Classify the spirochaetes. Describe Borrelia and the non-venereal treponematoses.

Classification of the Spirochaetes

Borrelia — Relapsing Fever

• Louse-borne (epidemic) relapsing fever — B.
• Recurrentis, spread by the body louse
• the organism is released only when the louse is crushed, so infection follows scratching rather than a bite → Tick-borne (endemic) relapsing fever — B.
• Duttonii and others, from soft ticks, with a rodent reservoir → After an incubation of about a week, abrupt high fever with rigors, headache, myalgia and hepatosplenomegaly → The fever ends by crisis after 3 to 6 days, as antibody clears the circulating organisms → Surviving organisms undergo antigenic variation of their surface lipoproteins → The new antigenic variant multiplies unrecognised — a relapse → The cycle repeats, with each relapse milder
• louse-borne disease has fewer relapses but higher mortality
• Diagnosis — demonstration of the spirochaete in a peripheral blood film (Giemsa or dark ground) during the fever; it disappears between attacks, so the timing of the sample is decisive
• Treatment — tetracycline or erythromycin; a severe jarisch-herxheimer reaction is common and may be fatal in louse-borne disease, so the first dose is given under observation
• LYME disease — B. Burgdorferi transmitted by Ixodes ticks; stage 1 gives erythema chronicum migrans, an expanding annular "bull's-eye" rash; stage 2 gives carditis with heart block, and neurological disease including facial palsy; stage 3 gives a chronic arthritis. Treated with doxycycline or ceftriaxone. It is a temperate-zone disease and rare in India

Non-venereal Treponematoses

• The non-venereal treponematoses are serologically indistinguishable from syphilis — VDRL and TPHA are positive in all of them. In a person from an endemic area a positive test must therefore be interpreted with the clinical picture and the geography, not taken as proof of sexually acquired infection

Laboratory Diagnosis of the Spirochaetes

• They are too slender for the Gram stain (except Borrelia, which is thicker and stains readily) and most cannot be cultured, so diagnosis depends on dark-ground microscopy, special stains, serology and molecular methods
• Dark-ground microscopy — of chancre exudate for T. Pallidum, and of blood or urine for leptospires; requires a fresh specimen and experience
• Giemsa-stained blood film — for Borrelia during a febrile episode
• Silver impregnation (Fontana, Warthin-Starry, Levaditi) for tissue sections
• Serology — VDRL, RPR, TPHA and FTA-ABS for treponemes; ELISA and microscopic agglutination for leptospires; ELISA and immunoblot for Lyme disease
• Culture — possible only for Leptospira (in Ellinghausen-McCullough-Johnson-Harris or Korthof medium) and, with difficulty, Borrelia; T. Pallidum and M. Leprae cannot be cultured at all

Comparison of the Three Genera

Applied Aspects

• Take the blood film during the fever in relapsing fever; between episodes the organism is absent from the circulation and the film is negative
• Give the first dose of antibiotic under observation in relapsing fever and in syphilis, because of the Jarisch-Herxheimer reaction
• Delousing and improved hygiene control epidemic relapsing fever, which is a disease of crowding, war, famine and displacement
• Interpret positive treponemal serology in the light of geography; in someone from a yaws-endemic region, past childhood infection is a real alternative explanation to sexually acquired syphilis
• Consider Vincent angina in a foul-smelling ulcerative sore throat with poor oral hygiene, and confirm it with a simple Gram-stained smear showing fusiform bacilli and spirochaetes together
• The eradication of yaws from India demonstrates what a single-dose oral antibiotic combined with active case finding can achieve against a treponemal disease, and is a useful comparison when considering syphilis control
• Spirochaetes cannot be seen on a Gram stain except Borrelia, so a request for "Gram stain and culture" will never find them; the laboratory must be told what is suspected
• Antigenic variation defeats vaccine development in relapsing fever, as it does in trypanosomiasis and gonorrhoea; where an organism can change its surface at will, immunity is always one step behind
• Consider relapsing fever in a returning traveller or displaced person with recurrent fevers, and examine a blood film taken during the febrile episode rather than between them
• Vincent angina is diagnosed on a simple smear showing fusiform bacilli and spirochaetes together, which is a cheap and decisive test in a foul-smelling ulcerative sore throat
• Lyme disease is rare in India and should not be diagnosed on serology alone in someone without exposure in an endemic temperate region; false positives are common and lead to prolonged inappropriate treatment
• Erythema chronicum migrans is a clinical diagnosis and warrants treatment without waiting for serology, which is often negative at that stage
• Treponemal serology cannot distinguish syphilis from yaws or bejel, so the geography and the childhood history matter as much as the test result
• Spirochaetal diseases share a tendency to relapse and to affect many systems, which is why they are classically described as great imitators and why they are so often diagnosed late
• Penicillin remains effective against every pathogenic treponeme, none of which has developed resistance — a striking exception among bacteria and one that has held for eighty years
• Ask about occupation, travel and animal or arthropod exposure in any unexplained relapsing or multisystem febrile illness; the spirochaetoses are diagnosed far more often by history than by routine investigation
• The axial filament is unique to this group and gives the corkscrew motility that lets them burrow through mucus, tissue and even intact skin — which is how leptospires enter through an abrasion and treponemes cross the placenta
• Most spirochaetal disease is treatable with cheap, old antibiotics, so the whole clinical problem is one of thinking of the diagnosis in time
• Yaws and syphilis are caused by organisms that cannot be told apart by any routine test, differing in transmission and geography rather than in structure or serology — which is why the clinical and social history carries so much weight
• Send the right specimen at the right moment; a blood film between fevers, a dark-ground preparation from a healed chancre, or leptospiral serology in the first week will all be negative in a patient who has the disease