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Article ; Online: Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing.

2024 Volume 15, Issue 1, Page(s) 747

Abstract: The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical ... ...

Abstract	The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.
MeSH term(s)	Humans ; Senegal/epidemiology ; Cross-Sectional Studies ; Malaria/diagnosis ; Malaria/epidemiology ; Plasmodium ; Fever/epidemiology ; Borrelia/genetics
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-44800-7
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Article ; Online: R

Wong, Wesley / Volkman, Sarah / Daniels, Rachel / Schaffner, Stephen / Sy, Mouhamad / Ndiaye, Yaye Die / Badiane, Aida S / Deme, Awa B / Diallo, Mamadou Alpha / Gomis, Jules / Sy, Ngayo / Ndiaye, Daouda / Wirth, Dyann F / Hartl, Daniel L

PNAS nexus

2022 Volume 1, Issue 4, Page(s) pgac187

Abstract: Multiple-strain (polygenomic) infections are a ubiquitous feature ... ...

Abstract	Multiple-strain (polygenomic) infections are a ubiquitous feature of
Language	English
Publishing date	2022-09-10
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgac187
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Article ; Online: Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering.

Sy, Mouhamad / Deme, Awa B / Warren, Joshua L / Early, Angela / Schaffner, Stephen / Daniels, Rachel F / Dieye, Baba / Ndiaye, Ibrahima Mbaye / Diedhiou, Younous / Mbaye, Amadou Moctar / Volkman, Sarah K / Hartl, Daniel L / Wirth, Dyann F / Ndiaye, Daouda / Bei, Amy K

Scientific reports

2022 Volume 12, Issue 1, Page(s) 938

Abstract: Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control ... ...

Abstract	Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal-a region of exceptionally low malaria transmission (entomological inoculation rate less than 1). Genetic identity (identity by state, IBS) was established using a 24-single nucleotide polymorphism molecular barcode, identity by descent was calculated from whole genome sequence data, and a hierarchical Bayesian regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.
MeSH term(s)	Adolescent ; Animals ; Child ; Child, Preschool ; Cluster Analysis ; Cohort Studies ; Female ; Genome, Microbial/genetics ; Genomics/methods ; Genotype ; Humans ; Malaria/epidemiology ; Malaria/parasitology ; Malaria/transmission ; Malaria, Falciparum/parasitology ; Male ; Molecular Epidemiology/methods ; Physical Distancing ; Plasmodium falciparum/genetics ; Polymorphism, Single Nucleotide/genetics ; Senegal/epidemiology
Language	English
Publishing date	2022-01-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-04572-2
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Article ; Online: Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations.

Oboh, Mary A / Ndiaye, Tolla / Diongue, Khadim / Ndiaye, Yaye D / Sy, Mouhamad / Deme, Awa B / Diallo, Mamadou A / Yade, Mamadou S / Volkman, Sarah K / Badiane, Aida S / Amambua-Ngwa, Alfred / Ndiaye, Daouda

Malaria journal

2021 Volume 20, Issue 1, Page(s) 38

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 ... ...

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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Antigens, Protozoan/genetics ; Child ; Child, Preschool ; Female ; Genetic Variation ; Humans ; Infant ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/parasitology ; Male ; Merozoite Surface Protein 1/genetics ; Middle Aged ; Nigeria/epidemiology ; Plasmodium falciparum/genetics ; Protozoan Proteins/genetics ; Senegal/epidemiology ; Young Adult
Chemical Substances	Antigens, Protozoan ; Merozoite Surface Protein 1 ; Protozoan Proteins ; merozoite surface protein 2, Plasmodium
Language	English
Publishing date	2021-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-020-03563-4
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Article: Improving diagnosis of non-malarial fevers in Senegal:

medRxiv : the preprint server for health sciences

2023

Abstract	The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata from febrile patients and healthy controls in a low malaria burden area. Using 16S and unbiased sequencing, we detected viral, bacterial, or eukaryotic pathogens in 29% of NMFI cases. Bacteria were the most common, with relapsing fever
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.24.23294564
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Article ; Online: Quality assessment of malaria microscopic diagnosis at the Aristide Le Dantec University Hospital of Dakar, Senegal, in 2020.

Garba, Mamane N / Dème, Awa B / Diongue, Khadim / Diédhiou, Younousse / Mbaye, Amadou M / Dia, NDèye M / Seck, N'Dèye A / Zoumarou, Daba / Ndiaye, Lamine / Yade, Mamadou S / Dièye, Baba / Sène, Aita / Tine, Abdoulaye / Touré, Mariama / Gadiaga, Nogaye / Fall, Awa / Ngom, Bassirou / Sow, Djiby / Ndiaye, Aliou /

BMC research notes

2024 Volume 17, Issue 1, Page(s) 68

Abstract: Background: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In ... ...

Abstract	Background: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. Methods: This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists' ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. Results: A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. Conclusion: This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.
MeSH term(s)	Humans ; Senegal ; Reproducibility of Results ; Malaria/diagnosis ; Malaria/parasitology ; Laboratories ; Hospitals, University
Language	English
Publishing date	2024-03-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-023-06571-0
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Article ; Online: Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal.

Ndiaye, Tolla / Sy, Mouhamad / Gaye, Amy / Siddle, Katherine J / Park, Daniel J / Bei, Amy K / Deme, Awa B / Mbaye, Aminata / Dieye, Baba / Ndiaye, Yaye Die / Ndiaye, Ibrahima Mbaye / Diallo, Mamadou Alpha / Diongue, Khadim / Volkman, Sarah K / Badiane, Aida Sadikh / Ndiaye, Daouda

Malaria journal

2020 Volume 19, Issue 1, Page(s) 403

Abstract: Background: Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology ... ...

Abstract	Background: Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform. Methods: Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out. Results: A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1, a high positive Tajima's D (TD) value was observed in the South (D = 2.0453) while negative TD value was recorded in the North (D = - 1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2, non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas (p = 0.001). Conclusion: This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.
MeSH term(s)	Adolescent ; Adult ; Aged ; Antigens, Protozoan/genetics ; Child ; Child, Preschool ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Merozoite Surface Protein 1/genetics ; Middle Aged ; Molecular Epidemiology ; Plasmodium falciparum/genetics ; Protozoan Proteins/genetics ; Senegal ; Young Adult
Chemical Substances	Antigens, Protozoan ; Merozoite Surface Protein 1 ; Protozoan Proteins ; merozoite surface protein 2, Plasmodium
Language	English
Publishing date	2020-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-020-03471-7
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Article ; Online: Genomic investigation of a dengue virus outbreak in Thiès, Senegal, in 2018.

Scientific reports

2021 Volume 11, Issue 1, Page(s) 10321

Abstract: Dengue virus is a major and rapidly growing public health concern in tropic and subtropic regions across the globe. In late 2018, Senegal experienced its largest dengue virus outbreak to date, covering several regions. However, little is known about the ... ...

Abstract	Dengue virus is a major and rapidly growing public health concern in tropic and subtropic regions across the globe. In late 2018, Senegal experienced its largest dengue virus outbreak to date, covering several regions. However, little is known about the genetic diversity of dengue virus (DENV) in Senegal. Here we report complete viral genomes from 17 previously undetected DENV cases from the city of Thiès. In total we identified 19 cases of DENV in a cohort of 198 individuals with fever collected in October and November 2018. We detected 3 co-circulating serotypes; DENV 3 was the most frequent accounting for 11/17 sequences (65%), 4 (23%) were DENV2 and 2 (12%) were DENV1. Sequences were most similar to recent sequences from West Africa, suggesting ongoing local circulation of viral populations; however, detailed inference is limited by the scarcity of available genomic data. We did not find clear associations with reported clinical signs or symptoms, highlighting the importance of testing for diagnosing febrile diseases. Overall, these findings expand the known range of DENV in Senegal, and underscore the need for better genomic characterization of DENV in West Africa.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; DNA, Viral/isolation & purification ; Dengue/blood ; Dengue/diagnosis ; Dengue/epidemiology ; Dengue/virology ; Dengue Virus/genetics ; Dengue Virus/isolation & purification ; Disease Outbreaks/statistics & numerical data ; Female ; Genome, Viral ; Humans ; Male ; Middle Aged ; Molecular Epidemiology ; Phylogeny ; Senegal/epidemiology ; Serogroup ; Young Adult
Chemical Substances	DNA, Viral
Language	English
Publishing date	2021-05-14
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-89070-1
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Article ; Online: Genetic evidence for imported malaria and local transmission in Richard Toll, Senegal.

Daniels, Rachel F / Schaffner, Stephen F / Dieye, Yakou / Dieng, Gnagna / Hainsworth, Michael / Fall, Fatou B / Diouf, Coumba Ndoffene / Ndiop, Medoune / Cisse, Moustapha / Gueye, Alioune Badara / Sarr, Oumar / Guinot, Philippe / Deme, Awa B / Bei, Amy K / Sy, Mouhamad / Thwing, Julie / MacInnis, Bronwyn / Earle, Duncan / Guinovart, Caterina /

Sene, Doudou / Hartl, Daniel L / Ndiaye, Daouda / Steketee, Richard W / Wirth, Dyann F / Volkman, Sarah K

Malaria journal

2020 Volume 19, Issue 1, Page(s) 276

Abstract: Background: Malaria elimination efforts can be undermined by imported malaria infections. Imported infections are classified based on travel history.: Methods: A genetic strategy was applied to better understand the contribution of imported ... ...

Abstract	Background: Malaria elimination efforts can be undermined by imported malaria infections. Imported infections are classified based on travel history. Methods: A genetic strategy was applied to better understand the contribution of imported infections and to test for local transmission in the very low prevalence region of Richard Toll, Senegal. Results: Genetic relatedness analysis, based upon molecular barcode genotyping data derived from diagnostic material, provided evidence for both imported infections and ongoing local transmission in Richard Toll. Evidence for imported malaria included finding that a large proportion of Richard Toll parasites were genetically related to parasites from Thiès, Senegal, a region of moderate transmission with extensive available genotyping data. Evidence for ongoing local transmission included finding parasites of identical genotype that persisted across multiple transmission seasons as well as enrichment of highly related infections within the households of non-travellers compared to travellers. Conclusions: These data indicate that, while a large number of infections may have been imported, there remains ongoing local malaria transmission in Richard Toll. These proof-of-concept findings underscore the value of genetic data to identify parasite relatedness and patterns of transmission to inform optimal intervention selection and placement.
MeSH term(s)	Communicable Diseases, Imported/classification ; Communicable Diseases, Imported/epidemiology ; Communicable Diseases, Imported/parasitology ; Incidence ; Malaria, Falciparum/classification ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/isolation & purification ; Senegal/epidemiology
Language	English
Publishing date	2020-08-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-020-03346-x
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Article ; Online: Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal.

Malaria journal

2020 Volume 19, Issue 1, Page(s) 134

Abstract: Background: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple ... ...

Abstract	Background: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. Methods: Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal. Results: In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. Conclusion: As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.
MeSH term(s)	Antimalarials/pharmacology ; Artemisinins/pharmacology ; Drug Resistance ; High-Throughput Nucleotide Sequencing ; Mutation ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/genetics ; Polymorphism, Single Nucleotide ; Protozoan Proteins/genetics ; Senegal
Chemical Substances	Antimalarials ; Artemisinins ; Protozoan Proteins
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Journal Article
ISSN	1475-2875
ISSN (online)	1475-2875
DOI	10.1186/s12936-020-03193-w
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