Spirochetes

Spirochetes are long, thin, tightly coiled, helical bacteria. They are Gram negative but stain poorly with standard Gram technique because of their thin diameter. Direct visualisation typically needs dark-field microscopy, silver staining or fluorescent antibody methods.

They are motile via internal, periplasmic flagella. These run within the periplasmic space between the outer membrane and the cell body, rather than externally as in most other flagellated bacteria. This produces a characteristic corkscrew-like motility.

Three genera are of major medical importance, each with a distinct transmission route and clinical pattern: Treponema, Borrelia, and Leptospira.

Morphology. Treponema pallidum is an extremely thin, tightly coiled spirochete. It is too thin to be reliably visualised by standard light microscopy or Gram stain. Dark-field microscopy of a fresh lesion specimen is needed to see the motile organism directly.

Transmission. Transmission is predominantly by sexual contact and direct contact with an infectious lesion. It can also be vertical, transplacentally from an infected mother to the fetus at any stage of untreated maternal infection, causing congenital syphilis.

Syphilis stages.

Primary syphilis presents as a single, painless, indurated ulcer, the chancre, at the site of inoculation. It is typically genital but may be extragenital, oral or anal. Painless regional lymphadenopathy is typically associated.

The chancre heals spontaneously even without treatment. Resolution of the visible lesion does not indicate resolution of infection.

Secondary syphilis occurs weeks to a few months after the primary chancre, which may have healed and gone unnoticed. It reflects haematogenous dissemination of the organism. Features are:

• A widespread rash characteristically involving the palms and soles. Relatively few other conditions classically involve this distribution.
• Generalised lymphadenopathy.
• In some patients, condylomata lata. These are broad, flat, highly infectious wart-like lesions in moist body areas, distinct from the pointed condylomata acuminata of genital HPV infection.

Secondary syphilis is also self-limited and resolves even without treatment. This again does not indicate cure of the underlying infection.

Latent syphilis is serologically confirmed infection without any clinical symptoms or signs. It can last years to decades. It is subdivided into two stages:

• Early latent, within the first year of infection. It can still relapse to secondary-stage manifestations and is still considered sexually transmissible in some cases.
• Late latent, beyond one year. It is generally no longer sexually transmissible, though transplacental transmission risk persists throughout untreated infection.

Tertiary syphilis occurs in a minority of untreated patients, years to decades after initial infection. It has several distinct patterns:

• Cardiovascular syphilis, classically aortitis with a predilection for the ascending aorta. It can cause aortic aneurysm and aortic regurgitation.
• Neurosyphilis, which can occur at any stage of infection, not exclusively tertiary disease. This nuance is frequently tested. It presents as meningitis, as meningovascular disease with a stroke-like presentation, or as the classic late parenchymal forms.
• Tabes dorsalis, a late parenchymal form, is dorsal column degeneration causing sensory ataxia and characteristic lightning pains.
• General paresis, the other late parenchymal form, is a progressive dementia with psychiatric features.
• Gummatous disease, with localised, granulomatous, destructive lesions that can affect skin, bone and other organs. It is now rare given widespread earlier treatment in most settings.

Congenital syphilis results from transplacental transmission, which can occur at any stage of untreated maternal infection. Risk and severity are generally greatest with more recent maternal infection and higher organism burden. It can cause stillbirth.

In surviving infected infants, manifestations are early or late:

• Early manifestations, within the first two years, resemble a florid secondary-syphilis-like picture. They include rash, hepatosplenomegaly and characteristic bone lesions.
• Late manifestations are classic stigmata, including Hutchinson teeth, saddle nose deformity and sabre shins. They reflect the long-term consequences of untreated early infection.

Diagnostic principles.

Nontreponemal tests (VDRL, RPR) detect antibodies against a nonspecific cardiolipin-based antigen. They are useful for screening. Titres correlate with disease activity, so they also monitor response to treatment. A falling titre after treatment indicates adequate response.

They are prone to false positives in several other conditions. These include certain autoimmune diseases, particularly antiphospholipid syndrome and systemic lupus erythematosus, pregnancy, and some other infections. This is a specific and clinically important limitation.

Treponemal tests (FTA-ABS, TPPA, and various treponemal-specific enzyme immunoassays) detect antibodies specific to T. pallidum itself. They are more specific than nontreponemal tests.

Treponemal tests remain positive for life after adequate treatment in most patients. They therefore cannot monitor treatment response or distinguish active from previously treated, cured infection. This limitation complements that of the nontreponemal tests.

The two test types are used together, because each compensates for the other's limitation. The algorithm is either traditional or reverse:

• Traditional: nontreponemal screening, then treponemal confirmation.
• Reverse: treponemal screening, then nontreponemal confirmation and activity assessment.

Dark-field microscopy of fluid from an active primary chancre provides direct organism visualisation. It needs specific expertise and fresh specimen handling, which limits its routine use compared with serology.

Cerebrospinal fluid examination, with CSF-specific VDRL testing, is required when neurosyphilis is suspected.

Lyme disease organisms are the Borrelia burgdorferi sensu lato complex. They are the principal cause in North America and, with some regional variation in causative species, Europe.

They are transmitted by the bite of an infected Ixodes tick, the black-legged or deer tick. The tick life cycle is maintained in a rodent and in deer, though deer are not thought to be a significant reservoir for the organism itself.

Effective transmission requires prolonged tick attachment, typically at least 36 to 48 hours. This is relevant to post-exposure risk assessment after a recognised tick bite.

They cause Lyme disease, which classically begins with erythema migrans. This is an expanding, often centrally clearing, target or bull's-eye skin lesion at the tick bite site. It typically appears days to a few weeks after the bite.

If untreated, early disseminated disease can follow weeks to months later. It includes facial nerve palsy, sometimes bilateral, and, less commonly, carditis with atrioventricular conduction block.

In a minority of untreated patients, late disease occurs. Most classically this is Lyme arthritis, typically a large-joint, often knee-predominant, intermittent or persistent monoarthritis or oligoarthritis.

Diagnosis is predominantly clinical in a patient with a classic erythema migrans lesion in an endemic area. Serology is often still negative at this very early stage, as there has been insufficient time for antibody development. A negative early serology result therefore does not exclude the diagnosis in this context.

For later-stage or disseminated disease, a two-tiered serological approach is standard. Initial enzyme immunoassay screening is followed by confirmatory Western blot for positive or equivocal results.

Relapsing fever organisms are various Borrelia species, with two epidemiological patterns.

• Tick-borne relapsing fever is transmitted by soft-bodied Ornithodoros ticks, maintained in a rodent reservoir. It is generally sporadic in distribution.
• Louse-borne relapsing fever is transmitted by the human body louse. Humans are the primary reservoir, rather than an animal. It is associated with crowding, poor hygiene and social disruption (war, famine, refugee settings). It can produce large epidemics under such conditions, unlike the sporadic tick-borne form.

Both forms produce the defining clinical feature that names the disease: recurring, self-limited febrile episodes separated by afebrile intervals.

This reflects antigenic variation of the organism's surface proteins. Successive waves of organism evade the antibody response generated against the previous antigenic variant. This produces the relapsing pattern.

Diagnosis relies on direct visualisation of the spirochete on a peripheral blood smear examined during a febrile episode, when organism burden in the blood is highest. This differs from the predominantly serological approach used for Lyme disease.

Zoonotic transmission. Leptospira is a zoonotic spirochete. It is maintained in the renal tubules of a wide range of animal reservoirs. Rodents are the most epidemiologically important globally, though many other mammals can also serve as reservoirs. The organism is shed into the environment in infected animal urine.

Human infection occurs through direct or indirect contact with water or soil contaminated by infected animal urine. The organism penetrates mucous membranes or breaks in the skin.

Classically associated exposures are recreational freshwater exposure, flooding, and occupational exposures such as farming, sewage work and veterinary work.

Major clinical syndromes. Most infections are mild, self-limited and nonspecific, causing a flu-like febrile illness. They are often not specifically diagnosed.

A minority progress to severe leptospirosis (Weil's disease). It classically features a triad:

• Jaundice, from hepatic involvement.
• Acute kidney injury.
• Haemorrhage, from vasculitis-related bleeding. This can be severe and includes pulmonary haemorrhage in the most severe cases.

This is a life-threatening presentation that needs prompt recognition and treatment.

Conjunctival suffusion is a classic, though nonspecific, examination clue in the appropriate epidemiological context (relevant freshwater or animal urine exposure history). It is redness of the conjunctiva without a true purulent discharge, which distinguishes it from typical conjunctivitis.

Diagnosis. Serology is the mainstay in routine practice. The microscopic agglutination test is the traditional reference method, alongside various enzyme immunoassays.

PCR is also available. Direct culture is available but less commonly used, given practical and technical constraints. Culture needs specialised media and prolonged incubation, which limits its routine clinical utility.