prosthetic valve); New valvular regugitation
Minor: Predisposition; Fever > 38C; Vascular phenomena (arterial emboli, septic pumonary conjunctival hemorrhages, Janeway lesions); Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots, Rheumatoid fever); Microbiologic evidence (positive BC that does meet major criteria).
3 sets of blood cultures needed; ideally 1 hr between first and last one.
Lab: Anemia present in 70-90% of cases, elevated ESR in 90%. Also hematuria, CRP, and procalcitonin.
TEE > TTE. TTE 88-94% in IVDA, more sensitive in large lesions, right sided lesions and favorable patient habitus. TEE always recommended in prosthetic valves, intermediate/high clinical suspicion.
No anticoagulation for native valves. Maintain anticoagulation for prosthetic valves.
Usually penillinase-resistant PCN or cephalosporin (Ceftriaxone, Nafcillin, Oxacillin, or Vancomycin) + aminoglycoside (Gentamicin, Tobramycin). Vancomycin added for IVDA, congenital heart dx, pts currently on oral abx, nosocomial, suspected MRSA – basically everyone). Just think Vancomycin + Gentamicin. Start immediately after cultures obtained if high clinical suspicion. New articles on oral cipro + rifampin for IVDA so that they don’t need PICC line.
Most require 4-6 weeks of tx. Some require valve replacement.
Not routine: mitral valve prolapse, HCOM, physiologic murmurs, prior CABG, previous surgical repair of atrial septal defect, VSD, PDA.
High risk: prosthetic valves, hx/o previous infective endocarditis, unprepared cyanotic congenital heart dx, repaired congenital defect with prosthetic material, cardiac transplants recipients who develop valve regurg due to structurally abnormal valve, repaired congenital heart defects with residual abnormality.
Recommended procedures: dental procedures involving gingival, periodical tooth, or oral mucosa manipulation. Lower recommendation (IIb) for infected skin, skin structure or musculoskeletal tissue. Low risk of bacteremia with abscess I&D. For other procedures, several organizations (AHA included )have stated no prophylaxis needed (GU, respiratory, GI). Still reasonable for tonsillectomy/adenoidectomy.
Treatment: IV: Vancomycin or Clindamycin if MRSA suspected with infected skin. Dental procedures: amoxicillin, cephalexin, clindamycin, or azithromycin. IV ampicillin, cefazolin, ceftriaxone, or clindamycin. Oral given 1 hour prior to procedure.
RNA virus: affects primarily CD4+ T-cells causing immune abnormalities, lymphopenia, autoimmune phenomena. Transmission occurs thru semen, vaginal secretions, blood or blood products, breast milk, and in utero transplacentally. No transmission has been documented to occur by casual contact.
RF: homosexuality/bisexuality, IVDA, heterosexual exposure, blood transfusion prior to 1985, maternal HIV infection
Acute retroviral syndrome: initial acute HIV infection. Flu-like illness – looks like mono. Occurs in 50-90% of pts. Develop 2-4 weeks after exposure. Fever (cyclic – afternoon/evening), fatigue, pharyngitis, rash, headache, oral ulcerations. Antibodies develop 3-8 weeks after infection, though can be longer. Usually become asymptomatic other than enlarged lymph nodes. Time from exposure to full-blown AIDS is 8.3 years and 2 years in children < 5yo. Viral load will be elevated in the acute phase, though unable to get result back in the ED.
Viral load and CD4+ T-cell count are used for HIV staging. Cocaine decreases CD4 production and increases viral reproduction up to 20x (Gruber, 2010).
Early infections, though not AIDS defining: thrush, vulvovaginal candidiasis, recurrent herpes zoster, ITP. Occur more frequently with CD4+ counts below 500.
AIDS: Defined by CDC by certain AIDS defining illnesses (Esophageal candidiasis, Cryptococcus, CMV retinitis, HSV, Kaposi sarcoma, Brain lymphoma, MAC, PCP, Brain toxoplasmosis, HIV encephalopathy, HIV wasting syndrome, Disseminated histoplasmosis, Isosporiasis, Disseminated Mycobacterium tuberculosis) or CD4+ count < 200. Advanced HIV occurs with CD4+ < 50 or disseminated MAC or CMV. AIDS-illnesses usually occur with either CD4+ < 200 or viral load > 50,000.
Can also look at total lymphocyte count to approximate CD4 count. < 1200 cells/mm with clinical symptoms are predictive of CD4+ < 200 (only 62% sensitivity though). ALC (total WBC x lymphocyte %): less than 1000 was 91% predictive of CD4 < 200 (67% sens, 96% spec); ALC < 2000 was 97% sensitive, 41% spec so ALC > 2000 was 95% predictive of CD4 > 200. (Shapiro, 1998).
HIV pts should not receive live vaccines (except MMR unless AIDS). Pneumococcal vaccine recommended >2yo. Influenza (inactivated) yearly.
Usually look for antibodies to HIV. ELISA (enzyme-linked immunosorbent assay): 99% specific and 98.5% sensitive. Western Blot: nearly 100% sensitive/specific. Acute HIV infection hard to detect since antibodies have not been formed yet. DNA PCR >99% sensitivity, viral load 95% sensitive, 95-100% viral culture sensitivity, 100% for most recent p24 antigen detection assays. Both p24 antigen and HIV RNA can be used for the acute phase.
Rapid HIV testing: UniGold Recombigen, Multispot HIV1/HIV2 Rapid Test, Reveal G3, OraQuick Advance HIV1/2 (only one FDA approved for oral fluid). Allow result to be given in 10-20 minutes. High sensitivity/specificity. Results come back preliminary positive; need confirmatory test with Western blot. Negative means negative – no further testing, though in early acute phase, may be false negative. Recent studies have shown a higher false-positive rate with rapid tests.
4th generation immunoassay: able to get positive within 2-4 weeks after infection, much faster than 3rd generation. Checks for possible antibodies and virus.
If CD4+ count > 500, generally have causes of fever similar to nonimmunocompromised pts. Counts 200-500, more likely to have bacterial respiratory infections. If < 200, common causes: early PCP pneumonia, central line infection, MAC infection, M. tuberculosis, CMV infection, drug fever, sinusitis. Non-infectious causes: neoplasm (non-Hodgkin lymphoma MCC) and drug fever. Send for serum cryptococcal antigen, blood fx for AFB
Disseminated MAC: CD4+ < 50-100. Fever, night sweats, weight loss, diarrhea. Goes to bone marrow causing anemia and high alk phos. Diagnosis by acid-fast stain blood culture. Use lysis-centrifugation is more sensitive for diagnosis. Tx: clarithromycin + ethambutol + rifabutin. Immune reconstitution illness to MAC: lymphadenitis after starting HAART. Continue HAART with antibiotics +/- steroids.
CMV: most common cause of serious viral dx in HIV. Commonly affects GI, pulmonary, CNS, retinitis.
Most common causes: AIDS dementia, Toxoplasma gondii, Cryptococcus neoformans. Need CT, then LP for most HIV patients with headache without clear alternative cause. If CD4 < 200, need to be even more aggressive. Noncontrast CT should be fine most of the time. CSF tests: opening pressure (crypto) cell count, glucose/protein, gram stain, India Ink stain (crypto), culture, viral culture, VDRL (syphilis), fungal culture, toxoplasmosis and cryptococcosis antigen assays, and coccidioidomycosis titer. Peripheral neuropathy (usually foot pain) can just be related to HIV, though can also be drug side effect. Also consider HSV, lymphoma, PML.
Symptoms to need CT (100% sens): new seizure, depressed/altered orientation, headache, different in quality than usual, prolonged headache (>3 days) (Rothman, 1999)
AIDS dementia: memory impairment / cognitive deficits. Occurs in 10-15% of HIV patients, more frequent if CD4 <100. Progressing disease. CT usually shows cortical atrophy and ventricular enlargement. CSF shows elevated protein. Gradually causes mental status changes, sometimes aphasia and motor abnormalities.
Toxoplasmosis: MCC focal encephalitis. Fever/headache/focal neuro/AMS/seizures. Most people have antibodies to it so serology not-useful though if negative, not toxo. CSF antibodies useful, though can be false negative. CT shows multiple subcortical lesions in basal ganglia. Contrast CT shows ring enhancing with edema (other causes of ring enhancing are lymphoma (usually single lesion with progressive symptoms over months, usually in the periventricular/corpus callosum), fungal, cerebral TB, though Toxo usually has multiple lesions). Tx: pyrimethamine + sulfadiazine + folinic acid (reduce pancytopenia). Dexamethasone 4mg q6hr reduces edema/mass effect. 20% of CT will have single lesion. Usually tx for toxo and if no improvement, will consider lymphoma.
Cryptococcosis: MC presenting sign: fever and headache, though can also have nausea, AMS, focal neuro deficits. Meningismus uncommon. Usually only if CD4<200. CSF: cryptococcal antigen testing (100% sens/spec) or india ink staining (60-80% sens). Usually have elevated ICP >25cm H20. Other CSF findings (cell count/protein/glucose) can be unremarkable. Serum cryptococcal antigen testing 95% sensitive. Tx: IV amphotericin B + oral flucytosine x 14d followed by 8 weeks fluconazole to clear CSF. Can have bone marrow suppression requiring lifelong fluconazole therapy.
MC abnormality is retinal microvasculopathy: cotton-wool spots similar to DM/HTN. Microaneurysms occur as well. Herpes zoster opthalmicus can also occur.
CMV Retinitis: Most frequent and serious ocular opportunistic infection in AIDS pts. Leading cause of blindness. Presents with visual acuity changes, visual field cuts, photophobia, scotoma (partial blind spot), eye redness, eye pain. Fundoscopic exam: fluffy white perivascular lesions with hemorrhage areas in them, ‘pizza pie’ or ‘cheese and ketchup’. Tx: Oral ganciclovir x 14-21 d +/- intraocular ganciclovir implants. Without detection, vision loss and blindness can occur. 10% still go blind.
HIV patients 2x more likely to have MI. Protease inhibitors (particularly long term) increase risk of MI.
Pneumocystis (PCP; P. jiroveci (new) or carinii (old)) pneumonia: MC opportunistic infection and MCC death among AIDS. Fever, nonproductive cough, SOB; usually gradual onset w/ fatigue. CXR: diffuse interstitial infiltrates, though 15-20% have neg findings. ABG will show alveolar-arterial gradient. High LDH > 220. Usual cause of hypoxia without other cause. Tx: Bactrim PO or IV x 3weeks. SE: rash, fever, neutropenia. Pentamidine alternative agent. If PaO2 < 70mm or A-a gradient > 35mm, give steroids (oral prednisone 40mg BID 3 week taper) (NNT 9-22). Or dapsone. 1/5 of compliant pts on PCP prophylaxis will still get it.
TB: 200-500x risk than general population. Usually occurs with CD4 200-500. Hemoptysis, night sweats, fever, weight loss, anorexia. Negative PPD common among late-stage AIDS. Diagnosis by sputum stain/culture. Need to have high suspicion in any AIDS patient due to high person/person transmission. Tx: 4-drug regiment (RIPE: Rifampin + Isoniazid + Pyrazinamide + Ethambutol). All HIV pts with +PPD should receive isoniazid + pyridoxine x 9-12mo (alt rifampin or rifabutin x 4mon).
Bacterial pneumonia still the MCC pulmonary infection in HIV patients. Disseminated fungal infection in severe immunosuppression: C. neoformans and Aspergillus fumigatus.
Candidiasis / Thrush: usually affects 90% of AIDS. Can be scraped off with erythematous base, usually on tongue/buccal mucosa. Hairy leukoplakia is usually adherent, white, thickened lesions on lateral tongue border – differentiate with KOH smear. When diagnosed in HIV, likely progression to AIDS. Oral/pharyngeal tx: Clotrimazole or nystatin suspension/troches 5x daily. Refractory cases: oral fluconazole. Severe: Amphotericin B. Odynophagia is basically esophagitis, usually in oral thrush pts with CD4 < 100. Tx: oral fluconazole or ketoconazole. Endoscope, biopsy, or IV caspofungin or amphotericin B for refractory cases. CMV and HSV can also be seen in the esophagus. Topical won’t work for esophageal form.
Diarrhea: Bacteria (shigella, salmonella, e.coli, entamoeba histolytica, campylobacter, MAC, Cdiff) – tx with cipro, parasites (giardia, cryptosporidium, isospora belli) – modified acid-fast stain, usually consult ID, viruses (CMV, HSV, HIV), fungi (H. capsulatum, C.neoformans). Usually unknown though. Drugs as well (nelfinavir and ritonavir). Late stage AIDS (CD4 < 100) can be related to CMV and MAC which need biopsy. AIDS-related enteropathy common as well. If profound GI bleeding, think CMV.
Proctatis: mainful defecation, rectal discharge. GC/C, Trepnema pallidum, HSV.
Low threshold to CT scan abdominal pain patient (may not have typical elevated WBC, peritoneal signs).
Kaposi Sarcoma: painless, raised, brown-black or purple papules/nodules that don’t blanch. Can be seen in oral cavity as well. No real tx, not associated with any worsening M&M.
Pruritic Papular Eruptions in HIV: presenting symptom in HIV in 25-75%; multiple, discrete red bumps which are pruritic, symmetric and diffusely distributed. Seen on extremities and trunk with sparing of mucous, palms, webspaces. Tx: steroids, emmollients, antihistamines. Usually resistant though.
HSV: can be more extensive than otherwise healthy pts. Herpes Zoster can be more complicated/prolonged. Disseminated or ophthalmic requires admission for IV acyclovir.
Scabies: scaly, persistent pruritic eruption, usually do not have classic intertriginous lesions. Tx: permethrin 5% cream x 1, ivermectin 200mcg/kg PO x 1, cortamiton. Norwegian scabies: more extensive version, less pruritic.
Usually 3 or 4 drugs: 2 nucleoside reverse transcriptase inhibitors + 1-2 protease inhibitors or 1 non-nucleoside reverse transcriptase inhibitor. Strongly recommended for CD4 < 350 or any hx/o AIDS defining illness, pregnancy, or co-infection with Hepatitis B. 6 classes of drugs now: NRTI (nucleotide reverse-transcriptase inhibitor, NNRTI (non-nucleotide reverse-transcriptase inhibitor), PI (protease inhibitor), FI (fusion inhibitor), INSTI (integrate strand transfer inhibitor), CCR5 (chemokine C-C motif receptor 5 antagonist).
HAART medications can decrease metabolism of some street drugs (Gruber, 2010).
Universal precautions with contact with blood/body fluids. Risk after parental exposure 0.32%, mucocutaneous exposure 0.09%. 80% of documented transmission have been with hollow-bore needle.
CDC: semen, vaginal fluid, CSF, synovial, pleural, peritoneal, pericardial, and amniotic fluid potentially infectious. Nasal or fecal, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.
Postexposure Propylaxis: One study found zidovudine prophylaxis reduced transmission by 79%. Risks for transmission: deep injury, visible blood on injuring device, needle placement in a vein or an artery of the source patient, source patient with late-stage HIV. Prophylaxis should be started within 1-2 hours, animal studies have shown little benefit if delayed by 24-36 hrs. CDC guidelines now recommend 3 drug regiment x 4 weeks over 2 drug regiment. Severe GI SE – 1/2 have SE, 1/3 will discontinue as a result.
CDC recommends prophylaxis for nonoccupational risk if < 72 hrs exposure with someone with known HIV. No prophylaxis with unknown HIV status source unless high risk for HIV. Consider in serious exposure if > 72hrs. All pts should be tested for antibodies initially, at 4-6 weeks, 3 months, and 6 months. 6 reported cases of transmission despite PEP. Antiretrovirals generally safe in first trimester (except EFV). No cases of transmission from source pt that is in the ‘window period.’
Preferred PEP regiment: FTC (emtricitabine) + TDF = Truvada combo + Raltegravir (RAL). ZDT can be used as alternative to TDF for renal failure pts and used with lamivudine (Combivir combo pill) instead of the others. Usually recommended 2 NRTIs + a INSTI, PI, or NNRTI. Other regiments should be consulted by ID.
References / Resources
Diagnosing and Treating HIV in the ED, Tim Lahey, Managing Medical Emergencies 2015, EMedHome