Chloroquine-resistant isolates of Plasmodium falciparum with alternative CG2 omega repeat length polymorphisms.

Abstract Background: In 2002, Zambia withdrew chloroquine as first line treatment for Plasmodium falciparum malaria due to increased treatment failure and world-wide spread of chloroquine resistance. The artemisinin combination regimen artemether-lumefantrine replaced chloroquine as first choice malaria treatment. The present study determined the prevalence of chloroquine resistance molecular markers in the malaria parasite Pfcrt and Pfmdr1 genes in Eastern Zambia at nine and thirteen years after the removal of drug pressure.Methods: We assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) the prevalence of the genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene in samples collected from Katete District during drug therapeutic efficacy assessments conducted in 2012 and 2016.Results: A total of 204 P. falciparum positive samples from 2012 and 2016 were further analysed for Pfcrt K76T and Pfmdr1 N86Y. 112 P. falciparum infected samples collected in 2012 were successfully amplified for Pfcrt and Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1. In 2012, the prevalence of Pfcrt 76K was 97.3%, 76T was 1.8%, and 0.8% had both 76K and 76T codons. The prevalence of Pfmdr1 86N was 97.9% and 86Y was 2.1%. In the 2016 samples, the prevalence of the respective parasite genotypes was 100% Pfcrt 76K and Pfmdr1 86N.Conclusion: This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, thirteen years following the withdrawal of CQ. These findings add to the body of evidence for a fitness cost in chloroquine-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to explore the feasibility of integration of the former best antimalarial in combination therapy in the future.

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Allelic Diversity Revealed Through SSR Polymorphisms at the Locus Encoding HMG-CoA Reductase in Rubber (Hevea brasiliensis)

Silvae Genetica ◽

10.1515/sg-2007-0009 ◽

2007 ◽

Vol 56 (1-6) ◽

pp. 58-65 ◽

Cited By ~ 1

Author(s):

T. Saha ◽

C. B. Roy ◽

M. Ravindran ◽

K. Bini ◽

M. A. Nazeer

Keyword(s):

Hevea Brasiliensis ◽

Genetic Relatedness ◽

Allelic Variation ◽

Allelic Diversity ◽

Repeat Length ◽

Mato Grosso ◽

Length Polymorphisms ◽

Wild Accessions ◽

Coa Reductase ◽

Microsatellite Alleles

AbstractThis study was carried out to define the extent of allelic variation of 3-hydroxy-3-methylglutaryl-CoA reductase gene (HMGR) in wild Hevea accessions, based on SSR polymorphisms existing at their 3’-untranslated regions (UTRs). Existence of two microsatellite alleles and their repeat compositions was demonstrated earlier in cultivated rubber clones. Both alleles contained perfect poly (AG)n repeats interrupted by a short sequence of 12 nucleotides and allelic variation at this microsatellite locus was the result of repeat length polymorphisms. In wild populations of rubber, nine microsatellite alleles (‘A’ to ‘I’) were identified at the HMGR locus revealing a wide allelic diversity compared to cultivated clones. Out of nine, four alleles (‘B’, ‘C’, ‘D’ and ‘G’) were present in higher frequencies than the others. In total, 15 allelic combinations were noticed for HMGR among wild accessions and four of them were unique. Twenty-five out of 60 wild accessions were found to be homozygous for the above four alleles (‘BB’, ‘CC’, ‘DD’ and ‘GG’) and the rest were heterozygous, characterized by 11 different allelic combinations. Repeat-length polymorphisms were noticed in these four alleles prevailing among wild Hevea accessions. Genetic relatedness of Mato Grosso accessions with cultivated Hevea clones, as revealed through this study, is in agreement with earlier reports on phylogenetic studies using molecular markers. This work is a significant step towards understanding the functional variability of HMGR for latex production in Hevea brasiliensis.

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The association of CAG repeat length polymorphisms of androgen receptor gene and spermatogenesis impairment in several Indonesian men

Medical Journal of Indonesia ◽

10.13181/mji.v13i4.154 ◽

2004 ◽

Vol 13 (4) ◽

pp. 215 ◽

Cited By ~ 1

Author(s):

Purnomo Soeharso ◽

Arfianti Arfianti ◽

Nukman Moeloek

Keyword(s):

Androgen Receptor ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Repeat Length ◽

Cag Repeat ◽

Length Polymorphisms ◽

Spermatogenesis Impairment

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Two novel serine repeat length polymorphisms (1043insS and 1043inssS) at exon 23 of theTSC1 gene

Human Mutation ◽

10.1002/1098-1004(200010)16:4<375::aid-humu18>3.0.co;2-t ◽

2000 ◽

Vol 16 (4) ◽

pp. 375-375 ◽

Cited By ~ 1

Author(s):

Judy R. Pipo ◽

Toshiyuki Yamamoto ◽

Hiromasa Takeda ◽

Shinji Maegawa ◽

Eiji Nanba ◽

...

Keyword(s):

Repeat Length ◽

Length Polymorphisms

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CAG and GGN Repeat Length Polymorphisms of Androgen Receptor Gene in Women with Breast Cancer: A Case-Control Study from South India

Journal of Cancer Therapy ◽

10.4236/jct.2012.325093 ◽

2012 ◽

Vol 03 (05) ◽

pp. 741-748

Author(s):

Durgadatta Tosh ◽

Bineet Panda ◽

Tipirisetti Nageswar Rao ◽

Arvind Babu ◽

Vishnupriya Satti ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

South India ◽

Case Control Study ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Case Control ◽

Repeat Length ◽

Length Polymorphisms ◽

Control Study

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Genetic variations in histidine-rich protein 2 and histidine-rich protein 3 of Myanmar Plasmodium falciparum isolates

Malaria Journal ◽

10.1186/s12936-020-03456-6 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Hương Giang Lê ◽

Jung-Mi Kang ◽

Jinyoung Lee ◽

Won Gi Yoo ◽

Moe Kyaw Myint ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Genetic Variation ◽

Comparative Analysis ◽

Amino Acid ◽

Structural Features ◽

Nested Polymerase Chain Reaction ◽

Blood Samples ◽

Malaria Rapid Diagnostic Tests ◽

Length Polymorphisms ◽

Polymerase Chain

Abstract Background Malaria rapid diagnostic tests (RDTs) are precious tools to diagnose malaria. Most RDTs used currently are based on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in a patient’s blood. However, concern has been raised in recent years that deletion of pfhrp2 in the parasite could affect the accuracy of PfHRP2-based RDTs. In addition, genetic variation in pfhrp2 might influence the accuracy and sensitivity of RDTs. In this study, the genetic variation in pfhrp2 and pfhrp3 in Myanmar P. falciparum isolates was analysed. Methods Blood samples were collected from malaria patients who were infected with P. falciparum in Mandalay, Naung Cho, Tha Beik Kyin, and Pyin Oo Lwin, Upper Myanmar between 2013 and 2015. The pfhrp2 and pfhrp3 were amplified by nested polymerase chain reaction (PCR), cloned and sequenced. Genetic variation in Myanmar pfhrp2 and pfhrp3 was analysed using the DNASTAR program. Comparative analysis of Myanmar and global pfhrp2 and pfhrp3 isolates was also performed. Results One-hundred and two pfhrp2 and 89 pfhrp3 were amplified from 105 blood samples, of which 84 pfhrp2 and 56 pfhrp3 sequences were obtained successfully. Myanmar pfhrp2 and pfhrp3 showed high levels of genetic variation with different arrangements of distinct repeat types, which further classified Myanmar pfhrp2 and pfhrp3 into 76 and 47 haplotypes, respectively. Novel amino acid changes were also found in Myanmar pfhrp2 and pfhrp3, but their frequencies were very low. Similar structural organization was shared by Myanmar and global pfhrp2 and pfhrp3, and differences in frequencies of repeat types and lengths were also observed between and among global isolates. Conclusion Length polymorphisms and amino acid substitutions generated extensive genetic variation in Myanmar pfhrp2 and pfhrp3. Comparative analysis revealed that global pfhrp2 and pfhrp3 share similar structural features, as well as extensive length polymorphisms and distinct organizations of repeat types. These results provide a better understanding of the genetic structure of pfhrp2 and pfhrp3 in global P. falciparum populations and suggest useful information to develop RDTs with improved quality.

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Decreased prevalence of the Plasmodium falciparum Pfcrt K76T and Pfmdr1 and N86Y mutations post-chloroquine treatment withdrawal in Katete District, Eastern Zambia

Malaria Journal ◽

10.1186/s12936-021-03859-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mwenda C. Mulenga ◽

Lungowe Sitali ◽

Ilinca I. Ciubotariu ◽

Moonga B. Hawela ◽

Busiku Hamainza ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Complete Recovery ◽

The Body ◽

Chloroquine Resistance ◽

Treatment Withdrawal ◽

Combination Regimen ◽

Drug Pressure ◽

Length Polymorphisms ◽

Chloroquine Treatment ◽

First Choice

Abstract Background In 2002, Zambia withdrew chloroquine as first-line treatment for Plasmodium falciparum malaria due to increased treatment failure and worldwide spread of chloroquine resistance. The artemisinin combination regimen, artemether–lumefantrine, replaced chloroquine (CQ) as first choice malaria treatment. The present study determined the prevalence of CQ resistance molecular markers in the Pfcrt and Pfmdr1 genes in Eastern Zambia at 9 and 13 years after the removal of drug pressure. Methods Samples collected from Katete District during the drug therapeutic efficacy assessments conducted in 2012 and 2016 were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to determine the prevalence of genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene. A total of 204 P. falciparum-positive DBS samples collected at these two time points were further analysed. Results Among the samples analysed for Pfcrt K76T and Pfmdr1 N86Y in the present study, 112 (82.4%) P. falciparum-infected samples collected in 2012 were successfully amplified for Pfcrt and 94 (69.1%) for Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1, respectively. In 2012, the prevalence of Pfcrt 76K (sensitive) was 97.3%, 76T (resistant) was 1.8%, and 0.8% had both 76K and 76T codons (mixed). Similarly in 2012, the prevalence of Pfmdr1 86N (sensitive) was 97.9% and 86Y (resistant) was 2.1%. In the 2016 samples, the prevalence of the respective samples was 100% Pfcrt 76K and Pfmdr1 86N. Conclusion This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, Eastern Zambia, 13 years following the withdrawal of CQ in the country. These findings add to the body of evidence for a fitness cost in CQ-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to monitor resistance countrywide and explore the feasibility of integration of the former best anti-malarial in combination therapy in the future.

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