[This corrects the article DOI: 10.3389/fimmu.2019.02480.]

Bejon, Philip

Blagborough, Andrew M

Bousema, Teun

Kamau, Alice

Kapulu, Melissa C

Muthui, Michelle K

Frontiers in Immunology

English

Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas.

Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression.

Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (β coefficient 0.21, 95% CI: 0.05–0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates.

Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses.MM and AK are funded via IDeAL Ph.D. Studentships awarded by the KEMRI-Wellcome Trust Research Programme through funding from the DELTAS Africa programme via the Wellcome Trust (107769). TB was supported by a grant from The Netherlands Organization for Scientific Research (Vidi fellowship; NWO Project 016.158.306). AB was funded by the MRC (New Investigator Research Grant; award number MR/N00227X/1) and the University of Cambridge JRG. PB and MK were supported by a Wellcome Trust grant (107499)

Apollo (Cambridge)

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population—The African falciparum Context: A Systematic Review and Meta-Analysis

Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas. Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression. Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (β coefficient 0.21, 95% CI: 0.05–0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates. Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses

Muthui, MK

Kamau, A

Bousema, T

Blagborough, AM

Bejon, P

Kapulu, MC

Spiral - Imperial College Digital Repository

Immune responses to gametocyte antigens in a malaria endemic population-the African falciparum context: a systematic review and meta-analysis

Muthui, Michelle K.

Blagborough, Andrew M.

Kapulu, Melissa C.

Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas. Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression. Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (beta coefficient 0.21, 95% CI: 0.05-0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates. Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses

Muthui, M.K.

Kamau, A.

Bousema, T.

Blagborough, A.M.

Bejon, P.

Kapulu, M.C.

NARCIS 

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population-The African falciparum Context: A Systematic Review and Meta-Analysis.

Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas. Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression. Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (β coefficient 0.21, 95% CI: 0.05-0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates. Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses

Kapulu, Melissa

Oxford University Research Archive

Immune responses to gametocyte antigens in a malaria endemic population—the African falciparum context: a systematic review and meta-analysis

Contains fulltext :
                  215640.pdf (publisher's version ) (Open Access)Background: Malaria elimination remains a priority research agenda with the need for interventions that reduce and/or block malaria transmission from humans to mosquitoes. Transmission-blocking vaccines (TBVs) are in development, most of which target the transmission stage (i.e., gametocyte) antigens Pfs230 and Pfs48/45. For these interventions to be implemented, there is a need to understand the naturally acquired immunity to gametocytes. Several studies have measured the prevalence of immune responses to Pfs230 and Pfs48/45 in populations in malaria-endemic areas. Methods: We conducted a systematic review of studies carried out in African populations that measured the prevalence of immune responses to the gametocyte antigens Pfs230 and Pfs48/45. We assessed seroprevalence of antibody responses to the two antigens and investigated the effects of covariates such as age, transmission intensity/endemicity, season, and parasite prevalence on the prevalence of these antibody responses by meta-regression. Results: We identified 12 studies covering 23 sites for inclusion in the analysis. We found that the range of reported seroprevalence to Pfs230 and Pfs48/45 varied widely across studies, from 0 to 64% for Pfs48/45 and from 6 to 72% for Pfs230. We also found a modest association between increased age and increased seroprevalence to Pfs230: adults were associated with higher seroprevalence estimates in comparison to children (beta coefficient 0.21, 95% CI: 0.05-0.38, p = 0.042). Methodological factors were the most significant contributors to heterogeneity between studies which prevented calculation of pooled prevalence estimates. Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses

Radboud Repository

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population-The African falciparum Context: A Systematic Review and Meta-Analysis

Oxford University Research Archive (ORA)

CORRECTIONpublished: 23 March 2020doi: 10.3389/fimmu.2020.00389Frontiers in Immunology | www.frontiersin.org 1 March 2020 | Volume 11 | Article 389Edited and reviewed by:Ian Marriott,University of North Carolina atCharlotte, United States*Correspondence:Michelle K. Muthuimmuthui@kemri-wellcome.orgSpecialty section:This article was submitted toMicrobial Immunology,a section of the journalFrontiers in ImmunologyReceived: 15 January 2020Accepted: 19 February 2020Published: 23 March 2020Citation:Muthui MK, Kamau A, Bousema T,Blagborough AM, Bejon P andKapulu MC (2020) Corrigendum:Immune Responses to GametocyteAntigens in a Malaria EndemicPopulation—The African falciparumContext: A Systematic Review andMeta-Analysis.Front. Immunol. 11:389.doi: 10.3389/fimmu.2020.00389Corrigendum: Immune Responses toGametocyte Antigens in a MalariaEndemic Population—The Africanfalciparum Context: A SystematicReview and Meta-AnalysisMichelle K. Muthui 1*, Alice Kamau 1, Teun Bousema 2,3, Andrew M. Blagborough 4,5,Philip Bejon 1,6 and Melissa C. Kapulu 1,61Department of Biosciences, KEMRI-Wellcome Trust Programme, Kilifi, Kenya, 2 Immunology and Infection Department,London School of Hygiene and Tropical Medicine, London, United Kingdom, 3 Radboud Institute for Health Sciences,Radboud University Medical Center, Nijmegen, Netherlands, 4Department of Life Sciences, Imperial College London,London, United Kingdom, 5Department of Pathology, University of Cambridge, Cambridge, United Kingdom, 6NuffieldDepartment of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United KingdomKeywords: immunity, Plasmodium falciparum, gametocytes, Pfs230, Pfs48/45A Corrigendum onImmune Responses to Gametocyte Antigens in a Malaria Endemic Population—The Africanfalciparum Context: A Systematic Review and Meta-AnalysisbyMuthui, M. K., Kamau, A., Bousema, T., Blagborough, A. M., Bejon, P., and Kapulu, M. C. (2019).Front. Immunol. 10:2480. doi: 10.3389/fimmu.2019.02480In the original article, there were errors in Tables 1, 2 and 3, and to the text. In Table 1, one ofthe two study sites from Amoah et al.’s study (Parasites & Vectors, 2018) was erroneously excludedfrom the table hence the study was presented as one site, the age range of study participants fromthe Stone et al. (Nature Communications, 2018) study site “Hauts-Bassins (Burkina Faso)” wasmistakenly indicated as “2–74” instead of “5–14” years and the reference for Skinner et al. given as“35” instead of “33”. These errors have been corrected and the amended table appears in this article.Furthermore, owing to the omission of the study site from Amoah et al.’s study, the figuresquoted in the text on the overall number of study sites and the total number of study sitesreporting seroprevalence to Pfs230 and Pfs48/45 were incorrect. The total number of study sitesfor Pfs230 was given as “14” instead of “15” and for Pfs48/45 given as “14” instead of “13”. Also, weinadvertently provided the total number of individual study locations (“23”) instead of the studysites—based on administrative region—(“17”) when providing a summary of the 12 studies that weincluded in the analysis. In addition, the citation for “Amoah et al.” was was incorrectly cited as“Acquah et al.” in the Results section, sub-section Pfs230, Seroprevalence, Paragraph 1.These errors have been corrected and amendments made to the relevant result sections,given below.Results section, sub-section Study Selection and Characteristics, Paragraph 1:“The 12 studies were carried out across 17 study sites, majority of which were in West Africa(Burkina Faso, Senegal, Gabon, Cameroon, Ghana, andMali) with only one study site in East Africa(Tanzania) and two study sites in Southern Africa (Zimbabwe) (Table 1). Ten articles (from 15study sites) measured responses to Pfs230 and nine articles (13 study sites) measured responses toPfs48/45. Six studies were longitudinal studies spread over the malaria transmission season with allbut one measuring responses to both Pfs230 and Pfs48/45. Studies predominantly used ELISA asthe immunoassay with only one study measuring responses using protein microarrays.”Muthui et al. Anti-Gametocyte Immunity in African PopulationsTABLE 1 | Characteristics of studies included in the systematic review and meta-analysis.Study(Reference)Year Country Region ofstudy sitecSamplesizeAge group(years)AntigendetectedSeasonalitytested (Y/N)Assay Seropositivitycut-offNegativecontroldSelectiverecruitmenteAmoah et al.(34)a2018 Ghana(Abura)Central 65 6–12 Pfs230 No ELISAR 2 SD Naïve NoAmoah et al.(34)a2018 Ghana(Obom)Greater Accra 75 6–12 Pfs230 No ELISAR 2 SD Naïve NoLamptey et al.(35)2018 Ghana Greater Accra 338 2–65 Pfs230 Yes ELISAR 3 SD Test sample NoStone et al.(20)b*2018a Burkina Faso Hauts-Bassins33 5–14 Pfs230 andPfs48/45No ELISAR 3 SD Test sample YesStone et al.(20)b*2018b Burkina Faso Centre-Nord 38 2–10 Pfs230 andPfs48/45No ELISA 3 SD Test sample YesStone et al.(20)b*2018 Cameroon Centre 140 5–16 Pfs230 andPfs48/45No ELISAR 3 SD Test sample YesBansal et al.(42)2017 Zimbabwe MashonalandCentral181 6–14 Pfs48/45 No ELISAR 2 SD Naïve NoPaul et al. (43) 2016 Zimbabwe Manicaland 150 6–16 Pfs48/45 No ELISAR 2 SD Naïve NoAteba-Ngoaet al. (44)b2016 Gabon Moyen -Ogooue286 3–50 Pfs230 andPfs48/45No ELISAR 3 SD Test sample NoJones et al.(19)b2015 Burkina Faso Nord 200 5–16 Pfs230 andPfs48/45Yes ELISAR 3 SD Test sample NoJones et al.(19)b2015 Ghana Greater Accra 108 5–17 Pfs230 andPfs48/45Yes ELISAR 3 SD Test sample NoJones et al.(19)b2015 Tanzania Tanga Region 202 3–15 Pfs230 andPfs48/45Yes ELISAR 3 SD Test sample NoSkinner et al.(33)b2015 Mali Koulikoro 3and Bamako225 2–25 Pfs230 andPfs48/45Yes MicroarrayR 2 SD NoTemplateNoMiura et al.(45)2013 Mali Kayes 2 45 18–60 Pfs230 No ELISAR 3 SD Naïve NoOuedraogoet al. (24)b*2018 Burkina Faso Centre-Nord 128 1–55 Pfs230 andPfs48/45Yes Two-siteELISAGe3 SD Naïve NoOuedraogoet al. (16)a2011 Burkina Faso Centre-Nord 296 1–>20 Pfs230 andPfs48/45Yes Two-siteELISAGe2 SD Naïve NoVan der Kolket al. (46)2006 Cameroon Centre 236 5–14 Pfs230 andPfs48/45No Two-siteELISAGe2 SD Naïve NoaSeroprevalence data provided by authors upon request.bSeroprevalence data calculated from data provided by original authors, or from data available on public repositories.b*Citation also includes citation of repository from which data was retrieved.cAdministrative region of study site from which participants were drawn, this was used infer predicted parasite prevalence rates standardized in 2 – 10-year olds (PfPR2−10 ) that wasthen used to assign transmission intensity at the time of sampling.dNegative control refers to the comparator used to assign seropositivity in the immunoassay. Naïve – malaria naïve volunteers; Sample – a proportion of statistically – defined seronegativeindividuals; No template - a ‘no DNA control’ used to detect reactivity to the expression vector used to produce protein for the array.eSelective recruitment refers to studies that only recruited parasite positive individuals for antibody measurements.RRecombinant protein; Gegametocyte extract.SD, standard deviation.TABLE 2 | Univariable meta-regression analysis of factors influencing reported seroprevalence to Pfs230.No. of studies(No. of Sites)Coefficient (β) Lower CI Upper CI p-value* Residual I2 I2 change (%)AgeChildren (ref.) 10 (14)Adults 6 (6) 0.21 0.05 0.38 0.04 95.36 2.09Asexual parasiteprevalence6 (10) −0.001 −0.005 0.002 0.51 95.37 2.08Gametocyte prevalence 4 (8) −0.002 −0.004 0.001 0.38 92.54 4.50Transmission intensityMesoendemic (ref.) 7 (8)Hyperendemic 6 (7) −0.06 −0.23 0.11 0.51 96.18 1.25(Continued)Frontiers in Immunology | www.frontiersin.org 2 March 2020 | Volume 11 | Article 389Muthui et al. Anti-Gametocyte Immunity in African PopulationsTABLE 2 | ContinuedNo. of studies(No. of Sites)Coefficient (β) Lower CI Upper CI p-value* Residual I2 I2 change (%)SeasonDry (ref.) 6 (9)Rainy 5 (7) 0.07 −0.12 0.27 0.51 96.24 1.19AssayELISA (ref.) 6 (11)Microarray 1 (1) 0.31 0.08 0.55 0.07 95.29 2.17Two-site ELISA 3 (3) 0.12 −0.06 0.29AntigenGametocyte extract (ref.) 3 (3)Recombinant protein 7 (12) −0.06 −0.25 0.13 0.51 96.31 1.12Antigen concentration+0.1µg/ml (ref.) 3 (7)1µg/ml 3 (4) 0.26 0.09 0.43 0.04 93.52 3.98Seropositivity cut-off2 SD (ref.) 4 (5)3 SD 6 (10) −0.22 −0.37 −0.06 0.04 95.16 2.30*p-values adjusted using the Benjamini and Hochberg correction for multiple testing; values in bold p < 0.05.+ Antigen concentration was only tested for studies using recombinant protein as antigen source.CI, confidence interval; SD, standard deviation.TABLE 3 | Univariable meta-regression analysis of factors influencing reported seroprevalence to Pfs48/45.No. of Studies(No. of Sites)Coefficient (β) Lower CI Upper CI p-value Residual I2 I2 change (%)AgeChildren (ref.) 9 (13)Adults 4 (4) 0.07 −0.12 0.27 0.49 94.90 −0.18Asexual parasiteprevalence4 (8) −0.003 −0.006 0.0003 0.11 91.41 3.96Gametocyte prevalence 4 (8) −0.003 −0.005 −0.002 0.003 70.82 25.24Transmission intensityHypoendemic (ref.) 1(1)Mesoendemic 5 (6) −0.47 −0.89 −0.06 0.11 93.91 0.87Hyperendemic 5 (6) −0.38 −0.80 0.04SeasonDry (ref.) 4 (6)Rainy 6 (8) 0.07 −0.09 0.24 0.47 93.12 1.70AssayELISA (ref.) 5 (9)Microarray 1 (1) 0.36 0.15 0.56 0.016 91.99 2.89Two-site ELISA 3 (3) 0.09 −0.07 0.24AntigenGametocyte extract (ref.) 3 (3)Recombinant protein 6 (10) −0.01 −0.19 0.17 0.91 94.91 −0.19Antigen concentration+0.1µg/ml (ref.) 3 (7)1µg/ml 2 (2) 0.30 0.06 0.54 0.043 92.65 2.20Seropositivity cut-off2 SD (ref.) 5 (5)3 SD 4 (8) −0.26 −0.39 −0.12 0.003 91.38 3.54*p-values adjusted using the Benjamini and Hochberg correction for multiple testing; values in bold p < 0.05.+Antigen concentration was only tested for studies using recombinant protein as antigen source.CI, confidence interval; SD, standard deviation.Frontiers in Immunology | www.frontiersin.org 3 March 2020 | Volume 11 | Article 389Muthui et al. Anti-Gametocyte Immunity in African PopulationsResults section, sub-section Pfs230, Seroprevalence,Paragraph 1:“Ten studies from across 15 study sites in Africa analyzedimmune responses to Pfs230. The range of seroprevalenceestimates was quite wide, ranging from 6% reported by Stoneet al. in Soumousso and Dande villages, Burkina Faso (20)to 72% reported by Amoah et al. (34) (Figure 2). Significantheterogeneity was observed between the studies (I2 = 97%; 95%CI: 96–98%; p< 0.01) therefore, a pooled prevalence estimate wasnot calculated.”Results section, sub-section Pfs48/45, Seroprevalence,Paragraph 1:“A total of 9 studies carried out over 13 study sites measuredimmune responses to Pfs48/45. The range of seroprevalenceestimates reported was 0% from Stone et al.’s study sites inBurkina Faso (20) to 64% reported by Paul et al. from theirstudy in the Makoni district in Zimbabwe (43). As with Pfs230,there was significant heterogeneity between the studies, I2 =96%(95% CI: 95–97%), and hence no pooled estimate was calculated(Figure 3).”Additionally, there were errors in Table 2 and Table 3,regarding the values for the No. of Studies (No. of Sites) underthe variable Antigen. For Table 2, the numbers were switchedaround for gametocyte extract and recombinant protein andhence the numbers for Gametocyte extract read “7 (12)” insteadof “3 (3)” and under the variable Recombinant protein read“3 (3)” instead of “7 (12).” For Table 3 one study was missingfrom the count hence the value for the No. of Studies (No. ofSites) under the variable Recombinant protein read “5 (10)”instead of “6 (10).” The corrected Tables 2 and 3 appear inthis article.The authors apologize for these errors and state that this doesnot change the scientific conclusions of the article in any way.The original article has been updated.REFERENCES34. Amoah LE, Acquah FK, Ayanful-Torgby R, Oppong A, AbankwaJ, Obboh EK, et al. Dynamics of anti-MSP3 and Pfs230 antibodyresponses and multiplicity of infection in asymptomatic children fromsouthern Ghana. Parasit Vectors. (2018) 11:5–13. doi: 10.1186/s13071-017-2607-5Copyright © 2020 Muthui, Kamau, Bousema, Blagborough, Bejon and Kapulu.This is an open-access article distributed under the terms of the Creative CommonsAttribution License (CC BY). The use, distribution or reproduction in other forumsis permitted, provided the original author(s) and the copyright owner(s) are creditedand that the original publication in this journal is cited, in accordance with acceptedacademic practice. No use, distribution or reproduction is permitted which does notcomply with these terms.Frontiers in Immunology | www.frontiersin.org 4 March 2020 | Volume 11 | Article 389