BASIC FACTS ABOUT MALARIA n Four Plasmodium species cause human malaria: P. falciparum (the most virulent), P. vivax, P. malariae, and P. ovale. Human.

BASIC FACTS ABOUT BASIC FACTS ABOUT MALARIAMALARIA

Four Four PlasmodiumPlasmodium species cause human species cause human malaria: malaria: P. falciparumP. falciparum (the most (the most virulent), virulent), P. vivaxP. vivax, , P. malariae,P. malariae, and and P. ovaleP. ovale. Human malaria is transmitted . Human malaria is transmitted by anopheline mosquitoes.by anopheline mosquitoes.

Malaria transmission occurs in more Malaria transmission occurs in more than 90 countries across the world. than 90 countries across the world. About 40% of the world´s population is About 40% of the world´s population is at risk.at risk.

PREVALENCEPREVALENCE The worldwide prevalence of malaria ranges between The worldwide prevalence of malaria ranges between 300-500 million clinical cases each year. More than 300-500 million clinical cases each year. More than 90% of them are in sub-Saharan Africa, where over 1 90% of them are in sub-Saharan Africa, where over 1 million deaths due to malaria occur each year.million deaths due to malaria occur each year.

In the Americas, malaria transmission is mostly In the Americas, malaria transmission is mostly linked to activities such as road building, mining, linked to activities such as road building, mining, and agricultural projects. One third of the and agricultural projects. One third of the population is at some risk of infection.population is at some risk of infection.

BIOLOGICAL ASPECTSBIOLOGICAL ASPECTS

Malaria parasites undergo both sexual Malaria parasites undergo both sexual and asexual reproduction during their and asexual reproduction during their complex life cycle. There are two complex life cycle. There are two hosts: a vertebrate and a mosquito hosts: a vertebrate and a mosquito vector. vector.

Malaria parasites are haploid during Malaria parasites are haploid during their development in vertebrate hosts, their development in vertebrate hosts, including humans. Sexual reproduction including humans. Sexual reproduction and meiosis take place in the vector.and meiosis take place in the vector.

CLINICAL ASPECTSCLINICAL ASPECTS

Severe complications of malaria in humans Severe complications of malaria in humans are virtually restricted to are virtually restricted to P. falciparumP. falciparum infections. In highly endemic areas, most infections. In highly endemic areas, most infected people are symptom-less. infected people are symptom-less.

Clinical symptoms of malaria include Clinical symptoms of malaria include fever and chills, headache, repeated fever and chills, headache, repeated vomiting, generalized convulsions, and vomiting, generalized convulsions, and coma. Most patients are anemic. High- coma. Most patients are anemic. High- risk groups include pregnant women, risk groups include pregnant women, under-five children, and non-immune under-five children, and non-immune travelers.travelers.

POPULATION GENETICSPOPULATION GENETICS

Population genetics studies the Population genetics studies the inheritance of genetic traits in inheritance of genetic traits in natural populations.natural populations.

Population genetics provides Population genetics provides insights into the spread of new insights into the spread of new alleles that make malaria alleles that make malaria parasites resistant to drugs, parasites resistant to drugs, vaccines etc.vaccines etc.

ORIGIN OF NEW ALLELESORIGIN OF NEW ALLELES

AllelesAlleles are alternative forms are alternative forms that exist, within a population, that exist, within a population, at a given locus.at a given locus.

New alleles are mostly created by New alleles are mostly created by mutations, i.e., changes in mutations, i.e., changes in nucleotide sequences, that are nucleotide sequences, that are either synonymous or non-either synonymous or non-synonymous.synonymous.

ORIGIN OF NEW ALLELESORIGIN 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.

POPULATION STRUCTUREPOPULATION STRUCTURE

In In clonalclonal populations, separate genetic populations, separate genetic lineages, with little recombination lineages, with little recombination between them, are maintained over between them, are maintained over generations.generations.

In In panmicticpanmictic populations, recombination populations, recombination breaks down discrete genetic lineages breaks down discrete genetic lineages by creating new combinations of by creating new combinations of alleles. alleles.

An An epidemicepidemic structure originates when a structure originates when a highly successful individual propagates highly successful individual propagates rapidly in a population over a few rapidly in a population over a few generations.generations.

EXAMPLES OF EXAMPLES OF POPULATION POPULATION STRUCTURE STRUCTURE

LINKAGE DISEQUILIBRIUMLINKAGE DISEQUILIBRIUM Recombination disrupts the physical Recombination disrupts the physical association between alleles at association between alleles at different loci. different loci.

If recombination rates are low, non-If recombination rates are low, non-random associations between alleles at random associations between alleles at different loci are maintained, creating different loci are maintained, creating linkage disequilibriumlinkage disequilibrium..

Linkage disequilibrium co-exists with Linkage disequilibrium co-exists with high recombination rates when some high recombination rates when some particular associations between alleles particular associations between alleles are favored by are favored by selectionselection..

PROBING THE POPULATION PROBING THE POPULATION STRUCTURE OF STRUCTURE OF Plasmodium Plasmodium

falciparumfalciparum Worldwide Worldwide P. falciparum P. falciparum populations populations differ in their recombination rates and differ in their recombination rates and population structure. population structure.

African populations are usually African populations are usually panmicticpanmictic, with no apparent linkage , with no apparent linkage disequilibrium.disequilibrium.

Outside Africa, populations often are at Outside Africa, populations often are at linkage disequilibrium, due to either linkage disequilibrium, due to either clonal reproductionclonal reproduction or or epidemic epidemic propagationpropagation of some lineages. of some lineages.

SELECTION OF NEW SELECTION OF NEW ALLELESALLELES

Mutant alleles may be selectively Mutant alleles may be selectively neutralneutral, if mutation confers the , if mutation confers the same same fitnessfitness to the parasite as to the parasite as the original allele, the original allele, deleteriousdeleterious or or advantageousadvantageous. .

Highly advantageous alleles (for Highly advantageous alleles (for instance, drug-resistance alleles) instance, drug-resistance alleles) are positively selected and are positively selected and rapidly spread in the population.rapidly spread in the population.

VARIATION IN ANTIGENIC VARIATION IN ANTIGENIC ALLELESALLELES

Despite the recent origin of Despite the recent origin of P. P. falciparumfalciparum, most antigens are highly , most antigens are highly polymorphic.polymorphic.

New antigenic alleles are created by New antigenic alleles are created by both non-sexual (mitotic) and sexual both non-sexual (mitotic) and sexual (meiotic) mechanisms.(meiotic) mechanisms.

New alleles are positively selected if New alleles are positively selected if they facilitate immune evasion. The they facilitate immune evasion. The immune system acts as a diversifying immune system acts as a diversifying force.force.

SOME TOPICS IN POPULATION SOME TOPICS IN POPULATION GENETICS OF MALARIA GENETICS OF MALARIA

PARASITESPARASITES

How often new alleles encoding phenotypes How often new alleles encoding phenotypes such as increased virulence, drug such as increased virulence, drug resistance or immune evasion arise and resistance or immune evasion arise and spread in natural parasite populations?spread in natural parasite populations?

How frequently sexual and non-sexual How frequently sexual and non-sexual mechanisms create new alleles?mechanisms create new alleles?

How mutation, recombination and selection How mutation, recombination and selection determine the evolution of determine the evolution of P. falciparumP. falciparum genome?genome?