CDC (clinical guidance for STIs)
Chancroid:
Cause: Chancroid is caused by a pleomorphic gram-negative rod called Haemophilus ducreyi.
Symptoms: this ulcerative disease usually beings as a soft apule, or bump, at the point of contact and develops into a “soft chancre” (in contrast to the hard symphilis chancre), which is very painful in men but may be unnoticed in women. Inguinal lymph nodes can become very swollen and tender.
Epidemiology: Chancroid is very common in the tropics and subtropics and is becoming more common in the U.S.
Transmission: Chancroid is transmitted exclusively through direct contact, especially sexually. The disease is associated with sex workers and poor hygiene. Uncircumcised men seem to be more commonly infected than those who have been circumcised. People may carry this bacgerium asymptomatically.
Chlamydai:
Videos: Chlamydia (discussion elementary bodies)
Chlamydai is the most common reportable infectious diasese in the U.S. Annually, more than 1 million cases are reported, but the actual infection rate may be 5-7 times more. Chlamydia trachomatis affects mostly young women, but it can occur in both men and women and in all age groups. It’s not difficult to treat, but if left untreated it can lead to more-serious health problems. See Mayo Clinic
Bacteria of the Chlamydia genus are Gram-negative, obligate intracellular pathogens that are responsible for a variety of human and veterinary diseases. Among them, Chlamydia trachomatis (C. trachomatis) and Chlamydia pneumoniae (C. pneumoniae) are significant human pathogens. While C. pneumoniae has both medical and veterinary relevance, C. trachomatis is a human-specific pathogen and the leading cause of bacterial sexually transmitted infections (STIs) and
infectious blindness (trachoma). Most C. trachomatis infections are asymptomatic, contributing to underdiagnosis and increased transmission. In women, untreated infections can lead to severe reproductive complications, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Furthermore, infections are associated with an elevated risk of cervical and ovarian cancer, as well as increased susceptibility to other STIs, such as Neisseria gonorrhoeae and HIV.
The sequences of both Chlamydia trachomatis and Chlamydiapneumoniae have been determined with the hope that a comparison between the two genomes will significantly enhance the understanding of both pathogens.
C. Trachomatis exhibits a unique biphasic developmental cycle, alternating between an infectious elementary body (EB) and a replicative reticulate body (RB). An elementary body is the small infectious form of certain bacteria. It is a metabolically inactive particle with a rigid cell wall that allows it to survive outside of a host cell and transmit infecdtion infection to a new one. Once inside a host cell, the EB converts to a different formed called a reticulate body which can replicate. Upon contact with a host cell, the chlamydial EB delivers pre-packaged type III secretion system (T3SS) effector proteins into the host cell to facilitate endocytosis of the EB.
signs and symptoms:
Chlamydia doesn’t usually cause any symptoms. So you may not realize that you have it. People with chlamydia who have no symptoms can still pass the disease to others. If you do have symptoms, they may not appear until several weeks after you have sex with an infected partner. See MedlinePlus
In males, the bacterium can cuase an inflmmation of the urethra. The symptoms mimic gonorrhea; discharge and painful urination. Females who experince symptoms have cervicitis, a discharge, and often sapingitis.
Certain strains of C. trachatis can invade the lymphatic tissues, resulting in alymphogramuloma venereum. The condition is accompannied by headache, fever, and muscle aches. The lymph nodes near the lesion begin to fill with granuloma cells and become enlarged and tender. These “nodes” can cause long term lymphatic obstruction that leads to chronic, deforming edema of the genitalia or anus. The disease is endemic to South America, Afica and Asia, but occasionally occurs in other parts of the wrold.
Babis born to mothers with chlamydia can develop eye infections and also pneumonia if they become infected.
causative agent: C. trachamatis is a very small gram negative bacterium. It lives inside host cells as an ogligate intracellular parasite.
-ransmission: The microbe shows an astoundingly borad distribution within the population and incidence is rising. Adolescent women are more likely than older women to harbor the bacterium because it prefers to infect cells that are prevalent on the adoslescent cervix. It is transmitted sexually.
Immune Response: The first and most important immune response to Chlamydia infection is a local one, whereby immune cells such as leukocytes are recruited to the site of infections, and subsequently secrete pro-inflammatory cytokines and chemokines such as interferon gamma. Immune cells also work to initiate and potentiate chronic inflammation through the production of reactive oxygen species (ROS), and the release of molecules with degradative properties including defensins, elastase, collagenase, cathespins, and lysozyme. This long-term inflammation can lead to cell proliferation (a possible precursor to cancer), tissue remodeling, and scarring, as well as being linked to the onset of autoimmune responses in genetically disposed individuals. See RedGrove
Detection: is with PCR or ELISA.
Prevention: avoiding contact with infected tissues and secretions or barrier protection is the only means of prevention.
Treatment: Chlamydia is treated with antibiotics. The recommended antibiotic treatment is doxycycline taken twice a day for seven days or azrithromycin taken in one single dose. Other alternative medications may be used but are not as effective as azrithromycin and doxycycline. Persons being treated for chlamydia should not have sexual intercourse for seven days after single dose therapy (azrithromycin) or until completion of all seven days of antibiotics (doxycycline). Patients can be re-infected if their sex partners are not treated. See NY State Dept Health
Gonorrhea:
Gonorrhea has been known as an STD since ancient times. N. gonorrhoeae belongs to the genus Neisseria, of which N. gonorrhoeae and Neisseria meningitidis (also known as the meningococcus) are the two pathogenic species, with the latter being a leading cause of bacterial meningitis. Phylogenetic analyses show that N. gonorrhoeae and N. meningitidis evolved from a common non-pathogenic ancestor, but now represent separate lineages that normally occupy distinct niches, the genital mucosa and nasopharyngeal mucosa, respectively.
Signs and symptoms: In the male, infection of the urethra elicity urethritis, painful urination, and a yellowish discharge, although a relatively large number of ases are symptomatic. In ost cases, infection is limited to the distal uronetical tract, but it can occasionally spread from teh urethra to the prostate gland and epididymis. See WebMD.
Differences in the developmental embryological origins of cells lining the urogenital tracts
of men and women have endowed these microenvironments with different surface molecules
that act as receptors and co-receptors for N. gonorrhoeae, and lead to differences in the
mechanisms by which N. gonorrhoeae survives in the male and female urogenital niches.
In the female, it is likely that both the urinary and genital tracts will be infected during sexual intercourse. A mucopurlent (containing mucos and pus) or bloody vaginal discharge occurs in a minortiy of the cases, along with painful urination if the urethra is affected.
Causative agent: N. gonorrhaeae is a pyogenic (pus forming) gram-negative diplococcus. It appears as pairs of kidney bean shaped bacterial, with their flat sides touching.
Transmission/cell entry: gonorrhea is a strictly human infection that ranks among the most common STDs. A successful pathogen must be able to efficiently transmit to new
hosts, and as an obligate human colonizer, N. gonorrhoeae cannot survive outside the host.
Neisseria gonorrhoeae (N. gonorrhoeae, gonococci, or GC), the etiologic agent of gonorrhea, is a human-obligate bacterial pathogen. The GC surface contains pili that mediate the adherence to host cells. Studies have shown that GC pili, coded by pilin genes, undergo remarkable changes during human experimental gonorrhea, possibly generated by DNA phase variation during infection. See Chen
N. gonorrhoeae mainly colonizes the genital mucosa, but it can also colonize the ocular,
nasopharyngeal, and anal mucosa.
Following transmission, N. gonorrhoeae establishes contact with the mucosal epithelium to
replicate and ultimately transmit to new hosts. N. gonorrhoeae is primarily a mucosal
colonizer, attaching to various epithelial surfaces. The primary event establishing infection
and the first step in pathogenesis is the bacterial adherence to the epithelium of the mucosa,
which is mediated through distinct bacterial surface structures (that include Type
IV pili, opacity (Opa) proteins, the LOS, and the major porin, also referred to as PorB.
During initial infection, following initial host cell interaction, N. gonorrhoeae attachment
and subsequent colonization depends largely on Type IV pili forming microcolonies on the
epithelial cell surface.
Diagnosis: Specific microbiologic diagnosis of N. gonorrhoeae infection should be performed for all persons at risk for or suspected of having gonorrhea; a specific diagnosis can potentially reduce complications, reinfections, and transmission. Culture, NAAT, and POC NAAT, such as GeneXpert (Cepheid), are available for detecting genitourinary infection with N. gonorrhoeae; culture requires endocervical (women) or urethral (men) swab specimens. Culture is also available for detecting rectal, oropharyngeal, and conjunctival gonococcal infection. NAATs and POC NAATs allow for the widest variety of FDA-cleared specimen types, including endocervical and vaginal swabs and urine for women, urethral swabs and urine for men, and rectal swabs and pharyngeal swabs for men and women. See CDC
Prevention/screening: no vaccine is available. Using condoms is an effective way to avoid transmission.
Annual screening for N. gonorrhoeae infection is recommended for all sexually active women aged <25 years and for older women at increased risk for infection (e.g., those aged ≥25 years who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI) (149). Additional risk factors for gonorrhea include inconsistent condom use among persons who are not in mutually monogamous relationships, previous or coexisting STIs, and exchanging sex for money or drugs. Clinicians should consider the communities they serve and consult local public health authorities for guidance regarding identifying groups at increased risk. Gonococcal infection, in particular, is concentrated in specific geographic locations and communities. MSM at high risk for gonococcal infection (e.g., those with multiple anonymous partners or substance abuse) or those at risk for HIV acquisition should be screened at all anatomic sites of exposure every 3–6 months (see Men Who Have Sex with Men). At least annual screening is recommended for all MSM. Screening for gonorrhea among heterosexual men and women aged >25 years who are at low risk for infection is not recommended (149). A recent travel history with sexual contacts outside the United States should be part of any gonorrhea evaluation. See CDC
Pathogenesis:
–Antibiotic resistance mechanisms (transformation): Natural transformation is the ability of bacteria to take up and incorporate macromolecular DNA efficiently. It is hypothesized that natural transformation evolved as a mechanism for using DNA as a food source or to aid in the repair of damaged chromosomes.
Neisseria gonorrhoeae is one of at least 44 species of bacteria that are naturally competent for genetic transformation. Phages able to infect N. gonorrhoeae are not known, and, although conjugative plasmids are present in some gonococcal isolates, transformation is the only mechanism for mobilization of gonococcal chromosomal loci. For gonococci, it is clear that transformation has been harnessed as a powerful mechanism for generating genetic diversity,
spreading advantageous alleles and mediating some forms of antigenic variation. Neisseria spp. are unusual in that they do not regulate competence like many other naturally competent bacteria, including Streptococcus pneumoniae, Bacillus subtilis and Haemophilus influenzae; rather, the Neisseriae are competent for natural transformation during all phases of growth. Like
H. influenzae, N. gonorrhoeae only takes up DNA that contains a genus-specific uptake sequence. In N. gonorrhoeae, the DNA uptake sequence (DUS) is a 10-base sequence (GCCGTCTGAA). See Dillard
—Vaccination:
——NGoXIM is a prophylactic vaccine against gonorrhea which has gained funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). NGoXIM candidates uses Intravacc’s outer-membrane vesicle (OMV) platform technology and Therapyx GneX12 sustained-release microspheres to deliver recombinant human IL-12 intranassaly. OMVs are speherical buddings that are rleased spontaneously on the oter membrane of many Gram-negative bacteria during growth. Such vesicles present surface antigens in a native conformation and have natural properites such as immunogenicity, self-adjuvation and uptake by immune cells. Those features make OMVs a good basis for vaccines against pathoglenic bacteria. The OMVs for the gonorrhea vaccine are dervied form genetically modified Neisseria gonorrhaeae. An intranasal vaccine also causes an immune response in other mucosal tissues such as the genital tract, thus hleping to endure induction of an immune resonse at the site of potential infection as with gonorrhea.
Symptoms: Urethral infections caused by N. gonorrhoeae can produce symptoms among men that cause them to seek curative treatment soon enough to prevent sequelae, but often not soon enough to prevent transmission to others. Among women, gonococcal infections are commonly asymptomatic or might not produce recognizable symptoms until complications (e.g., PID) have occurred. PID can result in tubal scarring that can lead to infertility or ectopic pregnancy. See CDC
Treatment: N gonorrhaeae ahs developed resistance to all current and previously used clases of antibiotics used to treat gonorrhoea, with ceftrizxone the sole remaining empirical treamtent option for first-line gonorrhaea monotherapy. In 2017-18, the WHO Gonococcal Antimicrobial Surveillance Programme (GASP) reported high global rates oinolone resistance, increasing azithromycin resistance, and, progressively increasing multidrug resistance, including to extended spectrum cephalosporins, such as ceftrizxone. f fluoroqu
Gonoorhoeae treatment includes treating chlamydia also since N. gonorrhaeae is freqeuntly coinfected with Chlamydia. CDC recommends a single dose of 500 mg of intramuscular ceftriaxone. Alternative regimens are available when ceftriaxone cannot be used to treat urogenital or rectal gonorrhea. Although medication will stop the infection, it will not repair any permanent damage done by the disease. The CDC has this bacterium in its Urgent Treat category for antibiotic resistance. See CDC
–Gepotidacin (GSK) is a novel, oral antibiotic used to treat uncomplicated urinary tract infections (uUTIs). It is the first new class of oral antibiotic for uUTIs such as gonorrhoaea in nearly 30 years and is being developed to combat increasing antibiotic resistance. Gepotidacin is particularly notable for its unique mechanism of action and its potential to address drug-resistant bacteria. Gepotidacin works by targeting bacterial DNA replication. It inhibits two key bacterial enzymes: DNA gyrase and topoisomerase IV.
–Zoliflodacin belongs to a new class of antibiotics, called spiropyrimidinetriones, which has a unique mechanism of action in the way that it inhibits a crucial bacterial enzyme called type II topoisomerase, which is essential for bacterial function and reproduction. Zoliflodacin is being developed exclusively for the treatment of gonorrhoea. By focusing solely on this indication, the aim is to limit the clinical use of this new treatment to the targeted infection only. This approach can help to minimize the likelihood of excessive use, which could potentially contribute to the development of resistance, and therefore preserve the usefulness of zoliflodacin in treating gonorrhoea infections for longer.
Zoliflodacin is an oral, first-in-class, spiropyrididinetrione antibiotic which stabilises and arrests the cleaved covalent complex of DNA gyrase with double stranded broken DNA and blocks ligation of this complex to form fused circular DNA. Zoliflodacin-resistant utatns indicate that the GyrB subunit of DNA gyrase is the primary target of zoliflodacin, unlike fluoroquinolones, which primarily interact with the GyrA subunit of DNA gyrase and the ParC subunit of topoisomeerase. Zoliflodacin matains activity against ciprofloxacin resistant, cetriaxone resistant, and azithroycin resisnt N Gonorrhaoeae, shwoing potent in vitro antibacterial activity with a minimum inhibiotry concentraiotn of 90% of isolates of 0-125 ug/mL. (Lucky, “Zoliflodacin verus ceftrizxone plus azithromycin for treatmnet of uncomplicated urogenital gonorrhaea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial” 2025).
In a phase 3 multinational clinical studyzoliflodacin was shown to be non-inferior to ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhaea and had a similar safety profile.
Innate Immune Response:
–Complement System: The ability of N. gonorrhoeae to evade recognition and attack from the human complement system is a major feature of host adaptation by this species, highlighted by the observation that N. gonorrhoeae resists the action of human complement but is sensitive to animal complement systems. However, Patients with complement deficiencies have been found to have a higher risk of systemic N. gonorrhoeae infection. In both the cervical epithelium and
human serum, the alternative and classical complement pathways respond to N. gonorrhoeae
infection by initiating the complement cascade to opsonize invading bacteria.
Adaptive Cell Response:
It is known that individuals that have been treated for gonorrhea can be repeatedly infected,
with no development of immunological memory. An experimental gonococcal infection
model study in men showed that initial infection failed to provide protection against repeated
infection with the identical strain within 21 days of initial infection. N. gonorrhoeae
evades the adaptive arm of the human immune system by several mechanisms. N.
gonorrhoeae undergoes antigenic and phase variation of the surface-exposed Type IV pili,
Opa proteins, and LOS to escape immunit.
Syphilis:
cause: Treonema pallidum which is a spirochete, regularly coiled cell with a gram-negative cell wall. See CDC
Symptoms: Untreated symphilis is marked by distinct clinical stages designated as primary, secondary and tertiary symphilis. The disease also has latent periods of varying duration during which it is quiescent. The primary stage is marked by the appearance of a hard chancre at the site of entry of the pathogen. Because these culcers tend to be pianless, they may escape notice, especially when they are on internal surfaces. The chancre heals spontaneously without scarring in 3-6 weeks. About 3-6 weeks after the chancre heals, the secondary stage appears. By then, many systems of the body ahve been invaded and simptoms include fever, ehadache and sore throat, followed by lymphadenopathy and peculiar red or brown rash that breaks out on all skin surfaces including the palms of the hands and soles of the feet. A person’s hair often falls out. Like the chancre, the lesions contain viable spirochetes and disappear spontaneously in a few weeks. The major complications at this stage occur in the bones, hair follicles, joints, liver, yes and brain. See Web MD–Transmission: Human appear to be the sole natural hosts and source of T. pallidum. The bacterium is extremely fastidious and sensitive and cannot survive for long oustide the host, being rapidly destroyed by heat, drying, disinfectants, soap, hogh oxygen tension and pH changes. It survives a few minutes to hours when protected by body secretions and about 36 hours in sotred blood. The risk of infection from an infected sexual partner is 12-20% per encounter.
Diagnosis: There is a rapid plasmin reagin (RPR) test which is coupled with an immunoassay specific for treponemal antigens.
Prevention: People identified as being at risk fo syphilis are given immediate prophylactive penicilline in a single long acting dose. The barrier effect of a condom provides excellent proteciton during the primary phase. Protective immunity apparently does arise in humans, allowing the prospect of an effective immunization program in the future, although no vaccine exists currently.
Treatment: Syphillis can have very serious consequences if left untreated. Current recommendations are for ciprofloxacin or levofloxacin. See Mayo Clinic. See Drugs.com. History of treatment
Protozoa:
Trichomonas vaginalis (see protozoa): is a sexually transmitted pathogen with the highest annual incidence of all curable and non-viral STIs. At the 2008, the prevalence of T. vaginalis was higher than Chlamydia trachomatis (100.4 million), Neisseria gonorrhoeae.
Treatment for STDs, Generally:
Doxycline: is used a PrEP or PEP to prevetn infections such as malaria and lyme disease and is now used to prevent STIs. Doxycline is a braod spectrum tetracycline antimicrobial. It is well absorbed and toelrated with a half-life of about 12 hours. Adverse effects most associated with doxycline include photosensitivty and gastrointestinal symptoms, including esophageal erosion and ulceration. Most adverse effects resolve with discontinuation of the medication. See CDC
Doxycline is the recommended treatment regiment for chalmydia and an alternative treatment for syphilis in nonpregnant patients with severe penicillin allergy or when penicillin is not available. Although currently not a recommended treatment for gonorhhea because of elevated antimicrobial resistance, it remains effective aginst many strains of No. gonorrhaeae in the US. See CDC
—Doxycycline Posexposure Prophylaxis: No vaccines and few chemoprophylaxis options exist for tghe prevention of bacterial sexually transmitted infections (STIs) (specifically synphilis, chlamydia, and gonorrhea). These infections have increased in the US and disproportionately affect gay, bisexual and other men who ahve sex with men (MSM) and transgender wormen (TGW).
The CDC recommends the use of doxycline postexposure prophylaxis (doxy PEP) as a novel STI prevention strategy for MSM and TGW who have had a bacterial STI (specifically syphilis, chamydia or gonorrhea) diagnosed in the past 12 months. CDc recommends that providers offer persons in these groups a preseription for doxy PEP to be self adminsitered within 72 horus after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 g every 24 hours. See CDC
Postexposure prophylaxis (PEP) involves taking a medication to prevent an infection after a possible exposure and is a common strategy for prevention of HIV and other infections. PEP is a form of chemoprophylaxis and is distinct from pre-exposure prophylaxis (PrET), which involves taking a medication before exposure occurs.