M15 - Urogenital and sexually-transmitted infections.pdf

M16 - Urogenital and sexuallytransmitted infections • Urinary Tract Infections (UTI) • Sexually Transmitted Infections (STI) Initially prepared by Prof Y. Guan Modified and presented by Dr David Smith- [email protected] 1 Urinary Tract Infections Learning Objectives: • Know what significant bact...

M16 - Urogenital and sexuallytransmitted infections • Urinary Tract Infections (UTI) • Sexually Transmitted Infections (STI) Initially prepared by Prof Y. Guan Modified and presented by Dr David Smith- [email protected] 1 Urinary Tract Infections Learning Objectives: • Know what significant bacteriuria and pyuria are and the locations and names of different types of UTIs • Name the common bacteria causing UTI and their likely sources • Explain the laboratory diagnosis of UTI • Know how to collect urine samples properly 2 The Urinary Tract And where bacteria could go Figure from Klein & Hultgren 2020 Nature Reviews Microbiology 18:211 3 Main types and clinical features of UTIs Infection leading to inflammation in the UT Inflammation in: urethra - urethritis urinary bladder - cystitis ureters – ureteritis kidneys – pyelonephritis • Urinary tract symptoms (difficult or painful urination) • Fever • Bacteriuria, pyuria, haematuria (bacteria, pus or blood in the urine) In 25% of untreated cases, lower urinary tract infections may affect the kidneys , causing pyelonephritis (bad). 4 From the European Association of Urology (https://uroweb.org) https://uroweb.org/guidelines/urological-infections/chapter/the-guideline 5 From the European Association of Urology (https://uroweb.org) https://uroweb.org/guidelines/urological-infections/chapter/the-guideline 6 Catheter Related UTI If there is a problem passing urine (paralysis, bladder injury/operation, enlarged prostate) a catheter may be inserted through the urethra to the bladder. When catheterization is long (>30 days), almost all patients will have bacteriuria. Treatment of asymptomatic bacteriuria is NOT indicated. Removal of indwelling catheters as soon as possible is the most important method for prevention & treatment of catheter-related bacteriuria or UTI. 7 Common Microbial Causes/Agents of UTIs Wagenlehner et al 2020 Nature Reviews Urology 17:586-600. 8 Common Microbial Causes/Agents of UTI Pathogens Community patients Escherichia coli Hospital patients 80% 40% Staphylococci 7% 3% Other G+ cocci 3% 16% Candida 5% 5% Proteus 4% 11% Other G- rods 1% 25% (Klebsiella, Enterobacter, Serratia, Pseudomonas) 9 Pathogenesis – the bacterial & host view Klein & Hultgren 2020 Nature Reviews Microbiology 18:211 Ortega Martell 2020 GMS Infectious Diseases 8:Doc21. doi: 10.3205/id000065 11 Pathogenesis – the bacterial & host view Wagenlehner et al 2020 Nature Reviews Urology 17:586-600. 12 Pathogenesis – the bacterial & host view 13 Common Microbial Causes/Agents of (next level) UTIs Wagenlehner et al 2020 Nature Reviews Urology 17:586-600. 14 Laboratory diagnosis of UTI Significant pyuria + significant bacteriuria Pyuria: leukocyte esterase dip stick test + or urine microscopy  10 WBC /mm3 (L) Bacteriuria: quantitative urine culture - standard loop method One loop (10l; 1ml = 10 x 102 l) of urine is plated on a suitable culture medium (CLED). The no. of colony-forming units (CFU) is counted after overnight incubation. Bacterial count in urine specimen obtained as follows: 10 CFU in disc = 103 CFU/ml in original urine sample 100 CFU in disc = 104 CFU/ml 15 Interpretation of quantitative urine culture result Bacterial Count True bacteriuria  105 CFU/ml Contaminants <105 CFU/ml # of isolates Identity of isolate usually one typical uropathogens e.g. E. coli, S. saprophyticus mixed Skin flora e.g. Corynebacterium spp, , -haemolytic streptococci False positive results (high number of bacteriuria) can result from poor collection technique (contamination from faecal or perineal flora) & delay in transport (bacteria can multiply in urine bottle). 16 Positive and negative results of bacteriuria 17 True bacteriuria and contamination 18 Treatment – by antibiotics Choice of antibiotic is based on results of culture & an Antibiotic sensitivity test Ampicillin Cephalothin Nitrofuratoin Co-trimoxazole 19 Other possibilities for laboratory diagnosis of UTI Table from: A review on urinary tract infections diagnostic methods: Laboratory-based and point-of-care approaches Santos et al. 2022 Journal of Pharmaceutical and Biomedical Analysis 219:114889 20 Newer Thoughts – The Urinary Microbiome A Perspective of the Urinary Microbiome in Lower Urinary Tract Infections — A Review Abstract Purpose of Review Greater availability of sequencing methods has broadened the knowledge of the urinary microbiome in an environment previously believed to be sterile. This review discusses internal and external influences that promote either a balance or a dysbiosis of the urinary tract and the future perspectives in understanding lower urinary tract infections. Recent Findings Efforts have been made to identify a “core” urinary microbiome in which Firmicutes and Bacteroidetes account for most of the bacterial representations. A shift to a Proteobacteria-dominant representation shapes the fingerprint of the infectious urinary microbiome; furthermore, the virome and the mycobiome are important modulators of the urinary microbiome, which have been recently explored to determine their role in the health-disease process of the lower urinary tract. Summary A disturbance of bacterial representation and diversity triggers a transition from health to disease; conversely, a functional cooperative interplay between the host and microbiome allows for basic metabolic and immune functions to take place. Pallares-Mendez et al. 2022 Current Urology Reports 23:235–244 21 Newer Thoughts – Don’t Use Antibiotics Problems – Resistance and Dysbiosis A practical guide on the non-antibiotic options available in the prevention of recurrent urinary tract infections in women Kucheria et al. 2023 Urologia (online first) https://doi.org/10.1177/03915603231193060 Abstract Urinary Tract infection (UTI) is one of the most common infections worldwide, patients present to multiple different specialities in the community, primary and secondary care. Antibiotics are considered standard first line therapy in the treatment of urinary tract infections, however there is an alarming rise in global antibiotic resistance rates, so much so that the World Health Organisation has labelled antibiotic resistance as one of the biggest challenges to public health in our lifetime, publishing a global action plan to tackle this challenge. As a result, there is an increasing need to discover non-antibiotic alternatives, recently a number of novel therapies have been introduced into clinical practice. These are divided into oral, topical, intravesical and immunomodulation therapies. The aim of this paper is to summarise the current non-antibiotic treatments as a practical guide to utilise in patient care. 22 Recommended readings (Browse them to see what is useful) Klein & Hultgren 2020 Urinary tract infections: microbial pathogenesis, host–pathogen interactions and new treatment strategies. Nature Reviews Microbiology 18:211 – PubMed ID: 32071440 Ortega Martell 2020 Immunology of urinary tract infections. GMS Infectious Diseases 8:Doc21. doi: 10.3205/id000065 – PubMed ID: 32821646 Wagenlehner et al 2020 Epidemiology, definition and treatment of complicated urinary tract infections. Nature Reviews Urology 17:586-600 – PubMed ID: 32843751 StatPearls – Search PubMed for “StatPearls UTI” UTI Bono, Leslie & Reygaert 2023 https://www.ncbi.nlm.nih.gov/books/NBK470195 Complicated UTI Sabih & Leslie 2023 https://www.ncbi.nlm.nih.gov/books/NBK436013 Bacteruria Crader, Kharsa & Leslie 2023 https://www.ncbi.nlm.nih.gov/books/NBK482276 23 SEXUALLY TRANSMITTED INFECTIONS (STI) Learning Objectives: • Describe the approach to a patient with an STI • List the – etiologic agents, – symptoms, – methods for diagnosis, and – treatments for common STIs like gonorrhoea, syphilis, NGU, and genital herpes • Appreciate that STIs always infect more than one patient 24 STIs (Background) • diseases that are transmitted mainly, but not exclusively, by sexual contact • usually manifest by having lesions in the genital area, but other body systems may also be affected • are of major medical importance world-wide Most increasing rather than decreasing in occurrence Horizontal transmission Vertical transmission 25 Dealing with STIs (Background) Management of patients requires: • accurate diagnosis; • compliance, • treatment on epidemiological grounds, • follow-up, • screening and contact tracing, • education Most STIs can be prevented by the use of condoms/barriers, Ultimate control of STIs? development of vaccines, more importantly?, behavioural changes 26 Treatment on epidemiological grounds – they are not single person diseases Treatment of patients who have no symptoms and signs of a particular STI but who have a definite history of contact with another patient with that specific STI. This is especially important in early syphilis, gonorrhoea and non-gonococcal urethritis (NGU). The purposes of this practice are: • To prevent re-infection • To break the chain of transmission • To detect and treat asymptomatic infection 27 10 most common STI’s: bacterial, viral, fungal, parasitic Pathogen Disease Comments Treatment Approx. incidence (million world wide) Papillomavirus Genital warts HPV16, HPV 18 associated with cervical cancer Surgical 32 (vaccine available) Chlamydia trachomatis (D-K serotypes) Non-specific UTI C. trachomatis (L1, L2, L3 serotypes) Lymphogranuloma venereum Tropical regions Doxycycline, erythromycin Candida albicans Vaginal thrush “predisposing factors” Nystatin, fluconazole Trichomonas vaginalis Vaginitis, urethritis Herpesvirus HSV-2 [HSV-1] Genital herpes Neisseria gonorrhoeae (yeast) Doxylcycline, azithromycin 97 Metronidazole 94 Acyclovir 21 Gonorrhea Common antibiotic 78 HIV AIDS HAART 50 Treponema pallidum Syphilis Penicillin 19 HBV Hepatitis Male homosexual Lamivudine “vaccine available” Hemophilus ducreyi Chancroid Mainly tropical Erythromycin (parasite) “latency” 28 Female anatomical sites affected by more common STIs STIs can affect genital and extragenital sites in women. Gonorrhoea and chlamydia typically present as cervicitis. Bacterial vaginosis (BV) and trichomoniasis can also cause cervicitis, but more commonly manifest as vaginitis. HSV and HPV most typically affect the vulva or external genitalia of women. Van Gerwen et al. 2022 Sexually transmitted infections and female reproductive health. Nature Microbiology 7:1116–1126 29 Bacterial STIs GONORRHOEA Gonorrhoea, the most common reportable STI, is caused by Neisseria gonorrhoeae. • Male patients typically have painful urination & discharge of pus. Blockage of the urethra and sterility are complications of untreated cases. • Female patients commonly are asymptomatic until the infection spread to the fallopian tubes (salpingitis). They can be important reservoirs maintaining cycles of infections among persons with multiple sexual partners. 30 Pus-containing discharge in A smear of pus from a patient an acute urethritis patient with gonorrhea 31 Neisseria gonorrhoeae on Thayer-Martin medium culture Gram stain of Neisseria gonorrhoeae (Gram -ve diplococci) 32 NONGONOCOCCAL URETHRITIS (NGU) • NGU is any inflammation of the urethra not caused by N. gonorrhoeae. • Most NGU cases are caused by Chlamydia trachomatis (L1, L2, L3 serotyps). Ureaplasma urealyticum, Mycoplasma hominis also cause NGU. • Symptoms of NGU tend to be milder and include urethral discharge and dysuria. • Salpingitis and sterility are important complications of untreated cases. 33 SYPHILIS • Syphilis is caused by the spirochete, Treponema pallidum, which is transmitted by direct contact of (intact) mucous membrane or breaks in skin with lesions containing the organism. • The primary lesion is called a chancre* (primary syphilis) a firm, painless ulcer at the site of infection. • The initial lesion heals spontaneously, even without treatment, but the bacteria will invade the blood and lymphatic system. * Not to be confused with chancroid, which is typically very, very painful and is caused by Haemophilus ducreyi. 34 SYPHILIS (further stages) • The appearance of a generalized rash on skin and mucous membrane marks the secondary stage of syphilis. Millions of spirochetes are present on the lesions of the rash (highly infectious!). • The patient then enters a latent period after the rash heals spontaneously. • After at least ten years, late syphilis in the form of gummatous, cardiovascular syphilis or neurosyphilis can appear if the patient is not treated. 35 Pathogenesis of syphilis Initial infection Multiplication of treponemes at site of infection 2- 10 weeks Primary chancre Primary syphilis Enlarged inguinal lymph nodes Spontaneous healing Proliferation of treponemes in regional lymph nodes Flu-like illness Myagia, headache, fever, mucococutaneous rash and spontaneous resolution Multiplication and production of lesions in lymph nodes, liver, muscle, skin and mucous membrane 1 – 3 months Secondary syphilis 2 -6 weeks Treponemes dormant in liver and spleen Latent syphilis 2 – 30 years Tertiary syphilis Neurosyphilis; cardiovascular syphilis; progressive destructive disease 36 Lesions of primary and secondary syphilis on a male Fig 1 and 2 from: Peeling et al. 2023, Syphilis. Lancet 2023; 402: 336–46 See also: Syphilis: A Modern Resurgence Ramchandani et al., Infectious Disease Clinics of North America. 2023 Jun;37(2):195-222 Figure adapted from USA CDC 37 Maculopapular lesions spread over the abdomen (A) and trunk in a patient with secondary syphilis Mercuri et al. 2022 Syphilis: a mini review of the history, epidemiology and focus on microbiota. New Microbiologica, 45:28-34 38 Treponema pallidum - spirochete *cannot be cultured in vitro Image US CDC Dr D. Cox 39 VDRL test – nontreponemal test - for antibodies related to cell damage from infection Dilution of patient’s serum – not specific follow up with a specific test if positive allows monitoring of treatment 1:64 +ve control 1:128 1:256 1:512 -ve control Treponema pallidum detected by FTA-Abs test (fluorescent treponemal antibody-absorption test) Treponemal test – binds to bacterium - specific Absorption step removes non-specific binding antibodies 41 Viral STIs Genital herpes • Genital herpes caused by HSV-2, and sometimes HSV-1. • The lesions appear after the incubation period of about 1 week and cause a burning sensation. After that, vesicles appear • In both genders, urination can be painful, and walking is quite uncomfortable. • Usually, the vesicles heal in a couple of weeks. • About 88% HSV-2 and 50% HSV-1 patients will have recurrences in 3 - 6 months intervals. See also StatPearls: Herpes simplex Type 2: https://www.ncbi.nlm.nih.gov/books/NBK554427/ 42 Lesions of genital herpes (b, c, d with HIV coinfection). Karagounis et al. 2021 American Journal of Clinical Dermatology 22:523–540 43 Genital warts • Genital warts are caused by papillomaviruses. • Some warts are multiple fingerlike projections, but others are relatively smooth or flat. • The incubation time is weeks to months. • The greatest danger from genital warts is the connection of the virus to cancer, especially in women. • Vaccination is available. Genital warts on male and female patients Karagounis et al. 2021 American Journal of Clinical Dermatology 22:523–540 StatPearls: Human Papillomavirus https://www.ncbi.nlm.nih.gov/books/NBK448132/ Human Papilloma Virus Vaccine https://www.ncbi.nlm.nih.gov/books/NBK562186/ 44 HIV/AIDS A viral disease frequently transmitted by sexual contact (for another lecture). Usually, all STI patients should be screened (after informed consent) for HIV. https://www.aids.gov.hk/english/surveillance/cumhivaids.jpg 45 Monkeypox – another STI? A zoonotic disease by a virus from the “smallpox family” (Orthopoxvirus genus in the family Poxviridae). Causes “pox” – skin pustules and eruptions. Self-limiting disease, generally low mortality. Spread by close, usually physical, contact with an infected person. Current outbreak largely spreading among homosexual men. Some evidence virus is present in semen. Many cases of lesions in the perineal region. Most hospitalizations in recent outbreak due to severe pain. Smallpox vaccine being administered – but behavioral change will stop spread. SilverSteele Twitter + BBC News Monkeypox lesions on palms. Public Health Image Library #12761 46 CHP has pages on Monkeypox https://www.chp.gov.hk/files/png/map_of_global_distribution_of_Mpox_confirmed_cases.png 47 Recent Monkeypox Cases World https://worldhealthorg.shinyapps.io/mpx_global/ Africa 48 27 infectious viruses found in semen • HIV, Hepatitis B, herpes; • Zika, dengue • Ebola, Marburg • Chikungunya • Mumps • Epstein-Barr • Chicken pox https://www.sciencemag.org/news/2017/09/human-semen-can-host-27-different-viruses Salam & Horby 2017 Emerging Infectious Diseases 23:1922 PubMed Id 29048276 49 Recommended readings (Browse them to see what is useful) Tuddenham et al. 2022 Diagnosis and Treatment of Sexually Transmitted Infections: A Review. JAMA 327:161-172 Van Gerwen et al. 2022 Sexually transmitted infections and female reproductive health. Nature Microbiology 7:1116–11 Mercuri et al. 2022 Syphilis: a mini review of the history, epidemiology and focus on microbiota. New Microbiologica, 45:28-34 Karagounis et al. 2021 Viral Venereal Diseases of the Skin American Journal of Clinical Dermatology 22:523–540 Satyaputra et al. 2021 The Laboratory Diagnosis of Syphilis. Journal of Clinical Microbiology 59:e00100-21 StatPearls Herpes simplex Type 2 Mathew & Sapra 2023 https://www.ncbi.nlm.nih.gov/books/NBK554427/ Human Papillomavirus Luria & Cardoza-Favara 2023 https://www.ncbi.nlm.nih.gov/books/NBK448132/ Human Papilloma Virus Vaccine Soca Gallego; Dominguez; Parmar 2023 https://www.ncbi.nlm.nih.gov/books/NBK562186/ 50