Co-infection Flashcards
Parasitism
symbiotic relationship where one species (parasite) benefits at expense of other (host)
Parasite / pathogen decrease the fitness of their hosts by infecting them
Co-infection
infection of single host by more than one pathogen species / strain
Co-infection is common (>1/3 humans have more than one parasite-> study in Africa)
Interactions between pathogen effect within host dynamics (Colonisation, Replication, Dissemination, Infection duration, Disease severity) and between host dynamics (transmission, recovery rate, death rate)
Outcome mediated by order of arrival in host and infection dose
Interaction mechanisms: Direct
positive= Direct facilitation
Example: nematode Trichuris muris eggs only hatch when in presence of gut bacteria (as shows are in correct env)
negative= Direct interferance (chemical weapons)
Example: bacteria on frog skin make anti-fungicides and nematodes secrete anti-bacterial which are upregulated in presence of bacteria
Interaction mechanisms: Top down (Immune mediated)
Heterologous immunity: exposure to / infection by one pathogens can induce / modify immune response against another unrelated pathogen (both innate + adaptive response)
Immune mediated facilitation: Immune respose to one agent benefits the other agent
1) Polarisation of immune response via cytokine milieu
- Cytokines for Th1 and Th2 differentiation pathways are mutually inhibitory
- Th1 (macrophages -> inctracellular)
- Th2 (B cells -> extracellular)
- Polarisation to one response can facilitate another pathogen entry
Example:
- HCV hepC antigen elicits type 1 cytokine, - Schistosoma mansoni stimulates Th2
- If co-infection then Th2 response to helminth reduces the ability to respond to HCV increasing viral persistence + accelerated liver fibrosis
Immune mediated competition: Immune response to one agent negatively impacts other agent
1) Priming of inate immune system
- Antigen binds to TLR of innate immune cells (e.g. macrophages and other lymphocytes) which release cytokines
- Antigen elicit adaptive immune response which also releases cytokines.
- Cytokine lead to Inflammatry response and production of antimicrobials.
Example: Eg. latent herpesvirus + bacterial co-infection
- mice latently infected w/ herpesvirus = resistant to infection by bacterial pathogens Yersinia pestis and Listeria monocytogenes
- IFNγ pre-made in herpes infected + causes macrophage activation + heightened basal innate immune reactivity
2) antibody cross reactivity
- Same antibodies work on antigens of closely related pathogen species
Example:
- Zika + dengue viruses share high sequence + structural protein homology
- nearly ½ dengue antibodies bind zika virus – some neutralise Zika
Example:
- IgEs from sera of children allergic to cow milk are capable of recognizing most parts of milk proteins from sheep, goat, and buffalo
- Mile allergans share part of their amino acid sequence
3) TCR cross reactivity
- single TCR recognises 2+ different peptide-MHC complexes – often peptide-MHCs of closely related pathogens
Example:
- BCG (M. bovis TB) vaccine induced T cells provide immunity to leprosy + poxviruses (too many pathogens to have a species T cell for each)
Interaction mechanisms: bottom up (Resource mediated)
Resource mediated competition:
Example: Rat infection by 2 different helminth parasites
- The distribution of the M.dubrius remains in the upper section and H.diminuta is displaced due to competition for space.
Example: competition for red blood cells (RBCs) between malaria and bloodsucking helminths
- reducing competition via deworming increased Plasmodium vivax densities 2.8-fold
Resource mediated faciliation:
Example: Colon produces mucus against the Trichuris muris promoting the growth of Mucispirillum
Case study: Helminths vs microparasites
Immune mediated facilitation:
- Microparasite requires Th1 response (macrophages)
- Macroparasite requires Th2 response (B cells)
- Helminths induce regulatory T cells (Treg) which suppress both Th1 and Th2 responses
- Helminths facilitate microparasite infection via Treg, Th1 (immune polarisation) supression, and IFNy repression
Resource mediated competition
- If microparasite is malaria and microparasite is hookworm, then both need red blood cells so competition and immune facilitation prevented
Effect is context dependent:
Resolving infection: Intensifies micro infection due to immune polarisation and supression
Example: p.chabaudi
Lethal infection (e.g. cerebral malaria): immuno supression regulates pathogens that lead to immuno pathology by down regulating immune response
Example: cerebral malaria (immuno supress inflam response in the brain)
Example: COVID-19 (immunosupress autoimmune response to cytokine release)
- helminth endemic countries showed fewer cases and deaths so far and helminth co-infection might reduce the severity of COVID-19
Effect of co-infection on between host dynamics
co-infection can effect tranmission by altering susceptibility, recovery and infection related mortality of either pathogen and therefore the R0
R0= lambda / sigma + mu + w
Complications of coinfection for disease management:
1) Treating one pathogen may worsen the impact of another
2) What’s optimal for indiv health may not be optimal for pop’n health
Example: TB and Helmonth -> Anthelmintic treatment (deworming)
- Deworming wild Buffalo increased immune response to TB reducing pathogen induced mortaility
- benefit individual as survive longer
- BUT increases transmission as host lives longer so disadvatages population
Example: HIV and malaria
- Co-infection increases transmission
- Without malaria, it would have taken an extra 2 years before ¼ of the population was HIV positive.
Disease management with co-infection
- Simple measures – avoid contact of indivs infected w/ parasites that interact to increase severity
- Control programme integration – deworm before vacination (e.g helminth co-infection reduces vaccine efficiency by reducing immune response -> production of memory cells)
- Control programme integration – Treat one infection to tackle another (e.g treat worms as part of TB control) -> Study found that vaccine campaigns in regions with neglected tropical diseases may be less likely to succeed than those in regions with fewer endemic parasites so first concentrate on endemic parasites
Or if first infection increases risk/ transmission etc of second considerably, vaccinate against first to protect against second.
- Vaccine design – different vaccine for co-infected indivs (cocktail of antigens)
- Targeted treatment or vaccination to co-infected – target more infectious indivs or those where vaccine will be most effective if resources limited (e.g. HIV infected indv have 37% higher chance of TB infection -> Treat HV infected individuals with TB vaccine (BCG) if limited)
- Holistic approach – clinical trials should monitor effects of co-infections not just single parasite
Evolution concequences of co-infection
a) New recombinant viruses
Example:
- reassortment of segmented RNA viruses upon co-infection from different swine flu strains from birds, pigs and humans lead to H1N1 swine flu
b) Evolution of protective symbioses
- Host may retain parasite that protects against a worse / more virulent one
- Mild pathogen that protects against co-infection pathogen may coevolve w/ host to protect host if it increases its own fitness
Example:
- faecalis (commonly found in gastro intestinal tract) protects against S. aureus in C. elegans
Overview
Interaction mechanimsms
Direct
- competition
- facilitation
Immune
- competition (cross reactivity, priming of adaptive and innate)
- facilitation (polarisation)
Case study: Helminths vs microparasites
- within host dynamics
- Between host dynamics
Evolutionary effect of co-infection
Disease management
