scholarly journals Genetic Profiling of thePlasmodium falciparumPopulation Using Antigenic Molecular Markers

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Purva Gupta ◽  
Ruchi Singh ◽  
Haris Khan ◽  
Adil Raza ◽  
Veena Yadavendu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Parasite Population ◽  
Genetic Profile ◽  
Resistance Development ◽  
Genetic Profiling ◽  
Molecular Genotyping ◽  
Parasite Populations

About 50% of malaria infections in India are attributed toPlasmodium falciparumbut relatively little is known about the genetic structure of the parasite populations. The molecular genotyping of the parasite populations by merozoite surface protein(msp1 and msp2)and glutamate-rich protein (glurp) genes identifies the existing parasite population in the regions which help in understanding the molecular mechanisms involved in the parasite’s drive for survival. This study reveals the genetic profile of the parasite population in selected regions across the country with varying degree of endemicity among them. We also report the prevalence ofPfcrtmutations in this parasite population to evaluate the pattern of drug resistance development in them.

scholarly journals Angiogenesis as a Therapeutic Target in Endometriosis

2014 ◽  
Vol 27 (4) ◽  
pp. 489 ◽  
Author(s):  
Dusan Djokovic ◽  
Carlos Calhaz-Jorge
Keyword(s):  
Drug Resistance ◽  
Literature Search ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Angiogenesis Inhibitors ◽  
Resistance Development ◽  
Key Factor ◽  
Successful Establishment ◽  
Multimodal Management ◽  
Gynecological Disorder

<p><strong>Introduction:</strong> Angiogenesis is a key factor for the successful establishment and growth of endometriotic lesions.<br /><strong>Material and Methods:</strong> We performed a literature search in PubMed and reviewed the most pertinent studies published until January 2014 and focused on the endometriosis-associated angiogenesis and/or anti-angiogenic strategies for the treatment of this gynecological disorder.<br /><strong>Results:</strong> The present review provides a concise summary of the known molecular mechanisms that promote vascularization of endometriotic lesions and may serve as potential therapeutic targets. We also present a systematic overview of the inclusive and exclusive anti-angiogenic agents that have been already studied in cell cultures, animal models and/or endometriosis patients.<br /><strong>Discussion and Conclusion:</strong> The integration of anti-angiogenic approaches in the multimodal management strategies for endometriosis patients will be conditioned by the outcomes of future assessments regarding the effectiveness of such treatments, the risk of drug resistance development and the incidence of unacceptable side effects.<br /><strong>Keywords:</strong> Angiogenesis Inhibitors/therapeutic use; Endometriosis/drug therapy.</p>

scholarly journals A brief review on the mode of action of antinematodal drugs

2017 ◽  
Vol 67 (2) ◽  
pp. 137-152 ◽  
Author(s):  
Melanie Abongwa ◽  
Richard J. Martin ◽  
Alan P. Robertson
Keyword(s):  
Drug Resistance ◽  
Mode Of Action ◽  
Drug Targets ◽  
Parasite Species ◽  
Effective Control ◽  
Macrocyclic Lactones ◽  
Resistance Development ◽  
Cholinergic Agonists ◽  
Nematode Parasites ◽  
Parasite Populations

Abstract Anthelmintics are some of the most widely used drugs in veterinary medicine. Here we review the mechanism of action of these compounds on nematode parasites. Included are the older classes of compounds; the benzimidazoles, cholinergic agonists and macrocyclic lactones. We also consider newer anthelmintics, including emodepside, derquantel and tribendimidine. In the absence of vaccines for most parasite species, control of nematode parasites will continue to rely on anthelmintic drugs. As a consequence, vigilance in detecting drug resistance in parasite populations is required. Since resistance development appears almost inevitable, there is a continued and pressing need to fully understand the mode of action of these compounds. It is also necessary to identify new drug targets and drugs for the continued effective control of nematode parasites.

scholarly journals An Evolution From a Predominant K1 Allelic Variant to MAD20 of msp1 Gene Between 2015 to 2019 in Metehara, Southeast Ethiopia

2021 ◽  
Author(s):  
Abeba Reda ◽  
Alebachew Messele ◽  
Hussein Mohammed ◽  
Ashenafi Assefa ◽  
Lemu Golassa ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Target Genes ◽  
Temporal Dynamics ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Southeast Ethiopia ◽  
Parasite Populations ◽  
Msp1 Gene

Abstract Background: The complexity and quantity of parasite populations circulating in a specific location are reflected in the genetic diversity of malaria parasites (s). Between 2015 and 2019, this study in Metehara, South east, Ethiopia. set out to investigate the temporal dynamics of genetic diversity and multiplicity as a result of evolutionary change in the genes that contribute to Plasmodium falciparum infection elimination. Method: Between 2015 and 2019, a cross-sectional study was carried out. from eighty-three dry blood spots from malaria patients who were screened for P. falciparum mono-infection by QPCR. From this seventy confirmed P. falciparum were genotyping to merozoite surface protein 1,2 and glutamate-rich protein using nested PCR.Result: Between 2015 and 2019, seventy (84.3%) of the isolates were successfully genotyped for all three target genes in both years. In 2015 and 2019, the allelic distributions of the three genes differed significantly (P= 0.001). Overall, the most common allelic families for msp1 and msp2 were K1 and FC27 respectively. For glurp, eight distinct genotypes were identified. In 2015, the genotyping of msp1, msp2 and glurp was 25 (86.2%), 25 (86.2%) and 24 (82.2%) respectively. K1, MAD20 and RO33 all have 19(65.5%), 3(10.3%) and 3(10.3%) msp1 allelic families respectively. In 2019 the genes were 30 (73.2%), 39 (95.1%) and 30 (73.2%). K1, MAD20, and RO33 were genotyped for 6 (14.6 percent), 18 (43.9 percent) and 6 (14.6 percent) genotyping respectively. Over all the multiplicity of infection was 1.67 (95 percent CI 1.54-1.74) and the heterozygosity index for msp1, msp2, and glurp was 0.48, 0.70, and 0.55 respectively.Conclusion: This study provides current information on the genetic diversity of P. falciparum populations in Metehara over five-year intervals, The progression of the dominant K1 variant from 2015 to MAD20 variant in 2019 was observed in this study.

scholarly journals The Plasmodium vivax Merozoite Surface Protein 3β Sequence Reveals Contrasting Parasite Populations in Southern and Northwestern Thailand

2014 ◽  
Vol 8 (11) ◽  
pp. e3336 ◽  
Author(s):  
Chaturong Putaporntip ◽  
Jun Miao ◽  
Napaporn Kuamsab ◽  
Jetsumon Sattabongkot ◽  
Jeeraphat Sirichaisinthop ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Parasite Populations ◽  
Northwestern Thailand

scholarly journals Drug Resistance Mechanisms in Tuberculosis

2020 ◽  
Author(s):  
Lanfranco Fattorini ◽  
Angelo Iacobino ◽  
Federico Giannoni
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Drug Distribution ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Diagnostic Methods ◽  
Drug Resistant ◽  
Resistance Development ◽  
Intrinsic Drug Resistance ◽  
Incident Cases

The increased incidence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, defined as resistant to at least isoniazid and rifampin, the two highly bactericidal first-line drugs, is a major concern for tuberculosis (TB) control. The worldwide estimate of almost half a million incident cases of MDR/rifampin-resistant TB, is causing increasing concern. In this view, it is important to continuously update the knowledge on the mechanisms involved in the development of drug-resistant TB. Clinical, biological and microbiological reasons account for the generation of resistance, including: (i) nonadherence of patients to their therapy, and/or errors of physicians in therapy management, (ii) complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, resulting in resistance development, (iii) intrinsic drug resistance of tubercle bacilli, (iv) formation of non-replicating, drug-tolerant bacilli inside the granulomas, (v) development of mutations in Mtb genes, which are the most important molecular mechanisms of resistance. Here, a piece of information on the interplay of these factors is provided, to facilitate the clinical and microbiological management of drug-resistant TB at the global level, with attention also to the most recent diagnostic methods.

scholarly journals Low levels of Plasmodium falciparum genetic diversity in two Nigerian communities bordering the Niger River

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Joshua Idakwo ◽  
Emmanuel T. Idowu ◽  
Kolapo M. Oyebola ◽  
Olubunmi A. Otubanjo
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Surface Protein ◽  
River Basins ◽  
Merozoite Surface Protein ◽  
North Central ◽  
Significant Difference ◽  
Polymerase Chain ◽  
Niger River ◽  
Parasite Populations

Introduction: Extensive genetic diversity of malaria parasites is a major draw back to ongoing control efforts. Population-specific investigation of genetic structure of the parasite is important for effective malaria intervention in endemic populations such as Nigeria where about one-third of the global burden of the disease is borne. This study describes the genetic diversity of Plasmodium falciparum isolates in the Niger River basins, North-Central Nigeria. Methodology: Parasite DNA w as extracted fr om finger -prick blood samples collected from eighty P. falciparum positive individuals. Polymerase Chain Reaction (PCR) genotyping was carried out to target K1, MAD20 and R033 allelic families of Merozoite Surface Protein (MSP) -1 gene and FC27 and 3D7 allelic families of MSP-2 gene. Results: Proportion of isolates with K1 family w as 28(70%) with two alleles in Idah and 16(40%) with two alleles in Ibaji. Proportion of isolates with MAD20 family was 8 (20%) and a total of two alleles were observed in Idah and 4(10%) with two alleles in Ibaji. RO33 proportion was 16 (40%) in Idah one allele and 8(20%) in Ibaji where the allelic family was also observed to be monomorphic. K1 was the most predominant MSP1 allele in the two parasite populations and the frequency of FC27 genotype was higher than 3D7 in both populations. Multiplicity of infection (Mol) with MSP-1 loci was higher in Ibaji (1.30) than Idah (1.05) while MoI with MSP-2 loci was lower in Ibaji (2.00) than Idah (2.13). However, there is no significant difference in the mean Mol between Idah and Ibaji (P > 0.05). The expected heterozygosity (HE) value was 0.56 for MSP-1 and 0.84 for MSP-2. Conclusion: Our findings revealed high levels of monoclonal infections with P. falciparum, suggesting low parasite diversity. This may be a pointer to a reduction in malaria transmission in the river basins.

scholarly journals Genetic population of Plasmodium knowlesi during pre-malaria elimination in Thailand

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Rungniran Sugaram ◽  
Patcharida Boondej ◽  
Suttipat Srisutham ◽  
Chanon Kunasol ◽  
Watcharee Pagornrat ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Knowlesi ◽  
Homology Modelling ◽  
Surface Protein ◽  
Drug Efficacy ◽  
Merozoite Surface Protein ◽  
Pcr Assay ◽  
Genetic Population ◽  
Merozoite Surface Protein 1 ◽  
Southern Thailand

Abstract Background Thailand is committed to eliminating malaria by 2024. From 2013 to 2020, the total number of malaria cases have decreased, from 37,741 to 4474 (an 88.1% reduction). However, infections with Plasmodium knowlesi, a monkey malarial pathogen that can also infect humans, have been increasingly observed. This study focused on the molecular analysis of P. knowlesi parasites causing malaria in Thailand. Methods Under Thailand’s integrated Drug Efficacy Surveillance (iDES), which includes drug-resistance monitoring as part of routine case-based surveillance and responses, specimens were collected from malaria patients (n = 966) between 2018 and 2020. Thirty-one mono P. knowlesi infections (3.1%), most of which were from eastern and southern Thailand, were observed and confirmed by nested PCR assay and DNA sequencing. To evaluate whether these pathogens were from different lineages, cluster analysis based on seven microsatellite genotyping markers and the merozoite surface protein 1 (pkmsp1) gene was carried out. The P. knowlesi pyrimethamine resistance gene dihydrofolate reductase (pkdhfr) was sequenced and homology modelling was constructed. Results The results of analysing the seven microsatellite markers and pkmsp1 sequence demonstrated that P. knowlesi parasites from eastern Thailand were of the same lineage as those isolated in Cambodia, while the parasites causing malaria in southern Thailand were the same lineage as those isolated from Malaysia. The sequencing results for the pkdhfr genes indicated the presence of two mutations, Arg34Leu and a deletion at position 105. On analysis with homology modelling, the two mutations were not associated with anti-malarial drug resistance. Conclusions This report compared the genetic populations of P. knowlesi parasites in Thailand from 2018 to 2020 and have shown similar lineages as those isolated in Cambodia and Malaysia of P. knowlesi infection in Thailand and demonstrated that the P. knowlesi parasites were of the same lineages as those isolated in Cambodia and Malaysia. The parasites were also shown to be sensitive to pyrimethamine.

scholarly journals Characterization of drug resistance and genetic diversity of Plasmodium falciparum parasites from Tripura, Northeast India

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
S. J. Patgiri ◽  
K. Sarma ◽  
N. Sarmah ◽  
N. Bhattacharyya ◽  
D. K. Sarma ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Surface Protein ◽  
Population Group ◽  
Merozoite Surface Protein ◽  
Northeast India ◽  
Chloroquine Resistance ◽  
Chloroquine Resistance Transporter ◽  
High Level ◽  
International Border

Abstract Monitoring of anti-malarial drug resistance is vital in Northeast India as this region shares its international border with Southeast Asia. Genetic diversity of Plasmodium parasites regulates transmission dynamics, disease severity and vaccine efficacy. P. falciparum chloroquine resistance transporter (Pfcrt), multidrug resistance-1 (Pfmdr-1) and kelch 13 propeller (PfK-13) genes which govern antimalarial drug resistance and three genetic diversity markers, merozoite surface protein 1 and 2 (Pfmsp-1, Pfmsp-2) and glutamate rich protein (Pfglurp) were evaluated from Tripura, Northeast India using molecular tools. In the Pfcrt gene, 87% isolates showed triple mutations at codons M74I, N75E and K76T. 12.5% isolates in Pfmdr-1 gene showed mutation at N86Y. No polymorphism in PfK-13 propeller was found. Polyclonal infections were observed in 53.85% isolates and more commonly in adults (p = 0.0494). In the Pfmsp-1 locus, the K1 allelic family was predominant (71.2%) followed by the 3D7/IC family (69.2%) in the Pfmsp-2 locus. RII region of Pfglurp exhibited nine alleles with expected heterozygosity of 0.85. The multiplicity of infection for Pfmsp-1, Pfmsp-2 and Pfglurp were 1.56, 1.31 and 1.06 respectively. Overall, the study demonstrated a high level of chloroquine resistance and extensive parasite diversity in the region, necessitating regular surveillance in this population group.

MOLECULAR MECHANISMS OF RESISTANCE IN ANTIMALARIAL CHEMOTHERAPY: The Unmet Challenge

2005 ◽  
Vol 45 (1) ◽  
pp. 565-585 ◽  
Author(s):  
Ravit Arav-Boger ◽  
Theresa A. Shapiro
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Point Mutations ◽  
Public Health Problem ◽  
Genetic Studies ◽  
Genetic Mechanisms ◽  
Clinically Significant ◽  
Parasite Populations

▪ Abstract  The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies. The prevention and management of drug resistance are among the most important practical problems of tropical medicine and public health. Leonard J. Bruce-Chwatt, 1972

scholarly journals Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mary A. Oboh ◽  
Tolla Ndiaye ◽  
Khadim Diongue ◽  
Yaye D. Ndiaye ◽  
Mouhamad Sy ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Allelic Diversity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Population Diversity ◽  
Allelic Polymorphism ◽  
Low Genetic Diversity ◽  
Study Sites ◽  
Infection Types ◽  
Parasite Populations

Abstract Background Characterizing the genetic diversity of malaria parasite populations in different endemic settings (from low to high) could be helpful in determining the effectiveness of malaria interventions. This study compared Plasmodium falciparum parasite population diversity from two sites with low (pre-elimination) and high transmission in Senegal and Nigeria, respectively. Methods Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) and Nigeria (93). Allelic polymorphism at merozoite surface protein 1 (msp1) and merozoite surface protein- 2 (msp2) genes were assessed by nested PCR. Results The most frequent msp1 and msp2 allelic families are the K1 and IC3D7 allelotypes in both Senegal and Nigeria. Multiplicity of infection (MOI) of greater that 1 and thus complex infections was common in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp1/2) than in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles was associated with heavy than with moderate parasite density. Meanwhile, equal proportions of K1 were observed in both heavy and moderate infection types in Nigeria. The IC3D7 subtype allele of the msp2 family was the most frequent in heavily parasitaemic individuals from both countries than in the moderately infected participants. Conclusion The unexpectedly low genetic diversity of infections high endemic Nigerian setting compared to the low endemic settings in Senegal is suggestive of possible epidemic outbreak in Nigeria.

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