Malaria is still one of the most important infectious diseases, endemic in the tropical and sub-tropical parts of about 102 countries, especially in the African continent. In Thailand, although the total number of malaria cases has been decreasing annually , malaria remains most prevalent along the Thai borders with Myanmar, Cambodia and Malaysia, including for Plasmodium falciparum, the agent of the most malignant form of malaria that accounts globally for some 300–600 million cases of clinical malaria and 1.5 – 2.7 million deaths each year. Although P. falciparum can cause the most severe of the four human forms of malaria , the clinical manifestations are not always severe, but are somewhat pleomorphic ranging from asymptomatic parasitaemia (carriers) to potentially fatal cerebral infection and multiple organ failure, making the epidemiology more complicated. Moreover, Thailand is a known epicenter of P. falciparum drug resistance . At present, P. falciparum strains have become more resistant, in terms of both resistance level and frequency in the population, to mefloquine, in addition to the widespread resistance to chloroquine, and sulphadoxine/pyrimethamine observed in many endemic areas, especially within those provinces located along the Thai-Myanmar border (i.e. Tak, Ranong and Kanchanaburi), or the Thai-Cambodian border (i.e. Trat, Chantaburi and Sa Kaeo). As a result of declining mefloquine efficacy, a combination of mefloquine and artesunate is now administered in those areas . The Plasmodium falciparum gene flow between transmission areas and the existent level of P. falciparum population genetic diversity are directly implicated in the spread of drug resistance. Understanding the genetic complexity and organization (structure) of P. falciparum populations is a crucial aspect for the control of this disease, since the genetic diversity and population structure of P. falciparum in each location will have profound impacts on clonal diversity , competitive or synergistic interactions amongst clones [6–8], dynamics of drug resistance , persistence of the asexual infection and gametocyte production , infectivity in each relevant mosquito vectors  and malaria vaccine development .
Globally, P. falciparum is known to exhibit a diverse and patchy array of population genetic characteristics, which are apparently correlated with local levels of endemicity and transmission intensity . However, the rapidly declining endemicity may lead to a more fragmented population structure with greater genetic isolation between endemic foci, whilst the decreased levels of gene flow may slow gene flow between populations and limit the spread of resistance between populations, but also enhance the rate of evolution of multiple resistance phenotypes . It thus may become increasingly important to understand the fragmented nature genetic structure of residual parasite populations.
The P. falciparum transmission rate [14, 15], and the migration of infected (carrier) human inhabitants , which differ in each endemic area, affect the genetic variation and population genetic structure of this parasite. For example, it is unclear whether parasites are commonly spread from one area to another by migrants or whether they emerge from local endemic populations. They will also be subjected to local host immunity, both in mosquitoes (species and local populations) and in their humans as hosts. Several studies have documented this relationship [16–18]. At a global scale, significant differences in the population structure of P. falciparum in different locations have been reported . A strong linkage disequilibrium, low genetic diversity and high levels of geographic genetic differentiation were observed in countries with a low transmission intensity (i.e. South America and Southeast Asia) [5, 19, 20], whilst random gene recombination amongst loci, a high genetic diversity and low levels of geographical differentiation were observed in regions of Africa where transmission is high . In contrast, a significant linkage disequilibrium with high genetic diversity was observed in the Republic of the Congo, an African region of high parasite transmission . Moreover, high linkage disequilibrium of P. falciparum populations in Kenya was also observed where this form of malaria is also transmitted at a relatively high frequency . Geographical variation in the extent of parasite inbreeding may have consequences for the success of potential malaria-control strategies. The degree of inbreeding modifies the effective recombination rate and so may affect the rate of increased drug resistance when more than one locus is involved. Higher inbreeding levels may allow a more rapid increase of multilocus drug resistant phenotypes [13, 23]. However, recombination between genetically different clones has a potential to generate parasites exhibit a range of responses to different drugs [14, 24].
Understanding of the genetic structure of P. falciparum, as well as other malaria parasites such as Plasmodium vivax, is essential for predicting how fast given phenotypes, such as drug or host resistance or novel antigenic variants, will originate and spread within and between populations . Studies of the population structure at a local scale are more likely to be informative rather than misleading, and are clearly needed to understand the dynamics of P. falciparum populations, and to lead to an efficient management of this disease agent in particular areas. Indeed, the genetic composition and evolutionary change of each P. falciparum population is of great importance to ascertain the ecophysiology of the parasite and host-parasite interactions, as well as the evolution of resistance in the pathogen. Studies using the extensive polymorphism in antigen coding loci provide little valid information on the population structure of P. falciparum since, being under strong but varying selection, they reflect the combined effects of population history and natural selection .
In Thailand, most P. falciparum population genetic studies have focused on the boundary with Myanmar in the western part using different genetic markers [5, 27, 28], but the P. falciparum genetic structure relies on the epidemiological and demographical situations encountered in different areas and may change within a relatively short period of time. In this report, the population genetic structure of P. falciparum, is evaluated in seven provinces of Thailand, using 12 polymorphic and apparently neutral nuclear microsatellite loci as genetic markers. These were also compared with samples from other endemic countries, while using the same loci described published literature for other populations. Such studies could later be extended to other endemic areas displaying different treatment policies and different uses of prophylactic anti-malarial drugs.