scholarly journals Time to scale up molecular surveillance for anti-malarial drug resistance in sub-saharan Africa

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Christian Nsanzabana
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Ex Vivo ◽  
Scale Up ◽  
Artemisinin Resistance ◽  
Drug Efficacy ◽  
Sub Saharan Africa ◽  
Surveillance Systems ◽  
Early Emergence ◽  
Emergence Of Resistance

AbstractArtemisinin resistance has emerged and spread in the Greater Mekong Sub-region (GMS), followed by artemisinin-based combination therapy failure, due to both artemisinin and partner drug resistance. More worrying, artemisinin resistance has been recently reported and confirmed in Rwanda. Therefore, there is an urgent need to strengthen surveillance systems beyond the GMS to track the emergence or spread of artemisinin and partner drug resistance in other endemic settings. Currently, anti-malarial drug efficacy is monitored primarily through therapeutic efficacy studies (TES). Even though essential for anti-malarial drug policy change, these studies are difficult to conduct, expensive, and may not detect the early emergence of resistance. Additionally, results from TES may take years to be available to the stakeholders, jeopardizing their usefulness. Molecular markers are additional and useful tools to monitor anti-malarial drug resistance, as samples collected on dried blood spots are sufficient to monitor known and validated molecular markers of resistance, and could help detecting and monitoring the early emergence of resistance. However, molecular markers are not monitored systematically by national malaria control programmes, and are often assessed in research studies, but not in routine surveillance. The implementation of molecular markers as a routine tool for anti-malarial drug resistance surveillance could greatly improve surveillance of anti-malarial drug efficacy, making it possible to detect resistance before it translates to treatment failures. When possible, ex vivo assays should be included as their data could be useful complementary, especially when no molecular markers are validated.

scholarly journals Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!

2019 ◽  
Vol 4 (1) ◽  
pp. 26 ◽  
Author(s):  
Christian Nsanzabana
Keyword(s):  
Molecular Markers ◽  
Half Life ◽  
Artemisinin Resistance ◽  
Surveillance Systems ◽  
Combination Therapies ◽  
Artemisinin Derivatives ◽  
Steep Decrease ◽  
Almost All ◽  
Greater Mekong Subregion ◽  
Fast Acting

Artemisinin-based combination therapies (ACTs) have become the mainstay for malaria treatment in almost all malaria endemic settings. Artemisinin derivatives are highly potent and fast acting antimalarials; but they have a short half-life and need to be combined with partner drugs with a longer half-life to clear the remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased susceptibility to artemisinins have emerged in the Greater Mekong Subregion (GMS), followed by ACTs’ failure, due to both decreased susceptibility to artemisinin and partner drug resistance. Therefore, there is an urgent need to strengthen and expand current resistance surveillance systems beyond the GMS to track the emergence or spread of artemisinin resistance. Great attention has been paid to the spread of artemisinin resistance over the last five years, since molecular markers of decreased susceptibility to artemisinin in the GMS have been discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious partner drug. This review outlines the different mechanisms of resistance and molecular markers associated with resistance to partner drugs for the currently used ACTs. Strategies to improve surveillance and potential solutions to extend the useful therapeutic lifespan of the currently available malaria medicines are proposed.

scholarly journals Landscape analysis – assessing countries' readiness to scale up nutrition actions in the WHO African region

2012 ◽  
Vol 12 (52) ◽  
pp. 6260-6273
Author(s):  
U Trübswasser ◽  
◽  
C Nishida ◽  
K Engesveen ◽  
F Coulibaly-Zerbo ◽  
...  
Keyword(s):  
Child Nutrition ◽  
Scale Up ◽  
Landscape Analysis ◽  
Sub Saharan Africa ◽  
World Health ◽  
Surveillance Systems ◽  
African Region ◽  
Human Resource Capacity ◽  
World Health Assembly Resolution ◽  
Sub Saharan

The purpose of this paper is to describe the use of the Landscape Analysis to assess strengths and weaknesses in combating malnutrition in Sub-Saharan Africa. The Landscape Analysis is an inter-agency initiative to assess gaps and constraints and to identify opportunities for effective nutrition actions in order to accelerate intersectoral action for improving nutrition. In-depth Country Assessments to evaluate countries' "readiness" to scale up nutrition action have been conducted since 2008 in Sub-Saharan Africa. "Readiness" was assessed in terms of the commitment and capacity of each country and the focus was high stunting burden countries. The main focus was countries with heavy burden of undernutrition. From 2008 to September 2011, a total of 14 countries had undertaken the Landscape Analysis Country Assessment. Nine of them were in Africa: Burkina Faso, Comoros, Cote d’Ivoire, Ethiopia, Ghana, Madagascar, Mali, Mozambique, and South Africa. Three additional countries (Guinea, Namibia and Tanzania) were also planning to complete the Landscape Analysis Country Assessment in early 2012. From the findings in the nine countries, the following recommendations have been made: • Existing nutrition architectures and coordination mechanisms should be strengthened and better utilized; • Nutrition needs to be mainstreamed and integrated in relevant sector policies; • Advocacy at high levels is needed to highlight the importance of the lifecourse perspective, focusing particularly on nutrition interventions from preconception until the first two years of life; • National nutrition policies need to be translated into programmatic actions; • Human resource capacity for public health nutrition needs to be built with high quality in-service trainings in the short-term and long-term strategies to provide pre-service trainings; • Community-based outreach should be strengthened by using existing channels; • National nutrition surveillance systems need to be strengthened to ensure adequate use of data for monitoring, evaluation, and planning purposes. As part of the implementation of the 2010 World Health Assembly resolution on Infant and Young Child Nutrition (WHA 63.23) WHO has proposed a process to help countries in developing scale-up plans, which incorporates the Landscape Analysis Country Assessment as a tool to help countries in undertaking the initial context mapping. The countries that have already undertaken an in-depth Country Assessment, such as the Landscape Analysis Country Assessment, are ready to move forward in implementing the next steps in developing scaling-up plans to accelerate action in nutrition. At the same time, WHO will support additional countries that have expressed interest in conducting the Country Assessment.

scholarly journals Sustained Ex Vivo Susceptibility of Plasmodium falciparum to Artemisinin Derivatives but Increasing Tolerance to Artemisinin Combination Therapy Partner Quinolines in The Gambia

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Alfred Amambua-Ngwa ◽  
Joseph Okebe ◽  
Haddijatou Mbye ◽  
Sukai Ceesay ◽  
Fatima El-Fatouri ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Ex Vivo ◽  
Artemisinin Combination Therapy ◽  
Artemisinin Resistance ◽  
The Gambia ◽  
Microsatellite Variation

ABSTRACT Antimalarial interventions have yielded a significant decline in malaria prevalence in The Gambia, where artemether-lumefantrine (AL) has been used as a first-line antimalarial for a decade. Clinical Plasmodium falciparum isolates collected from 2012 to 2015 were analyzed ex vivo for antimalarial susceptibility and genotyped for drug resistance markers (pfcrt K76T, pfmdr1 codons 86, 184, and 1246, and pfk13) and microsatellite variation. Additionally, allele frequencies of single nucleotide polymorphisms (SNPs) from other drug resistance-associated genes were compared from genomic sequence data sets from 2008 (n = 79) and 2014 (n = 168). No artemisinin resistance-associated pfk13 mutation was found, and only 4% of the isolates tested in 2015 showed significant growth after exposure to dihydroartemisinin. Conversely, the 50% inhibitory concentrations (IC50s) of amodiaquine and lumefantrine increased within this period. pfcrt 76T and pfmdr1 184F mutants remained at a prevalence above 80%. pfcrt 76T was positively associated with higher IC50s to chloroquine. pfmdr1 NYD increased in frequency between 2012 and 2015 due to lumefantrine selection. The TNYD (pfcrt 76T and pfmdr1 NYD wild-type haplotype) also increased in frequency following AL implementation in 2008. These results suggest selection for pfcrt and pfmdr1 genotypes that enable tolerance to lumefantrine. Increased tolerance to lumefantrine calls for sustained chemotherapeutic monitoring in The Gambia to minimize complete artemisinin combination therapy (ACT) failure in the future.

scholarly journals No Polymorphism inPlasmodium falciparum K13Propeller Gene in Clinical Isolates from Kolkata, India

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Moytrey Chatterjee ◽  
Swagata Ganguly ◽  
Pabitra Saha ◽  
Biswabandhu Bankura ◽  
Nandita Basu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Artemisinin Resistance ◽  
Drug Regimen ◽  
Clinical Isolates ◽  
Wild Genotype ◽  
Emergence Of Resistance ◽  
Sulphadoxine Pyrimethamine

Molecular markers associated with artemisinin resistance inPlasmodium falciparumare yet to be well defined. Recent studies showed that polymorphisms inK13gene are associated with artemisinin resistance. The present study was designed to know the pattern of polymorphisms in propeller region ofK13gene among the clinical isolates collected from urban Kolkata after five years of ACT implementation. We collected 59 clinical isolates from urban Kolkata and sequenced propeller region ofK13gene in 51 isolates successfully. We did not find any mutation in any isolate. All patients responded to the ACT, a combination of artesunate + sulphadoxine-pyrimethamine. The drug regimen is still effective in the study area and there is no sign of emergence of resistance against artemisinin as evidenced by wild genotype ofK13gene in all isolates studied.

Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients

AIDS ◽  
2011 ◽  
Vol 25 (17) ◽  
pp. 2183-2188 ◽  
Author(s):  
Avelin F. Aghokeng ◽  
Charles Kouanfack ◽  
Christian Laurent ◽  
Eugenie Ebong ◽  
Arrah Atem-Tambe ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Treatment ◽  
Scale Up ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Drug Naïve ◽  
Sub Saharan ◽  
Hiv 1

scholarly journals Monitoring of efficacy, tolerability and safety of artemether–lumefantrine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Bayode R. Adegbite ◽  
Jean R. Edoa ◽  
Yabo J. Honkpehedji ◽  
Frejus J. Zinsou ◽  
Jean C. Dejon-Agobe ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Uncomplicated Malaria ◽  
Artemisinin Resistance ◽  
Public Health Problem ◽  
World Health ◽  
Major Public Health Problem ◽  
Open Label

Abstract Background Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (AS–AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS–AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86–100) and 95% (95% CI 84–99) for AL and AS–AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion This study showed that AL and AS–AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True

scholarly journals Geographic Differences in Antimalarial Drug Efficacy in Uganda Are Explained by Differences in Endemicity and Not by Known Molecular Markers of Drug Resistance

2006 ◽  
Vol 193 (7) ◽  
pp. 978-986 ◽  
Author(s):  
Damon Francis ◽  
Samuel L. Nsobya ◽  
Ambrose Talisuna ◽  
Adoke Yeka ◽  
Moses R. Kamya ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Antimalarial Drug ◽  
Drug Efficacy ◽  
Geographic Differences

scholarly journals Pre-existing partner-drug resistance facilitates the emergence and spread of artemisinin resistance: a consensus modelling study

2021 ◽  
Author(s):  
Oliver John Watson ◽  
Bo Gao ◽  
Tran Dang Nguyen ◽  
Thu Nguyen-Anh Tran ◽  
Melissa A Penny ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Artemisinin Resistance ◽  
Primary Outcome Measure ◽  
Health Concern ◽  
Drug Resistant ◽  
First Line ◽  
Resistance Evolution ◽  
First Line Therapy ◽  
Early Emergence ◽  
Resistant Genotypes

Background. Artemisinin-resistant genotypes have now emerged a minimum of five times on three continents despite recommendations that all artemisinins be deployed as artemisinin combination therapies (ACTs). Widespread resistance to the non-artemisinin partner drugs in ACTs has the potential to limit the clinical and resistance benefits provided by combination therapy. Methods. Using a consensus modelling approach with three individual-based mathematical models of Plasmodium falciparum transmission, we evaluate the effects of pre-existing partner-drug resistance and ACT deployment on artemisinin resistance evolution. We evaluate settings where dihydroartemisinin-piperaquine (DHA-PPQ), artesunate-amodiaquine (ASAQ), or artemether-lumefantrine (AL) are deployed as first-line therapy. We use time until 0.25 artemisinin resistance allele frequency (the establishment time) as the primary outcome measure. Findings. Higher frequencies of pre-existing partner-drug resistant genotypes lead to earlier establishment of artemisinin resistance. Across all scenarios and pre-existing frequencies of partner-drug resistance explored, a 0.10 increase in partner-drug resistance frequency on average corresponded to 0.7 to 5.0 years loss of artemisinin efficacy. However, the majority of reductions in time to artemisinin establishment were observed after the first increment from 0.0 to 0.10 partner-drug resistance genotype frequency. Interpretation. Partner-drug resistance in ACTs facilitates the early emergence of artemisinin resistance and is a major public health concern. Higher grade partner-drug resistance has the largest effect, with piperaquine-resistance accelerating early emergence of artemisinin-resistant alleles the most. Continued investment in molecular surveillance of partner-drug resistant genotypes to guide choice of first-line ACT is paramount.

scholarly journals A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Seidina A. S. Diakité ◽  
Karim Traoré ◽  
Ibrahim Sanogo ◽  
Taane G. Clark ◽  
Susana Campino ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Malaria Transmission ◽  
Resistance Gene ◽  
Artemisinin Resistance ◽  
Chloroquine Resistance ◽  
Malaria Control Programme ◽  
Codon Substitution

Abstract Background Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission. Methods Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger’s 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species. Results The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel. Conclusions This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel.

scholarly journals Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Najia Karim Ghanchi ◽  
Bushra Qurashi ◽  
Hadiqa Raees ◽  
Mohammad Asim Beg
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Single Nucleotide Polymorphisms ◽  
Low Frequency ◽  
Artemisinin Resistance ◽  
University Hospital ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Low Frequencies

Abstract Background K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan. Methods Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. The k13 propeller gene (k13) was amplified using nested PCR. Double-strand sequencing of PCR products was performed using Sanger sequencing methodology. Sequences were analysed with MEGA 6 and Bio edit software to identify specific SNP combinations. Results All isolates analysed for k13 propeller allele were observed as wild-type in samples collected post implementation of ACT in Pakistan. C580Y, A675V, Y493H and R539T variants associated with reduced susceptibility to artemisinin-based combination therapy (ACT) were not found. Low frequency of M476I and C469Y polymorphisms was found, which is significantly associated with artemisinin resistance. Conclusion Low frequencies of both nonsynonymous and synonymous polymorphisms were observed in P. falciparum isolates circulating in Southern Pakistan. The absence of known molecular markers of artemisinin resistance in this region is favourable for anti-malarial efficacy of ACT. Surveillance of anti-malarial drug resistance to detect its emergence and spread need to be strengthened in Pakistan.

Sign in / Sign up

Export Citation Format

Share Document