**2.4** *Treponema pallidum* **(TP)**

This bacterium (a spirochete) causes the sexually transmitted disease called syphilis. It is among the oldest known infectious diseases. The categorization of the disease into clinical stages is based on the clinical manifestations, especially if left untreated and this categorization guides the patient's treatment and follow-up. Patients with syphilis might seek treatment or be treated on the basis of signs or symptoms (clinical manifestations). The prevalence of syphilis in pregnancy in developing countries is between 2.5 and 17%. In sub-Saharan Africa, the prevalence of TP among high-risk groups in the 1980s was 4–32%, while among the low-risk groups in the same period was 0.01–33% [22–25]. The prevalence of the organism among high-risk groups in the 1990s was 2–29% and among the low-risk group in the same period was 1–29% [22–25]. In the same vein, this high prevalence is occurring in places where we have a paucity of manpower and equipment for testing and etiologic treatment of patients, with the resultant morbidity and mortality associated with the disease.

*Primary syphilis*: The classical presentation of primary syphilis is a single painless ulcer (chancre) at the infection site within 2–10 weeks postexposure and it can also manifest with atypical, multiple, or painful lesions [32]. The lesion will ulcerate eventually but heals within 2–4 weeks even without treatment [33].

*Secondary syphilis*: Hematogenous spread of syphilis occurs 4–10 weeks after primary syphilis and leads to secondary syphilis. This may manifest in the form of skin rash, mucocutaneous lesions, and lymphadenopathy. This age is characterized by nonspecific systemic symptoms, such as fever, malaise, arthralgia, weight loss, sore throat, and headache, in addition to a maculopapular rash on the trunk and extremities. Condyloma latum, which are gray or white wart-like spirochete-filled lesions that also appear in secondary syphilis. They appear adjacent to the primary chancre. If left untreated, the syphilitic symptoms will spontaneously resolve after 3–12 weeks. Relapse of symptoms in the first year (early latent syphilis) may be experienced by ¼ of the patients if the condition is left untreated.

*Tertiary syphilis:* This may manifest in the form of cardiac conditions, gummatous lesions, tabes dorsalis, and general paresis [32].

Latent syphilitic infections are otherwise subclinical infections (without symptoms and signs) and can be detected through serologic assays. Latent syphilitic infections are classified as (a) early latent syphilis—acquired within the preceding year, (b) late latent syphilis, and (c) latent syphilis of unknown duration.

Central Nervous System (CNS) syphilis, TP infection can spread to the CNS. This can happen at any stage of syphilis and result in neurosyphilis. Within the first few months or years of TP infection, CNS clinical symptoms and signs knowns as syphilitic meningitis can be noticed. These features may include cranial nerve abnormalities, meningitis, meningovascular syphilis, cerebrovascular accident, and acute altered mental state. Tabes dorsalis and general paresis are some of the neurologic features that may be noticed in patients with up to 10 to >30 years of TP infection [1].

The involvement of the ocular/visual system or the auditory system is referred to as ocular syphilis and otosyphilis, respectively. These commonly occur at the early stages of the TP infection and can manifest with or without other CNS affectation. They can also occur at any other stage of the disease. Panuveitis is the most common manifestation of ocular syphilis. Other manifestations of ocular syphilis are affectation of the anterior and posterior segment of the eye, including conjunctivitis, anterior uveitis, posterior interstitial keratitis, optic neuropathy, and retinal vasculitis. Patients with ocular syphilis may develop permanent/irreversible blindness. Clinical manifestations of the otosyphilis are tinnitus, vertigo, and sensorineural deafness. Hearing loss can involve one side of the ear or both sides. The hearing loss may also be sudden in onset and progress fast. Otosyphilis may lead to irreversible deafness.

Dark-field examinations and molecular tests for detecting TP directly from lesion exudate or tissue are the definitive methods for diagnosing early syphilis and congenital syphilis [33]. Syphilis is diagnosed by seeing the spirochetes on a darkfield microscopic exam of scrapings from chancres. The next diagnostic method is a demonstration of spirochetes in biopsy specimens stained with Warthin-Starry silver. Alternatively, a direct fluorescent antibody test for TP is performed by some laboratories [33]. Other investigations include the non-treponemal (not specific for treponemal antibodies) serologic tests, such as rapid plasma regain and Venereal Disease Research Laboratory (VDRL), which have a false-negative rate of up to 25%. If the non-treponemal tests return positive, a confirmatory treponemal test such as the fluorescent treponemal antibody absorption test should be conducted on the patient.

The CDC recommended regimen for primary and secondary syphilis among adults includes benzathine penicillin G 2.4 million units intramuscularly in a single dose. The recommended regimen for syphilis among infants and children includes benzathine penicillin G 50,000 units/kg body weight intramuscularly, up to the adult dose of 2.4 million units in a single dose. For patients with penicillin allergy, the regimen of Doxycycline (100 mg orally two times/day for 14 days) [34, 35] or tetracycline (500 mg orally four times/day for 14 days) have been used for years and can be effective [34, 35]. Due to gastrointestinal side effects, Doxycycline may be preferred to tetracycline.

Most patients in developing countries may not be opportune to have diagnostic investigations carried out for their symptoms before treatment due to a lack of hospitals and trained personnel and poverty. They may even experience delayed or absent treatment with the attendant sequelae.
