Application of genomics to field investigations of malaria by the international centers of excellence for malaria research

Abstract

Success of the global research agenda toward eradication of malaria will depend on development of new tools, including drugs, vaccines, insecticides and diagnostics. Genomic information, now available for the malaria parasites, their mosquito vectors, and human host, can be leveraged to both develop these tools and monitor their effectiveness. Although knowledge of genomic sequences for the malaria parasites, Plasmodium falciparum and P. vivax, have helped advance our understanding of malaria biology, simply knowing this sequence information has not yielded a plethora of new interventions to reduce the burden of malaria. Here we review and provide specific examples of how genomic information has increased our knowledge of parasite biology, focusing on P. falciparum malaria. We then discuss how population genetics can be applied toward the epidemiological and transmission-related goals outlined by the International Centers of Excellence in Malaria Research groups recently established by the National Institutes of Health. Finally, we propose genomics is a research area that can promote coordination and collaboration between various ICEMR groups, and that working together as a community can significantly advance the value of this information toward reduction of the global malaria burden.

New Insights into Clonality and Panmixia in Plasmodium and Toxoplasma

“…That selfing and inbreeding amount to clonality is a view shared by most authors working on Plasmodium (Anderson et al, 2000;Annan et al, 2007;Beck et al, 2009;Conway, 2007;Griffing et al, 2011;Mu et al, 2005;Mzilahowa et al, 2007;Nkhoma et al, 2013;Razakandrainibe et al, 2005;Volkman et al, 2012a) and Toxoplasma (Beck et al, 2009;Grigg and Sundar, 2009;Lehmann et al, 2004;Sibley and Ajioka, 2008;Su et al, 2012;Wendte et al, 2010). However, clonality does not limit itself to selfing and inbreeding and can have other origins (mitotic propagation and several cases of parthenogenesis, gynogenesis, and hybridogenesis).…”

“…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.…”

“…Discussions of pathogen population structure have focused on the "clonality/sexuality debate" (Tibayrenc et al, 1990). Clonality is here understood as scarcity or absence of genetic recombination, a definition widely accepted for all kinds of pathogens (Tibayrenc and Ayala, 2012), including Plasmodium (Anderson et al, 2000;Annan et al, 2007;Beck et al, 2009;Conway, 2007;Griffing et al, 2011;Heitman, 2006;Mu et al, 2005;Nkhoma et al, 2013;Razakandrainibe et al, 2005;Volkman et al, 2012a) and Toxoplasma (Beck et al, 2009;Heitman, 2006;Khan et al, 2011;Rajendran et al, 2012;Sibley and Ajioka, 2008;Smith, 2009;Su et al, 2003Su et al, , 2010Wendte et al, 2011). Clonality does not amount to genetic monomorphism, an erroneous definition still used by some researchers (Tibayrenc and Ayala, 2012).…”

The International Centers of Excellence for Malaria Research

“…2,3 This supplement described each of the Centers, their research projects, and their scientific scope. The articles described how individual Centers planned to implement multidisciplinary research approaches in the context of local and regional control efforts to provide evidencebased findings which inform the future course of malaria control and elimination efforts.…”