with oral chloroquine. Alternatively, hydroxychloroquine may be used at recommended doses. In addition, any of the regimens listed for the treatment of chloroquine-resistant malaria may be used for the treatment of chloroquine-sensitive. P. falciparum. malaria. Prompt initiation of an effective regimen isMissing: dissertation Aug 17, · An ancillary role for PfMDR1 in chloroquine resistance cannot be ruled out though. A genetic cross and mapping studies between a chloroquine resistant clone and a chloroquine sensitive clone resulted in the identification of a 36 kb region on chromosome 7 associated with chloroquine blogger.comg: dissertation AN ABSTRACT OF THE DISSERTATION OF TM showed no activity against bacteria, malarial parasites, and most tested mammalian cells, but it has potent growth inhibitory activity against chloroquine-sensitive strain D6, and two chloroquine-resistant strains Dd2Author: Wanli Lu
Mechanisms of drug action and resistance
Malaria Journal volume 18Article number: 76 Cite this article. Metrics chloroquine resistant bacteria dissertation. Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance.
This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr - 1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use.
A review protocol was developed, registered in PROSPERO CRD and published in a peer-reviewed journal. Mesh terms and Boolean operators AND, OR were used. Data extraction form was designed in Excel chloroquine resistant bacteria dissertation sheet Data extraction was done by three reviewers NL, BB and MOdiscrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I 2 -statistic.
Additional targeted search resulted in three 03 eligible articles. Average genotyping success rate was Prevalence of Pfcrt 76T was as follows; East Africa Prevalence of Pfmdr - 1 86Y was; East Africa Over half, The average time years since discontinuation of chloroquine use to data collection was 8.
The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites chloroquine resistant bacteria dissertation steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr - 1 N86Y mutations still persist at moderate frequencies in most malaria affected countries. Chloroquine was once an important medicine used in malaria treatment especially due to its affordability, ease of use and high anti-malarial efficacy.
However, due to high level of resistance among Plasmodium falciparum parasites, chloroquine was withdrawn from malaria treatment in most malaria endemic countries [ 1 ]. Chloroquine resistance reached fixation levels across malaria endemic countries by late s [ 4 ], chloroquine resistant bacteria dissertation. As a result artemisinin agents and their derivatives were introduced in malaria treatment and have since been the first-line anti-malarial agents [ 3 ].
Chloroquine resistant bacteria dissertation use of artemisinin-based combination therapy ACT in malaria treatment, chloroquine resistant bacteria dissertation, is limited by the high cost, pill burden and currently emerging risk of decreased P.
falciparum parasite sensitivity [ 567 ]. Due to lack of current effective alternative agents to ACT, malaria treatment faces uncertain future which could expose populations most affected by the disease to the risk of increased malaria-associated mortality as previously seen with chloroquine [ 2 ].
Recent studies have indicated emergence of P. falciparum parasites susceptible to chloroquine following cessation of its use [ 4chloroquine resistant bacteria dissertation, 8 ], chloroquine resistant bacteria dissertation.
However, considerations to re-introduce chloroquine in malaria treatment is faced with the challenge of inadequacy of information on current extent of chloroquine sensitivity and the uncertainty over how this might affect future resistance. The current review was intended to collate evidence and provide current evidence on genotypic and phenotypic chloroquine resistance among P. falciparum parasites in malaria affected countries.
A systematic review protocol was developed following STREGA [ 9 ] and PRISMA-P [ 10 ] guidelines. The review sought to establish the prevalence of Pfcrt K76T and Pfmdr1 N86Y alleles among Plasmodium falciparum parasites in malaria affected countries since official discontinuation of chloroquine use in malaria treatment. Electronic search for Pubmed data base is reported in the published protocol [ 11 ].
The search terms were restricted to title and abstract during article search in each data base. There was no language restriction in article search, articles not published in English were translated using Google translator before screening for inclusion or exclusion.
The reference lists of included articles were screened and for any reference that could potentially be eligible for inclusion in the review, a full text article was retrieved. In addition, authors of included articles were contacted for any relevant publications on the review topic but did obtain any response. All article citations retrieved from database searches were exported into EndNote software version X7 Thomson Reuters, and duplicates removed.
The articles were grouped into relevant categories as indicated in the PRISMA flow diagram Fig. The titles and abstracts were screened using a priori criteria [ 11 ]. Articles that reported on at least one of the chloroquine resistance alleles, Pfcrt K76T or Pfmdr1 -N86Y were considered for inclusion. Articles that reported prevalence of the above chloroquine resistance alleles and genotyped more than P.
falciparum DNA samples were included. Studies that reported multiple parasite resistance genotype infections among patients were included in the review. Studies that assessed prevalence of resistance alleles Pfcrt K76T or Pfmdr1 -N86Y following cessation of chloroquine use in malaria treatment were included. The review included studies that assessed prevalence of chloroquine resistance alleles both before and after official discontinuation of chloroquine use in malaria treatment [ 11 ].
Citations whose full text articles could not be retrieved 02 were considered for exclusion Fig. A second librarian RSvalidated electronic search in PubMed by performing an independent and duplicate search. A second reviewer EAO screened all full text articles excluded by the first reviewer MO. Any discrepancies among the reviewers were resolved by discussion and consensus. Two reviewers NL and BB performed duplicate and independent data extraction.
Any disagreement between the reviewers was resolved by discussion and consensus. Any further disagreement between the two reviewers was referred to the third reviewer for a final decision MO. Data extraction form was developed in Excel spread sheetpre-tested on 5 articles and adjusted as appropriate. The following data was extracted from included articles, author, chloroquine resistant bacteria dissertation, citation, country where study was chloroquine resistant bacteria dissertation, study design, method of sample collection, years covered by data collection, year when chloroquine use was officially stopped, duration years since discontinuation of chloroquine use, whether chloroquine is still being used in the study area, In vitro assay IC 50genotyping success rate, DNA extraction method, laboratory where genotyping was done, prevalence of Pfcrt 76T before and after cessation in chloroquine use, prevalence of Pfmdr - 1 86Y before and after discontinuation of chloroquine use, trends in prevalence of chloroquine resistance alleles Pfcrt 76T, Pfmdr - 1 86Ynature of malaria transmission, prevalence of mixed genotype infections, prevalence of other mutations F, chloroquine resistant bacteria dissertation, D, Dand factors associated with chloroquine malaria treatment outcomes [ 11 ].
Descriptive data synthesis was conducted with findings from a single primary study being the unit of analysis. Sub-groups were created, region West Africa, East Africa, Southern Africa, and Asiastudy-design cross sectional, cohort, RCTs and non-randomized clinical trials. Extracted data was analyzed using Open Meta Analyst software [ 12 ]. Descriptive summaries of study outcomes were generated including; year of official cessation of chloroquine use, chloroquine in vitro IC 50duration from discontinuation of chloroquine use to data collection, chloroquine resistance alleles, factors associated with chloroquine resistance, genotyping success rate, allele calling algorithms, chloroquine use, and trends in genotypic chloroquine resistance.
DerSimonian—Laird DL random effects analysis was performed to establish a summary estimate of prevalence of P. falciparum Pfcrt 76T and Pfmdr1 86Y resistance chloroquine resistant bacteria dissertation in malaria affected regions using Open Meta Analyst software.
Sub-group analysis was performed, region East Africa, Southern Africa, chloroquine resistant bacteria dissertation, West Africa, Asia and study design cross sectional, Non-randomized clinical trials and RCTs. Heterogeneity in included articles was inferred from the summary estimates of I 2 - statistic. Due to high level of heterogeneity in the included studies the authors were chloroquine resistant bacteria dissertation to perform quantitative data analysis.
The variables that were missing from included articles were recorded as not reported. No statistical test was applied in handling missing data. However, available information was used in recalculating some variables in addition to contacting authors. In this method correlation of the articles is interpreted from the analysis output in Open Meta Analyst software where 1, represent perfect correlation and 0 no correlation.
Additional searches resulted in 03 articles. After removing duplicates, articles remained and their titles and abstracts were screened for inclusion using a priori criteria. A total of 3, articles were excluded after title and abstract screening. Full text chloroquine resistant bacteria dissertation the remaining articles were obtained and screened using a set criteria.
Two 02 citations were excluded as their full text could not be obtained. A total of articles were excluded as they did not meet the a priori inclusion criteria. Review data was extracted from a total of 38 articles that met the a priori inclusion criteria Fig.
Eleven 11 studies were conducted in East Africa, six 6 were from Southern Africa, fourteen 14 from West Africa and seven 7 from Asia Table 1. A total of twenty-six 26 studies were cross-sectional, eight 08 RCTs, three 03 non-randomized clinical trials and one 01 cohort study. For Pfcrt 76T allele, genotyping was done in a total of 28, DNA samples with 18, being successfully genotyped, While genotyping was done for Pfmdr - 1 86Y mutation in a total of 17, DNA samples with 16, being successfully genotyped, One study by Baraka et al.
The other 37 articles reported using either of the following DNA extraction methods, Chelex, Quiagen blood mini kit, Takara DNA blood mini kit, chloroquine resistant bacteria dissertation, phenol—chloroform, Accu-Prep Genomic DNA extraction kit, methanol fixation method, QIAxtractor system, and Nucleospin Genomic DNA blood pure kit. Sub-group analysis was done based on regions from where the studies were done, chloroquine resistant bacteria dissertation, East Africa, Southern Africa, chloroquine resistant bacteria dissertation, West Africa and Asia.
Heterogeneity was further assessed in sub-groups based on study designs Cross-sectional, RCTs and non-randomized trials. In East Africa, average prevalence of Pfcrt K76T resistance alleles is In Southern Africa, average prevalence of Pfcrt K76T resistance allele is In West Africa, chloroquine resistant bacteria dissertation, average prevalence of Pfcrt K76T resistance alleles is In Asia, the average prevalence of Pfcrt 76T resistance allele is A total of 26 studies were conducted following cross-sectional study design and reported average prevalence of chloroquine resistance alleles as Pfcrt 76T, Three studies were done following non-randomized clinical trial design and reported average prevalence of chloroquine resistance alleles as Pfcrt 76T, Eight studies used RCT design and reported average prevalence of chloroquine resistance alleles was Pfcrt 76T, These included, Mozambique [ 1617 ]; Kenya [ 18192021chloroquine resistant bacteria dissertation, 22 ]; Benin [ 23 chloroquine resistant bacteria dissertation Uganda [ 24 ]; Ghana [ 252627 ]; India [ 28 ]; Gabon [ 29 ]; Senegal [ 3031 ]; Cameroon [ 32 ]; Southern Thailand [ 33 ]; Guinea-Bissau [ 34 ]; Grande Comoros [ 35 ]; Malaysia [ 36 ] and Madagascar [ 37 ].
Of the 38 studies, only 4 Nine of the 38 studies were done after more than 10 years since cessation of chloroquine use. A study by Mungthin et al. Majority of countries officially stopped chloroquine use in malaria treatment in Range — India was the first country to stop chloroquine use chloroquine resistant bacteria dissertation Guinea-Bissau in West Africa continued using chloroquine in malaria treatment until The average duration of time since official change in malaria treatment policy to data collection of the individual included studies is 8.
Five studies,
Chloroquine \u0026 Hydroxychloroquine - Mechanism of Action, Targets (Malaria, Viruses), Adverse Effects
, time: 11:16
Nov 19, · On the Mechanism of Chloroquine Resistance in Plasmodium falciparum. Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine Cited by: 89 Mar 12, · This incomplete reversal of resistance is a drawback to efforts considering potential re-emerging role of chloroquine in malaria control and elimination efforts. Chloroquine resistance alleles Pfcrt 76T and Pfmdr-1 86Y are selected for by the current artemisinin-based combinations used in malaria treatment [57, 58]. The wide spread use of artemisinin agents in malaria treatment across malaria endemic regions could be contributing to the observed persistence of chloroquine resistance Cited by: 26 May 08, · Resistance" ().Theses and Dissertations (ETD). However, the emergence of bacterial resistance has limited the efficacy of sulfonamides, and an increasing trend in drug resistance has sulfadoxine and sulfalene in Chloroquine-resistant malaria combination with quinine. 3
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