Local population structure of Plasmodium: impact on malaria control and elimination

Abstract

BackgroundRegardless of the growing interest in detecting population structures in malarial parasites, there have been limited discussions on how to use this concept in control programmes. In such context, the effects of the parasite population structures will depend on interventions’ spatial or temporal scales. This investigation explores the problem of identifying genetic markers, in this case microsatellites, to unveil Plasmodium genetic structures that could affect decisions in the context of elimination. The study was performed in a low-transmission area, which offers a good proxy to better understand problems associated with surveillance at the final stages of malaria elimination.MethodsPlasmodium vivax samples collected in Tumeremo, Venezuela, between March 2003 and November 2004 were analysed. Since Plasmodium falciparum also circulates in many low endemic areas, P. falciparum samples from the same locality and time period were included for comparison. Plasmodium vivax samples were assayed for an original set of 25 microsatellites and P. falciparum samples were assayed for 12 microsatellites.ResultsNot all microsatellite loci assayed offered reliable local data. A complex temporal-cluster dynamics is found in both P. vivax and P. falciparum. Such dynamics affect the numbers and the type of microsatellites required for identifying individual parasites or parasite clusters when performing cross-sectional studies. The minimum number of microsatellites required to differentiate circulating P. vivax clusters differs from the minimum number of hyper-variable microsatellites required to distinguish individuals within these clusters. Regardless the extended number of microsatellites used in P. vivax, it was not possible to separate all individual infections.ConclusionsMolecular surveillance has great potential; however, it requires preliminary local studies in order to properly interpret the emerging patterns in the context of elimination. Clonal expansions and clusters turnovers need to be taken into account when using molecular markers. Those affect the number and type of microsatellite markers, as well as, the expected genetic patterns in the context of operational investigations. By considering the local dynamics, elimination programmes could cost-effectively use molecular markers. However, population level studies need to consider the local limitations of a given set of loci in terms of providing epidemiologically relevant information.

New Insights into Clonality and Panmixia in Plasmodium and Toxoplasma

“…In confirmation of Anderson et al's (2000) observations, persistent MLGs were observed in P. falciparum for as long as 8 years (Nkhoma et al, 2013). Many authors have come to use the very terms "clones" and "clonal population structure" for describing the population structure of Plasmodium (Annan et al, 2007;Chenet et al, 2012;Ferreira et al, 2007;Griffing et al, 2011;Heitman, 2006;Karunaweera et al, 2008;Nkhoma et al, 2013;Razakandrainibe et al, 2005), which would have been unthinkable 20 years ago. In some populations, restrained recombination manifests itself, not only by LD and ubiquitous MLGs but also by a tendency of natural populations to be structured into lasting, stable clusters, which cannot be accounted for by isolation by distance and time.…”

“…We will call it here the "starving sex hypothesis". It has been accepted by many authors in order to account for the observed population structure of Plasmodium (Arnott et al, 2012;Branch et al, 2011;Chenet et al, 2012;Conway, 2007;Ferreira et al, 2007;Gupta et al, 2012;Imwong et al, 2006Imwong et al, , 2007Iwagami et al, 2009;Mobegi et al, 2012;Mu et al, 2005;Mzilahowa et al, 2007;Neafsey, 2013;Neafsey et al, 2008;Nkhoma et al, 2013;Schultz et al, 2010;Volkman et al, 2012a,b). It can be challenged, as we will further see, since many observations are at odds with it, both in P. falciparum and in Plasmodium vivax.…”

“…Many studies have ascertained evidence for clonality and restrained recombination, based on the analysis of LD in many populations of P. falciparum (Annan et al, 2007;Branch et al, 2011;Chenet et al, 2012;Griffing et al, 2011;Iwagami et al, 2009;Manske et al, 2012;Nkhoma et al, 2013;Razakandrainibe et al, 2005;Volkman et al, 2007Volkman et al, , 2012a and P. vivax (Chenet et al, 2012;Imwong et al, 2007;Iwagami et al, 2012;Karunaweera et al, 2008;Rezende et al, 2010). Consequently, the panmictic model was considered to be "oversimplified" in Plasmodium (Heitman, 2006).…”

“…However, (i) it is the very and only statistic appropriate for testing rarity or absence of recombination, on which the definition of PCE is based; (ii) when enough loci are surveyed, its power of resolution is high (Tibayrenc and Ayala, 2012;Tibayrenc et al, 1990); and (iii) it is widely used as a circumstantial evidence for clonality by many authors working on Plasmodium (Anderson et al, 2000;Arnott et al, 2012;Branch et al, 2011;Chenet et al, 2012;Conway, 2007;Ferreira et al, 2007;Imwong et al, 2007;Iwagami et al, 2009Iwagami et al, , 2012Karunaweera et al, 2008;Mu et al, 2005;Nkhoma et al, 2013;Orjuela-Sánchez et al, 2010;Rezende et al, 2010;Volkman et al, 2007Volkman et al, , 2012a and Toxoplasma (Khan et al, 2011;Lehman et al, 2004;Rajendran et al, 2012;Su et al, 2006), as well as on other pathogens (Tibayrenc and Ayala, 2012). As asserted here, only the LD approach has been able to refute the panmictic prejudice in Plasmodium and Toxoplasma (Tibayrenc et al, 1990(Tibayrenc et al, , 1991.…”

Molecular Investigation into a Malaria Outbreak in Cusco, Peru: Plasmodium falciparum BV1 Lineage is Linked to a Second Outbreak in Recent Times

“…8,9 Moreover, since the P. falciparum population underwent strong drug selection, expansions of few drug-resistant parasite lineages is expected. 10 Epidemiological data suggest that the Cusco P. falciparum outbreak was the result of human migration from Loreto Department when a road construction company set up a camp in Rosalina to build a road to Kiteni, Echarate District. 2 In September 2013, prior to the outbreak, two road workers who were originally from Iquitos were diagnosed with severe malaria and, because of their critical condition, were subsequently transferred to another city for medical examination.…”