HEALTH AND COMMUNITY

Doll - research on lung cancer

British Doctor study:

• smokers have a higher risk of: lung cancer, heart disease, chronic lung disease

• risk of this increased with no. of cigarettes smoked, duration of smoking

• stopping smoking reduced risk

UK public health response to smoking

cancer rate 2012-2014

• tobacco tax

• UK smoking ban 2007

• 2012-2014: north south divide in lung cancer rates

• higher rates in north compared to south

• reduce cancer by avoiding cancer risk factors

non-avoidable cancer

risk factor

PROSTATE CANCER

risk factor: age

TESTICULAR CANCER

risk factor: age, having testicles, ethnicity, previous testicualr cancer, HIV/AIDS

what is PSA

PSA - prostate specific antigen, a protein produced by normal prostate cells

• as prostate enlarges with age, PSA levels rise

PSA testing - advantages

• can detect prostate cancer before symptoms arise, allows for intervention that can prevent spread

PSA testing - disadvantages

• raised PSA doesn’t equal prostate cancer

• low PSA doesn't equal no prostate cancer

100% avoidable cancer

CERVICAL CANCER

• all cases of cervical cancer are preventable as they are associated with sexual activity

Public health response to cervical cancer

• girls get HPV vaccine (2 doses)

• boys are also given HPV vaccine

• HPV associated tumours of lips, anus, penis associated with MSM population

non-communicable disease

diseases of long duration and slow progress that are not contagious

risk factors of disease

aspects of behaviour associated with an increase in occurrence of disease

modifiable risk factor

a factor that can be controlled or reduced

reduce physical inactivity, tobacco use, alcohol use, unhealthy diet

non-modifiable risk factor

a factor that can’t be controlled

age, sex, race, family history

epidemiology

study of disease in a population

descriptive epidemiology

studies frequency of health events in terms of person/ place/ time

analytical epidemiology

studies the association between risk factors and disease

diabetes

risk factors

complications of diabetes

• chronic disease where pancreas doesn’t produce insulin OR body doesn’t respond to insulin produced

• risk factors:

  • obesity

  • age

  • genetics

    • genetic predisposition: genetic and environment contribute to type II diabetes - diabetes clusters in families

  • ethnicity/ race

    • ethnic predisposition: type II diabetes 3x greater in south asians compared to European population

• complications of diabetes:

  • cardiovascular disease

  • kidney disease

  • sexual dysfunction

diabetes - mellitus type 2

• body not able to respond to insulin

• due to excess weight and physical inactivity

diabetes epidemic

cost of UK diabetes

diabetes epidemic - 4.3 million cases

cost - £23.7 million

• 14% of hospital beds due to diabetes

MIC and HIC change in diabetes cases

MIC - biggest increase in cases

HIC - smallest increase in cases

EMERGING DISEASE

+example

• newly appeared in a population

• arise due to: zoonotic spillover and environmental change

HIV

• spillover form zoonoses (primates) infected with SIV

RE-EMERGING DISEASE

+example

• previously declined disease that begins to increase again

• arise due to: declining vaccination, vector expansion, breakdown of public health system

MEASLES

• 6500 death Rep Dem Congo - no access to vax and civil war (so limited resources)

• 800+ death Philippines - vax skepticism

zoonoses

disease that can jump from vertebrate to human

why might some diseases be mistaken for emerging disease

better detection of disease:

• improved diagnostic sensitivity

• new diagnostic practices

• improved education, increase in reporting

• improved classification of diseases

how is Malaria affected by hydrological change

• potential to create new breeding sites for the vector (mosquitoes)

• changes environment and modifies ecosystem

upstream from Cahora Bassa Dam = lake

• lake: stagnant water - large-scale breeding site

Cahora Bassa Dam

Mozambique

• creates new breeding sites, influencing mosquito habitats

• leads to plasmodium development and increases their survival rate - mosquito enters host (local pop/ labourers/ migrant) that then infects human population which causes death

MEASLES

how did re-emergence occur

1. re-emerging virus

2. measles morbillivirus

3. R₀ =18

4. droplet and aerosol transmission

5. vaccine = MMR

re-emergence - OUTBREAK

• 1st most deaths - Dem Rep Congo - 6500 deaths

• occurred due to cost of vaccination and no access to resources due to civil war

• 2nd most deaths - Phillipenes - 800+ deaths

• due to vaccine skepticism

WHO - flagged pathogens

flagged to prevent PHEIC (public health emergencies of international concern)

30 pathogens

‘prototype’ pahtogens - model species for research of vaccine development

MPOX - monkeypox virus

monkeypox virus

followed by eradication of smallpox

MPOX emerged in asia

affects primarily MSM

vaccine for MPOX but no antiviral treatment

BII

BIODIVERISTY INTACTNESS INDEX

• estimates biodiversity remains on average across ecological community in a region

LPI

GLOBAL LIVING PLANET INDEX

measures world biodiversity

tracks how populations of wild vertebrates change over time

Intact wilderness

where most wilderness is intact and human footprint value is low

Wild species pressure

population reductions due to exploitation and loss of habitat

mammals as reservoirs of human disease

birds - influenza

primates - SIV > HIV

Bat - rabies, ebola, coronavirus

HIV - human immunodeficiency virus

HIV-1

HIV-2

zoonotic origin of HIV: SIV - simian immunodeficiency virus (original found in African primates)

• gave rise to HIV-1

• which is principle cause of AIDS pandemic

• poss due to hunting/ eating chimps

Ebola

40% death rate

R₀ = 2.5

Zoonotic reservoir = Bats

MERS - Middle East Respiratory Syndrome

MERS-CoV

35% death rate

zoonotic reservoir = Bats now camels

MDR

multi-drug resistant (3+)

XDR

extensively drug resistant

EMERGING: LYME DISEASE

• Boreli Burgdorferi

• Spirochete - long coiled structure able to move through tissue

• Vector-borne transmission (ticks), zoonotic reservoir (small mammals)

Boreli Brugdorferi twisted like a spiral spring, crawled through the woods like a tick taxi and hid inside tiny mice

Epidemiology of Lyme disease

Boreli Burgdorferi - epidemic continues to expand

B. burgdorferi presents OPSA (outer surface protein A) used for attachment

B. burgdorferi enters vertebrate host epithelium + migrates into tissue and joints

how to treat Boreli Burgdorferi - Lyme disease

• no vaccine

• reduce expose to tick bites

• treat with doxycycline if caught early enough

EMERGING: CHOLERA

• vibriocholorae

• gram negative, rod shaped

• caught from contaminated food + water

• proteins produced by vibriocholorae = cholera enterotoxin + hemagglutinin

• causes diarrhoea due to toxin

  • cholera toxin causes Cl- ions to be excreted from cells on intestines

  • osmotic pressure draws water into lumen of gut - diarrhoea

Epidemiology of Cholera

+example

led to global pandemics

indicator of a lack of socio-economic developm

cholera Haiti epidemic - 2010

• earthquake

• case fatality rate = 5%

how to treat vibriocholorae - Cholera

cholera vaccine - antibiotic treatment

Shigella

gram negative

sexually transmitted

invade epithelial cells and produce toxin

200,000 annual deaths

causes diarrhoea

multidrug resistance detected in shigella species

water deprivation statistics

2.1 Billion lack safe water

4.5 Billion lack toilets

WASH

water, sanitation, hygiene

disease prevention depends on preventing disease from contaminated water, reduce open defecation

how to make water safe?

what should be absent from water?

filtration

sewage treatment

wastewater management

E.coli and coliform bacteria should be absent from water

waterborne diseases

• bacterial

• viral

• protozoan

BACTERIAL

• vibrio cholerae

• escherichia coli

VIRAL

• noravirus

• rotavirus

PROTOZOAN

• cryptosporidum parvum

• giardia

Norovirus

highly contagious

rapid spread

RNA virus - high mutation rate

Cryptosporidium parvum

• mechanism

protozoan parasite

causes severe diarrhoea

thick walled sporulated oocyst exits host and contaminates food and water

then enters another host

oocyst secretes proteins, sporozoite invades and intracellularly enters epithelium and replicates

pathways for pathogens in food

agent > source > contamination > suitability > consumption > growth conditions > consumption

agent = biological, physical, chemical, allergen

source = food handler, natural food contamination, direct food contamination, water based

advantages and disadvantages of microbes in food

adv:

food enhancement

additives for safety and longevity

disadv:

lack of food safety

food spoilage

Lactobacillaceae

gram positive bacteria

• probiotic - yoghurt/ kefir/ miso/ sauerkraut

INTRINSIC - food preservation

low water activity

acidic pH

antimicrobial chemicals

competitive microflora

ALL INHIBIT MICROBIAL GROWTH

EXTRINSIC - food preservation

heat treatment - destroys spores

refrigeration

modified atmosphere packaging

UV/ gamma radiation

Hurdle technology

combination of intrinsic and extrinsic food preservation techniques to improve food safety

better food quality

more effective pathogen control

may select more resistant organisms

Enterobacteriaceae

gram negative rod

Salmonella

• found in the intestinal tract of birds and animals

• human contamination due to consumption of food/ water

2 diseases due to Enterobacteriaceae

Gastroenteritis

• vomitting diarrhoea, fever, muscle aches

• superficial infection of gut

Typhoid fever

• vomitting diarrhoea

• invasive infection of lymph nodes, liver, spleen, gall bladder

Campylobacter jejuni

gram negative spiral bacterium

found in poultry

infection prevented by sufficient cooking, hygiene, safe procesing

Listeria

gram positive rod

found in RTE food, chilled food, unpasteurised food

forms biofilms

disease: listeriosis - cause: septicaemia, meningitis, CNS infection

low incidence, high mortality

Escherichia coli

Enterobactericeae - eschericia coli

gram negative rod shaped

infects colon - causes diarrhoea, severe abdominal pain, vomitting

cause: Haemolytic Uraemic Syndrome

• kidney failure

HACCP

+how did scheme start

Hazard analysis + critical control points

identify, control, evaluate hazards during food production and processing

instead of food just being tested at the END

advantage of HACCP: less food waste due to better food monitoring strategies

brought about by food safety concerns on NASA trips

7 HACCP principles

1. hazard analysis

2. identify critical control points (CCPs)

3. establish critical limits

4. establish monitoring procedure

5. create corrective actions

6. verification of HACCP food safety plan

7. record keeping

Maillard Reaction

• occurs during cooking, allows for non-enzymatic browning of food

• between amino acids (proteins) + reducing sugars —- to make complex savoury flavours in meats and bread

modern hurdle technologies

• radio frequencies/ microwave heating

• irradiation

• high pressure

• pronation

• pulsed electrical field

• electrolysed water

• enzymes

• active film packaging

CASE STUDY: Shire foods

• RTE foods

• use of spiral blast freezers - but food must be destroyed to see if fully frozen

SO

• infrared technology: non-destructive temperature testing by infrared technology, records surface temperature only

NOW

• microwave radiometry: measure thermal radiation rather than surface temp

  • less vulnerable to hot and cold sports

  • can measure temp through packaging

CASE STUDY: Pate

• meat pate production - Kazakhstan

• impacted by ecological problems due to proximity to nuclear site

CASE STUDY: Canteloupe

• 33 deaths

• causative agent - L.monocytogenes

• outbreak traced to cantaloupe produced by a farm in Colorado

  • unsanitary conditions in processing facility, failure to apply HACCP to new washing facility

variability in HACCP in HIC/LMIC

HIC - high enforcement

LMIC - lack infrastructure for strict enforcement

• limited access to safe water, for sanitation, lack of refrigeration

small business challenge in adopting HACCP:

• high cost, lack of expertise, resource limitations

Biofilm

microbial cells associated with a surface, enclosed in an extracellular matrix

extracellular polymeric substance (EPS)

formation of biofilms allow bacteria to become tolerant to antibiotics and generate resistance

difference between complex biofilms and less complex biofilms

complex biofilms - biofilms in industrial water

less complex biofilms: on medical devices (artificial heart valve)

cystic fibrosis - biofilm

CF - mucus in lungs = thick and sticky

traps bacteria

forms biofilms

Biofilm formation

• planktonic cells = motile bacteria

• bacteria differentiate and produce the extracellular matrix (sticky slime layer)

• these multiply and aggregate

• so biofilm become fully mature

• some bacteria leave the biofilm to start new biofilms elsewhere

Bactericidal vs. Bacteriostatic

Bactericidal: antibiotics kill bacteria

Bacteriostatic: antibiotics inhibit growth of bacteria

antibiotics that inhibit cell wall synthesis

B-lactams

• penicillins

• cephalosporins

• carbapenems

• monobactams

Glycopeptides

• vancomycin

antibiotics that inhibit nucleic acid synthesis

quinolones

antibiotics that inhibit folate synthesis

sulfonamides

trimethoprim

antibiotics that inhibit protein synthesis

30S subunit

• aminoglycosides - high affinity binding to the 30S ribosomal subunit

• tetracyclines - bind to the 30S ribosomal subunit and block entry of tRNA molecules into the A-site of the ribosome preventing new amino acids form growing the peptide chain

50S subunit

• macrolides

• amphenicols - bind to the 50S ribosomal subunit and inhibits formation of peptide bonds

by interfering with protein synthesis, protein products can misfold

how do B-lactams target PBPs

PBP make crosslinks (peptide bonds) between peptidoglycans, B-lactams bind to PBPs

B-lactam ring binds to the active site of the PBP, cell wall cross links STOPS

how do quinolones inhibit nucleic acid synthesis

quinolones: bactericidals

topoisomerase: regulate supercoiling in DNA/RNA synthesis using DNA gyrase

REGULAR DNA REPLICATION:

• DNA must unwind and untangle

• DNA gyrase and topoisomerase cut and reseals DNA to relieve tension

quinolones bind to topoisomerase/ DNA gyrase to prevent DNA strands from being resealed after cutting

• causes breaks in DNA and failure of DNA replication/ transcription

superbugs

bacteria that is resistant to antibiotics use to treat it - MDR

• staphylococcus aureus (MRSA)

• escherichia coli

• acinetobacter spp

• klebsiella pneumoniae

• pseudomonas aeruginosa

• mycobacterium tuberculosis

what are the mechanisms of the development of antibiotic resistance

vertical gene transfer: genetic information will pass from one generation to the next within a family (transfer to daughter cells during reproduction - binary fission)

horizontal gene transfer: genetic information can spread across several bacterial species (between unrelated bacteria)

anthropogenic drivers of antibiotic resistance

anthropogenic = caused by human activity

community acquired resistance = excessive use develops antibiotic resistant bacteria

• farming practices - antibiotics used as growth promoters

• horticultural practices - antibiotics used as growth promoters

• veterinary practices - antibiotics for treatment of pets disease

LEADS TO OVER-PRESCRIPTION OF ANTIBIOTICS

intrinsic/acquired antibiotics resistance

intrinsic: naturally present

• eg: bacteria lacking a cell wall are resistant to penicillin because penicillin targets cell wall synthesis

acquired: developed

• resistance that bacteria gain over time through mutations or horizontal gene transfer

non-specific antibiotics resistance

porins: down regulation of porins that limits antibiotics entry into the cell - REDUCES PERMEABILITY

efflux pumps: over-expression of proteins expel antibiotics form cell

specific antibiotic resistance

antibiotic inactivation

target modification

what is the importance of bacterial characterisation

to control spread of antibiotic resistance, need to find antibiotic resistant bacterial strains

requires accurate isolate typing methods

bacterial strain typing methods

phenotypic methods: detecting characteristics expressed by bacteria (shape/ size/ staining)

genotypic methods: analysing bacterial DNA + presence/ absence of specific genes

phenotyping methods: gram stain

• detects peptidoglycan - different in gram negative and gram positive cell walls

• problem: poor species resolution

phenotyping methods: biotyping

examine metabolic activity (sugar fermentation, enzymatic action)

• advantages: most strains are typeable

• disadvantages: poor discriminatory power

phenotyping methods: antibiogram

antibiogram = antibiotic susceptibility

• strain discrimination based on antibiotic resistance

advantage: all stains are typeable and easy to interpret

disadvantage: acquisition of antibiotic resistance due to mutations can alter patterns of antibiotic resistance

phenotyping methods: phage typing

based on their susceptibility to bacteriophages, different bacterial strains are sensitive to different phages

phenotpying methods: serotyping

strain discrimination based on binding of specific antibodies to their cell surface antigens

strains differentiated by antigenic differences = SEROTYPES

advantages: serotyping allows differentiation of bacterial species to many distinct serotypes

disadvantage: poor discriminatory power

RFLP

restriction fragment length polymorphism

restriction enzymes cleave the DNA into fragments of varying lengths

PFGE

pulsed field gel electrophoresis

separate DNA fragments on basis of size

highly discriminative an faster than other genotyping methods

requires hours, technical

carbapenem resistance in pseudomonas aeruginosa

1. down regulation of porins, membrane = less permeable

2. acquisition of carbapenemases

3. up regulation of efflux pumps, carbapenemas pumped out of cell

modified hodge test

test used to detect carbapenemase-producing bacteria

these bacteria produce enzymes that break down carbapenem antibiotics

gram positive superbug example

staphylococcus aureus

separating staphylococcus and streptococcus

staphylococcus - catalase positive - forms reactive oxygen species, bubbles form

streptococcus - catalase negative

genotyping methods: MLST

multiocus sequence typing (MLST): molecular typing method that characterises bacteria based on DNA sequences of housekeeping gene s

reservoirs of S.aureus (+ MRSA)