A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

Havryliuk, Tatiana; Ferreira, Marcelo Urbano

doi:10.1590/s0074-02762009000100011

Cited by 53 publications

(60 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12,33 Such genetic diversity is essential for parasite fitness and survival, and it is thought that this diversity must be reduced to limit parasite adaptation and population expansion. 5,40 Thus, although the implementation of malaria prevention measures seem to have reduced P. vivax prevalence in East Sepik, an even greater reduction in prevalence may be required to decrease population genetic diversity for both P. vivax and P. falciparum. 38 The genetic complexity and unique biology of P. vivax infections, coupled with the enormous burden of both species, will present major challenges for malaria elimination in PNG.…”

Section: Discussionmentioning

confidence: 99%

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

Arnott

Barnadas

Senn

et al. 2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Despite having the highest Plasmodium vivax burden in the world, molecular epidemiological data from Papua New Guinea (PNG) for this parasite remain limited. To investigate the molecular epidemiology of P. vivax in PNG, 574 isolates collected from four catchment sites in East Sepik (N = 1) and Madang (N = 3) Provinces were genotyped using the markers MS16 and msp1F3. Genetic diversity and prevalence of P. vivax was determined for all sites. Despite a P. vivax infection prevalence in the East Sepik (15%) catchments less than one-half the prevalence of the Madang catchments (27-35%), genetic diversity was similarly high in all populations (H e = 0.77-0.98). High genetic diversity, despite a marked difference in infection prevalence, suggests a large reservoir of diversity in P. vivax populations of PNG. Significant reductions in transmission intensity may, therefore, be required to reduce the diversity of parasite populations in highly endemic countries such as PNG.

show abstract

Section: Discussionmentioning

confidence: 99%

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

Arnott

Barnadas

Senn

et al. 2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…Over the last two decades, molecular markers have revealed that many natural P. vivax infections comprise a complex mixture of clonal populations; that is, multipleclone vivax infections are fairly common in human hosts (Havryliuk & Ferreira 2009). The earliest attempts to investigate the clonal diversity of P. vivax isolates in human infections focused on characterisation of phenotypes using monoclonal antibodies or isoenzymes (Udagama et al 1987, Joshi et al 1989, an approach that required blood samples with relatively high parasitaemias.…”

Section: Neutral or Nearly Neutral Molecular Markersmentioning

confidence: 99%

“…The evolutionary and epidemiological consequences of multiple-clone P. vivax infections have not been well-investigated. However, experimental rodent malaria models suggest that, for two or more genetically distinct clones in the same host, intra-host competition for limited resources may select for P. vivax traits repre- senting major public health challenges, such as increased virulence, transmissibility and antimalarial drug resistance (reviewed by Havryliuk & Ferreira 2009). …”

Section: Neutral or Nearly Neutral Molecular Markersmentioning

confidence: 99%

Molecular markers and genetic diversity of Plasmodium vivax

Brito

Ferreira

2011

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

Enhanced understanding of the transmission dynamics and population genetics for Key words: malaria -Plasmodium vivax -genetic markers -genetic diversity -multiple-clone infections -microsatellitesMarkers and genetic diversity of P. vivax • Cristiana Ferreira Alves de Brito, Marcelo Urbano Ferreira 13 tual heterozygosity (H E ) values. Virtual H E is the average probability that a pair of alleles randomly obtained from the population is different. Whenever appropriate, in this review we provide H E estimates obtained using different markers for different populations.Molecular markers under selection -Until recently, most genetic markers available for characterising natural P. vivax populations were orthologues of previously identified P. falciparum antigen-coding genes. The wellcharacterised polymorphic regions in these genes have been extensively used to analyse genetic diversity patterns in P. falciparum (Roy et al. 2008). A similar approach has been explored in vivax-oriented studies (Cui et al. 2003a). The following single-copy genes in P. vivax have often been used in these studies: gam1, coding for the gametocyte antigen 1, csp, coding for the circumsporozoite protein (CSP), msp1 and msp3alpha, coding for the merozoite surface proteins (MSP)-1 and 3α, respectively, ama1, coding for the apical membrane antigen 1, and dbp, coding for the Duffy binding protein (DBP) ( Table I).A notable feature of several P. vivax surface antigens (including major vaccine-candidate molecules) is tandem arrays of relatively short amino acid motifs. The CSP in P. vivax (PvCSP), an abundant antigen on the surface of sporozoites that has been extensively used as a vaccine development target, has immunodominant B-cell epitopes that map to central repeats between nonrepetitive sequences (Nardin & Zavala 1998). PvCSP displays two major types of nonapeptide repeats [most commonly GDRA(D/A)GQPA and ANGA(G/D)(N/D)QPG], which define the variants known as VK210 and VK247, respectively (Arnot et al. 1985, Rosenberg et al. 1989 (Fig. 1). Both VK210 and VK247 variants are globally distributed, but geographic biases have been described (Cochrane et al. 1990, Qari et al. 1993a. Similar repetitive sequences are found in Brazil, Southeast Asia and Papua New Guinea (Qari et al. 1991(Qari et al. , 1992. However, markedly divergent sequence variants were found in isolates from China and North Korea (Mann et al. 1994). Although VK210 and VK247-type sequences often occur in sympatric parasite populations, there are no examples of a hybrid repeat array with both repeat types (Lim et al. 2005).A third type of repeat unit [APGANQ(E/G)GAA], identical to that described for Plasmodium simiovale, characterises the so-called P. vivax-like parasites (Qari et al. 1993a). Although P. vivax-like CSP repeats have been found in parasite isolates across the world, its global distribution remains unconfirmed (Gopinath et al. 1994). In Brazil, P. vivax-like parasites have been identified only in mixed-clone infections with VK210-type or VK247-type parasites (Machado...

show abstract

“…While parasite diversity on a population scale allows for resistant parasite populations to expand under drug pressure, in-host diversity impacts the development of drug resistance by affecting sexual recombination rates and allowing competitive suppression among co-infecting drug-resistant and drug-sensitive clones. 7,8 Previous studies have shown high genetic diversity but limited MOI among P. vivax infections in Southeast Asia. [9][10][11][12] However, the genotyping methods used in these studies are often limited in their ability to detect minority clones, leading to an underestimation of MOI.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12] However, the genotyping methods used in these studies are often limited in their ability to detect minority clones, leading to an underestimation of MOI. 8 The heteroduplex tracking assay (HTA) is a genotyping technique that has proven adept at uncovering minority variants within malaria infections and in infections with other agents. [13][14][15][16] Thus, it provides a more accurate picture of within-host genetic diversity.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

Lin¹,

Patel²,

Kharabora³

et al. 2013

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (H E = 0.86) but closely related (G ST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 ( pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants.

show abstract

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

Cited by 53 publications

References 52 publications

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

Molecular markers and genetic diversity of Plasmodium vivax

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms

Contact Info

Product

Resources

About