Syphilis

=__**Disease/Drug of interest** : __=

====**Motivation and Background** : Syphilis is a bacterial infection that may be either congenital or acquired through sexual contact or by exposure to contaminated needles. The disease is of both individual and public health importance and in addition to its direct morbidity, increases risk of HIV infection and can cause lifelong morbidity in children born to infected mothers. This infection is cause by Treponema pallidum, a spirochete, which is a thin coil-shaped bacterium that enters the body through the mucous membranes or breaks in the skin [1]. Treponema pallidum is an endemic in lower-income countries but occurs at a lower rate in middle-income countries. Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. Acquired syphilis has four stages, including primary, secondary, latent, and tertiary, and can be spread by sexual contact during the first three of these four stages [1]. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system [2]. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.

====


 * References: **
 * [1] Hook, E. W., Syphilis. //Lancet// **2016**.
 * [2] Singh, A. E.; Romanowski, B., Syphilis: Review with emphasis on clinical, epidemiologic, and some biologic features. //Clinical Microbiology Reviews// **1999,** //12// (2), 187-+.
 * [3] Hook, E. W.; Marra, C. M., ACQUIRED SYPHILIS IN ADULTS. //New England Journal of Medicine// **1992,** //326// (16), 1060-1069.
 * [4] Bicillin® L-A (penicillin G benzathine injectable suspension) Disposable Syringe (accessed Feb 5, **2017**)).
 * [5] National Center for Biotechnology Information. PubChem Compound Database; CID=25137901, (https://pubchem.ncbi.nlm.nih.gov/compound/25137901).
 * [6] Anon. **2016**. “Syphilis.” //Centers for Disease Control and Prevention//. Retrieved February 5, 2017 ([]).
 * [7] Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. //The Journal of Clinical Investigation//. **2011**;121(12):4584-4592. doi:10.1172/JCI57173.

**External links:**
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https://pubchem.ncbi.nlm.nih.gov/compound/25137901

https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=5765

=**__Target Information : __ **The target of the drug of interest, PGB, is to inhibit the multiplication and biosynthesis of bacterium Treponema pallidum interfering with bacterial cell wall synthesis during active multiplication [4] **. **=
 * Size ** : **molecular weight of the protein**: T. Pallidum is very small in size with a length that ranges from 6 to 20 um and a diameter range of 18-20 um. // T. pallidum // is a member of the spirochete family which are characterized by their distinct helical shape.


 * Location ** : //T. pallidum // are found intracellularly within the cytoplasmic substance of fibroblasts, interstitial and Leydig cells, and of spermatocytes

=__**Drug Information**** : **__=


 * Schematic figure of drug ** :
 * Formula ** : C 48 H 56 N 6 O 8 S 2


 * Molecular weight ** : 909.1364 g/mol
 * CAS Number ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">1538-09-6


 * Delivery method ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">administered by a deep intramuscular injection


 * Side effects ** :
 * skin rashes (including maculopapular eruptions and exfoliative dermatitis Urticaria)
 * chills
 * fever
 * edema
 * arthralgia
 * prostration
 * anaphylaxis (including shock and death)


 * Other names ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">Bicillin L-A, Benzylpenicillin, Penicillin G, Penicillin G K for Inj; Bicillin LA; Pfizerpen


 * Maker or company ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">Pfizer


 * Is it patented ** ? yes, it <span style="font-family: Calibri,sans-serif; font-size: 11pt;">was patented as Benzathine benzylpenicillin in 1950


 * Clinical Trials Info ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">So far there are 34 studies found for Penicillin G Benzathine on the ClinicalTrial.Gov Database.

__** Origin ** : __ <span style="font-family: Calibri,sans-serif; font-size: 11pt;">Benzathine is originated by the reaction of dibenzylethylene diamine with two molecules of Penicillin G. It’s a natural antibacterial antibiotic derived directly from strains of fungi of the genus Penicillium and other soil-inhabiting fungi grown on special culture media.

<span style="font-family: Calibri,sans-serif; font-size: 11pt;">The treatment of persons who are allergic to penicillin involves the use of other antibiotics, which may require the administration of multiple doses; therefore, their efficacy depends on the compliance of the patient [3]. Studies of **tetracycline** (24 to 32 g given over a period of two weeks) have shown that its efficacy is similar to that of penicillin; **doxycycline** can be considered equally efficacious [3].
 * Alternatives to this drug ** :


 * Miscellaneous ** : <span style="font-family: Calibri,sans-serif; font-size: 11pt;">Persons who receive syphilis treatment must abstain from sexual contact with new partners until the syphilis sores are completely healed. Also, people who had syphilis must notify their sex partners so that they also can be tested and receive treatment if is necessary.

<span style="font-family: Calibri,sans-serif; font-size: 11pt;">Penicillin G Benzathine can also be used to treat mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci, as well as Venereal infections (yaws, bejel, and pinta) [4]. Rheumatic fever and/or chorea can also be treated as Prophylaxis with penicillin G benzathine, which has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis [4].
 * Other uses ** : can this drug be used to treat other diseases/conditions?