PANCE Blueprint Infectious Disease (3%)

Lessons

1. Infectious Disease Flashcards (Members Only)
   1. Infectious Disease Quick Cram Cards

2. Pediatric Vaccinations (Picmonic)
3. Fungal Disease (PEARLS)
   1. Candidiasis

      Very common in AIDS patients, EGD of esophageal Candidiasis will demonstrate linear erosions on endoscopy, treat with fluconazole.
   2. Cryptococcosis

      AIDS-defining illness, diagnose with CSF and serum serology.

      • Transmission is through inhalation. Budding yeast found in soil contaminated with pigeon/bird droppings.
      • India ink may be positive.
      • Treat with amphotericin B + flucytosine for two weeks followed by fluconazole for 10 weeks.
      • Prophylaxis: fluconazole if CD4 < 100.
   3. Histoplasmosis

      AIDS-defining illness, associated with soil containing birds and bat droppings in the Mississippi and Ohio River Valleys

      • Highest risk is with a CD4 < 100. Patients develop fever and multiorgan failure; fulminant disease, septic shock, and death are common.
      • ↑ Alkaline phosphatase and LDH, (+) blood cultures if disseminated
      • Itraconazole orally for weeks to months or Amphotericin B  if severe or failed Itraconazole
      • In general antifungal prophylaxis with itraconazole is not administered to prevent primary infection without special indications.
   4. Pneumocystis (HIV patients)

      Originally called Pneumocystis carinii pneumonia, then renamed Pneumocystis jirovecii but still referred to as PCP.

      • Most common opportunistic infection in patients with HIV especially if CD4 count < 200.
      • Chest x-ray characteristically shows diffuse, bilateral perihilar infiltrates.
      • Treat with trimethoprim-sulfamethoxazole (Bactrim) and steroids. If sulpha allergy, pentamidine.
      • Prophylaxis with daily Bactrim for high-risk patients with a CD4 < 200 or with a history of PJP infection.
4. Bacterial Disease (PEARLS)
   1. Acute rheumatic fever

      Although rheumatic fever follows a streptococcal throat infection (strep throat), it is not an infection. Rather, it is an inflammatory reaction to Group A Strep with the formation of antistreptolysin antibodies (ASO) which react with proteins on the synovium, heart muscle, and heart valves.

      • Jones criteria: 2 major criteria or 1 major and 2 minor criteria are required for diagnosis, along with evidence of preceding GAS infection.
        • Major criteria: carditis, chorea, erythema marginatum, polyarthritis, subcutaneous nodules.
        • Minor criteria: arthralgia, elevated ESR or C-reactive protein, fever, prolonged PR interval (on ECG).
      • Treat with Penicillin G.
      • Antistreptococcal prophylaxis with Penicillin G/V should be maintained continuously for 5-10 years after the initial episode of ARF to prevent recurrences.
   2. Botulism

      Gram-positive bacteria associated with home canned food products

      • Presents as muscle weakness and respiratory paralysis, “floppy babies.”
      • Exposure to moist heat at 120° C (248° F) for 30 min kills the spores. Toxins, on the other hand, are readily destroyed by heat and cooking food at 80° C (176° F) for 30 min safeguards against botulism.
      • Honey (no honey for babies) - it is recommended that you wait until your baby is at least 12 months before introducing honey.
      • Treatment: Botulinum antitoxin
   3. Chlamydia

      The most common sexually transmitted infections

      • Gram-negative, intracellular rod.
      • Asymptomatic, dysuria.
      • Diagnosis: Nucleic acid amplification test (NAAT) is the gold standard.
      • Gram stain reveals no organisms.
      • Azithromycin 1g PO x 1 + Ceftriaxone 250 mg x 1 to cover for Gonorrhea, doxycycline PO x 7 days is alternative.
      • In pregnancy azithromycin 1 gm x 1 dose or amoxicillin TID x 7 days.
   4. Cholera

      Caused by Vibrio cholerae a gram-negative bacteria which secretes a toxin that causes a life-threatening, rice water diarrhea.

      • Typically through contaminated water or seafood.
      • Diagnosis is confirmed by stool culture.
      • Endemic areas: India, Southeast Asia, Africa, Middle East, Southern Europe, Oceania, South and Central America.
      • Treat with oral rehydration + antibiotics (macrolides, fluoroquinolones, and tetracyclines).
   5. Diphtheria

      URI with thick gray pseudomembrane in the throat that bleeds if scrapped in someone who wasn’t vaccinated.

      • May have neck swelling due to enlarged cervical lymphadenopathy (BULL NECK).
      • Rare in the US due to routine vaccination at 2,4,6 and 15-18 months with a booster at 4-6 years of age.
      • Treat with antitoxin and antibiotic (penicillin or macrolide).
   6. Gonococcal infections

      Caused by Neisseria gonorrhoeae - gram-negative diplococci.

      • Women: often asymptomatic. Prolonged infection can result in pelvic inflammatory disease when the bacterium travels into the pelvic peritoneum.
      • Men: yellow, creamy, profuse and purulent discharge.
      • Ceftriaxone 250 mg IM in a single dose + treatment for chlamydia (azithromycin 1 g PO single dose or doxycycline 100 mg PO BID for 7 days).
      • Gonococcal pharyngitis is usually asymptomatic but may cause a sore throat.
      • Neonatal conjunctivitis and pharyngitis.
      • Disseminated infections can occur resulting in septic arthritis, tenosynovitis, and pustules on the hands and feet.
   7. Salmonellosis

      Although there are many types of Salmonella, they can be divided into two broad categories: those that cause typhoid and enteric fever and those that primarily induce gastroenteritis:

      • Enteric fever (salmonella typhi): a flu-like bacterial infection characterized by fever, GI symptoms, and headache. Transmitted via the consumption of fecally contaminated food or water.
        • GI symptoms may be marked constipation or "pea soup diarrhea."
        • Rose spots may be present (2-3 mm papule on trunk usually).
        • More common in the developing world (usually immigration cases).
      • Gastroenteritis (salmonella Typhimurium, Enteritidis, and Newport): results from improperly handled food that has been contaminated by animal or human fecal material.
        • It is estimated that 1 in 10,000 egg yolks is infected with Salmonella enteritidis.
      • Treat with ceftriaxone or other medications based on sensitivity.
   8. Shigellosis

      Gram-negative bacteria shigella that results in watery diarrhea or dysentery (the frequent and often painful passage of small amounts of stool that contains blood, pus, and mucus).

      • Illness starts abruptly with diarrhea, lower abdominal cramps, and tenesmus accompanied by fever, chills, anorexia, headache, and malaise.
      • Stools are loose and mixed with blood and mucus. The abdomen is tender; dehydration is common.
      • Treat with TMP-SMX or ciprofloxacin
   9. Tetanus

      Tetanus results from a toxin produced by the anaerobic bacteria Clostridium tetani. The toxin makes muscles become rigid and contract involuntarily (spasm).

      • Clostridium tetani spores are ubiquitous in soil. The spores germinate in wounds where the bacteria produce a neurotoxin (tetanospasmin), which interferes with neurotransmission at spinal synapses of inhibitory neurons. The result is uncontrolled spasm and exaggerated reflexes.
      • Puncture wounds are most susceptible. The elderly, migrant workers, newborns, and injection drug users are at particular risk.
      • Treatment: Immunoglobulin, wound debridement and penicillin. High mortality.
      • Vaccination: 
        • DTaP is usually given at 2, 4, 6, and 12 to 15 months, with an additional dose at 4 to 6 years
        • Tdap adolescent preparation is recommended at age 11 to 12 years for those who have completed the recommended childhood DTP/ DTaP vaccination series and have not received a tetanus and diphtheria toxoid (Td) booster dose.
        • Subsequent boosters are recommended every 10 years.
5. Mycobacterial Disease (PEARLS)
   1. Atypical mycobacterial disease

      Mycobacterium avium complex (MAC) - HIV patients with CD4 < 50

      • Very common. Fever, diarrhea, weight loss, anemia.
      • Present in soil and water (not person to person).
      • Symptoms rarely occur in immunocompetent patients (increased in bronchiectasis). HIV patients when CD4 < 50.
      • Diagnose with AFB and culture.
      • Treat with clarithromycin + ethambutol for at least 12 months (+/- rifampin).
      • Prophylaxis for HIV patients with (azithromycin or clarithromycin) if CD4 < 50.
   2. Tuberculosis (ReelDx)

      Mycobacterium tuberculosis - transmitted by respiratory droplets.

      • Classic findings include fever, night sweats, anorexia and weight loss.
      • PPD Rules: Area of induration = raised area (not the red area).
        • < 5 mm in HIV.
        • < 10 mm in high-risk area (healthcare worker or possible known exposure).
        • < 15 mm for non exposed.
      • Diagnose TB with sputum for AFB smears and cultures.
        • CXR - upper (apical) cavitary lesions.
        • Ghon complex (calcified lymph + lesions).
      • Latent TB - treat with Isoniazid for 9 months.
      • Active treatment: quad therapy (RIPE): Four drugs x 8 weeks then two drugs x 16 weeks. All are Hepatotoxic so you need to get baseline labs.
        • Rifampin (RIF): Orange body fluids, hepatitis - "remember R = red/orange body fluids."
        • Isoniazid (INH): peripheral neuropathy (give with B6- pyridoxine 25 to 50 mg/day).
        • Pyrazinamide (PZA): Hyperuricemia (Gout).
        • Ethambutol (EMB): Optic neuritis, red-green blindness - "remember E = eyes."
      • Patients with active TB will need two negative AFB smears and cultures in a row negative for therapy cessation.
      • Prophylaxis for household members: Isoniazid for 1 year.
6. Parasitic Disease (PEARLS)
   1. Helminth (worm-like parasites) infestations
      1. Malaria

         Periods chills, fever ( every 3 days) and sweats. Caused by plasmodium vivax, p. malaria, p.ovale, p. falciparum (most virulent).

         • Transmitted by Anopheles mosquito.
         • Splenomegaly typically after > 4 days of symptoms.
         • Diagnose with Giemsa stain peripheral smear (thin and thick) - parasites in RBCs, thrombocytopenia, increased LDH.
         • Treat with chloroquine or mefloquine for chloroquine-resistant p. falciparum.
         • Recommendations for drugs to prevent malaria differ by country of travel and can be found in the country-specific tables of the Yellow Book.
           • Doxycycline 100 mg once daily (started one day before travel, and continued for four weeks after returning).
           • Mefloquine 250 mg once weekly (started two-and-a-half weeks before travel, and continued for four weeks after returning).
           • Atovaquone/proguanil (Malarone) 1 tablet daily (started one day before travel, and continued for 1 week after returning). Can also be used for therapy in some cases.
         • In areas where chloroquine remains effective:
           • Chloroquine 300 mg once weekly, and proguanil 200 mg once daily (started one week before travel, and continued for four weeks after returning).
           • Hydroxychloroquine 400 mg once weekly (started one to two weeks before travel and continued for four weeks after returning).
      2. Pinworms

         Also known as enterobiasis vermicularis, is a human parasitic disease caused by the pinworm (a type of roundworm). The most common symptom is itching in the anal area. This can make sleeping difficult.

         • Perianal itching especially at night (eggs are laid at night).
         • Eggs cling to the fingers while itching and are transmitted to other people either directly or through food or surfaces.
         • The eggs can thrive for 2-3 weeks on an inanimate object.
         • Diagnosis is with "scotch tape test' done in the early morning. Can see the football-shaped ova under microscopy.
         • Treatment is with albendazole or mebendazole.
      3. Toxoplasmosis

         Toxoplasma gondii is a parasitic protozoa that causes the disease toxoplasmosis.

         • Triad of encephalitis + chorioretinitis + intracranial calcifications in AIDS patients with a CD4 < 100.
         • Pregnant female with exposure to cat feces: Toxoplasmosis is the reason we tell pregnant mothers not to change cat litter.
         • CT of the brain shows ring-enhancing lesions.
         • Enzyme-linked immunoassay (ELISA) - positive for anti-toxoplasma IgG and IgM.
         • Congenital toxoplasmosis is part of ToRCH syndrome.
         • Prophylaxis for all HIV patients with CD4 count < 100 with Bactrim.
7. Spirochetal Disease (PEARLS)
   1. Lyme disease

      7 mins

      Caused by Borrelia burgdorferi (gram negative spirochete) that is spread by Ixodes (deer) tick.

      • Early localized: usually 7-10 days after bite - erythema migrans rash “bullseye.”
      • Early disseminated: 1-12 weeks after bite - musculoskeletal, flu-like syndrome, consisting of malaise, fatigue, chills, fever, headache, stiff neck, myalgias, and arthralgias that may last for weeks, cardiac (AV block).
      • Late disease: persistent synovitis and arthritis.
      • ELISA testing will be positive by 3rd week
      • Treat with doxycycline or amoxicillin (10-21 days) is started immediately after diagnosis.
      • Prophylaxis: doxycycline 200 mg x 1 dose within 72 hours if Ixodes tick.
   2. Rocky Mountain spotted fever

      Caused by Rickettsia rickettsii a species of bacterium that is spread to humans by the American dog tick (Dermacentor variabilis).

      • 2-14 days after tick bite will develop flu-like symptoms: fevers and chills, myalgias, and headache.
      • Red maculopapular rash first on wrists and ankles (palms and soles) then spreading centrally over 2-3 days. The face is usually spared.
      • Indirect fluorescent antibody (IFA) test remains the standard method of diagnosis of RMSF.
      • Treat with doxycycline or chloramphenicol second line.
   3. Syphilis

      Caused by the spirochete Treponema pallidum.

      • The disease has 3 phases, with an incubation period of about 3 weeks:
        • Primary syphilis: presents as a painless chancre in the genital or groin region persisting 3 to 6 weeks.
        • Secondary syphilis: presents as an erythematous rash involving the palms and soles or a condyloma lata which is similar to the lesions of primary syphilis in its infectivity but differs in appearance.
        • Tertiary syphilis (latent): Affects about 30% and is a representation of widespread systemic involvement and can present with major vessel changes, such as in the aorta, permanent CNS changes (neurosyphilis), or even benign mucosal growths called gummas.
      • Diagnosis is by RPR/VDRL and confirmed by treponemal antibody-absorption test (FTA-ABS). Lyme disease can cause a false positive.
      • Treatment is with IM benzathine penicillin for primary and secondary disease. IV penicillin G (for Gummas) for congenital and late disease.
8. Viral Infectious Disease (PEARLS)
   1. Cytomegalovirus infections (ReelDx)

      Enveloped double-stranded linear DNA virus in the herpesvirus family. It is also called human herpesvirus 5. It can cause infections that have a wide range of severity.

      • CMV can cause a syndrome that is similar to infectious mononucleosis but lacks severe pharyngitis.
      • CMV can cause pneumonia and inflammation of the retina (CMV retinitis) and esophagus in the immunosuppressed, especially in transplant recipients. Associated with a CD4 count < 50.
      • A severe systemic disease can develop in neonates. It is one of the TORCHES infections and can cause hearing loss, seizures, and petechial rash in newborns.
      • Visualization of owl’s eye inclusions in a cell is highly specific for cytomegalovirus.
      • Ganciclovir, valganciclovir, foscarnet, and cidofovir are effective against CMV.
   2. Epstein-Barr virus infections (ReelDx)

      Epstein Barr mononucleosis is a viral illness characterized by a classic triad of fever + lymphadenopathy + pharyngitis.

      • Diagnosed with positive heterophile antibody screen (Monospot) - may not appear early in the illness (positive within 4 weeks).
      • Atypical lymphocytes with enlarged nuclei and prominent nucleoli.
      • Maculopapular rash develops in 80% of patients treated with ampicillin
      • Left upper quadrant pain secondary to splenomegaly and are at risk for splenic rupture - athletes should avoid vigorous sports for at least the first three to four weeks of the illness.
      • Treatment is supportive.

   3. Erythema infectiosum (Slapped Cheek/ReelDx)

      Erythema infectiosum is caused by parvovirus B-19.

      • Slapped cheek rash on the face with circumoral pallor 2-4 days of lacy reticular rash on extremities.
      • Diagnosis is clinical and treatment is symptomatic.
   4. Herpes simplex (ReelDx)

      • HSV 1 - Oral lesions commonly called cold sores (tongue, lips etc.)
      • HSV 2 - Genital lesions (vulva, vagina, cervix, glans, prepuce, and penile shaft)
      • HHV 3 - VZV (Varicella Zoster Virus commonly known as chickenpox or shingles)
      • HHV 4 - EBV (Ebstein Barr Virus is commonly known as infectious mononucleosis [mono or glandular fever])
      • HHV 5 - CMV (Cytomegolo Virus is the most common virus transmitted to a pregnant woman's unborn child)
      • HHV 6 - Roseolovirus is more commonly known as the 6th disease or Roseola Infantum
      • HHV 7 - Similar to HHV6 (not yet classified)
      • HHV 8 - A type of rhadinovirus known as the Kaposi's sarcoma-associated herpesvirus (KSHV)
   5. HIV infection

      • All CD4 counts
        • Tuberculosis: Tuberculin skin testing. Therapy for latent infection should be administered to those who test positive and are without evidence of active disease.
      • CD4 counts ≤250 cells/microL
        • Coccidioidomycosis: Perform annual IgG and IgM serologic screening and - fluconazole therapy to such patients if they have a newly positive serologic test.
      • CD4 counts ≤200 cells/microL
        • Pneumocystis: trimethoprim-sulfamethoxazole (TMP-SMX)
      • CD4 counts ≤150 cells/microL
        • Histoplasmosis: In general, do not administer antifungal prophylaxis with itraconazole.
      • CD4 counts ≤100 cells/microL
        • Toxoplasma: Administer suppressive therapy with TMP-SMX to prevent reactivation of T. gondii in patients with a CD4 count ≤100 cells/microL and a positive toxoplasmosis IgG serology.
        • Cryptococcus: Preventive therapy for cryptococcal disease is generally not recommended because of drug interactions, adverse effects, the potential for antifungal drug resistance, cost, and the lack of overall survival benefit.
      • CD4 counts ≤50 cells/microL
        • Mycobacterium avium complex (MAC): For patients who are initiating antiretroviral therapy (ART), do not routinely administer antimicrobial prophylaxis .
   6. Human papillomavirus infections (Lecture)

      • Cutaneous warts: serotypes 1, 2, and 4 - hands, fingers, and soles of feet.
      • Anogenital warts (condylomata acuminata): serotypes 6 and 11 - koilocytes (epithelial cells with structural changes characteristic of HPV infection).
      • Cervical intraepithelial neoplasia: serotypes 16, 18, 31, and 33 - are preneoplastic. Can progress to squamous cell carcinoma or spontaneously resolve.
      • Koilocytic squamous epithelial cells in clumps are found on a Pap smear and are typical of cervical warts.
      • A vaccine against HPV types 6 and 11 (genital warts) and 16 and 18 (cervical cancer) is available - recommended for males and females age 11 to 12 years and is approved for ages 9 thru 26.
   7. Influenza (ReelDx)

      Fevers, chills, coryza, and myalgias.

      • Rapid antigen test can be performed in the clinic.
      • Oseltamivir (Tamiflu) or zanamivir (Relenza) - (treats A and B) give before 48 hours.
        • Amantadine and rimantadine (adamantanes) Adamantanes = Influenza A.
      • Therapy is supportive - acetaminophen and/or ibuprofen and OTC cold medications.
      • Do not take ASPIRIN - can result in Reyes disease leading to hepatorenal failure and death.
      • Annual vaccine recommended for everyone ≥ 6 mo unless contraindicated.
   8. Rubeola (Measles)

      Measles is caused by a paramyxovirus and is transmitted by respiratory droplets, it has a 10-12 day incubation period. It progresses in three phases characterized by a prodrome, enanthem, and exanthem.

      • Prodrome: 1-3 days of a "the three C's" - cough, coryza, conjunctivitis, as well as fever.
      • Enanthem (48 hours prior to exanthem) - Koplik spots - are pathognomonic for measles and present as small red spots with a blue-white center on the buccal mucosa.
      • Exanthem (2-4 days after onset of fever): consists of a morbilliform, brick red erythematous, maculopapular, blanching rash, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities.
      • Treatment is supportive with anti-inflammatories.
   9. Mumps

      Caused by the paramyxovirus and causes painful parotid gland swelling along with low-grade fever, myalgias, and headache.

      • Orchitis in males - mumps causes unilateral, orchitis in males.
      • Mumps is the most common cause of pancreatitis in children.
      • MMR vaccine is given at 12-15 months then again at 4-6 years of age.
   10. Rabies

       Caused by a ribonucleic acid (RNA) rhabdovirus affecting mammals, including humans.

       • Transmission via dogs, raccoons, skunks, bats, fox, coyote.
       • Hydrophobia (inability to swallow water) is a classic symptom. Pharyngeal spasms, aerophobia (fear of drafts of fresh air) and hyperactivity.
       • Negri bodies (eosinophilic inclusion bodies in the cytoplasm of hippocampal nerve cells) are considered pathognomonic and are found in the brain of dead animals.
       • Post-exposure treatment: Rabies immunoglobulin + inactivated vaccine (4 doses over 14 days)
       • Fatal when there are neurological symptoms.
   11. Roseola (HHV 6)

       Also known as exanthema subitum, caused by Herpesvirus 6 or 7 - only childhood exanthem that starts on the trunk and spreads to the face. 

       • High fever 3-5 days in small children then rose pink maculopapular blanchable rash on trunk/back and face.
   12. Rubella (German Measles)

       Presents with high fever followed by 3C's - a cough, coryza (erythematous mucous membranes, nasolabial usually) and conjunctivitis, along with tender postauricular lymphadenopathy. Following this is a diffuse, light pink maculopapular rash that first appears on the face and then spreads to the trunk and extremities within 24 hours.

       • The rash usually lasts about three days, hence the name three-day measles.
       • In pregnancy, rubella is a TORCH infection and can cause serious complications, including hearing loss, ocular and cardiovascular defects and mental retardation.
       • Immunoglobulin administration is indicated for use in exposed individuals to alter clinical disease.

   13. Varicella-zoster virus infections (ReelDx)

       Varicella (chicken pox): primary infections - clusters of vesicles on an erythematous base.

       • Dew drops on a rose petal in different stages.
       • Starts on the face and spreads down.
       • Acutely causes chickenpox - becomes latent in the dorsal root ganglion.
       • Symptomatic treatment may use acyclovir in special populations.

       Herpes zoster (shingles): varicella reactivation causing maculopapular rash along one dermatome.

       • Identified via tzanck smear with visualization of multinucleated giant cells.
       • Zoster Opthalmicus: shingles involving CCN V, dendritic lesions on slit lamp exam if keratoconjunctivitis is present.
       • Zoster Oticus (Ramsay-Hunt Syndrome): facial nerve (CN VIII) otalgia, lesions on the ear, auditory canal and TM, facial palsy auditory symptoms.
       • Treat shingles with acyclovir, valacyclovir, and famciclovir - given within 72 hours to prevent post-herpetic neuralgia.
       • Postherpetic Neuralgia: pain > 3 months, paresthesias or decreased sensation. Treat with gabapentin or TCA, topical lidocaine gel, and capsaicin.
       • Herpes zoster vaccine is a live, attenuated virus vaccine - vaccination is recommended for immunocompetent adults > 60 years of age.