Spirochetes are a group of bacteria with a corkscrew- or question mark-shape that are visualized using a method called dark-field microscopy.
You don’t need to know the following for USMLE, but I will clarify for some students who ask: even though H. pylori also has spiral-shape similar to spirochetes, it is not a spirochete. Apparently, spirochetes are unique in that they use axial filaments or endoflagella for movement, whereas other bacteria use “regular flagella.”
Treponema pallidum
Causes syphilis.
Spirochete (spiral/cork screw-shaped bacterium) visible under dark-field microscopy.
Primary syphilis = painless chancre (painless ulcer) on genitalia.
Don’t confuse the painless chancre of primary syphilis with chancroid, which is a painful chancre-appearing lesion (-oid means “looks like but ain’t”) caused by the bacterium Haemophilus ducreyi.
Secondary syphilis = 6 weeks to 6 months after appearance and disappearance of the initial chancre, patient can get body rash that includes palms + soles, and condylomata lata (painless genital plaques). Don’t confuse condylomata lata with condylomata acuminata (genital warts).
Tertiary syphilis = years later, patient can get gummas (appear as painless chancres but are on other areas of the body such as the face/nose), arthritis, and ascending aortitis (tree-barking of vasa vasorum).
Neurosyphilis can occur at any stage; it is not sequential where we have 1 –> 2 –> 3 –> neurosyphilis. There is a 2CK Neuro Q that gives neurosyphilis in an 18-year-old.
Neurosyphilis presents as tabes dorsalis (obliteration of dorsal columns, with loss of vibration/proprioception + a positive Romberg sign, where patient falls over when standing with eyes closed), Argyll-Robertson pupil (i.e., “prostitute pupil”; accommodates but doesn’t react), and “stroke without hypertension” (i.e., sometimes findings akin to stroke but in a younger patient).
Diagnosis of primary syphilis is made via visualizing the spirochetes from a chancre scraping under dark-field microscopy.
Diagnosis of secondary, tertiary, and neurosyphilis can be done with serology, where a VDRL and/or RPR is done first (sensitive but not specific); an FTA is done as confirmatory (specific but not sensitive).
VDRL test mixes the patient’s serum with cardiolipin antigen. If antibodies against T. pallidum are present, the test demonstrates clumping/flocculation. The RPR enhances this reaction by using charcoal particles. There is an NBME Q floating around where they say something about a patient whose test results demonstrate clumping with charcoal particles, and the answer is SLE.
Patients with SLE who have anti-phospholipid syndrome can get false-positive VDRL/RPR tests because this syndrome is often caused by antibodies against cardiolipin (in SLE, we simply call these antibodies “lupus anticoagulant”).
FTA mixes a patient’s serum with fluorescent Treponema antibodies. If binding occurs, this confirms the diagnosis of syphilis.
USMLE will show you 24-year-old male with rash on his back + KOH prep is negative + ask what’s most likely to diagnose–> answer = FTA.
Treatment for all syphilis types is penicillin.
If patient has Hx of anaphylaxis to beta-lactams but is pregnant or has tertiary or neurosyphilis, the answer is desensitize + give penicillin. This is because penicillin is the most efficacious and needs to be given in severe cases.
If patient has Hx of mere rash to beta-lactams, but not anaphylaxis, then the beta-lactam can be given anyway.
Killing of T. pallidum spirochetes can sometimes cause a hypersensitivity-type response by the immune system known as Jarisch-Herxheimer reaction. USMLE will say patient was given penicillin for syphilis + gets fever, chills, and myalgias. This is different from beta-lactam allergy, which would be a rash or anaphylaxis (swelling + low BP).
Congenital syphilis can cause tooth abnormalities (mulberry molars/incisors), “saber shins” (bone abnormalities), saddle nose, deafness, and cataracts. There is NBME Q floating around where they are vague + give basically no info apart from “tooth abnormalities,” where the answer is congenital syphilis. So this finding is especially important for USMLE.
Borellia burgdorferi
Spirochete; spiral/corkscrew-shaped.
Causes lyme disease; spread by Ixodes tick (same as Ehrlichia, Babesia, and Anaplasma).
Primary Lyme causes a classic target rash known as erythema chronicum migrans, but a HY point is that the rash need not be a target on USMLE. It can merely be circular with no clearing, but the target is classic.
Bells palsy can also be seen in primary Lyme. What the USMLE will do is give two side by side images: 1) circular rash on limb that is not a target; 2) Bells palsy, where the student needs to infer this is Lyme disease even though rash isn’t a target, since Bells palsy is HY for Lyme.
Secondary Lyme tends to cause arthritis. Some sources say Bell’s palsy is part of secondary Lyme (occurs at least one month after initial infection), but I’ve seen USMLE give it as part of initial/primary infection.
Tertiary Lyme can cause CNS and/or heart problems.
Treatment is doxycycline for most cases of Lyme.
Ceftriaxone is given for advanced Lyme involving the CNS or heart.
For children <8 and pregnant women, give amoxicillin in place of doxycyline.
There is an NBME Q of a pregnant woman with non-disseminated Lyme, where ceftriaxone is correct over doxycycline, and amoxicillin isn’t listed. In other words, if USMLE doesn’t want doxy as the answer, they will not play trivia as to whether it’s ceftriaxone or amoxicillin to be used as the alternative. But you could be aware that, in theory, ceftriaxone is harder-hitting and preferred if cases are more severe.
Borellia recurrentis
Causes a condition known as relapsing fever.
Spread by body lice, not Ixodes tick the way Lyme disease is.
Leptospira interrogans
Question mark-shaped spirochete.
Leptospirosis can present as flu-like illness, jaundice, pulmonary hemorrhage, and meningoencephalitis.
It is usually spread by animal urine.
There’s two ways USMLE asks Leptospira:
1) They’ll be hyper-obvious and say there’s a farmer with a weird, flu-like illness where he was walking in animal urine. Answer is just simply Leptospira.
2) They’ll give easy vignette of syphilis or Lyme disease, followed by asking which of the following organisms is most taxonomically similar (i.e., which of the following is also a spirochete), and the answer is just Leptospira.
Mycobacterium tuberculosis
Has unique cell wall composed of mycolic acid that is difficult to gram stain. Requires acid-fast stain.
Produces cord factor (asked on NBME) as a virulence factor.
Can present similar to lung cancer, where patient can have B symptoms (i.e., fever, night sweats, weight loss) and hemoptysis.
Living in a homeless shelter or immigrant status from endemic area is buzzy. I’ve seen rural India and Albania as two locations in NBME Qs. Prisoners/prison workers, healthcare workers, and TB laboratory personnel are of course at risk as well.
Can cause cavitations and calcification in the lung grossly; on histo, causes caseating granulomatous inflammation.
Ghon foci/complexes are textbook descriptors for TB lesions but not assessed eponymously on USMLE. A Ghon focus is a localized area of inflammation. If lymph nodes are involved, the combination of the lesion + lymph node(s) is called a Ghon complex.
Can cause constrictive pericarditis (can also calcify).
Disseminated TB (miliary TB) can affect multiple organ systems, leading to psoas abscess, Pott disease (TB infection of the vertebrae), adrenal insufficiency, meningitis, osteomyelitis, and arthritis.
First step in diagnosis is PPD test (type IV hypersensitivity).
If PPD test is (+), the next best step is CXR.
If PPD is (+) but CXR (-), next best step is “treat for latent TB, “ or “give TB prophylaxis.” This is isoniazid (INH) for 9 months + vitamin B6 (since INH can cause B6 deficiency). It is exceedingly HY you know that neuropathy in a patient being treated for TB has B6 deficiency.
If PPD and CXR are both (+), the next best step is “treat for active TB,” which is RIPE for 2 months + RI for 4 more months (6 months total). RIPE = rifampin, isoniazid, pyrazinamide, ethambutol.
BCG vaccine is live-attenuated. USMLE wants you to know Hx of BCG vaccine does not change management based on PPD guidelines.
If USMLE asks you how long after TB exposure will someone’s sputum cultures be positive, the answer is 2-5 weeks.
Interferon-gamma release assay (Quantiferon Gold) can be used in patients who have Hx of BCG to reduce false (+)s, but USMLE doesn’t assess it. The reason I mention it is because they want you to know interferon-gamma is required for stimulation of alveolar macrophages to control TB.
Patients who have IFN-gamma or IL-12 receptor deficiency have susceptibility to TB infections. If this immuno stuff sounds confusing, I talk about this in detail in my HY Immuno PDF.
TNF-alpha is also required to suppress TB. Therefore drugs such as infliximab, adalimumab, and etanercept increase risk of TB, which is why they should be avoided in silicosis patients (who have increased risk of TB).
What is considered a positive PPD test (in terms of # of mm of induration) differs depending on risk factors:
What is considered a positive PPD test (in terms of # of mm of induration) differs depending on risk factors:
>5mm (+): Hx of close contact to someone with active TB; immunocompromised patient (AIDS, organ transplant recipient receiving immunosuppressants, chronic corticosteroid user); calcification on CXR.
>10mm (+): Health care worker or prisoner/prison worker; immigrant from endemic area; TB laboratory personnel, children <4.
>15mm (+): everyone else.
If a PPD test is (+), never repeat it. If it is negative, it must be repeated in 1-2 weeks (i.e., sometimes false-negatives).
Rifampin is a DNA-dependent RNA polymerase (just remember “RDR” –> Rifampin DNA-dependent RNA polymerase). It can cause orange tears/secretions. It also upregulates P-450.
Isoniazide is a mycolic acid synthesis inhibitor. It can cause B6 deficiency (neuropathy and/or seizures) and high anion-gap metabolic acidosis (the I in MUDPILES refers to isoniazid/iron tablets). It also inhibits P-450.
Pyrazinamide inhibits fatty acid synthesis.
Ethambutol inhibits carbohydrate synthesis (arabinosyl transferase). It causes optic neuritis, sometimes with changes in color vision.
Mycobacterium leprae
Causes leprosy; affects skin and peripheral nerves.
Highest yield point for USMLE is that M. leprae grows best at cooler temperatures, which is why it affects areas like the nose and peripheral nerves. Shows up on an NBME Q where they ask what is most characteristic of the causal organism, and the answer is something like “temperature sensitive.”
Dapsone is used as part of the treatment. It’s HY to know it can cause hemolysis in G6PD.
Mycobacterium avium intracellulare
MAI can cause lung infections similar in presentation to TB; can also cause GI infections. These types of infections are classically seen in immunocompromised patients (i.e., AIDS with CD4 count <50). Azithromycin prophylaxis is no longer indicated for AIDS patients.
MAI can also cause an obscure pneumonitis called “hot tub lung,” which can occur in immunocompetent patients. Shows up on an NBME exam as guy who moved into new apartment building with a hot tub. MAI present in hot tub vapors can cause lung inflammation (hence pneumonitis).
Mycobacterium marinum
Causes red lesion(s) on finger/hand in workers at, or kids who go to, water parks/aquariums.
USMLE will give Pseudomonas and S. aureus as distractors. So be aware of M. marinum as buzzy cause of skin infection associated with water parks and aquariums.
Mycobacterium scrofulaceum
Causes lymphadenopathy in the neck, sometimes with a skin lesion. Not HY, but you can be aware it exists.
