BASIC FACTS ABOUT MALARIA

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BASIC FACTS ABOUT MALARIA

• Four Plasmodium species cause human malaria P.
  falciparum (the most virulent), P. vivax, P.
  malariae, and P. ovale. Human malaria is
  transmitted by anopheline mosquitoes.
• Malaria transmission occurs in more than 90
  countries across the world. About 40 of the
  worlds population is at risk.

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PREVALENCE

• The worldwide prevalence of malaria ranges
  between 300-500 million clinical cases each year.
  More than 90 of them are in sub-Saharan Africa,
  where over 1 million deaths due to malaria occur
  each year.
• In the Americas, malaria transmission is mostly
  linked to activities such as road building,
  mining, and agricultural projects. One third of
  the population is at some risk of infection.

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BIOLOGICAL ASPECTS

• Malaria parasites undergo both sexual and asexual
  reproduction during their complex life cycle.
  There are two hosts a vertebrate and a mosquito
  vector.
• Malaria parasites are haploid during their
  development in vertebrate hosts, including
  humans. Sexual reproduction and meiosis take
  place in the vector.

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CLINICAL ASPECTS

• Severe complications of malaria in humans are
  virtually restricted to P. falciparum infections.
  In highly endemic areas, most infected people are
  symptom-less.
• Clinical symptoms of malaria include fever and
  chills, headache, repeated vomiting, generalized
  convulsions, and coma. Most patients are anemic.
  High- risk groups include pregnant women,
  under-five children, and non-immune travelers.

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POPULATION GENETICS

• Population genetics studies the inheritance of
  genetic traits in natural populations.
• Population genetics provides insights into the
  spread of new alleles that make malaria parasites
  resistant to drugs, vaccines etc.

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ORIGIN OF NEW ALLELES

• Alleles are alternative forms that exist, within
  a population, at a given locus.
• New alleles are mostly created by mutations,
  i.e., changes in nucleotide sequences, that are
  either synonymous or non-synonymous.

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ORIGIN OF NEW ALLELES

• Short repeat sequences commonly found in malarial
  antigens are particularly prone to mutations and
  mitotic recombination.
• Sexual recombination during meiosis also
  generates new alleles by exchanging blocks of
  sequences between homologous chromosomes.

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POPULATION STRUCTURE

• In clonal populations, separate genetic lineages,
  with little recombination between them, are
  maintained over generations.
• In panmictic populations, recombination breaks
  down discrete genetic lineages by creating new
  combinations of alleles.
• An epidemic structure originates when a highly
  successful individual propagates rapidly in a
  population over a few generations.

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EXAMPLES OF POPULATION STRUCTURE
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LINKAGE DISEQUILIBRIUM

• Recombination disrupts the physical association
  between alleles at different loci.
• If recombination rates are low, non-random
  associations between alleles at different loci
  are maintained, creating linkage disequilibrium.
• Linkage disequilibrium co-exists with high
  recombination rates when some particular
  associations between alleles are favored by
  selection.

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PROBING THE POPULATION STRUCTURE OF Plasmodium
falciparum

• Worldwide P. falciparum populations differ in
  their recombination rates and population
  structure.
• African populations are usually panmictic, with
  no apparent linkage disequilibrium.
• Outside Africa, populations often are at linkage
  disequilibrium, due to either clonal reproduction
  or epidemic propagation of some lineages.

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SELECTION OF NEW ALLELES

• Mutant alleles may be selectively neutral, if
  mutation confers the same fitness to the parasite
  as the original allele, deleterious or
  advantageous.
• Highly advantageous alleles (for instance,
  drug-resistance alleles) are positively selected
  and rapidly spread in the population.

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VARIATION IN ANTIGENIC ALLELES

• Despite the recent origin of P. falciparum, most
  antigens are highly polymorphic.
• New antigenic alleles are created by both
  non-sexual (mitotic) and sexual (meiotic)
  mechanisms.
• New alleles are positively selected if they
  facilitate immune evasion. The immune system acts
  as a diversifying force.

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SOME TOPICS IN POPULATION GENETICS OF MALARIA
PARASITES

• How often new alleles encoding phenotypes such as
  increased virulence, drug resistance or immune
  evasion arise and spread in natural parasite
  populations?
• How frequently sexual and non-sexual mechanisms
  create new alleles?
• How mutation, recombination and selection
  determine the evolution of P. falciparum genome?