STI_Bb_copy

MANCHESTER 1824

Institution: The University of ManchesterTopic: Sexually transmitted diseasesAuthor: Gavin Humphreys

Intended Learning Outcomes

  1. Drug Interaction:

    • Demonstrate how the drug interacts with its biological target(s) using relevant examples specific to sexually transmitted infections (STIs).

Gonorrhoea- ceftriaxone - beta lactam antibiotic

penicillin binding protein biniding

inhibits transpeptidation. osmotic pressure leads to bactericidal effect.

Ciprofloxacin- is a fluoroquinolone. targets DNA gyrase and topoisomerase IV, prevents DNA supercoiling and replication.

  1. Pharmacist's Role:

    • Describe how pharmacists can enhance patient care and outcomes for infection management, including patient education, counseling, and ensuring adherence to medication regimens.

    • promotion of safe sex

    • contraceptive options

    • sexual health campaigns

    • referring to GP/ GUM clinic

    • STI testing.

  2. Infectious Diseases Transmission:

    • Understand the spread of infectious diseases, including vectors and reservoirs, and the role of epidemiology in controlling outbreaks through vaccination, public health education, and effective surveillance.

    • Gonorrhoea- spread by direct mucosal contact and sperm, and vertical transmission (mum to baby)

    • syphilis - direct sexual contact, vertical transmission

    • chalmydia - sexually transmitted

    • Gennital warts- caused by H[V, transmitted by sexual contact.

  3. Virulence Factors:

    • Analyze virulence factors involved in the pathogenic process for STIs, including adherence factors, toxins, and immune evasion strategies, with specific case studies demonstrating these mechanisms.

    • gonorrhoea - actively coats itseld in host derived compounds. Leads to inactivation of complement cascade and bacterial killing.

Current Background (2023 Data)

STI Diagnoses in England:

  • Total Diagnoses: 401,800

  • Breakdown by STI:

    • Chlamydia: 194,970 (the most frequently diagnosed STI, largely impacting youth).

    • Gonorrhoea: 79,268 (notably increasing in trends).

  • Consultation Statistics:

    • Total consultations: 4,610,410 (across face-to-face, internet, and telephone mediums).

  • Trends:

    • Gonorrhoea and syphilis cases are experiencing significant increase, while chlamydia cases remain stable.

  • Affected Demographics:

    • Young people, particularly those aged 15-24, demonstrate a disproportionate incidence of STIs, highlighting the need for targeted intervention and educational programs in this group.

Gonorrhoea Overview

  • Pathogen: Neisseria gonorrhoeae

  • Characteristics:

    • An obligate human pathogen, meaning it is exclusively transmitted between humans, with a poor survival rate outside of its host environment. Does not rely on a capsule. an obligate human pathogen- likes human hosts.

  • Common Sites of Infection:

    • Primarily infects the urogenital tract, but can also infect the anal canal, pharynx, and conjunctiva, leading to a range of clinical presentations.

  • Transmission Methods:

    • Occurs through direct mucosal contact during sexual intercourse, as well as vertical transmission from mother to child during childbirth. Eyes can become infected.

Gonorrhoea Pathogenesis

  • Adherence Mechanism:

    • The pathogen utilizes various strategies to compete with resident microbiota for colonization, such as the production of adhesins and biofilms.

    • Adheres to the host epithelia via type 4 pili. Also used opacity proteins, where it will attach to the ceacam on the surface of the host epithelia. Might go onto form micro-coloniesthat can evade the host's immune response, facilitating persistent infection and increasing the likelihood of transmission to new hosts. Also capable of epithelial invasion via transcytosis.

  • Invasion Process:

    • Neisseria gonorrhoeae interacts with neutrophils, utilizing peptidoglycan and Opa protein to facilitate colonization and evade immune detection.

    • Will release fragments of peptidoglycan from its cell wall- will bleb off peptidoglycan and lipo-oligosaccharide. Activates tolite receptors, macrophages, dendritic cells and NOD receptors- these lead to activation of inflammatory transcription factors. cytokine and chemokine release, neutrophil recruitment to the site, and this will cause uptake and will phagocytose the Neisseria. This causes the release of purulent exudate- symptoms

  • Immune Response Activation:

    • Influx of immune cells triggered by recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) such as NOD and TLR, leading to acute inflammatory responses.

    • Does not have a capsule, doesnt make exotoxins- symptms are down to host immune activation. not got a big arsenal of virulence factors.

Immune Evasion

  • Complement Resistance:

    • N. gonorrhoeae is capable of coating itself in host-derived compounds, which inhibits components of the complement cascade (e.g., inactivation of C3b), allowing persistence and evasion from opsonization and phagocytosis. mimics the host so immune system doesnt respond.

    • because gonorrhoea doesnt produce a capsule, these infections are usually not very serious.

Gonorrhoea Symptoms

Male Symptoms:

  • Common Symptoms:

    • Urethral discharge occurs in over 80% of cases, with dysuria (painful urination) experienced by more than 50%.

    • Testicular pain is rare but can occur.

    • Frequently asymptomatic presentations may occur in rectal and pharyngeal cases, further complicating diagnosis.

Female Symptoms:

  • Common Symptoms:

    • Increased vaginal discharge is observed in up to 50% of cases, with lower abdominal pain in about 25%.

    • Intermenstrual bleeding is rare.

    • Rectal and pharyngeal infections often remain asymptomatic, which warrants routine screening due to the risk of complications such as pelvic inflammatory disease (PID) this is when the infection ascends from its original location.

Symptomatology Insights

  • Asymptomatic Nature:

    • The asymptomatic nature of gonorrhoea is prevalent in both genders, leading to underdiagnosis and increased transmission rates.

    • Men typically present symptoms more overtly, while women often remain undiagnosed due to non-specific symptoms, emphasizing the importance of proactive screening.

    • Symptoms corresponding to neutrophil influx may indicate symptomatic status and guide clinical decision-making.

Gonorrhoea Treatment Guidelines

Referral:

  • Referral Protocol:

    • Patients exhibiting symptoms or at risk of STIs should be promptly referred to Gueneral urology medicine (GUM) clinics or sexual health specialists for further evaluation and management.

First-Line Treatments:

  • Recommended Treatments- uncomplicated:

    • Ciprofloxacin: 500mg administered as a single dose, where susceptibility is confirmed.

    • Ceftriaxone: 1g intramuscular (IM) single dose recommended in cases with unknown susceptibility.

    • will be a culture swab/ urine sample ideally before treatment started.

Severe Cases:

  • Hospitalization Criteria:

    • Systemic gonorrhoea necessitates immediate hospitalization and may require intravenous antibiotics and supportive care.

Antibiotic Mechanisms

Ceftriaxone:

  • Mechanism of Action:

    • A beta-lactam antibiotic that binds to penicillin-binding proteins (PBPs), inhibiting trans-peptidisation which causes a bactericidal effect by disrupting cell wall synthesis.

Ciprofloxacin:

  • Mechanism of Action:

    • A fluoroquinolone that targets DNA gyrase and topoisomerase IV, disrupting DNA replication and preventing bacterial cell division.

Additional Sections

Syphilis Overview

  • Pathogen: Treponema pallidum- obligate human pathogen.

  • Transmission Methods: Direct sexual contact and vertical transmission during pregnancy present significant risk.

  • Disease Progression: Characterized by a long latent period, syphilis progresses through multiple stages over a typical duration of approximately 10 years, complicating early diagnosis.

Syphilis Symptoms

Primary Stage:

  • A single painless sore (chancre) appears, which typically resolves spontaneously within three weeks.

Secondary Stage:

  • Patients may experience systemic symptoms such as fever, headache, and a maculopapular rash, transitioning into a latent phase if left untreated. infected but have no symptoms- can still be infected.

Tertiary Stage:

  • Severe complications manifest, leading to significant cardiac and neurological issues if the infection is not addressed promptly. neurological more common in HIV.

  • can get severe lesions

Syphilis Treatment

Diagnostic Challenges:

  • Syphilis presents with a range of non-specific or asymptomatic symptoms, complicating timely diagnosis and treatment.

Referral:

  • Urgent referral to GUM specialists is recommended for laboratory diagnostics, comprehensive sexual health screening, and HIV testing.

First-Line Therapy:

  • Benzathine benzylpenicillin administered via IM injection; dosage varies based on infection stage. long acting antibiotic formulation.

Chlamydia Overview

  • Pathogen: Chlamydia trachomatis- atypical pathogen - obligate human pathogen. alternated between a replicating and non replicating form. non replicating form is infectious.

  • Characteristics: An obligate human intracellular pathogen is recognized as the most common STI in the UK, exhibiting a unique lifecycle that transitions from a replicating reticulate body to a non-replicating elementary body- infectious.

  • elementary bodies- growth mode is non replicating to disperse itself. Intracellular, so gets endocytosed into the host cell. Once inside, will germinate when it interacts with glycogen. Then will move into reticulate form- replicating non infectious growth mode. Replicate every 2-3 hours. 7-21 day incubation period overall. When replication finished, will shift back into elementary body, and then released from the cell by exocytosis

Chlamydia Symptoms

Asymptomatic Cases:

  • Incidence of Asymptomatic Infection: Estimates suggest that 70% of women and 50% of men remain asymptomatic, contributing to sustained transmission within populations.

Symptomatic Manifestations:

  • Symptoms in men can include urethral inflammation, discharge, and pain, while women may experience cervical inflammation along with abnormal discharge.

Potential Infections:

  • Chlamydia can also infect the conjunctiva, rectum, and nasopharynx, warranting comprehensive sexual health assessments.

National Chlamydia Screening Programme (NCSP)

  • Target Group: Women aged under 25 are recommended screening in specific healthcare settings to promote early detection and intervention.

  • Testing Method: Nucleic acid amplification tests (NAAT) are utilized through swab or urine collection to detect infections accurately.

  • Goals: These initiatives aim to enhance early detection, prevent and control STIs, and reduce long-term health consequences associated with untreated infections.

Chlamydia Treatment Protocols

Referral Guidance:

  • Referrals: Patients presenting with uncomplicated cases should be referred to GUM clinics for specialized management.

First-Line Treatment Options:

  • Doxycycline: 100mg taken twice daily for a duration of 7 days is the recommended treatment.

  • Alternatives during Pregnancy: Erythromycin, amoxicillin, and azithromycin serve as alternative treatments for pregnant individuals.

  • Testing Requirements: Routine follow-up or 'test of cure' is not typically required for uncomplicated chlamydia cases.

Genital Warts Overview

  • Etiology: Caused by human papillomavirus (HPV), with significant implications for public health.

  • Health Risks: It is a known causative agent of genital warts and is linked to cervical cancer.

  • Vaccination: The HPV vaccination is strongly recommended for individuals aged 12-13 (both genders) to reduce cancer risks; the Gardasil9 vaccine shows an efficacy rate of 96.7%.

  • warts tend to go away on their own, but takes a while.

Mpox Historical Context

  • Historical Timeline: The Mpox virus was discovered in 1958, with outbreaks reported in the Congo and misdiagnosed cases in Denmark. Significant outbreaks occurred in 2003 in non-endemic regions, spurring public health responses.

  • Current Theories: Key updates provided by the WHO regarding the public health emergency status of Mpox highlight the need for ongoing research and vaccination strategies.

  • not just a sti, but is common in men who have sex with men.

  • less serious than smallpox.

Mpox Treatment Recommendations

Vaccination Protocols:

  • Pre-exposure Vaccination: A series of 2 doses with a minimum interval of 28 days apart is recommended for high-risk populations.

  • Post-exposure Vaccination: A single dose should be administered unless future exposure risk is evident.

  • Antiviral Options: Tecovirimat is identified as an envelope wrapping inhibitor, indicating a need for novel antiviral strategies in Mpox management.

Role of the Pharmacist in STI Management

Key Responsibilities:

  • Pharmacists play a crucial role in advocating for safe sex practices, providing contraceptives, and engaging in sexual health campaigns to enhance public awareness.

  • They should refer patients to general practitioners (GPs) or GUM clinics for STI testing and coordinate multidisciplinary care as required.

Resource Reference

  • Pharmaceutical Journal: A valuable resource for healthcare professionals focusing on sexual health, providing current research, treatment advancements, and educational materials.