Urinary Tract and Sexually Transmitted Diseases

Question 1

Describe UTI, Pathogenesis of UTIs, Symptoms of lower and URT infections,and predisposing conditions

Answer 1

• Urinary tract infections (UTIs) are the commonest – particularly in females: 20–30% may have recurrent UTIs
• Although the majority of infections are acute and short-lived, they contribute to a significant amount of morbidity in the population.
• Epidemiologically, UTIs occur in two settings:

> community-acquired

> hospital (nosocomially)-acquired – mostly associated with catheterization (less common than community acquired, contribute significantly to overall nosocomial infection rates, ~40% )

• Few viruses and very few parasites cause UTIs

Pathogenesis of UTI + Predisposition

Predisposition to UTIs: anything that (i) disruputs normal urine flow, (ii) compelte emptying of blader of (Iii) facilitates access of organsisms to the bladder

• Shorter female urethra more susceptible to infection
• Bacterial virulence factors

Acute Lower UTI - distal parts of urethra, urinary bladdder, urethra

Characteristic features:

• Dysuria (burning pain on passing urine)
• Urgency
• Freqeuncy of urination
• UTIs in elederly and those with indwelling catheters = asymptomatic
• Urine bcomes cloudy -bacteria and immune cells
• May progress to upper UTI

Upper UTIs = most of ureters, kidneys

• Kidney infection –> pyelonephritis
• Present with lower uti, usually with fever
• Reccurent episodes may result in damage of renal tissue (function) –> hypertension –> more kidney damage
• Infection associarted with renal calculus (stone) –> obstruction

Lab Diagnosis and Treatment

• Bacteriuria - MSC (mid-stream urine) > 100,000 organims/mL
• Most lower UTI resolve in 2-4 week –> antibiotics reduce duration of symptoms

Question 2

What is Syphilis? –-> Causative bacterium and its general features, pathogenesis and clinical features of the three distinct stages including congenital infections, detection and treatment

Answer 2

Treponema pallidum – thin, Gram-negative spirochete

• World-wide distribution, serious problem in both resourcerich and resource-poor countries
• On the rise over the last 5 years in developed countries (location based dating app like tinder increasing STIs)
• T. pallidum enters the body through minute abrasions on the skin/mucous membranes, replicates very slowly, ~3 weeks
• Evades recognition and elimination – surface rich in lipid that are antigenically unreactive
• Transmission requires close personal contact (sexual contact) –> organism doesnt survive well outside the body

Pathogenesis and Clinical Features (3 classical stages)

• May not go thorugh all three stages and a substantial proportion remainse remains permanently free of disease after suffering the primary or secondary stages

Primary syphilis – slow proliferation of treponemas at site of infection; forms a firm, painless, non-itchy skin ulceration

Secondary stage – further multiplication and lesions in lymph node, liver, joint, muscle, skin and mucous membranes

• causes a diffuse rash, frequently involving palms of the hands & soles of the feet; may also cause sores in the mouth or vagina; flu-like symptoms (headache, myalgia, fever)

Tertiary syphilis - Progressive destructive disease: ‘gummas’, which are soft, tumour-like balls of inflammation which typically affect the skin, bone, and liver, but can occur anywhere

Cogenital syphilis - Foetus will not contract disease if infected mother is treated early in pregnancy

• May result in spontaneous abortion, stillbirths, premature
• Congenital abnormalities may be present at birth
• Silent infection, may take >2 years to develop

Detection

• At present, several serologic tests are needed to confirm diagnosis - none of these tests distinguishes syphilis from other, non-sexually transmitted treponeme infections
• Confirmation with dark-field microscopy or immunofluorescent labelling
• Congenital syphilis is completely preventable if women are screened serologically early in pregnancy (< 3 months) and those who are positive are treated with penicillin

Treatment

• Penicillin is very active against T. pallidum
• Prevention of secondary and tertiary disease depends upon early diagnosis and adequate treatment

Question 3

What is gonorrhoea? For Gonorrhoea – causative bacterium and its general features, virulence factors and pathogenesis, clinical features, diagnosis and treatment

Neisseria gonorrhoeae (the ‘gonococcus’)

Answer 3

• Gram-negative, diplococci
• Only infects humans – usually close contact (sexual contact) –> does not survive well outside body
• Asymptomatic infection common – almost always women, form the major reservoir of infection
• Vertical transmission – infected mother to baby during childbirth

Gonococci Virulence Factors

• Entry – usually via the vagina/urethral mucosa of the penis, can also attach to throat or rectal mucosa
• Adhesion and invasion facilitated by various virulence factors
• Prevent the bacteria from being washed away by urine/vaginal discharges
• the gonococci rapidly multiply and spread through the cervix or up the urethra in men

Pathogenesis

• Invade non-ciliated epithelial cells –> internalize the bacteria, allow them to multiply within intracellular vacuole => protected from phagocytes and antibodies
• Vacuoles discharges bacterial into sub-epithelial connective tissues, to traverse epithelial barrier
• Damage is due to inflammatory responses elicited by the organism (e.g. LPS)
• Infection is usually localized, but in some cases bacteria isolates can invade the bloodstream and so spread to other parts of the body

Clinical features

Symptoms develop within 2–7 days and are characterized:

> Males – urethral discharge and pain on passing urine (dysuria)

>Females - vaginal discharge

• However, at least 50% have mild symptoms or are completely asymptomatic
• If untreated, 10-20% develop:

pelvic inflammatory disease (PID), chronic pelvic pain, infertility resulting from damage to the fallopian tubes.

Diagnosis and treatment

• Microscopy and culture of urethral/vaginal discharges, combine with symptoms
• Antibacterial agents of choice are Cephalosporins•

Resistance to antibacterials has developed:

• penicillinase-producing N. gonorrhoeae were first observed in 1976
• – resistance to fluoroquinolones has also developed

Question 4

What is chlamydia? – causative bacterium and its general features, its unique life cycle, clinical features, detection and treatment

Answer 4

Chlamydia trachomatis – Gram-negative, ovoid in shape, very small, obligate intracellular parasite, non-motile

• Dfferent infections are caused by different serotypes
• Transmitted through sexual intercourse
• Women are often asymptomatic
• Vertical transmission through birth canal – ocular infection of neonate, and risk of developing pneumonia

Life cycle and pathogenesis (life cycle consist of two stages)

• Initially it enters through minute abrasions in mucosa
• Elementary body (EB) for extracellular survivial and infection

> Enters target cell by triggering endocytosis, and prevents fusion of endosome with lysosome

>The EB germinates into the reticulate body as a result of the glycogen that is produced

• Reticulate body (RB) - vegetative form, proliferates rapidly
• ​> After division, the RB transforms back to EB form and is released by the cell by exocytosis
• Causing cell damage and inflammation

Detection

• Clinical features are not distinctive
• Isolation and culturing in tissue culture – form characteristic inclusion bodies
• Microscopy with specific fluorescent antibodies
• Molecular amplification assays e.g. PCR

Treatment

• Doxycycline or azithromycin
• Erythromycin should be used for babies of infected mothers
• Early diagnosis and treatment of cases and of their sexual partners is important in order to avoid complications and reduce opportunities for transmission

Question 5

What is HIV?– viral structure, key viral genes and replication cycle, transmission, pathogenesis, development of clinical features and treatment

Answer 5

HIV is a lentivirus – name derived from Latin for slow

• Enveloped, ssRNA
• HIV is a retrovirus
• Significant problem in the world, particularly sub-Saharan Africa

> Synthesises a DNA copy of its genome which can integrate into the host cell genome as provirus

• HIV is non oncogenic but is cytopathic (host cell changes structure cos of virus)
• HIV is genetically variable due to low fidelity of reverse transcriptase

> Variant genomes are often found in the same individual

> Can respond differently to treatment

> making treatment more difficult

Viral Features

HIV major genes

• gag – capsid matrix proteins
• pol – reverse transcriptase
• env – envelope proteins (gp120 &41)
• The env gene is highly variable (hampers vaccine development)

Two distinct types: HIV -1 and HIV -2

• HIV -2 is less pathogenic
  HIV -1 worldwide
• HIV 2- west africa
• HIV from cross species infections by simian viruses (SIV) in rural africa –> Possibly as long ago as 1800’s

Replication cycle

Attachment and entry

• gp120 protein binds to CD4 molecules and a chemokine receptor (CCR5, CXCR4)
• g41 protein enable fusion with cell membrane or endocytosis

Integration - provirus

• The viral reverse transcriptase copies viral RNA genome into DNA and integrates into host DNA

Virion Production

• Cell machinery produces RNA transcripts of viral genome
• plus all other necessary proteins

Exit

• Virions exit through exocytosis, enveloped

Development of diease - Clinical features

Primary (acute) HIV infection

• 2-4 weeks after infection
• Fatigue, rash, headache, nausea, night sweats

Clinical Latency

• Asymptomatic but still infectious
• Upto 10 years - longer without treatment

Aids (Acquired Immune Deficiency Syndrome)

• Untreated HIV infection will eventually progress to AIDS
• due to eventual destruction of significant number Th cells

Results in the severe suppression of immune system

• predisposes patient to opportunistic infections, severe
• Protozoa (toxoplasma gondii), Fungi (Candida, Cryptococcus, pneumocystis), Bacteria (Tuberculosis), Viruses (Hepatitis B)

A number of cancers caused by viral infections are also associated with AIDS patients

> Kaposi’s sarcoma (HSV - 8)

> Burkitt’s lymphoma (Epstein-Barr virus)

>Anogenital cancer (PPV)

>Non-Hodgkins Lymphoma

Transmission

• Sexual contact (including genito-oral sex)
• Parenteral exposure to contaminated blood or blood products
• Perinatal infection via birth or breast feeding
• Not transmitted by casual contact e.g. kissing, touching, mosquitoes etc.

Treatment

• Highly active anti-retroviral therapy (HAART) is a cocktail of anti-viral reagents – prolongs survival but doesn’t eradicate HIV

> Nucleoside analogues and non-nucloeisde inhibitors of reverse trasnscriptase
>Viral protease inhibitors, intergrase inhibitors, fusion inhibitors fusion ihibitors, CCR5 antagonists

• Reduces transmission from mother to infant
• Developing countries cannot afford these expensive drugs
• No vaccine presently available, due to major variationa at major antigens