Lecture 1: Global Impact of Infectious Diseases
Diversity of Infectious Agents
- viruses, bacteria & fungi usually cause acute infections
- parasites cause chronic infections
protozoa (protists) and worms (helminths)
Parasitism
- type of symbiosis
- symbiosis: interaction between two different organisms living in close physical association
- parasitism: relationship between two species where one species is benefited and other is harmed
- organisms can be mutualistic, commensal or parasitic under different conditions in different hosts
etc
Stages of Infectious Disease
- incubation period: time between infection and first occurrence of symptoms
- prodromal period: short time of generalised, mild symptoms
not all infectious diseases have this stage
- illness: most severe stage when symptoms most evident and host immune system has responded
- convalescence: body gradually returns to normal
time depends on pathogen and damage
sometimes may not occur if infection is chronic
Biological Response Gradient
- uncommon for pathogens to have same severity in all infected individuals
- severity of infected individual depends on infecting dose, age, gender, genetics, nutritional status &
co-infection with other pathogens
Disease Progression: Invasion:
- entry into host and transmission from one host to another
- inhalation, direct skin contact, oral transmission, intra-uterine, sexual transmission
- direct inoculation, insect bite
- route of transmission influences disease control measures
Disease Progression: Multiplication
- some pathogens multiply in body but others can’t
- protists can cause diseases following inoculation of only a few infectious stages as they can multiply
quickly
disease severity may depend on how quickly they multiply
- most helminths can’t multiply in body
disease severity depends on no. of infectious stages acquired by host over time
,Disease Progression: Spread
- ability of organism to move from initial infection site to other areas of body
- includes movement between body systems
- some infectious agents can undergo developmental changes at same time which can affect host
immune response
Disease Progression: Pathogenesis
- causation & development of clinical disease influenced by:
1) no. of pathogenic organisms present
2) virulence of organism
direct killing of host cells, blockages in host organs, toxins, inappropriate activity of immune
system
3) reaction of host e.g. degree of resistance
Global Burden of Disease
- incidence: no. of new infection cases occurring in population in defined period of time
- prevalence: total no of infected individuals in population at given point in time
includes old & new cases
- mortality: total no. of deaths in population in defined period of time
Mortality
- some countries have had shifts in burden of infectious diseases
- in other countries, infectious diseases
Economics
- high income countries have 70% of deaths for people aged 70+ and 1% of deaths are <15
deaths are predominantly due to long term chronic diseases
- low income countries have 20% of deaths for people aged 70+ and 40% of deaths are <15
deaths are predominantly due to infectious diseases
- higher income countries also spend more money on health per person
Disability
- mortality doesn’t give full picture of diseases burden by individuals of different population
- morbidity: amount of disease in a population
- disability adjusted life year (DALY) is measure used to give indication of overall burden of disease
DALY
- measure life years lost due to premature mortality & equivalent years lost due to morbidity
- calculates by adding ‘years of life lost (YLL) to premature mortality’ and ‘years lost to lived with
,disability (YLD)
- DALY = YLL + YLD
- allows comparison to be made across range of health issues
- provides quantitative basis for deciding health policies & evaluating cost effectiveness of control
programmes
- only measures direct health loss and doesn’t consider economic impacts resulting from disease e.g.
lost agriculture, lost school attendance etc
- doesn’t account for direct costs of treatment, surveillance & prevention measures
- doesn’t consider social stigma associated with disease e.g. loss of tourism, health system overload
Increasing Importance of Infectious Diseases
- drug resistant pathogens & vectors
- refugee movement
- rapid & widespread air travel
- increased immuno-deficient people
- lifestyle e.g. urbanisation, drug use
- natural / social disasters
- environmental changes
- pandemics
, Lecture 2: Innate Immune System
Immune System
- lymphatic system in blood
- bone marrow, thymus, lymph nodes & spleen in organs
- innate & adaptive properties in cells
- antibodies, cytokine, complements etc in molecules
Mechanical Barriers: Skin
- dead cells & bacteria
- sebaceous gland has fatty acids, lactic acid & low pH
- skin is dry preventing bacterial growth
Mechanical Barriers: Tight Junctions
- stop ingested antigens passing into body
Mechanical Barriers: Mucosal Surfaces
- lining of many organs coated with slippery mucus that traps microorganisms
- cilia brushes out mucus
Physiological Barriers: pH & Environment
- low pH in stomach kills pathogens
- normal commensal microbiota out-compete pathogenic strains for nutrients
Physiological Barriers: Chemical Mediators
- anti-microbial peptides – defensins damage pathogens
- anti-microbial proteins: lysozyme in tears & saliva
- cytokines – interferons induce anti-viral cell state
- complements –MAC lyses bacteria
enzyme cascade that joins together forming core structure (membrane attached complex) that is
inserted in bacterial membrane
Effective Parasites as Pathogens
- evade innate immune response
- use vectors, can hook to avoid being flushed or burrow straight through skin
- too big to be phagocytosed
Innate Immune Cells: Phagocytes
- macrophages survey body, sample environment and display them to show other cells what’s going
on in body
- neutrophils kill pathogens by rapidly ingesting them or by releasing granule content
send messages to other cells and sacrifice themselves by releasing their DNA & coating it in
histones to kill bacteria by extracellular trapping
- dendritic cells are professional antigen presenting cells that activate T cells
Innate Immune Cells: Granulocytes
- neutrophils
- natural killer cells that target & kill cancerous or infected cells
- eosinophils release granular content to kill pathogens
important in allergies as they use cell signalling to activate mast cell
- mast cells contain histamines that increase vasodilation & enhance inflammation
Diversity of Infectious Agents
- viruses, bacteria & fungi usually cause acute infections
- parasites cause chronic infections
protozoa (protists) and worms (helminths)
Parasitism
- type of symbiosis
- symbiosis: interaction between two different organisms living in close physical association
- parasitism: relationship between two species where one species is benefited and other is harmed
- organisms can be mutualistic, commensal or parasitic under different conditions in different hosts
etc
Stages of Infectious Disease
- incubation period: time between infection and first occurrence of symptoms
- prodromal period: short time of generalised, mild symptoms
not all infectious diseases have this stage
- illness: most severe stage when symptoms most evident and host immune system has responded
- convalescence: body gradually returns to normal
time depends on pathogen and damage
sometimes may not occur if infection is chronic
Biological Response Gradient
- uncommon for pathogens to have same severity in all infected individuals
- severity of infected individual depends on infecting dose, age, gender, genetics, nutritional status &
co-infection with other pathogens
Disease Progression: Invasion:
- entry into host and transmission from one host to another
- inhalation, direct skin contact, oral transmission, intra-uterine, sexual transmission
- direct inoculation, insect bite
- route of transmission influences disease control measures
Disease Progression: Multiplication
- some pathogens multiply in body but others can’t
- protists can cause diseases following inoculation of only a few infectious stages as they can multiply
quickly
disease severity may depend on how quickly they multiply
- most helminths can’t multiply in body
disease severity depends on no. of infectious stages acquired by host over time
,Disease Progression: Spread
- ability of organism to move from initial infection site to other areas of body
- includes movement between body systems
- some infectious agents can undergo developmental changes at same time which can affect host
immune response
Disease Progression: Pathogenesis
- causation & development of clinical disease influenced by:
1) no. of pathogenic organisms present
2) virulence of organism
direct killing of host cells, blockages in host organs, toxins, inappropriate activity of immune
system
3) reaction of host e.g. degree of resistance
Global Burden of Disease
- incidence: no. of new infection cases occurring in population in defined period of time
- prevalence: total no of infected individuals in population at given point in time
includes old & new cases
- mortality: total no. of deaths in population in defined period of time
Mortality
- some countries have had shifts in burden of infectious diseases
- in other countries, infectious diseases
Economics
- high income countries have 70% of deaths for people aged 70+ and 1% of deaths are <15
deaths are predominantly due to long term chronic diseases
- low income countries have 20% of deaths for people aged 70+ and 40% of deaths are <15
deaths are predominantly due to infectious diseases
- higher income countries also spend more money on health per person
Disability
- mortality doesn’t give full picture of diseases burden by individuals of different population
- morbidity: amount of disease in a population
- disability adjusted life year (DALY) is measure used to give indication of overall burden of disease
DALY
- measure life years lost due to premature mortality & equivalent years lost due to morbidity
- calculates by adding ‘years of life lost (YLL) to premature mortality’ and ‘years lost to lived with
,disability (YLD)
- DALY = YLL + YLD
- allows comparison to be made across range of health issues
- provides quantitative basis for deciding health policies & evaluating cost effectiveness of control
programmes
- only measures direct health loss and doesn’t consider economic impacts resulting from disease e.g.
lost agriculture, lost school attendance etc
- doesn’t account for direct costs of treatment, surveillance & prevention measures
- doesn’t consider social stigma associated with disease e.g. loss of tourism, health system overload
Increasing Importance of Infectious Diseases
- drug resistant pathogens & vectors
- refugee movement
- rapid & widespread air travel
- increased immuno-deficient people
- lifestyle e.g. urbanisation, drug use
- natural / social disasters
- environmental changes
- pandemics
, Lecture 2: Innate Immune System
Immune System
- lymphatic system in blood
- bone marrow, thymus, lymph nodes & spleen in organs
- innate & adaptive properties in cells
- antibodies, cytokine, complements etc in molecules
Mechanical Barriers: Skin
- dead cells & bacteria
- sebaceous gland has fatty acids, lactic acid & low pH
- skin is dry preventing bacterial growth
Mechanical Barriers: Tight Junctions
- stop ingested antigens passing into body
Mechanical Barriers: Mucosal Surfaces
- lining of many organs coated with slippery mucus that traps microorganisms
- cilia brushes out mucus
Physiological Barriers: pH & Environment
- low pH in stomach kills pathogens
- normal commensal microbiota out-compete pathogenic strains for nutrients
Physiological Barriers: Chemical Mediators
- anti-microbial peptides – defensins damage pathogens
- anti-microbial proteins: lysozyme in tears & saliva
- cytokines – interferons induce anti-viral cell state
- complements –MAC lyses bacteria
enzyme cascade that joins together forming core structure (membrane attached complex) that is
inserted in bacterial membrane
Effective Parasites as Pathogens
- evade innate immune response
- use vectors, can hook to avoid being flushed or burrow straight through skin
- too big to be phagocytosed
Innate Immune Cells: Phagocytes
- macrophages survey body, sample environment and display them to show other cells what’s going
on in body
- neutrophils kill pathogens by rapidly ingesting them or by releasing granule content
send messages to other cells and sacrifice themselves by releasing their DNA & coating it in
histones to kill bacteria by extracellular trapping
- dendritic cells are professional antigen presenting cells that activate T cells
Innate Immune Cells: Granulocytes
- neutrophils
- natural killer cells that target & kill cancerous or infected cells
- eosinophils release granular content to kill pathogens
important in allergies as they use cell signalling to activate mast cell
- mast cells contain histamines that increase vasodilation & enhance inflammation
