Serological Markers of Exposure to Plasmodium falciparum and Plasmodium vivax Infection in Southwestern Ethiopia

Brook Jeang Program in Public Health, University of California Irvine, Irvine, California;

Search for other papers by Brook Jeang in
Current site
Google Scholar
PubMed
Close
,
Ming-Chieh Lee Program in Public Health, University of California Irvine, Irvine, California;

Search for other papers by Ming-Chieh Lee in
Current site
Google Scholar
PubMed
Close
,
Paula Embury Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio;

Search for other papers by Paula Embury in
Current site
Google Scholar
PubMed
Close
,
Delenasaw Yewhalaw School of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma University, Jimma, Ethiopia;
Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia;

Search for other papers by Delenasaw Yewhalaw in
Current site
Google Scholar
PubMed
Close
,
David Narum Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by David Narum in
Current site
Google Scholar
PubMed
Close
,
Christopher King Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio;

Search for other papers by Christopher King in
Current site
Google Scholar
PubMed
Close
,
Wai-Hong Tham Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia

Search for other papers by Wai-Hong Tham in
Current site
Google Scholar
PubMed
Close
,
James Kazura Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio;

Search for other papers by James Kazura in
Current site
Google Scholar
PubMed
Close
,
Guiyun Yan Program in Public Health, University of California Irvine, Irvine, California;

Search for other papers by Guiyun Yan in
Current site
Google Scholar
PubMed
Close
, and
Arlene Dent Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio;

Search for other papers by Arlene Dent in
Current site
Google Scholar
PubMed
Close
Restricted access

ABSTRACT.

As malaria control and elimination efforts ramp up in Ethiopia, more sensitive tools for assessing exposure to coendemic Plasmodium falciparum and Plasmodium vivax are needed to accurately characterize malaria risk and epidemiology. Serological markers have been increasingly explored as cost-effective tools for measuring transmission intensity and evaluating intervention effectiveness. The objectives of this study were to evaluate the efficacy of a panel of 10 serological markers as a proxy for malaria exposure and to determine underlying risk factors of seropositivity. We conducted cross-sectional surveys in two sites of contrasting malaria transmission intensities in southwestern Ethiopia: Arjo in Oromia Region (low transmission) and Gambella in Gambella Regional State (moderate transmission). We measured antibody reactivity against six P. falciparum (AMA-1, CSP, EBA175RIII-V, MSP-142, MSP-3, RH2ab) and four P. vivax (DBPII[Sal1], EBP2, MSP-119, RBP2b) targets. We used mixed effects logistic regressions to assess predictors of seropositivity. Plasmodium spp. infection prevalence by quantitative polymerase chain reaction was 1.36% in Arjo and 10.20% in Gambella. Seroprevalence and antibody levels against all 10 antigens were higher in Gambella than in Arjo. We observed spatial heterogeneities in seroprevalence across Arjo and smaller variations across Gambella. Seroprevalence in both sites was lowest against PfCSP and highest against PfAMA-1, PfMSP-142, and PvMSPS-119. Male sex, age, and agricultural occupation were positively associated with seropositivity in Arjo; associations were less pronounced in Gambella. Our findings demonstrate that seroprevalence and antibody levels to specific Plasmodium antigens can be used to identify high-risk groups and geographical areas where interventions to reduce malaria transmission should be implemented.

    • Supplemental Materials (PDF 351 KB)

Author Notes

Address correspondence to Arlene Dent, Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106. E-mail: aed9@case.edu

Authors’ addresses: Brook Jeang, Ming-Chieh Lee, and Guiyun Yan, Program in Public Health, University of California Irvine, Irvine, CA, E-mails: bjeang@uci.edu, mingchil@uci.edu, and guiyuny@uci.edu. Paula Embury, Christopher King, James Kazura, and Arlene Dent, Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, E-mails: paula.embury@case.edu, cxk21@case.edu, jxk14@case.edu, and aed9@case.edu. Delenasaw Yewhalaw, School of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma University, Jimma, Ethiopia, and Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia, E-mail: yewhalawd@gmail.com. David Narum, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: dnarum@niaid.nih.gov. Wai-Hong Tham, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia, and Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia, E-mail: tham@wehi.edu.au.

  • 1.

    Ketema T , Bacha K , Getahun K , del Portillo HA , Bassat Q , 2021. Plasmodium vivax epidemiology in Ethiopia 2000–2020: a systematic review and meta-analysis. PLoS Negl Trop Dis 15: e0009781.

    • Search Google Scholar
    • Export Citation
  • 2.

    Price RN , Commons RJ , Battle KE , Thriemer K , Mendis K , 2020. Plasmodium vivax in the era of the shrinking P. falciparum map. Trends Parasitol 36: 560570.

    • Search Google Scholar
    • Export Citation
  • 3.

    World Health Organization , 2018. World Malaria Report 2018. Geneva, Switzerland: WHO.

  • 4.

    Lo E et al., 2017. Transmission dynamics of co-endemic Plasmodium vivax and P. falciparum in Ethiopia and prevalence of antimalarial resistant genotypes. PLoS Negl Trop Dis 11: e0005806.

    • Search Google Scholar
    • Export Citation
  • 5.

    Hailemeskel E et al., 2019. Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia. Int J Parasitol Drugs Drug Resist 11: 812.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ethiopian Public Health Institute , 2016. Ethiopia National Malaria Indicator Survey 2015. Addis Ababa, Ethiopia: Ethiopian Public Health Institute, Ministry of Health.

    • Search Google Scholar
    • Export Citation
  • 7.

    Tusting LS , Bousema T , Smith DL , Drakeley C , 2014. Measuring changes in Plasmodium falciparum transmission: precision, accuracy and costs of metrics. Adv Parasitol 84: 151208.

    • Search Google Scholar
    • Export Citation
  • 8.

    Auburn S , Cheng Q , Marfurt J , Price RN , 2021. The changing epidemiology of Plasmodium vivax: insights from conventional and novel surveillance tools. PLoS Med 18: e1003560.

    • Search Google Scholar
    • Export Citation
  • 9.

    Cook J , Kleinschmidt I , Schwabe C , Nseng G , Bousema T , Corran PH , Riley EM , Drakeley CJ , 2011. Serological markers suggest heterogeneity of effectiveness of malaria control interventions on Bioko Island, Equatorial Guinea. PLoS One 6: e25137.

    • Search Google Scholar
    • Export Citation
  • 10.

    Pothin E , Ferguson NM , Drakeley CJ , Ghani AC , 2016. Estimating malaria transmission intensity from Plasmodium falciparum serological data using antibody density models. Malar J 15: 79.

    • Search Google Scholar
    • Export Citation
  • 11.

    Greenhouse B et al., 2019. Priority use cases for antibody-detecting assays of recent malaria exposure as tools to achieve and sustain malaria elimination. Gates Open Res 3: 131.

    • Search Google Scholar
    • Export Citation
  • 12.

    Corran P , Coleman P , Riley E , Drakeley C , 2007. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol 23: 575582.

    • Search Google Scholar
    • Export Citation
  • 13.

    King CL , Davies DH , Felgner P , Baum E , Jain A , Randall A , Tetteh K , Drakeley CJ , Greenhouse B , 2015. Biosignatures of exposure/transmission and immunity. Am J Trop Med Hyg 93: 1627.

    • Search Google Scholar
    • Export Citation
  • 14.

    Aka KG et al., 2021. Influence of host-related factors and exposure to mosquito bites on the dynamics of antibody response to Plasmodium falciparum antigens. Trop Med Infect Dis 6: 185.

    • Search Google Scholar
    • Export Citation
  • 15.

    Weber GE et al., 2017. Sero-catalytic and antibody acquisition models to estimate differing malaria transmission intensities in western Kenya. Sci Rep 7: 16821.

    • Search Google Scholar
    • Export Citation
  • 16.

    Duffy PE , Patrick Gorres J , 2020. Malaria vaccines since 2000: progress, priorities, products. NPJ Vaccines 5: 48.

  • 17.

    Hawaria D , Getachew H , Zhong G , Demissew A , Habitamu K , Raya B , Lee M-C , Yewhalaw D , Yan G , 2019. Ten years malaria trend at Arjo-Didessa sugar development site and its vicinity, southwest Ethiopia: a retrospective study. Malar J 18: 145.

    • Search Google Scholar
    • Export Citation
  • 18.

    Haileselassie W et al., 2021. The effect of irrigation on malaria vector bionomics and transmission intensity in western Ethiopia. Parasit Vectors 14: 516.

    • Search Google Scholar
    • Export Citation
  • 19.

    Degife AW , Zabel F , Mauser W , 2021. Climate change impacts on potential maize yields in Gambella Region, Ethiopia. Reg Environ Change 21: 60.

    • Search Google Scholar
    • Export Citation
  • 20.

    Bereczky S , Mårtensson A , Gil JP , Färnert A , 2005. Short report: rapid DNA extraction from archive blood spots on filter paper for genotyping of Plasmodium falciparum. Am J Trop Med Hyg 72: 249251.

    • Search Google Scholar
    • Export Citation
  • 21.

    Zhong D , Hemming-Schroeder E , Wang X , Kibret S , Zhou G , Atieli H , Lee M-C , Afrane YA , Githeko AK , Yan G , 2020. Extensive new Anopheles cryptic species involved in human malaria transmission in western Kenya. Sci Rep 10: 16139.

    • Search Google Scholar
    • Export Citation
  • 22.

    Longley RJ et al., 2020. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat Med 26: 741749.

    • Search Google Scholar
    • Export Citation
  • 23.

    Mazhari R et al., 2020. A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against Plasmodium vivax antigens in a multiplexed bead-based assay using Luminex technology (Bio-Plex 200 or MAGPIX). PLoS One 15: e0238010.

    • Search Google Scholar
    • Export Citation
  • 24.

    Ondigo BN , Park GS , Gose SO , Ho BM , Ochola LA , Ayodo GO , Ofulla AV , John CC , 2012. Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens. Malar J 11: 427.

    • Search Google Scholar
    • Export Citation
  • 25.

    Perraut R , Varela M-L , Mbengue B , Guillotte M , Mercereau-Puijalon O , Vigan-womas I , 2015. Standardization of a multiplex magnetic bead-based for simultaneous detection of IgG to Plasmodium antigens. J Immunol Tech Infect Dis 4: 18.

    • Search Google Scholar
    • Export Citation
  • 26.

    Gebremariam EB , 2017. The politics of youth employment and policy processes in Ethiopia. IDS Bull 48: 3.

  • 27.

    Feleke SM , Brhane BG , Mamo H , Assefa A , Woyessa A , Ogawa GM , Cama V , 2019. Sero-identification of the aetiologies of human malaria exposure (Plasmodium spp.) in the Limu Kossa district of Jimma zone, south western Ethiopia. Malar J 18: 292.

    • Search Google Scholar
    • Export Citation
  • 28.

    Leonard CM , Assefa A , Sime H , Mohammed H , Kebede A , Solomon H , Drakeley C , Murphy M , Hwang J , Rogier E , 2022. Spatial distribution of Plasmodium falciparum and Plasmodium vivax in northern Ethiopia by microscopic, rapid diagnostic test, laboratory antibody, and antigen data. J Infect Dis 225: 881890.

    • Search Google Scholar
    • Export Citation
  • 29.

    Keffale M et al., 2019. Serological evidence for a decline in malaria transmission following major scale-up of control efforts in a setting selected for Plasmodium vivax and Plasmodium falciparum malaria elimination in Babile district, Oromia, Ethiopia. Trans R Soc Trop Med Hyg 113: 305311.

    • Search Google Scholar
    • Export Citation
  • 30.

    Assefa A et al., 2019. Multiplex serology demonstrate cumulative prevalence and spatial distribution of malaria in Ethiopia. Malar J 18: 246.

  • 31.

    Ashton RA et al., 2015. Geostatistical modeling of malaria endemicity using serological indicators of exposure collected through school surveys. Am J Trop Med Hyg 93: 168177.

    • Search Google Scholar
    • Export Citation
  • 32.

    Hawaria D , Demissew A , Kibret S , Lee M-C , Yewhalaw D , Yan G , 2020. Effects of environmental modification on the diversity and positivity of anopheline mosquito aquatic habitats at Arjo-Dedessa irrigation development site, southwest Ethiopia. Infect Dis Poverty 9: 9.

    • Search Google Scholar
    • Export Citation
  • 33.

    Demissew A , Hawaria D , Kibret S , Animut A , Tsegaye A , Lee M-C , Yan G , Yewhalaw D , 2020. Impact of sugarcane irrigation on malaria vector Anopheles mosquito fauna, abundance and seasonality in Arjo-Didessa, Ethiopia. Malar J 19: 344.

    • Search Google Scholar
    • Export Citation
  • 34.

    Ashton RA , Kefyalew T , Tesfaye G , Pullan RL , Yadeta D , Reithinger R , Kolaczinski JH , Brooker S , 2011. School-based surveys of malaria in Oromia Regional State, Ethiopia: a rapid survey method for malaria in low transmission settings. Malar J 10: 25.

    • Search Google Scholar
    • Export Citation
  • 35.

    Alemu K , Worku A , Berhane Y , Kumie A , 2014. Men traveling away from home are more likely to bring malaria into high altitude villages, northwest Ethiopia. PLoS One 9: e95341.

    • Search Google Scholar
    • Export Citation
  • 36.

    Chan Y , Fornace K , Wu L , Arnold BF , Priest JW , Martin DL , Chang MA , Cook J , Stresman G , Drakeley C , 2021. Determining seropositivity – a review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases. PLoS Negl Trop Dis 15: e0009457.

    • Search Google Scholar
    • Export Citation
  • 37.

    Markwalter CF , Nyunt MH , Han ZY , Henao R , Jain A , Taghavian O , Felgner PL , Han KT , Nyunt MM , Plowe CV , 2021. Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots. Malar J 20: 378.

    • Search Google Scholar
    • Export Citation
  • 38.

    Ondigo BN , Hamre KES , Frosch AEP , Ayodo G , White MT , John CC , 2020. Antibody profiles to P. falciparum antigens over time characterize acute and long-term malaria exposure in an area of low and unstable transmission. Am J Trop Med Hyg 103: 21892197.

    • Search Google Scholar
    • Export Citation
  • 39.

    Arnold BF , Priest JW , Hamlin KL , Moss DM , Colford JM Jr , Lammie PJ , 2014. Serological measures of malaria transmission in Haiti: comparison of longitudinal and cross-sectional methods. PLoS One 9: e93684.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 237 237 45
Full Text Views 251 251 2
PDF Downloads 255 255 2
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save