Plasmodium falciparum drug resistance gene status in the Horn of Africa: A systematic review

Jalei, Abdifatah Abdullahi; Chai่jaroenkul, Wanna; Na‐Bangchang, Kesara

doi:10.5897/ajpp2018.4942

Cited by 8 publications

(5 citation statements)

References 37 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Commercial slide scanning and detection systems show promise [26, 27] but are currently expensive. With persisting high burden of malaria [28] and the rise of drug resistance strains [29, 30, 31], affordable, high-throughput and quantitative diagnostic tests are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

Soto-Montoya

Voisin

et al. 2019

Preprint

View full text Add to dashboard Cite

Access to quantitative, robust, yet affordable diagnostic tools is necessary to reduce global infectious disease burden. Manual microscopy has served as a bedrock for diagnostics with wide adaptability, although at a cost of tedious labor and human errors. Automated robotic microscopes are poised to enable a new era of smart field microscopy but current platforms remain cost prohibitive and largely inflexible, especially for resource poor and field settings. Here we present Octopi, a low-cost ($250-$500) and reconfigurable autonomous microscopy platform capable of automated slide scanning and correlated bright-field and fluorescence imaging. Being highly modular, it also provides a framework for new disease-specific modules to be developed.We demonstrate the power of the platform by applying it to automated detection of malaria parasites in blood smears. Specifically, we discovered a spectral shift on the order of 10 nm for DAPI-stained Plasmodium falciparum malaria parasites. This shift allowed us to detect the parasites with a low magnification (equivalent to 10x) large field of view (2.56 mm 2 ) module.Combined with automated slide scanning, real time computer vision and machine learningbased classification, Octopi is able to screen more than 1.5 million red blood cells per minute for parasitemia quantification, with estimated diagnostic sensitivity and specificity exceeding 90% at parasitemia of 50/ul and 100% for parasitemia higher than 150/l. With different modules, we further showed imaging of tissue slice and sputum sample on the platform. With roughly two orders of magnitude in cost reduction, Octopi opens up the possibility of a large robotic microscope network for improved disease diagnosis while providing an avenue for collective efforts for development of modular instruments.One sentence summary: We developed a low-cost ($250-$500) automated imaging platform that can quantify malaria parasitemia by scanning 1.5 million red blood cells per minute.Lack of cost-effective diagnostics is a major hurdle in global fight against infectious disease, 2 specially in resource poor settings [1]. This leaves our world in a highly vulnerable position 3 with therapeutic drugs being either overused, leading to drug resistant strains or not acces-4 sible to people who actually need these treatments [2]. Since health care is delivered around 5 the world in a tiered structure, local context such as high cost, lack of trained personal or 6 low throughput of many available diagnostics tests plays a large detrimental role on quality 7 of delivered health-care [3]. 8 Because of the versatility and wide adoption of manual microscopy [4] and its role in 9 direct visual identification of parasites [5], it remains a WHO gold standard for numerous 10 diseases [1]. Despite technological advancements in related fields, the practice of conventional 11 manual microscopy has remained largely unchanged over the last half century and suffers 12 from several drawbacks. With an average lab technician spending 6 to 8 hours imaging and 13 ...

show abstract

Section: Introductionmentioning

confidence: 99%

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

Soto-Montoya

Voisin

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Across malaria-endemic regions, large-scale deployment of anti-malarial drugs has led to the emergence of drug resistance to chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) antifolate drugs [ 3 – 5 ]. Like many other countries, Ethiopia has switched from CQ to SP in 1998 and from SP to artemether–lumefantrine (AL) in 2004 [ 6 ] for the treatment of uncomplicated P. falciparum malaria in response to the development of parasite resistance.…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

Abera

Kibet

Degefa

et al. 2021

Malar J

View full text Add to dashboard Cite

Background Plasmodium falciparum parasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was a paucity of data on genomic characterization and evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. Methods Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine their genetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi. Results A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified in Ethiopian P. falciparum isolates. About 84% of the Ethiopian P. falciparum isolates had a FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within-host diversity of Ethiopian infections was significantly different from East African (p < 0.001), but not Southeast Asian infections (P > 0.05). A significant population structure has been observed by PCA and population differentiation between Ethiopian parasites and East African (Fst ~ 10%) and Southeast Asian populations (Fst ~ 18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection was found that include ama1, trap, eba175, and lsa3, previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13. Conclusion Plasmodium falciparum populations in the central region of Ethiopia was structurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.

show abstract

“…Across malaria-endemic regions, large-scale deployment of antimalarial drugs has led to the emergence of drug resistance to chloroquine (CQ) and Sulfadoxine/Pyrimethamine (SP) antifolate drugs [3][4][5]. Like many other countries, Ethiopia has switched from CQ to SP in 1998 and from SP to AL in 2004 [6]for the treatment of uncomplicated P. falciparum malaria in response to the development of parasite resistance.…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

Beyene

Kibet

Degefa

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Plasmodium falciparumparasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there wasthe paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. Method: Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine theirgenetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi.Result: A total of 18,517high-quality single-nucleotide polymorphisms (SNPs) were identifiedin Ethiopian P. falciparum isolates.About 84% of the Ethiopian P. falciparum isolates hadan FWS value >0.95showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areaswith low transmission intensity. Within host diversity of Ethiopian infectionswas significantly differentfrom East African (p < 0.001) but not Southeast Asian infections (P >0.05). We observed significant population structureby PCA andpopulation differentiation between Ethiopian parasitesand East Africa (Fst~ 10%) and Southeast Asia populations (Fst ~18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, we found a total of 125 genes under balancing selection that includedama1, trap, eba175, and lsa3previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt,Pfdhfr,Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13.Conclusion: Plasmodium falciparumpopulation in the central region of Ethiopia wasstructurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carryfixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.

show abstract

Plasmodium falciparum drug resistance gene status in the Horn of Africa: A systematic review

Cited by 8 publications

References 37 publications

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

Contact Info

Product

Resources

About