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Antigenic, genetic and biological
diversity amongst pathogens
associated with disease/ outbreak
DOI: 10.13140/RG.2.2.19800.26884
https://www.researchgate.net/publication/372656607_Antigenic_genetic_and_biological_d
iversity_amongst_pathogens_associated_with_disease_outbreak
Bhoj R Singh
Division of Epidemiology, ICAR-IVRI,
Izatnagar-243122, India
brs1762@gmail.com
It is about
Abstract: This presentation briefly describes the
Antigenic, genetic and biological diversity amongst
pathogens and their origin and emergence. It also
discusses their association with different forms
associated with disease/ outbreak. The presentation
also enlists diversity in strains causing some common
livestock diseases in India.
Key words: Strains, variants, clones, clades, lineages,
serotypes, serovars, phase-conversion, antigenic shift,
antigenic drift, epidemics, endemic, LSD, Pasteurellosis,
Brucellosis, FMD, PPR, MDR-TB, Spatiotemporal, Host
variability
Diversity/ Biodiversity
Diversity: The wide variety of something, or the condition of having or
being composed of differing elements, in terms of pathogens, the
wide variety of strains/ variants, and phenotypic or genotypic
elements, means their genetic variants reflected as phenotypical
variations like their virulence factors, antigenic composition,
physiological and biochemical characters, i.e., Biodiversity of the
pathogen, variation among living organisms from different places
and from the same place too. It includes genetic diversity, physical
variability, species and strain variability etc.
Genetic diversity: Genetic diversity is the variation in genes and
genotypes within a species. It plays an important role in the
survival of a species. Its creation is outcome of mutation, a natural
process. It enable the species to adapt to different niche. It is
responsible for individuality or clonality (the lack of genetic
diversity) of an individual and vanishes with the death of the
individual but enable species to survive with progenies.
• Antigenic variation or antigenic diversity, the mechanism through which
pathogens change their protein/ carbohydrate/ lipo-polysacharides expressed on
its surface either to avoid host immune response (achieving antigenic escape) or
to persist/ re-infect the host or to widen its host range. If a pathogen can create a
wide shift/ drift in its antigens (the molecules identified by the host immune
system) and can alter its dominant antigen, the pathogen can then evade the
host's acquired immunity.
• Antigenic variation can be by altering a variety or single dominant surface
molecules through genetic switch over that is site-specific DNA inversions (phase
variation), gene-conversion (either allelic, one allele, a homologous DNA with
variation, of the same gene replaces another allele, or ectopic (meaning that one
paralogous, or duplicated DNA sequence or the two copies of a genes alternate
another), or hyper-mutation or recombination of sequence cassettes. Gene
silencing phenomenon may lead to expression of a phenotypically heterogeneous
population in progeny of a clone, that is individuals of the same genotype. The
effective changes may lead to antigenic diversity and diversity in virulence.
• Antigenic variation may be outcome of genetic variation or no genetic variation
(variation in expression) i.e., just phenotypic variation.
• Antigenic drift is the gradual change in the genetic makeup of a virus/ pathogen,
and over a long period of time result in antigenically different strains while
antigenic shift is the sudden onset of a new virus through abrupt changes
(through cross breeding or acquisition of new charcters) and creating
antigenically different strain over a short period of time or suddenly. Often,
antigenic drift is responsible for endemicity of disease and antigenic shift for
epidemics/ pandemics.
Strains and Variants
• All strains are variants, but all variants are not new
strains.
• A variant is one when a pathogen changes (mutates)
from the original version—for example, an error in the
genetic code happens when the pathogen is
replicating.
• A variant is like a new “take” on the original pathogen
usually a small step for evolution.
• A strain is when a pathogen has so many variations
after generation of many variants (drift) or suddenly
due to some major antigenic/ virulence change (shift)
that one of the variants starts acting differently—for
example, it’s much more transmissible than the
previous version, much more pathogenic or non-
pathogenic or avirulent.
Pathogens and variations
• Many diseases= many pathogens
• Same disease = same pathogen (Tuberculosis)
• One disease = one pathogen (Typhoid)
• One disease = Many pathogens (multiple aetiology) (Brucellosis, Diarrhea,
dysentery, vomiting)
• Many diseases = Single pathogen (E. coli infections, role of variants or diversity
among E. coli strains).
• No disease = But pathogen
• Disease = No-identifiable pathogen
• One outbreak (one epidemic) = one strain (single peak!)
• One outbreak (one epidemic) = many strains (many peaks! Single or multiple host
populations)
• Many outbreaks (epidemics) = single strain (different populations/ same
population)
• Many outbreaks = many strains (Single peak, multiple peaks!)
• Different outbreaks (of different diseases/ in different species of hosts) = One
strain
• Dimension of an epidemic = Spatiotemporality, Host variability (definitive/
mechanical/ intermediate/ fomites/ environment)
Variants of pathogens
WHO label PANGO lineage First outbreak Earliest sample
Delta B.1.617.2 India Oct 2020
Omicron B.1.1.529 South Africa 9 Nov 2021
Alpha B.1.1.7 United Kingdom 20 Sep 2020
Gamma P.1 (B.1.1.28.1) Brazil Nov 2020
Beta B.1.351 South Africa May 2020
Covid-19 Pandemic and strains of SARS CoV-2
There are thousands of variants of SARS-CoV-2, and subtypes of the virus can
be put into larger groupings such as lineages or Clades, monophyletic groups of
strains originating from the same ancestor .
By the end of 2020, the original L strain of the COVID virus had gone through
multiple mutations, including the S, V, and G strains. Then emerged many more
variants and designated as strains due to their dominance.
Variants of Rabies virus
• The genus Lyssavirus includes rabies virus, Lagos bat,
Mokola virus, Duvenhage virus, European bat virus 1 &
2, and Australian bat virus.
• In the USA: racoon variant, bat variant, fox variant, and
skunk variant
• In India: Rabies virus isolates from India are grouped
into two distinctly separate lineages with majority of
the Indian isolates in the Arctic like 1 lineage and the
remaining isolates in the sub-continental lineage. They
belong to five genetic clusters: GC1 to GC5.
• Vaccine strains: Common attenuated vaccine strains of
rabies virus are SAG2 and SAD B19.
Pasteurella multocida
• Pasteurella multocida have been classified into five serotypes (A, B, D, E, and F)
according to the specificity of capsular antigens, and 16 Heddleston serotypes
based on the lipopolysaccharide (LPS) antigens. A and D were determined by the
hyaluronidase sensitivity and acriflavin agglutination tests, respectively.
• The capsular type A P. multocida mainly causes pneumonia and serious bovine
respiratory diseases.
• P. multocida B:2 causes bovine haemorrhagic septicaemia (HS) in India and E:2 in
Africa, leading to rapid fatalities in cattle and buffaloes.
• Pasteurella serotypes in India: Serotypes A:1, A:3, A:1,3, A:4, B:2, D:1, and -:1 are
common among the livestock population.
Pasteurellosis in Chicken/ fowl Capsular serotype F:3
Fowl cholera Capsular serotype A:1
Pasteurellosis in Turkey birds Capsular serotype A:3
Bovine respiratory infection Capsular serotype A
Haemorhagic septicemia in bovids B:2 and E:2
Pig pneumonia Capsular serotype A
Atrophic rhinitis disease in
Swine
Capsular serotype D producing dermonecrotoxin
PMT
Disease in Dogs and cats Capsular serotype A, rare D and E,F 4
FMDV serotypes/ strains and variants in India
• Four FMDV serotypes (O, A, C, and Asia1) have so far been detected in India. Serotype C
has not been reported in the country since 1995. Historically, serotype O has been the
most common and dominant type in India, followed by serotypes Asia1 and A.
• The virus strains circulating in India were placed within pool 2, one of seven major virus
pools identified based on their geographic distribution pattern.
• The PanAsia lineage was found in India as early as 1982, and was responsible for the
majority of the outbreaks in the country between 1996 and 2003, later, PanAsia-2
became the predominant strain and replaced the parent PanAsia strain in 2004, and
dominated till 2007.
• The O/ME-SA/Ind2001 lineage appeared in the year 2001, and emerged as dominant
lineage in 2008 overcoming the PanAsia lineage in 2009. The emergence of variants led
to the origin of at least five sub-lineages. The sub-lineages O/ME-SA/Ind2001d (emerged
in 2008), and O/ME-SA/Ind2001e (appeared in 2015) are the main strains involved in
serotype O outbreaks nowadays. Both the circulating sub-lineages have a close
antigenic relationship with the vaccine strain INDR2/1975.
• Of the genotypes of FMDV type A in India, four genotypes (2, 10, 16, and 18) have been
detected. Since 2001, genotype 18 has been exclusively prevailing in the field. However,
since 2019, a novel genetic branch designated as ‘G-18/non-deletion/2019’ lineage is the
most prominent one.
• Asia-1, three lineages (B, C, and D) are in India, lineage B dominated from 1964 to 2000,
and lineage C (sub-lineage CI) since 1979. Lineage D, identified in 2001, circulated
exclusively between 2002 and 2004. Now, serotype Asia1 isolates collected in 2020
clustered within G-IX (BD-18), a new genetic group that emerged in Bangladesh in
January 2018 and replaced lineage G-VIII
PPR strains and lineages in India
Based on the F and N gene of the different PPRV
isolates/strains from different parts of the
world, the presence of four different lineages
(I, II, III & IV) of the virus has been established.
The lineage IV (Asian lineage) is represented
by isolates from the Arabian Peninsula, the
Middle East, and Asia, including India. Till now,
there was no report of circulation of other
lineages of PPRV except Asian lineage IV in
India.
LSDV strains in India
•In contrast to the vaccine-like LSDV strains circulating in
China and Russia, the LSDV strains circulating in the Indian
subcontinent since 2019 are similar to Kenyan-type LSDV
strains.
LSDV/2022 strain currently circulating in India and other South
Asian countries causes higher mortality than the parent
strain. The high mortality may be due to the capacity of the
virus (LSDV/2022) to cause severe haemorrhages and
extensive nodule formation in the visceral organs,
especially the lungs.
Gujarat Biotechnology Research Centre (GBRC) researchers
revealed that the strain circulating in Gujarat and Rajasthan
has higher infectivity and mortality than its predecessor
LSDV/2022 and maybe a different strain.
Variants of Mycobacterium tuberculosis
• Mycobacteria associated with TB and included in MTB
complex: Mycobacterium tuberculosis, M. bovis, M. microti, M.
africanum, M. pinnipedii, M. caprae, M. canettii and M. orygis.
• TB is caused by a wide diversity of spoligotypes with predominance
of four genotype lineages: Beijing, CAS, EAI and T. The Beijing
genotype was the most frequent single spoligotype and was
strongly associated with multi-drug resistant (MDR)-TB isolates.
• Beijing and F15/LAM4/KZN strains have been most prevalent in XDR
and MDR outbreaks.
• The mass of ongoing transmission with MDR-TB isolates in northern
India is linked to the Beijing genotype followed by the CAS1_Delhi
lineage. HIV-seropositive patients had a significantly higher
proportion of clustered isolates than HIV-seronegative patients, and
compared with the wild-type (wt) isolates, the isolates
with katG315Thr mutation are considerably more likely to be
clustered in HIV patients.
• MTB H37Rv strain is often used for laboratory studies on TB
because F15/LAM4/KZN and Beijing strains are slow growers in the
7H9 medium.
Quiz
• Why do variant pathogens emerge?
• How does biological diversity play a role in
becoming a disease endemic?
• What is the role of antigenic diversity in the
emergence of epidemics or pandemics?
• Give the list of antigenic variants of the
Influenza virus those lead to pandemics.
• What are antigenic shift and antigenic drift,
and which is associated with the pandemic?

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Epidemiology of antigenic, genetic and biological diversity amongst pathogens associated with disease outbreaks.pptx

  • 1. Antigenic, genetic and biological diversity amongst pathogens associated with disease/ outbreak DOI: 10.13140/RG.2.2.19800.26884 https://www.researchgate.net/publication/372656607_Antigenic_genetic_and_biological_d iversity_amongst_pathogens_associated_with_disease_outbreak Bhoj R Singh Division of Epidemiology, ICAR-IVRI, Izatnagar-243122, India brs1762@gmail.com
  • 2. It is about Abstract: This presentation briefly describes the Antigenic, genetic and biological diversity amongst pathogens and their origin and emergence. It also discusses their association with different forms associated with disease/ outbreak. The presentation also enlists diversity in strains causing some common livestock diseases in India. Key words: Strains, variants, clones, clades, lineages, serotypes, serovars, phase-conversion, antigenic shift, antigenic drift, epidemics, endemic, LSD, Pasteurellosis, Brucellosis, FMD, PPR, MDR-TB, Spatiotemporal, Host variability
  • 3. Diversity/ Biodiversity Diversity: The wide variety of something, or the condition of having or being composed of differing elements, in terms of pathogens, the wide variety of strains/ variants, and phenotypic or genotypic elements, means their genetic variants reflected as phenotypical variations like their virulence factors, antigenic composition, physiological and biochemical characters, i.e., Biodiversity of the pathogen, variation among living organisms from different places and from the same place too. It includes genetic diversity, physical variability, species and strain variability etc. Genetic diversity: Genetic diversity is the variation in genes and genotypes within a species. It plays an important role in the survival of a species. Its creation is outcome of mutation, a natural process. It enable the species to adapt to different niche. It is responsible for individuality or clonality (the lack of genetic diversity) of an individual and vanishes with the death of the individual but enable species to survive with progenies.
  • 4. • Antigenic variation or antigenic diversity, the mechanism through which pathogens change their protein/ carbohydrate/ lipo-polysacharides expressed on its surface either to avoid host immune response (achieving antigenic escape) or to persist/ re-infect the host or to widen its host range. If a pathogen can create a wide shift/ drift in its antigens (the molecules identified by the host immune system) and can alter its dominant antigen, the pathogen can then evade the host's acquired immunity. • Antigenic variation can be by altering a variety or single dominant surface molecules through genetic switch over that is site-specific DNA inversions (phase variation), gene-conversion (either allelic, one allele, a homologous DNA with variation, of the same gene replaces another allele, or ectopic (meaning that one paralogous, or duplicated DNA sequence or the two copies of a genes alternate another), or hyper-mutation or recombination of sequence cassettes. Gene silencing phenomenon may lead to expression of a phenotypically heterogeneous population in progeny of a clone, that is individuals of the same genotype. The effective changes may lead to antigenic diversity and diversity in virulence. • Antigenic variation may be outcome of genetic variation or no genetic variation (variation in expression) i.e., just phenotypic variation. • Antigenic drift is the gradual change in the genetic makeup of a virus/ pathogen, and over a long period of time result in antigenically different strains while antigenic shift is the sudden onset of a new virus through abrupt changes (through cross breeding or acquisition of new charcters) and creating antigenically different strain over a short period of time or suddenly. Often, antigenic drift is responsible for endemicity of disease and antigenic shift for epidemics/ pandemics.
  • 5. Strains and Variants • All strains are variants, but all variants are not new strains. • A variant is one when a pathogen changes (mutates) from the original version—for example, an error in the genetic code happens when the pathogen is replicating. • A variant is like a new “take” on the original pathogen usually a small step for evolution. • A strain is when a pathogen has so many variations after generation of many variants (drift) or suddenly due to some major antigenic/ virulence change (shift) that one of the variants starts acting differently—for example, it’s much more transmissible than the previous version, much more pathogenic or non- pathogenic or avirulent.
  • 6. Pathogens and variations • Many diseases= many pathogens • Same disease = same pathogen (Tuberculosis) • One disease = one pathogen (Typhoid) • One disease = Many pathogens (multiple aetiology) (Brucellosis, Diarrhea, dysentery, vomiting) • Many diseases = Single pathogen (E. coli infections, role of variants or diversity among E. coli strains). • No disease = But pathogen • Disease = No-identifiable pathogen • One outbreak (one epidemic) = one strain (single peak!) • One outbreak (one epidemic) = many strains (many peaks! Single or multiple host populations) • Many outbreaks (epidemics) = single strain (different populations/ same population) • Many outbreaks = many strains (Single peak, multiple peaks!) • Different outbreaks (of different diseases/ in different species of hosts) = One strain • Dimension of an epidemic = Spatiotemporality, Host variability (definitive/ mechanical/ intermediate/ fomites/ environment)
  • 7. Variants of pathogens WHO label PANGO lineage First outbreak Earliest sample Delta B.1.617.2 India Oct 2020 Omicron B.1.1.529 South Africa 9 Nov 2021 Alpha B.1.1.7 United Kingdom 20 Sep 2020 Gamma P.1 (B.1.1.28.1) Brazil Nov 2020 Beta B.1.351 South Africa May 2020 Covid-19 Pandemic and strains of SARS CoV-2 There are thousands of variants of SARS-CoV-2, and subtypes of the virus can be put into larger groupings such as lineages or Clades, monophyletic groups of strains originating from the same ancestor . By the end of 2020, the original L strain of the COVID virus had gone through multiple mutations, including the S, V, and G strains. Then emerged many more variants and designated as strains due to their dominance.
  • 8. Variants of Rabies virus • The genus Lyssavirus includes rabies virus, Lagos bat, Mokola virus, Duvenhage virus, European bat virus 1 & 2, and Australian bat virus. • In the USA: racoon variant, bat variant, fox variant, and skunk variant • In India: Rabies virus isolates from India are grouped into two distinctly separate lineages with majority of the Indian isolates in the Arctic like 1 lineage and the remaining isolates in the sub-continental lineage. They belong to five genetic clusters: GC1 to GC5. • Vaccine strains: Common attenuated vaccine strains of rabies virus are SAG2 and SAD B19.
  • 9. Pasteurella multocida • Pasteurella multocida have been classified into five serotypes (A, B, D, E, and F) according to the specificity of capsular antigens, and 16 Heddleston serotypes based on the lipopolysaccharide (LPS) antigens. A and D were determined by the hyaluronidase sensitivity and acriflavin agglutination tests, respectively. • The capsular type A P. multocida mainly causes pneumonia and serious bovine respiratory diseases. • P. multocida B:2 causes bovine haemorrhagic septicaemia (HS) in India and E:2 in Africa, leading to rapid fatalities in cattle and buffaloes. • Pasteurella serotypes in India: Serotypes A:1, A:3, A:1,3, A:4, B:2, D:1, and -:1 are common among the livestock population. Pasteurellosis in Chicken/ fowl Capsular serotype F:3 Fowl cholera Capsular serotype A:1 Pasteurellosis in Turkey birds Capsular serotype A:3 Bovine respiratory infection Capsular serotype A Haemorhagic septicemia in bovids B:2 and E:2 Pig pneumonia Capsular serotype A Atrophic rhinitis disease in Swine Capsular serotype D producing dermonecrotoxin PMT Disease in Dogs and cats Capsular serotype A, rare D and E,F 4
  • 10. FMDV serotypes/ strains and variants in India • Four FMDV serotypes (O, A, C, and Asia1) have so far been detected in India. Serotype C has not been reported in the country since 1995. Historically, serotype O has been the most common and dominant type in India, followed by serotypes Asia1 and A. • The virus strains circulating in India were placed within pool 2, one of seven major virus pools identified based on their geographic distribution pattern. • The PanAsia lineage was found in India as early as 1982, and was responsible for the majority of the outbreaks in the country between 1996 and 2003, later, PanAsia-2 became the predominant strain and replaced the parent PanAsia strain in 2004, and dominated till 2007. • The O/ME-SA/Ind2001 lineage appeared in the year 2001, and emerged as dominant lineage in 2008 overcoming the PanAsia lineage in 2009. The emergence of variants led to the origin of at least five sub-lineages. The sub-lineages O/ME-SA/Ind2001d (emerged in 2008), and O/ME-SA/Ind2001e (appeared in 2015) are the main strains involved in serotype O outbreaks nowadays. Both the circulating sub-lineages have a close antigenic relationship with the vaccine strain INDR2/1975. • Of the genotypes of FMDV type A in India, four genotypes (2, 10, 16, and 18) have been detected. Since 2001, genotype 18 has been exclusively prevailing in the field. However, since 2019, a novel genetic branch designated as ‘G-18/non-deletion/2019’ lineage is the most prominent one. • Asia-1, three lineages (B, C, and D) are in India, lineage B dominated from 1964 to 2000, and lineage C (sub-lineage CI) since 1979. Lineage D, identified in 2001, circulated exclusively between 2002 and 2004. Now, serotype Asia1 isolates collected in 2020 clustered within G-IX (BD-18), a new genetic group that emerged in Bangladesh in January 2018 and replaced lineage G-VIII
  • 11. PPR strains and lineages in India Based on the F and N gene of the different PPRV isolates/strains from different parts of the world, the presence of four different lineages (I, II, III & IV) of the virus has been established. The lineage IV (Asian lineage) is represented by isolates from the Arabian Peninsula, the Middle East, and Asia, including India. Till now, there was no report of circulation of other lineages of PPRV except Asian lineage IV in India.
  • 12. LSDV strains in India •In contrast to the vaccine-like LSDV strains circulating in China and Russia, the LSDV strains circulating in the Indian subcontinent since 2019 are similar to Kenyan-type LSDV strains. LSDV/2022 strain currently circulating in India and other South Asian countries causes higher mortality than the parent strain. The high mortality may be due to the capacity of the virus (LSDV/2022) to cause severe haemorrhages and extensive nodule formation in the visceral organs, especially the lungs. Gujarat Biotechnology Research Centre (GBRC) researchers revealed that the strain circulating in Gujarat and Rajasthan has higher infectivity and mortality than its predecessor LSDV/2022 and maybe a different strain.
  • 13. Variants of Mycobacterium tuberculosis • Mycobacteria associated with TB and included in MTB complex: Mycobacterium tuberculosis, M. bovis, M. microti, M. africanum, M. pinnipedii, M. caprae, M. canettii and M. orygis. • TB is caused by a wide diversity of spoligotypes with predominance of four genotype lineages: Beijing, CAS, EAI and T. The Beijing genotype was the most frequent single spoligotype and was strongly associated with multi-drug resistant (MDR)-TB isolates. • Beijing and F15/LAM4/KZN strains have been most prevalent in XDR and MDR outbreaks. • The mass of ongoing transmission with MDR-TB isolates in northern India is linked to the Beijing genotype followed by the CAS1_Delhi lineage. HIV-seropositive patients had a significantly higher proportion of clustered isolates than HIV-seronegative patients, and compared with the wild-type (wt) isolates, the isolates with katG315Thr mutation are considerably more likely to be clustered in HIV patients. • MTB H37Rv strain is often used for laboratory studies on TB because F15/LAM4/KZN and Beijing strains are slow growers in the 7H9 medium.
  • 14. Quiz • Why do variant pathogens emerge? • How does biological diversity play a role in becoming a disease endemic? • What is the role of antigenic diversity in the emergence of epidemics or pandemics? • Give the list of antigenic variants of the Influenza virus those lead to pandemics. • What are antigenic shift and antigenic drift, and which is associated with the pandemic?