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Mårtensson, Andreas
Publications (10 of 37) Show all publications
Amaratunga, C., Andrianaranjaka, V. H., Ashley, E., Bethell, D., Bjorkman, A., Bonnington, C. A., . . . Woodrow, C. (2019). Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments: a WWARN individual patient data meta-analysis. BMC Medicine, 17, 1-20, Article ID 1.
Open this publication in new window or tab >>Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments: a WWARN individual patient data meta-analysis
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2019 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 17, p. 1-20, article id 1Article in journal (Refereed) Published
Abstract [en]

Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have identified almost 200 different non-synonymous mutant pfk13 genotypes. Most mutations occur at low prevalence and have uncertain functional significance. To characterize the impact of different pfk13 mutations on parasite clearance, we conducted an individual patient data meta-analysis of the associations between parasite clearance half-life (PC1/2) and pfk13 genotype based on a large set of individual patient records from Asia and Africa.

Methods: A systematic literature review following the PRISMA protocol was conducted to identify studies published between 2000 and 2017 which included frequent parasite counts and pfk13 genotyping. Four databases (Ovid Medline, PubMed, Ovid Embase, and Web of Science Core Collection) were searched. Eighteen studies (15 from Asia, 2 from Africa, and one multicenter study with sites on both continents) met inclusion criteria and were shared. Associations between the log transformed PC1/2 values and pfk13 genotype were assessed using multivariable regression models with random effects for study site.

Results: Both the pfk13 genotypes and the PC1/2 were available from 3250 (95%) patients (n=3012 from Asia (93%), n=238 from Africa (7%)). Among Asian isolates, all pfk13 propeller region mutant alleles observed in five or more specific isolates were associated with a 1.5- to 2.7-fold longer geometric mean PC1/2 compared to the PC1/2 of wild type isolates (all p≤0.002). In addition, mutant allele E252Q located in the P. falciparum region of pfk13 was associated with 1.5-fold (95%CI 1.4-1.6) longer PC1/2. None of the isolates from four countries in Africa showed a significant difference between the PC1/2 of parasites with or without pfk13 propeller region mutations.Previously, the association of six pfk13 propeller mutant alleles with delayed parasite clearance had been confirmed. This analysis demonstrates that 15 additional pfk13 alleles are associated strongly with the slow-clearing phenotype in Southeast Asia.

Conclusion: Pooled analysis associated 20 pfk13 propeller region mutant alleles with the slow clearance phenotype, including 15 mutations not confirmed previously.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-375814 (URN)10.1186/s12916-018-1207-3 (DOI)000455890500001 ()30651111 (PubMedID)
Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-02-01Bibliographically approved
Dahal, P., Simpson, J. A., Abdulla, S., Achan, J., Adam, I., Agarwal, A., . . . Stepniewska, K. (2019). Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis. Malaria Journal, 18, Article ID 225.
Open this publication in new window or tab >>Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
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2019 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 18, article id 225Article in journal (Refereed) Published
Abstract [en]

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.

Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.

Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.

Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Plasmodium falciparum, Treatment efficacy study, Competing risk event
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-391014 (URN)10.1186/s12936-019-2837-4 (DOI)000474589900001 ()31277713 (PubMedID)
Funder
Wellcome trust, 200909
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved
Ghindilis, A. L., Chesnokov, O., Ngasala, B., Smith, M. W., Smith, K., Mårtensson, A. & Oleinikov, A. V. (2019). Detection of sub-microscopic blood levels of Plasmodium falciparum using Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) assay with an attomolar detection limit. Scientific Reports, 9, Article ID 2901.
Open this publication in new window or tab >>Detection of sub-microscopic blood levels of Plasmodium falciparum using Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) assay with an attomolar detection limit
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2901Article in journal (Refereed) Published
Abstract [en]

Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) based on signal rather than target amplification under isothermal conditions was developed for nucleic acid assays. The initial signal was generated by hybridization of single stranded DNA targets to immobilized recognition probes followed by hybrid cleavage with specific restriction endonuclease (REase), and release of trigger oligonucleotides (Tr1). The signal amplification chamber contained two bead types carrying single-stranded amplification probes and two amplification REases. The probes consisted of multiple tandem repeats of either Tr1 or another trigger Tr2, with the tandem-Tr1 anchored to the beads through the antisense Tr2 linker and vice versa. Addition of the recognition reaction solution and Tr1 hybridization to the anti-Tr1 linkers started cleavage and release of additional Tr1 and Tr2, resulting in exponential signal amplification. The cleavage cascade also released horseradish peroxidase (HRP) pre-attached to the amplification probes, and the resultant signal was measured colorimetrically. A TORCA assay was developed for detection of Plasmodium falciparum parasites in blood. It had the detection limit in the attomolar concentration range, successfully detecting sub-microscopic P. falciparum infections at less than 0.75 infected erythrocytes per microliter. Further TORCA optimization will likely produce the quantitative isothermal alternative to PCR at a fraction of its cost.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-379581 (URN)10.1038/s41598-019-39921-9 (DOI)000459799800050 ()30814636 (PubMedID)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Björkman, A., Shakely, D., Ali, A. S., Morris, U., Mkali, H., Abbas, A. K., . . . Mårtensson, A. (2019). From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination. BMC Medicine, 17, Article ID 14.
Open this publication in new window or tab >>From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination
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2019 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 17, article id 14Article in journal (Refereed) Published
Abstract [en]

Substantial global progress in the control of malaria in recent years has led to increased commitment to its potential elimination. Whether this is possible in high transmission areas of sub-Saharan Africa remains unclear. Zanzibar represents a unique case study of such attempt, where modern tools and strategies for malaria treatment and vector control have been deployed since 2003. We have studied temporal trends of comprehensive malariometric indices in two districts with over 100,000 inhabitants each. The analyses included triangulation of data from annual community-based cross-sectional surveys, health management information systems, vital registry and entomological sentinel surveys. The interventions, with sustained high-community uptake, were temporally associated with a major malaria decline, most pronounced between 2004 and 2007 and followed by a sustained state of low transmission. In 2015, the Plasmodium falciparum community prevalence of 0.43% (95% CI 0.23-0.73) by microscopy or rapid diagnostic test represented 96% reduction compared with that in 2003. The P. falciparum and P. malariae prevalence by PCR was 1.8% (95% CI 1.3-2.3), and the annual P. falciparum incidence was estimated to 8 infections including 2.8 clinical episodes per 1000 inhabitants. The total parasite load decreased over 1000-fold (99.9%) between 2003 and 2015. The incidence of symptomatic malaria at health facilities decreased by 94% with a trend towards relatively higher incidence in age groups > 5 years, a more pronounced seasonality and with reported travel history to/from Tanzania mainland as a higher risk factor. All-cause mortality among children < 5 years decreased by 72% between 2002 and 2007 mainly following the introduction of artemisinin-based combination therapies whereas the main reduction in malaria incidence followed upon the vector control interventions from 2006. Human biting rates decreased by 98% with a major shift towards outdoor biting by Anopheles arabiensis. Zanzibar provides new evidence of the feasibility of reaching uniquely significant and sustainable malaria reduction (pre-elimination) in a previously high endemic region in sub-Saharan Africa. The data highlight constraints of optimistic prognostic modelling studies. New challenges, mainly with outdoor transmission, a large asymptomatic parasite reservoir and imported infections, require novel tools and reoriented strategies to prevent a rebound effect and achieve elimination.

Place, publisher, year, edition, pages
BMC, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-377702 (URN)10.1186/s12916-018-1243-z (DOI)000458075500001 ()30665398 (PubMedID)
Funder
Swedish Research CouncilSwedish Civil Contingencies AgencyWellcome trust
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Rhedin, S. A., Eklundh, A., Ryd-Rinder, M., Naucler, P., Mårtensson, A., Gantelius, J., . . . Alfven, T. (2019). Introducing a New Algorithm for Classification of Etiology in Studies on Pediatric Pneumonia: Protocol for the Trial of Respiratory Infections in Children for Enhanced Diagnostics Study. JMIR Research Protocols, 8(4), Article ID e12705.
Open this publication in new window or tab >>Introducing a New Algorithm for Classification of Etiology in Studies on Pediatric Pneumonia: Protocol for the Trial of Respiratory Infections in Children for Enhanced Diagnostics Study
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2019 (English)In: JMIR Research Protocols, ISSN 1929-0748, E-ISSN 1929-0748, Vol. 8, no 4, article id e12705Article in journal (Refereed) Published
Abstract [en]

Background: There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics.

Objective: The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovims resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens.

Methods: Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification-based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard.

Results: A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019.

Conclusions: The findings from the TREND study can be an important step to improve the management of children with clinical CAP.

Place, publisher, year, edition, pages
JMIR PUBLICATIONS, INC, 2019
Keywords
pneumonia, child, preschool, respiratory tract infections, microbiological techniques, diagnostic tests, routine
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-387222 (URN)10.2196/12705 (DOI)000466496800030 ()31025954 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, ALF-20150503EU, FP7, Seventh Framework Programme, HMT-20150818EU, FP7, Seventh Framework Programme, 615458
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Silva, M., Ferreira, P. E., Otienoburu, S. D., Calçada, C., Ngasala, B., Björkman, A., . . . Veiga, M. I. (2019). Plasmodium falciparum K13 expression associated with parasite clearance during artemisinin-based combination therapy. Journal of Antimicrobial Chemotherapy, 74(7), 1890-1893
Open this publication in new window or tab >>Plasmodium falciparum K13 expression associated with parasite clearance during artemisinin-based combination therapy
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 7, p. 1890-1893Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Delayed parasite clearance and, consequently, reduced efficacy of artemisinin-based combination therapies have been linked with Plasmodium falciparum K13 gene SNPs in Southeast Asia. In Africa, significantly prolonged clearance has not yet been observed and the presently restricted variation in parasite clearance cannot be explained by K13 polymorphisms.

OBJECTIVES: Our aim was to study the in vivo pfK13 transcriptional response in patients treated with artemether-lumefantrine and explore whether the pfk13 transcripts can explain the patients' parasite clearance outcomes.

PATIENTS AND METHODS: A total of 47 Tanzanian children with microscopically confirmed uncomplicated P. falciparum malaria were hospitalized and received artemether-lumefantrine treatment (clinical trial ID: NCT00336375). RNA was extracted from venous blood samples collected before treatment initiation and at five more timepoints after treatment. cDNA was synthesized and pfk13 transcripts measured by real-time PCR.

RESULTS: A wide range of pfk13 transcript variation was observed throughout all timepoints after artemether-lumefantrine treatment. Taking parasite clearance data together with the pfk13 transcripts profile, we observed a negative correlation inferring that pfk13 down-regulation is associated with longer parasite clearance time.

CONCLUSIONS: The findings suggest that a reduced PfK13 transcriptional response may represent a first step towards artemisinin tolerance/resistance.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-389948 (URN)10.1093/jac/dkz098 (DOI)000474267600019 ()30869127 (PubMedID)
Funder
Swedish Research Council, VR-2014-3134Sida - Swedish International Development Cooperation Agency, SWE-200-165
Available from: 2019-08-01 Created: 2019-08-01 Last updated: 2019-09-13Bibliographically approved
Mwaiswelo, R., Ngasala, B., Jovel, I., Xu, W., Larsson, E., Malmberg, M., . . . Mårtensson, A. (2019). Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania.. American Journal of Tropical Medicine and Hygiene, 100(5), 1179-1186
Open this publication in new window or tab >>Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania.
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2019 (English)In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 100, no 5, p. 1179-1186Article in journal (Refereed) Published
Abstract [en]

Prevalence of and risk factors associated with polymerase chain reaction (PCR)-determined Plasmodium falciparum positivity were assessed on day 3 after initiation of treatment, pre-implementation and up to 8 years post-deployment of artemether-lumefantrine as first-line treatment for uncomplicated malaria in Bagamoyo district, Tanzania. Samples originated from previously reported trials conducted between 2006 and 2014. Cytochrome b-nested PCR was used to detect malaria parasites from blood samples collected on a filter paper on day 3. Chi-square and McNemar chi-squared tests, logistic regression models, and analysis of variance were used as appropriate. Primary outcome was based on the proportion of patients with day 3 PCR-determined P. falciparum positivity. Overall, 256/584 (43.8%) of screened patients had day 3 PCR-determined positivity, whereas only 2/584 (0.3%) had microscopy-determined asexual parasitemia. Day 3 PCR-determined positivity increased from 28.0% (14/50) in 2006 to 74.2% (132/178) in 2007-2008 and declined, thereafter, to 36.0% (50/139) in 2012-2013 and 27.6% (60/217) in 2014. When data were pooled, pretreatment microscopy-determined asexual parasitemia ≥ 100,000/µL, hemoglobin < 10 g/dL, age < 5 years, temperature ≥ 37.5°C, and year of study 2007-2008 and 2012-2013 were significantly associated with PCR-determined positivity on day 3. Significant increases in P. falciparum multidrug resistance gene 1 N86 and P. falciparum chloroquine resistant transporter K76 across years were not associated with PCR-determined positivity on day 3. No statistically significant association was observed between day 3 PCR-determined positivity and PCR-adjusted recrudescence. Day 3 PCR-determined P. falciparum positivity remained common in patients treated before and after implementation of artemether-lumefantrine in Bagamoyo district, Tanzania. However, its presence was associated with pretreatment characteristics. Trials registration numbers: NCT00336375, ISRCTN69189899, NCT01998295, and NCT02090036.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-389947 (URN)10.4269/ajtmh.18-0729 (DOI)30860013 (PubMedID)
Available from: 2019-08-01 Created: 2019-08-01 Last updated: 2019-08-01
Morris, U., Msellem, M. I., Mkali, H., Islam, A., Aydin-Schmidt, B., Jovel, I., . . . Björkman, A. (2018). A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission.. BMC Medicine, 16(1), Article ID 215.
Open this publication in new window or tab >>A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission.
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2018 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, no 1, article id 215Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Mass drug administration (MDA) has the potential to interrupt malaria transmission and has been suggested as a tool for malaria elimination in low-endemic settings. This study aimed to determine the effectiveness and safety of two rounds of MDA in Zanzibar, a pre-elimination setting.

METHODS: A cluster randomised controlled trial was conducted in 16 areas considered as malaria hotspots, with an annual parasite index of > 0.8%. The areas were randomised to eight intervention and eight control clusters. The intervention included two rounds of MDA with dihydroartemisinin-piperaquine and single low-dose primaquine 4 weeks apart in May-June 2016. Primary and secondary outcomes were cumulative confirmed malaria case incidences 6 months post-MDA and parasite prevalences determined by PCR 3 months post-MDA. Additional outcomes included intervention coverage, treatment adherence, occurrence of adverse events, and cumulative incidences 3, 12, and 16 months post-MDA.

RESULTS: Intervention coverage was 91.0% (9959/10944) and 87.7% (9355/10666) in the first and second rounds, respectively; self-reported adherence was 82.0% (881/1136) and 93.7% (985/1196). Adverse events were reported in 11.6% (147/1268) and 3.2% (37/1143) of post-MDA survey respondents after both rounds respectively. No serious adverse event was reported. No difference in cumulative malaria case incidence was observed between the control and intervention arms 6 months post-MDA (4.2 and 3.9 per 1000 population; p = 0.94). Neither was there a difference in PCR-determined parasite prevalences 3 months post-MDA (1.4% and 1.7%; OR = 1.0, p = 0.94), although having received at least the first MDA was associated with reduced odds of malaria infection (aOR = 0.35; p = 0.02). Among confirmed malaria cases at health facilities, 26.0% and 26.3% reported recent travel outside Zanzibar in the intervention and control shehias (aOR ≥ 85; p ≤ 0.001).

CONCLUSIONS: MDA was implemented with high coverage, adherence, and tolerability. Despite this, no significant impact on transmission was observed. The findings suggest that two rounds of MDA in a single year may not be sufficient for a sustained impact on transmission in a pre-elimination setting, especially when the MDA impact is restricted by imported malaria. Importantly, this study adds to the limited evidence for the use of MDA in low transmission settings in sub-Saharan Africa.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721186 (registration date: March 29, 2016).

Keywords
Adherence, Coverage, Dihydroartemisinin-piperaquine, Effectiveness, Elimination, Low transmission, Malaria, Mass drug administration, Safety, Single low-dose primaquine
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-369728 (URN)10.1186/s12916-018-1202-8 (DOI)000452741600001 ()30526588 (PubMedID)
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2019-01-15Bibliographically approved
Rivas, L., Reuterswärd, P., Rasti, R., Herrmann, B., Mårtensson, A., Alfven, T., . . . Andersson-Svahn, H. (2018). A vertical flow paper-microarray assay with isothermal DNA amplification for detection of Neisseria meningitidis. Talanta: The International Journal of Pure and Applied Analytical Chemistry, 183, 192-200
Open this publication in new window or tab >>A vertical flow paper-microarray assay with isothermal DNA amplification for detection of Neisseria meningitidis
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2018 (English)In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 183, p. 192-200Article in journal (Refereed) Published
Abstract [en]

Paper-based biosensors offer a promising technology to be used at the point of care, enabled by good performance, convenience and low-cost. In this article, we describe a colorimetric vertical-flow DNA microarray (DNAVFM) that takes advantage of the screening capability of DNA microarrays in a paper format together with isothermal amplification by means of Recombinase Polymerase Amplification (RPA). Different assay parameters such as hybridization buffer, flow rate, printing buffer and capture probe concentration were optimized. A limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop scanning. The DNA-VFM was applied as a proof of concept for detection of Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was determined to be between 38 and 2.1 x 10(6) copies/VFMassay, depending on the choice of DNA capture probes. The presented approach provides multiplex capabilities of DNA microarrays in a paper-based format for future point-of-care applications.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Microarray, Paper-based biosensor, Point-of-care, Gold nanoparticles, Neisseria meningitidis
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-356185 (URN)10.1016/j.talanta.2018.02.070 (DOI)000430645800026 ()29567164 (PubMedID)
Funder
Swedish Research CouncilEU, European Research Council, 615458
Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-02Bibliographically approved
Inoue, J., Jovel, I., Morris, U., Aydin-Schmidt, B., Islam, A., Segurado, A. C., . . . Mårtensson, A. (2018). Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field Isolates Collected from the Brazilian Amazon Basin between 1984 and 2011. American Journal of Tropical Medicine and Hygiene, 99(6), 1504-1507
Open this publication in new window or tab >>Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field Isolates Collected from the Brazilian Amazon Basin between 1984 and 2011
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2018 (English)In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 99, no 6, p. 1504-1507Article in journal (Refereed) Published
Abstract [en]

Artemisinin resistance, presently confined to Southeast Asia and associated with mutations in the Plasmodium falciparum K13 (PfK13) propeller domain, represents a serious threat to global malaria control. This study aimed to provide baseline information for future artemisinin resistance surveillance, by analyzing the PfK13 propeller domain in P. falciparum field isolates collected from the Brazilian Amazon Basin between 1984 and 2011. A total of 152 P. falciparum mono-infections were assessed, of which 118 (78%) were collected before and 34 (22%) after the introduction of artemisinin-based combination therapy (ACT) in 2006. An 849-base pair fragment encoding the PfK13 propeller was amplified by nested PCR and sequenced in both directions. The sequences were compared with the reference sequence of P. falciparum 3D7. All samples showed wild-type sequences, thus, no mutations were observed. The results are in agreement with other recent reports and do not provide evidence for presence of PfK13 propeller domain polymorphisms associated with artemisinin resistance among P. falciparum field isolates in the Brazilian Amazon Basin neither before nor after the implementation of ACT.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-364659 (URN)10.4269/ajtmh.18-0554 (DOI)000452400500025 ()30277206 (PubMedID)
Available from: 2018-10-30 Created: 2018-10-30 Last updated: 2019-01-21Bibliographically approved
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