Ahmed D (Pathogenicity & STIs) Flashcards
What are pathogens?
Organisms that have the potential to cause disease.
The different types of pathogens and the severity of the disease that they cause are very diverse.
- Bacteria
- Viruses
- Fungi
- Parasites
What is virulence?
What is virulence?
The degree of pathogenicity of a particular organism
Pathogenicity
Three characteristics:
- Invasiveness
- Infectivity
- Pathogenic potential
- Toxigenicity (ability for virus to withstand toxic chemicals)
Determinants of pathogenicity
A pathogen must successfully achieve these steps or stages of pathogenesis to cause diseases
- Ability to be transported to the host
- Adhere to, colonise, or invade the host
- Multiply in the host
- Evade host defences
- Possess mechanical, chemical, or molecular ability to damage the host
Transmission
Direct contact
- host to host
Indirect contact transmission
- contamination of inanimate objects
Droplet transmission
- coughing, sneezing
Food and water born transmission
- salmonella, cholera, hep A
Vector transmission
- mosquitos (malaria) and ticks (Lyme disease)
Route of entry for invading pathogen
Skin- breaks protective barrier, bites
Mucous membrane- ingestion, inhaled through respiratory system, eyes and nose, sexual contact
Adhesion and colonisation
Adhesion refers to the capability of pathogenic microbes to attach to the cells of the body using adhesion factors (adhesins)
Adhesins- specialised molecules or structures on the pathogens cell surface to bind complementary receptor sites on the host cell surface. Each organism has a specific region/cell where the pathogen will attach
Entry of pathogen
Once adhesion is successful, invasion can proceed; penetrate epithelium after attachment.
Accomplished through production of lytic substances (toxins)
- attack ground substance and basement membranes of intestinal linings
- degrading carbohydrate-protein complexes
- disrupt cell surface
Some pathogens use passive mechanisms (not related to pathogen)
- Lesions, ulcers in mucous membrane, Tissue damage from another organism’s eukaryotic internalisation pathway (endocytosis)
Toxigenicity (virulence factors)
Exotoxins - produced from the cells
- among the most lethal substances known
- associated with specific cases
- high immunogenic
- neurotoxins, cytotoxins, enterotoxins depending on mechanism of action
Endotoxins- produced from the cell surface
- LPS bound to the host
- toxic in high doses
- weakly immunogenic
- cause fever, shock, blood coagulation, weakness, diarrhoea, inflammation, intestinal haemorrhage, fibrinolysis
(- can be dead and toxins still released from outside)
Evasion of host immune system
Rely on recognition of foreign material- identify self from non-self.
Many mechanisms involved
- mimic host molecules
- create cysts
- bind to fibrinogen and complement factors in plasma
- leukocidins- cause degranulation of lysosomes
- bind to immunoglobulins by Fc end (Fc located on tail of antibody and they use this region to bind and initiate immune response. Bacteria bind here so they they are not able to initiate a response)
- produce porins to escape phagocytosis
Infection
Following invasion, successful multiplication of the pathogen leads to infection.
Infections can be described as local, focal, or systemic, depending on he extent of the infection.
Local infection: is confined to a small area of the body, typically near the portal of entry. e.g. pneumonia is confined to the lungs, ear infections, wound infections.
Focal infection: a localised pathogen, or the toxins it reduces, can spread to a secondary location. E.g. a dental hygienist nicking the gum with a sharp tool can lead to a local infection in the gum by Streptococcus bacteria of the normal oral microbiota
Systemic infection: when an infection becomes disseminated throughout the body.
Several STIs are either always systemic or can become systemic infections. e.g. HIV- affects T helper cells which causes immune system to be weakened and spreads round body.
What are the key traits required for a microbe to be pathogenic?
Transmission, adhere to host, invade host, multiply, evade host defences, cause damage to host
What do the terms pathogenic and virulent mean?
Pathogenic- ability to cause disease
Virulent- degree of pathogenicity/severity
Sexually Transmitted Infections
Are spread predominantly by unprotected sexual contact. Some STIs can also be transmitted during pregnancy, childbirth and breastfeeding and through infected blood or blood products.
More than 1 million STIs are acquired everyday worldwide, the majority of which are asymptomatic.
Each year there are an estimated 374 million new infections with 1 of 4 curable STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis
Drug resistance is a major threat to reducing the burden of STIs worldwide
Types of STIs
Bacterial
- Chlamydia (most common in UK)
- Gonorrhoea
- Syphilis (2nd most common in UK)
- Non-specific urethritis
Viral
- Genital warts
- Genital herpes (least common in UK)
- HIV/AIDS
- HPV
Fungal
- Thrush (not technically an STI but usually grouped with them
Parasite
- Scabies
- Pubic lice
- Trichomonas vaginalis
Chlamydia
Bacterial infection
Gram negative (stains pink as cell wall is thinner)
Lacks peptidoglycan cell wall
Non-motile
Smallest bacterium with 2 forms
- elementary bodies (smaller) cocci
- reticulate bodies (larger) pleomorphic
- Intracellular pathogen
- Growth only in vesicles within host cells
- Do not have genes required for ATP production
- Require host cells to provide ATP
- Require the two forms for development
- Three species cause disease
- Chlamydia trachomatic - STD
- Chlamydia pneumoniae - pneumonia
- Chlamydia psittaci - from birds
Life cycle of chlamydia
All chlamydiae share a developmental cycle in which they alternate between extracellular, infectious elementary body (EB) and the intracellular, non-infectious reticulate body (RB).
0-6 hrs - EB attachment and entry by endocytosis (or break down wall using toxins)
6-12 - transition of EB to RN
12-24 - replication
24-36 - RBs reorganise back to EBs
46-48 -
48-72 - lysis or extrusion
What is the difference between EBs and RBs (chlamydia)
EB
- Small (0.2-0.1 micrometers)
- Dormant
- Resistant to environmental stress
- Infective form
- Infect through abrasions/lacerations
- Attach to limited array of cells
RB
- Larger (0.6-1.5 micrometers)
- Non-infective
- Obligate intracellular form
- Replicate by binary fission within phagosomes
Disease (chlamydia)
- Enters host cell via abrasions and lacerations then endocytose by target cell.
- EBs infect limited array of cells (that contain the receptors for EBs). Conjunctiva, cells lining the trachea, bronchi, urethra, uterus, uterine tubes, anus, rectum.
- Disease caused by inflammatory response at the infection site (inflammatory response- histamine release, vasodilation)
- Second infection causes hypersensitive immune response.
- Can result in blindness, sterility or sexual dysfunction.
- Once bacteria has entered host cell and starts to multiply a genital lesion appears.
- Lesion is relatively short lived and often missed especially in women as it develops internally.
- As infection develops lymph nodes become inflamed and headaches and flu like symptoms occur.
- In rare occasions, genital sores, constriction or the urethra and genital elephantiasis can occur.
Epidemiology of chlamydia
Bacteria can be transmitted via droplets, hands, contaminated formats or flies.
500 million people contract ocular infections every year.
Children carry pathogen in digestive and respiratory tracts (therefore signs of bacteria does not necessarily indicate abuse).
Chlamydia infects about 131 million people worldwide each year.
It is the second leading cause of more than 1 million new STIs that occur daily.
in 2019 there were 468,342 new STI diagnoses made at sexual health services in England with almost half being attracted to chlamydia.
Chlamydia symptoms
In women
- Often asymptomatic (85%)
- An unusual vaginal discharge
- Pain when urinating
- Low abdominal pain
- Bleeding between perios
- Pain during or bleeding after sex
- Immune response to second infection can lead to pelvic inflammatory disease
In men
- 75% men have symptoms
- A white/cloudy watery discharge
- Pain or burning sensation when urinating
- Testicular pain or swelling
Chlamydia diagnosis and treatment
Diagnosis- urine test or swab
Treatment- antibiotics
- Azithromycin (single dose)
- Doxycycline (7 days)
- Erythromycin (14 days)
Why are penicillin and cephalosporins not suitable for a chlamydia infection?
They are effective against gram positive bacteria and chlamydia is gram negative. They target peptidoglycan synthesis but in gram negative bacteria there is a lipopolysaccharide layer surrounding the peptidoglycan layer which prevents the penicillin attacking.
Gonorrhoea
Neisseria gonorrhoea.
Gram negative (pink stain).
Diplococci.
True pathogen.
Second most common STI.
Occurs in humans only.
Infected epithelial cells in mucosal membrane of genital, urethra, digestive tract, cervix, uterus, rectum, pharynx, mouth.
Can enter the bloodstream to cause infection of joints, heart and meninges.
Can be passed to child during childbirth and infect cornea.
Mostly transmitted sexually so can be an indication of child abuse.
Pathogenesis of gonorrhoea
As few as 100 pairs of cells required for disease to occur.
Adhere to epithelial cells via fimbrae and capsules.
Secrete a protease that cleaves IgA- evading immune system by secreting IgA.
The bacteria can be endocytised and multiply in neutrophils .
Once multiplying the bacteria can invade deeper tissue via phagocytosis.
Epidemiology of gonorrhoea
in 2020 WHO estimated 82.4 million new infections among adults aged 15 to 49.
Higher risk of infection for females than makes.
Risk increases with higher sexual promiscuity.
In 2018, 7689 diagnosis’s in England.
Substantially under diagnosed and underreported worldwide. It is estimated that more than half of infections are unidentified or unreported.
Gonorrhoea symptoms
In women
- Often asymptomatic
- Often mistaken for bladder infection
- Infects cervix
- Can lead to pelvic inflammatory disease
In men
- Insufferably symptomatic
- Acute inflammation
- Painful urination
- Purulent discharge
- Can invade prostate and epididymis to cause infertility
Gonorrhoea diagnosis and treatment
Diagnosis
- Swab from cervix is more accurate but urine sample is possible
- Swab of discharge or urine sample in men
Treatment
- Single intramuscular antibiotic injection of ceftriaxone followed by single oral antibiotic dose of azithromycin
- It is sometimes possible to have another antibiotic tablet instead of an injection
What microbe is responsible to gonorrhoea infections and what are its identifying structural features?
Neisseria gonorrhoeae.
It is gram negative, non-spore forming, non-motile, encapsulated, kidney bean shaped.
Which host cells are infected by this neisseria gonorrhoeae?
Invades the epithelial cells
How does neisseria gonorrhoeae cause disease and spread in the host population?
The bacteria attaches to epithelial cells and then penetrates the cells and multiplies inside.
It is spread by sexual contact and also from mother to baby during childbirth.
What is the treatment plan for gonorrhoea? How can it be prevented?
Treatment is a single antibiotic injection into buttock or thigh. Gonorrhoea rapidly develops resistance to antibiotics so the less antibiotic used the better. Timely diagnosis through routine screening is needed.
It can be prevented by using condoms and not having unprotected sex.
What microbe is responsible for syphilic infection and what are its identifying structural features?
Treponema palladium is the microbe responsible. It does not have a cell wall
Which host cells are infected by treponema palladium?
Attaches to epithelial and endothelial cells. CD4 T cells and macrophages are the predominate cell type in primary syphilis.
How does treponema palladium cause disease (4 stages) and how is it spread through a population?
Primary- multiple source, round and painless
Secondary- skin rash and sores
Latent- no visible signs and symptoms
Tertiary- affects heart and muscles
It is spread through sexual contact.
What is the treatment plan for syphilis? How can it be prevented?
Single infection of benzylpenicillin G is the initial treatment.
Can be prevented by wearing condoms
Non-gonococcal urethritis
Inflammation of urethra
Symptoms include
- painful/burning sensation when urinating
- tip of the penis irritated and sore
- white or cloudy discharge
Genital herpes
Caused by Human Herpes Virus (HHV)/ Herpes Simplex Virus (HSV)
Herpesviridae
Double stranded DNA
Icosahedral capsid
Enveloped
150-200nm diameter (large virus)
Pathogenicity of genital herpes
Active lesions are the usual source of infection.
Enter the body through abrasion/laceration.
Virus binds to epithelial cells and enter the cells to reproduce.
Reproduction causes inflammation and cell death.
Infected ells fuse with neighbouring uninfected cells to form a structure- syncytium
The virus can then spread cell to cell causing a painful lesion.
HSV disease
Type 1- mostly spreads by oral contact and causes infections in or around the mouth
Type 2- spray by sexual contact and causes genital herpes
Epidemiology of HSV
in 2016 3.7 billion people under the age of 50 had HSV-1 infection. Most HSV-1 infections are acquired during childhood.
An estimated 491 million people worldwide aged 15-49 had genital herpes caused by HSV-2 infection.
HSV-2 infects women almost twice as often as men
Most HSV-2 infections acquired between ages 15-29 yrs old.
Neonatal herpes
Foetus infected in utero or during birth.
30% fatality rate if infection affects cutaneous or oral cells.
80% fatality if the CNS is affected.
Mother to have C-section if lesions present at time of birth.
Acyclovir used in late stages of pregnancy to suppress outbreak or cure infection
Diagnosis of herpes
Characteristic lesions
Microscopic examination of tissue to reveal syncytia (structure)
Serology testing for antibodies to antigens (looking for IgM and IgG antibodies)
Treatment and prevention of herpes
Valaciclovir.
Iododeoxyuridine.
Acyclovir can be used over 6-12 months to clear infection.
Condoms not successful at preventing spread of disease.
People with lesions must abstain from sexual intercourse.
Asymptomatic individuals can still shed virus.
Circumcision may reduce risk of infection by 25%.
