Historical Shifts in Brazilian P. falciparum Population Structure and Drug Resistance Alleles

AbstractMalaria continues to be an important health problem in Honduras despite major progress achieved reducing its incidence in the last two decades. In a context of case reduction, continuing surveillance of parasite diversity and drug resistance is an important component to assist effective malaria control strategies and support risk assessments. In this study, we employed next generation sequencing on collected Plasmodium vivax and P. falciparum samples from the Hospital Escuela (University Hospital) in Honduras between 2005 and 2017. Hospital Escuela is the main public health hospital in Honduras and receives suspected malaria cases from endemic regions within the country. The resulting sequencing data was used to assess complexity of infections, parasite population structure, parasite diversity and drug resistance profiling. All P. vivax samples and all autochtonous P. falciparum samples were monoclonal and presented a low intra population diversity (π = 0.25 and 0.07, respectively). Genotyping of drug resistance markers showed that three P. falciparum samples presented the chloroquine resistant haplotype SVMNT on pfcrtr (positions 72–76). Epidemiological data suggested that two of these samples were imported cases from Africa whereas the third one was a local case. Three suspected imported cases (two of which were also pfcrt mutants) presented the pfmdr1 86Y mutation that further enhances the CQ resistant genotype. No evidence was found for kelch13 artemisinin resistance associated mutations nor parasite genetic background mutations. Discriminant analysis of principal components and phylogenetic analysis showed two P. vivax and two P. falciparum parasite sub-populations with limited recombination between them. It also confirmed the closer relationship of the three imported cases with African strains. Our findings showed that local Honduras P. falciparum strains do not hold CQ resistance polymorphisms which aligns with clinical data reported by the country and supports the continuity of CQ based treatment in Honduras. In addition, our findings highlight the need of using genomic approaches to provide key information about parasite biology including drug resistance, population structure and HRP2/HRP3 deletions which are becoming relevant as the country move towards elimination.

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Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance

Genome Research ◽

10.1101/gr.123430.111 ◽

2011 ◽

Vol 21 (12) ◽

pp. 2143-2156 ◽

Cited By ~ 280

Author(s):

T. Downing ◽

H. Imamura ◽

S. Decuypere ◽

T. G. Clark ◽

G. H. Coombs ◽

...

Keyword(s):

Drug Resistance ◽

Population Structure ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Leishmania Donovani ◽

Clinical Isolates ◽

Whole Genome

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Molecular snapshot of Mycobacterium tuberculosis population structure and drug-resistance in Kyrgyzstan

Tuberculosis ◽

10.1016/j.tube.2013.05.008 ◽

2013 ◽

Vol 93 (5) ◽

pp. 501-507 ◽

Cited By ~ 9

Author(s):

Igor Mokrousov ◽

Jainagul Isakova ◽

Violeta Valcheva ◽

Almaz Aldashev ◽

Nalin Rastogi

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Population Structure

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Characterization of the population structure, drug resistance mechanisms and plasmids of the community-associated Enterobacter cloacae complex in China

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkx361 ◽

2017 ◽

Vol 73 (1) ◽

pp. 66-76 ◽

Cited By ~ 8

Author(s):

Kai Zhou ◽

Wei Yu ◽

Xiaoli Cao ◽

Ping Shen ◽

Haifeng Lu ◽

...

Keyword(s):

Drug Resistance ◽

Population Structure ◽

Enterobacter Cloacae ◽

Resistance Mechanisms ◽

Enterobacter Cloacae Complex

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Genetic diversity, population structure and drug resistance of Mycobacterium tuberculosis in Peru

Infection Genetics and Evolution ◽

10.1016/j.meegid.2012.02.002 ◽

2012 ◽

Vol 12 (3) ◽

pp. 577-585 ◽

Cited By ~ 24

Author(s):

C.A. Taype ◽

J.C. Agapito ◽

R.A. Accinelli ◽

J.R. Espinoza ◽

S. Godreuil ◽

...

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Population Structure

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Evolution of Drug Resistance in Different Sublineages of Mycobacterium tuberculosis Beijing Genotype

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00324-06 ◽

2006 ◽

Vol 50 (8) ◽

pp. 2820-2823 ◽

Cited By ~ 50

Author(s):

Igor Mokrousov ◽

Wei Wei Jiao ◽

Gui Zhi Sun ◽

Jia Wen Liu ◽

Violeta Valcheva ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Population Structure ◽

Selective Pressure ◽

Beijing Genotype ◽

Beijing Family ◽

Antituberculosis Drugs ◽

Beijing Area ◽

Resistance Patterns ◽

Mechanisms Of Adaptation

ABSTRACT We compared the population structure and drug resistance patterns of the Mycobacterium tuberculosis strains currently circulating in the Beijing area of China. One hundred thirteen of 123 strains belonged to the Beijing family genotypes defined by spoligotyping. The Beijing genotype strains were further subdivided into old and modern sublineages on the basis of NTF locus analysis. A stronger association with resistance to the more recently introduced antituberculosis drugs has been observed for old versus modern strains of the Beijing genotype, suggesting that its different sublineages may differ in their mechanisms of adaptation to drug selective pressure.

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Local differentiation in Plasmodium falciparum drug resistance genes in Sudan

Parasitology ◽

10.1017/s0031182003003020 ◽

2003 ◽

Vol 126 (5) ◽

pp. 391-400 ◽

Cited By ~ 88

Author(s):

A. A. ABDEL-MUHSIN ◽

M. J. MACKINNON ◽

P. AWADALLA ◽

E. ALI ◽

S. SULEIMAN ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Population Structure ◽

Resistance Genes ◽

Microsatellite Loci ◽

Balancing Selection ◽

Dry Season ◽

Chloroquine Resistance ◽

Multi Drug Resistance ◽

Eastern Region

Studies of population genetic structure of parasites can be used to infer which parasite genes are under selection. Here, the population structure of 4 genes associated with drug resistance of Plasmodium falciparum (the chloroquine resistance transporter, pfcrt, dihydrofolate reductase, dhfr, dihydropteroate synthase, dhps, and multi-drug resistance, pfmdr-1) were examined in parasite populations in 3 villages in eastern Sudan and in an urban area of Khartoum, the capital. In order to differentiate the effects of drug selection from neutral influences on population structure, parasites were also genotyped for 3 putatively neutral microsatellite loci (polyα, TA81 and pfg377), and for 2 antigenic loci that are either under balancing selection or neutral, merozoite surface protein 1 and 2, (MSP-1 and MSP-2). Cross-sectional surveys were carried out during the peak transmission (wet) season and in the ensuing dry season. No significant variation in frequencies of MSP-1 and MSP-2 alleles was seen among villages in the eastern region and between the villages and Khartoum, nor between the wet and dry season. However, the drug resistance genes, pfmdr-1, pfcrt and dhfr and to a lesser extent the microsatellite loci showed high FST values when comparing villages with Khartoum, indicating strong geographical differentiation at these loci. Moreover, variation in frequencies of the drug resistance genes, pfmdr-1, pfcrt and dhfr, was observed between the wet and dry season. These differences most probably reflect the variation in drug pressure between each region, and in drug usage between the wet and dry season in a given region.

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Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes

10.1101/2020.05.09.085225 ◽

2020 ◽

Author(s):

Kara A. Moser ◽

Rashid A. Madebe ◽

Ozkan Aydemir ◽

Mercy G. Chiduo ◽

Celine I. Mandara ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Population Structure ◽

Genetic Relatedness ◽

Sub Saharan Africa ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Molecular Inversion Probes ◽

Parasite Populations ◽

The Impact

ABSTRACTHigh-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programs, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania country-wide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, roughly separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from geographically close districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts, and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.SIGNIFICANCEDocumenting dynamics of malaria parasite genomics in high-transmission settings at scale in sub-Saharan Africa is critical for policy and decision making to support ongoing malaria elimination initiatives. Using molecular inversion probes, we genotyped over 1,000 Tanzanian Plasmodium falciparum samples collected country-wide in 2017 at hundreds of variable polymorphic positions across the genome. Frequencies of known drug resistance mutations were higher in northern districts of the country compared to the south. Results also showed a distinct isolation-by-distance pattern (whereby increasing geographic distance was correlated with decreasing genetic relatedness), as well as signals of higher genetic sharing between several southern districts. These results provide, for the first time, a picture of current within-country diversity of Tanzanian P. falciparum populations.

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