Microbiology PDF Notes

Microbiology STI Principles 500 million new STI cases each year which is a large burden of disease ○ Due to several factors: Lack of education (prevention and their existence) Taboo; prevents people being tested and diagnosed Asymptomatic for a long time,...

Microbiology STI Principles 500 million new STI cases each year which is a large burden of disease ○ Due to several factors: Lack of education (prevention and their existence) Taboo; prevents people being tested and diagnosed Asymptomatic for a long time, allowing it to be passed on No cure (but also not lethal) Unwilling to get tested Risky behaviors are hard to change General principles about STIs ○ Generally fragile and survive poorly outside the body Thus, transmission requires close contact and/or direct transmission of body fluid ○ It is possible to get multiple infections at the same time and one infection may increase the risk of another Eg. HIV transmission increases 5-10x with other STIs (as there are more WBCs for HIC to infect)→ test for multiple STIs Microbiological Causes of Disease Microbiological Causes of: ○ Cervicitis and urethritis: inflammation of the cervix and urethra Causes dysuria, itching and can include discharge Organisms: N. gonorrhoea, C. trachomatis, M. genitalium and HSV ○ Vaginosis: disruption of vaginal flora Causes unpleasant odour and/or vaginal discharge Organisms: T. vaginalis, C. albicans and G. vaginalis ○ Genital ulcer: Organisms: HSV, C. trachomatis, T. pallidum, H. ducreyi ○ Pelvic inflammatory disease: Causes chronic pelvic pain, fallopian tube damage and infertility Organisms: C. trachomatis, N. gonorrhoea, G. vaginalis and Mycoplasma hominis Viral Causes of STIs Covered here: ○ Human papillomavirus (HPV) ○ Human immunodeficiency virus (HIV) ○ Herpes simplex (HSV) ○ Hepatitis B (HBV) More than 200 million people are infected with HBV, more important as a GIT virus Human Papillomavirus (HPV) Epidemiology: Around 30 million infections and around 250,000 cancer deaths a year Viral Structure: Double stranded DNA virus with 120 different types ○ 40 types infect the genital tract and 80% of females acquire a genital HPV infection by 50 Some types are a necessary but insufficient cause of cervical, anal, vulvar and penile cancer ○ HPV-16 and 18 are found in 64-79% of cervical cancer, types 31 and 45 are high risk Transmission: Transmitted via skin to skin contact, doesn’t need to involve intercourse (eg. on fingers) ○ Enters squamous epithelial cells via microabrasions and replicates on keratinocytes ○ Often the infection resolves naturally HPV generates warts as its viral proteins E6 and E7 disrupts p53 and Rb (this overgrowth of cells allows the virus to replicate) ○ This causes infected cells to grow faster than normal cells producing warts ○ If it integrates into the genome, it is more likely to cause cancer Human Papillomavirus (HPV) Diagnosis: Incubation period of 1-6 months Diagnosed with clinical observation of lesions ○ Subclinical diagnosis is from dilute acetic acid causing whitening of warts The aim of diagnosing HPV is to prevent the associated cancers and is done through cytology: ○ Papanicolaou (Pap) smear test; to detect early epithelial change ○ Identification of cervical intraepithelial neoplasia and early cervical cancers Treatment/Prevention: Cosmetic, non-specific and just aims to control growth ○ Liquid nitrogen, excision or caustic agents Preventative vaccine: ○ Nonavalent vaccine which protects against infection (includes at least HPV-16, 18, 6 and 11) ○ The earlier it is given to a population, the better it is at preventing cancer Human Immunodeficiency Virus (HIV) Epidemiology: Around 40 million people are infected with around 1 million deaths each year Viral Structure: Two types, HIV 1 and 2, both retroviruses of the lentivirus family ○ Encodes a reverse transcriptase (pol gene) Causes acquired immunodeficiency syndrome (AIDS) and infects CD4+ cells ○ Includes; Th cells, monocytes, dendritic cells and microglia (CNS immune cells) CD4 is a receptor for the gp120 envelope protein on HIV with CCD5 an important co-receptor Transmission: Transmitted in bodily fluids (again doesn’t have to be sexual contact) ○ Non-sexual: blood (contaminated blood products, needle sharing) or mother to child (vertical transmission) ○ Sexual transmission: male to male (especially with anal intercourse) and male to female Female to male is more common in Africa or Asia Other STIs increase the likelihood of transmission due to more blood swapping and more immune cells Human Immunodeficiency Virus (HIV) Pathogenesis: Initial acute phase: ○ Massive loss of CD4 T cells with a profoundly weak immune system and lots of virions ○ Lasts a few weeks and feels like a flu Second chronic phase: ○ HIV replication get checked by the immune system but results in chronic immune activation Increases risk of opportunistic infection and lasts several years AIDS onset: ○ Many diseases herald the presence of AIDS and is a result of HIV-induced immunocompromise Infections are in unusual tissues (eg. CMV in the brain or retina) Tumours; Kaposi’s sarcoma, B cell lymphoma Treatment: Drugs mostly target reverse transcriptase in HIV replication with nucleoside RT inhibitors (NRTI), non-nucleoside RT inhibitors (NNRTI) and there are also protease inhibitors and fusion inhibitors No one should die from HIV these days and if treated properly won’t even be infectious Herpes Simplex (HSV) Epidemiology: Around 500 million people are infected with around 20 million new infections/year Genital Herpes Cause by the herpes simplex virus which is a double-stranded DNA virus and has two types: ○ HSV-1: transmitted by saliva and causes 70% of oral cold sores and 50% of new genital herpes ○ HSV-2: transmitted by sexual contact and causes genital blisters and ulcers Pathogenesis: 75% of infections may be asymptomatic ○ If symptoms are present, primary lesion form 4-7 days after infection ○ Usually present on the penis and vulva but can be intravaginal Causes pain, itching, burning sensation, dysuria common in women (similar to UTI) Could also have a fever, low grade headache, malaise, myalgias, inguinal lymphadenitis Lesions heal over 3-4 weeks but recurrence is common, 70-90% recur within the year ○ The primary lesion is multiple, widespread with lesions at different stages ○ Recurrent lesions are grouped and at the identical stage of development Herpes Simplex (HSV) Pathogenesis: Neonatal herpes arises from exposure to HSV in the birth canal This has serious consequences such as skin and eye disease, cognitive impairment, organ dysfunction and death ○ Thus, it is important to prevent transmission and this is a reason for elective caesarean sections Diagnosis: Initial diagnosis is from clinical symptoms but the gold standard is a PCR (faster and more sensitive than a culture as viral culture has a poor sensitivity) ○ The base of the genital lesion is swabbed for vesicle fluid ○ HSV antigen detection can be done and looks for IgG against glycoprotein G Treatment: Antiviral drugs aim to reduce the severity of symptoms and time to resolution ○ Aciclovir (IV or oral), valaviclovir and famiciclovir are the drugs, topical use not recommended To prevent transmission, avoid sex is lesions are present and use condoms consistently ○ It is to transmit HSV even with a condom but the odds are reduced Bacterial Causes of STIs Covered here: ○ Chlamydia trachomatis ○ Neisseria gonorrhoea ○ Treponema pallidum ○ Haemophilus ducreyi Commonly called chancroid Not common in Australia but widespread in African and South American countries Chlamydia trachomatis (Chlamydia) Epidemiology: Around 130 million infections per year, it is common in Australia and worldwide ○ 1 in 50 between 19 and 55 have a new infection every year Causative bacteria: Chlamydia trachomatis is an obligate intracellular because it is an ATP parasite (can’t make ATP) ○ Causes persistent, chronic infections and has a range of different serotypes: A, B and C can cause trachoma, a serious eye disease D-K can cause genital infections L1, 2 and 3 cause systemi STI lymphogranuloma venereum (infection in draining lymph nodes) Symptoms: Symptoms are observed 7-14 days after the infection with watery/mucopurulent discharge and dysuria ○ In a number of people it can be asymptomatic Chlamydia trachomatis (Chlamydia) Complications: Can cause chlamydial cervicitis and urethritis It can be asymptomatic in both females and males but is more common in females ○ This is bad as complications are rare in males but complications in females can be serious causing: Pelvic inflammatory disease, chronic pain, ectopic pregnancy and infertility (due to damage from the immune system) Diagnosis: Symptoms don’t differentiate STIs, gonorrhoea and chlamydia present quite similarly Cell culture is 100% specific (but not sensitive) and take 48-72 hours) Direct antigen methods such as ELISA or direct immunofluorescence can be used but has a low sensitivity PCR based methods are done on urine samples, is fast (2-4 hours) and has high sensitivity Treatment: Curable disease Treated with a single dose of azithromycin and a 10 day course of doxycycline 5% with N. gonnorhoea are co-infected with C. trachomatis so check for both Neisseria gonorrhoea (Gonorrhoea) Epidemiology: Causes around 78 million infections per year Causative Bacteria: Neisseria gonorrhoea is a Gram-negative diplococci which only infects human and survives poorly in the environment Pathogenesis: Generally enters via the vaginal or urethral mucosa of the penis but also the throat and rectal mucosa Initially attaches via pili which have high antigenic variation (with other outer membrane proteins, eg. Opa) Invades non-ciliated epithelial cells and replicates in the vacuole and releases through the basement membrane ○ Damage to the host is actually a result of the inflammatory response (alongside the mucopurulent symptoms Vertical transmission during vaginal delivery is possible Neisseria gonorrhoea (Gonorrhoea) Symptoms: Observed within 2-7 days with vaginal or urethral discharge and dysuria Females are OFTEN ASYMPTOMATIC Complications: In males this is often rare Females are asymptomatic more often and as such complications are more common, including: ○ Pelvic inflammatory disease (10-20% of untreated cases due to scarring from the immune response) ○ Chronic pelvic pain ○ Fallopian tube damage and infertility ○ Bloodstream infections (1-3% of cases, can lead to septic arthritis) Diagnosis: The purulent discharge is hard to distinguish from chlamydia and so requires testing PCR is the most common way but microscopy of urethral discharge can visualise Gram-negative intracellular diplococci Neisseria gonorrhoea (Gonorrhoea) Treatment: Treated with IM ceftriaxone with azithromycin ○ In general there is a significant resistance to penicillins This is a notifiable disease and requires partner notification and contact tracing ○ Safe sex will aid in prevention Check for other STIs as there is a likely co-infection with chlamydia Treponema pallidum (Syphilis) Epidemiology: Causes around 6 million infections/year and prevalence is increasing in Australia Pathogenesis: Syphilis is caused by Treponema pallium and has four stages of infection if untreated; primary, secondary, latent and tertiary (which causes neurosyphilis and cardiovascular syphilis) Transmission: Transmitted through sexual contact with a 15-30% risk of infection after sex with an infected partner ○ Has as ID50 of around 60 organisms Incubation period is 9-90 days with an average of 2-4 weeks Vertical transmission can occur in the placenta (big problem in Africa) Treponema pallidum (Syphilis) Symptoms: Primary: presents as a painless primary chancre and is typically only one lesion ○ Presents In women on the cervix, labia or urethra and in men on the penis or ano-rectum (MSM) Lesions at extragenital sites (fingers, lips, nipples) are uncommon Secondary: Is due to systemic spread of treponema and occurs 7-10 weeks after the primary lesion ○ Presents as a highly infectious skin rash that resolves in 3 months Tertiary: This is a cell mediated response to chronic infection which results in soft tissue destruction and gummas (granulomas from chronic inflammation) ○ Occurs in 3-30 years and develops in 30% of patients ○ Cardiovascular syphilis: leaking of the aortic valve ○ Neurosyphilis: dementia and psychotic symptoms Treponema pallidum (Syphilis) Diagnosis: Microscopy can be done on exudate from the primary chancre (which is very infectious) Serology has two groups, non-treponemal tests and treponemal tests which have high specificity ○ Non-treponemal tests; detects antibodies against cardiolipin (a host membrane component indicative of host damage) and has two types: RPR (rapid plasma reagin test) and VDRL (venereal disease research laboratory test) These have low sensitivity and specificity as other things can cause this damage ○ Treponemal tests have three types: ELISA looking for a patient antibody, TPHA (T. pallidum HaemAgglutination assay) and FTA-ABS (fluorescent treponemal antibody-absorbed test) ○ Both are generally use Treatment: High dose penicillin (doxycycline and erythromycin are used if allergic) Prevention: Safe sex, and diagnosis and treatment early prevents late stage complications Other Genital Infections Covered here: ○ Trichomonas vaginalis (a protozoa) ○ Candida albicans (a fungi) Trichomonas vaginalis Causative Agent: Trichomonas vaginalis is a flagellated protozoon Causes trichomoniasis and causes 143 million infections/year Symptoms: In women, it presents with; cervicitis, malodorous profuse frothy vaginal discharge and itch or soreness ○ 50% of women are asymptomatic and most men are asymptomatic (unusual to have dysuria and discharge) Transmission: Vaginal, oral or anal sexual intercouse Diagnosis: Diagnosed through PCR on first pass urine or high vaginal swab Treatment: Treated with metronidazole or tinidazole Candida albicans Causative agent: Candida albicans is a diploid fungus and is normal oral, gut and vaginal flora ○ Overgrowth leads to development of vaginal candidiasis (thrush) Symptoms: Presents with irritation, inflammation, cheesy discharge and may have dysuria Predisposing Factors: Includes: ○ Hormonal changes (menses, pregnancy) ○ Diabetes ○ Reduced cell-mediated immunity Candida albicans is an increasing cause of mortality in immunocompromised patients ○ Antibiotic treatment Anything that impacts the normal flora is a predisposing factor Treatment: Topical or oral antifungal (eg. fluconazole)