Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial

Semira Abdelmenan, Hiwot Teka, Jimee Hwang, Samuel Girma, Sheleme Chibsa, Eric Tongren, Matthew Murphy, Mebrahatom Haile, Dereje Dillu, Jawar Kassim, Sinknesh Behaksra, Fitsum G Tadesse, Joshua Yukich, Yemane Berhane, Alemayehu Worku, Joseph Keating, Ayele Zewde, Endalamaw Gadisa, Semira Abdelmenan, Hiwot Teka, Jimee Hwang, Samuel Girma, Sheleme Chibsa, Eric Tongren, Matthew Murphy, Mebrahatom Haile, Dereje Dillu, Jawar Kassim, Sinknesh Behaksra, Fitsum G Tadesse, Joshua Yukich, Yemane Berhane, Alemayehu Worku, Joseph Keating, Ayele Zewde, Endalamaw Gadisa

Abstract

Background: Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention.

Methods: The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach.

Discussion: This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination.

Trial registration: ClinicalTrials.gov NCT04241705 . Registration date: January 27, 2020.

Keywords: Cluster randomized controlled trial; Ethiopia; Malaria; Reactive case detection; Targeted mass drug administration.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Randomization procedure, interventions, and evaluation timeline
Fig. 2
Fig. 2
Malaria transmission settings of woredas in East Hararghe zone, Oromia regional state, Ethiopia, 2017

References

    1. World malaria report 2019 [Internet]. [cited 2022 Mar 7]. Available from:
    1. Taffese HS, Hemming-Schroeder E, Koepfli C, Tesfaye G, Lee M, Kazura J, Yan GY, Zhou GF. Malaria epidemiology and interventions in Ethiopia from 2001 to 2016. Infect Dis Poverty. 2018;7(1):103. doi: 10.1186/s40249-018-0487-3.
    1. Federal Democratic Republic of Ethiopia Ministry of Health. National Malaria Strategic Plan: 2017 - 2020. Malaria Control and Elimination Program; 2017.
    1. Deribew A, Dejene T, Kebede B, Tessema GA, Melaku YA, Misganaw A, Gebre T, Hailu A, Biadgilign S, Amberbir A, Yirsaw BD, Abajobir AA, Shafi O, Abera SF, Negussu N, Mengistu B, Amare AT, Mulugeta A, Mengistu B, Tadesse Z, Sileshi M, Cromwell E, Glenn SD, Deribe K, Stanaway JD. Incidence, prevalence and mortality rates of malaria in Ethiopia from 1990 to 2015: analysis of the global burden of diseases 2015. Malar J. 2017;16(1):271. doi: 10.1186/s12936-017-1919-4.
    1. Federal Democratic Republic of Ethiopia Ministry of Health. Malaria Diagnosis and Treatment Guidelines for Health Workers in Ethiopia. Disease Prevention and Control Directorate National Malaria Control and Elimination Program; 2017.
    1. Ouattara AK, Bisseye C, Bazie BVJTE, Diarra B, Compaore TR, Djigma F, Pietra V, Moret R, Simpore J. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso. Asian Pac J Trop Biomed. 2014;4(8):655–658. doi: 10.12980/APJTB.4.2014APJTB-2014-0100.
    1. Luzzatto L, Nannelli C, Notaro R. Glucose-6-Phosphate Dehydrogenase Deficiency. Hematol Oncol Clin North Am. 2016;30(2):373–393. doi: 10.1016/j.hoc.2015.11.006.
    1. Ashley EA, Recht J, White NJ. Primaquine: the risks and the benefits. Malar J. 2014;13(1):418. doi: 10.1186/1475-2875-13-418.
    1. Douglas NM, Nosten F, Ashley EA, Phaiphun L, van Vugt M, Singhasivanon P, White NJ, Price RN. Plasmodium vivax Recurrence Following Falciparum and Mixed Species Malaria: Risk Factors and Effect of Antimalarial Kinetics. Clin Infect Dis. 2011;52(5):612–620. doi: 10.1093/cid/ciq249.
    1. Snounou G, White NJ. The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand. Trends Parasitol. 2004;20(7):333–339. doi: 10.1016/j.pt.2004.05.004.
    1. White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10(1):297. doi: 10.1186/1475-2875-10-297.
    1. Filipe JAN, Riley EM, Drakeley CJ, Sutherland CJ, Ghani AC. Determination of the Processes Driving the Acquisition of Immunity to Malaria Using a Mathematical Transmission Model. PLOS Comput Biol. 2007;3(12):e255. doi: 10.1371/journal.pcbi.0030255.
    1. Felger I, Maire M, Bretscher MT, Falk N, Tiaden A, Sama W, Beck HP, Owusu-Agyei S, Smith TA. The Dynamics of Natural Plasmodium falciparum Infections. PLOS ONE. 2012;7(9):e45542. doi: 10.1371/journal.pone.0045542.
    1. Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3(1):1237. doi: 10.1038/ncomms2241.
    1. Bousema T, Okell L, Felger I, Drakeley C. Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nat Rev Microbiol. 2014;12(12):833–840. doi: 10.1038/nrmicro3364.
    1. Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G. Detection of a substantial number of sub-microscopic Plasmodium falciparum infections by polymerase chain reaction: a potential threat to malaria control and diagnosis in Ethiopia. Malar J. 2013;12(1):352. doi: 10.1186/1475-2875-12-352.
    1. Golassa L, Baliraine FN, Enweji N, Erko B, Swedberg G, Aseffa A. Microscopic and molecular evidence of the presence of asymptomatic Plasmodium falciparum and Plasmodium vivax infections in an area with low, seasonal and unstable malaria transmission in Ethiopia. BMC Infect Dis. 2015;15(1):310. doi: 10.1186/s12879-015-1070-1.
    1. Tadesse FG, van den Hoogen L, Lanke K, Schildkraut J, Tetteh K, Aseffa A, Mamo H, Sauerwein R, Felger I, Drakeley C, Gadissa E, Bousema T. The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia. Malar J. 2017;16(1):99. doi: 10.1186/s12936-017-1749-4.
    1. Ouédraogo AL, Gonçalves BP, Gnémé A, Wenger EA, Guelbeogo MW, Ouédraogo A, Gerardin J, Bever CA, Lyons H, Pitroipa X, Verhave JP, Eckhoff PA, Drakeley C, Sauerwein R, Luty AJF, Kouyaté B, Bousema T. Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso. J Infect Dis. 2016;213(1):90–99. doi: 10.1093/infdis/jiv370.
    1. Tadesse FG, Slater HC, Chali W, Teelen K, Lanke K, Belachew M, Menberu T, Shumie G, Shitaye G, Okell LC, Graumans W, van Gemert GJ, Kedir S, Tesfaye A, Belachew F, Abebe W, Mamo H, Sauerwein R, Balcha T, Aseffa A, Yewhalaw D, Gadisa E, Drakeley C, Bousema T. The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia. Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;66(12):1883–1891. doi: 10.1093/cid/cix1123.
    1. Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther. 2013;11(6):623–639. doi: 10.1586/eri.13.45.
    1. Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, et al. “Asymptomatic” Malaria: A Chronic and Debilitating Infection That Should Be Treated. PLOS Med. 2016;13(1):e1001942. doi: 10.1371/journal.pmed.1001942.
    1. Portugal S, Tran TM, Ongoiba A, Bathily A, Li S, Doumbo S, Skinner J, Doumtabe D, Kone Y, Sangala J, Jain A, Davies DH, Hung C, Liang L, Ricklefs S, Homann MV, Felgner PL, Porcella SF, Färnert A, Doumbo OK, Kayentao K, Greenwood BM, Traore B, Crompton PD. Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017;64(5):645–653. doi: 10.1093/cid/ciw849.
    1. Sturrock HJW, Hsiang MS, Cohen JM, Smith DL, Greenhouse B, Bousema T, Gosling RD. Targeting Asymptomatic Malaria Infections: Active Surveillance in Control and Elimination. PLOS Med. 2013;10(6):e1001467. doi: 10.1371/journal.pmed.1001467.
    1. Scott CA, Yeshiwondim AK, Serda B, Guinovart C, Tesfay BH, Agmas A, Zeleke MT, Guesses GS, Ayenew AL, Workie WM, Steketee RW, Earle D, Bezabih B, Getachew A. Mass testing and treatment for malaria in low transmission areas in Amhara Region. Ethiopia. Malar J. 2016;15(1):305. doi: 10.1186/s12936-016-1333-3.
    1. CSA. Federal Democratic Republic of Ethiopia, Central Statistical Agency, Population Projection of Ethiopia for All Regions At Wereda Level from 2014 to 2017. 2017.
    1. Hillmen P, Hall C, Marsh JCW, Elebute M, Bombara MP, Petro BE, Cullen MJ, Richards SJ, Rollins SA, Mojcik CF, Rother RP. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350(6):552–559. doi: 10.1056/NEJMoa031688.
    1. MOH. National Malaria Guidelines. Disease, Prevention and Control. Addis Ababa, Ethiopian Federal Ministry of Health. 2018.
    1. Hermsen CC, Telgt DS, Linders EH, van de Locht LA, Eling WM, Mensink EJ, et al. Detection of Plasmodium falciparum malaria parasites in vivo by real-time quantitative PCR. Mol Biochem Parasitol. 2001;118(2):247–251. doi: 10.1016/S0166-6851(01)00379-6.
    1. Wampfler R, Mwingira F, Javati S, Robinson L, Betuela I, Siba P, Beck HP, Mueller I, Felger I. Strategies for detection of Plasmodium species gametocytes. PloS One. 2013;8(9):e76316. doi: 10.1371/journal.pone.0076316.
    1. Stone W, Sawa P, Lanke K, Rijpma S, Oriango R, Nyaurah M, Osodo P, Osoti V, Mahamar A, Diawara H, Woestenenk R, Graumans W, van de Vegte-Bolmer M, Bradley J, Chen I, Brown J, Siciliano G, Alano P, Gosling R, Dicko A, Drakeley C, Bousema T. A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance. J Infect Dis. 2017;216(4):457–467. doi: 10.1093/infdis/jix237.
    1. Kafsack BFC, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, Williams AE, Drought LG, Kwiatkowski DP, Baker DA, Cortés A, Llinás M. A transcriptional switch underlies commitment to sexual development in human malaria parasites. Nature. 2014;507(7491):248–252. doi: 10.1038/nature12920.
    1. Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C, Dickens NJ, Religa AA, Bushell E, Graham AL, Cameron R, Kafsack BFC, Williams AE, Llinás M, Berriman M, Billker O, Waters AP. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature. 2014;507(7491):253–257. doi: 10.1038/nature12970.
    1. Poran A, Nötzel C, Aly O, Mencia-Trinchant N, Harris CT, Guzman ML, Hassane DC, Elemento O, Kafsack BFC. Single-cell RNA sequencing reveals a signature of sexual commitment in malaria parasites. Nature. 2017;551(7678):95–99. doi: 10.1038/nature24280.
    1. Wu L, Hall T, Ssewanyana I, Oulton T, Patterson C, Vasileva H, Singh S, Affara M, Mwesigwa J, Correa S, Bah M, D'Alessandro U, Sepúlveda N, Drakeley C, Tetteh KKA. Optimisation and standardisation of a multiplex immunoassay of diverse Plasmodium falciparum antigens to assess changes in malaria transmission using sero-epidemiology. Wellcome Open Res. 2019;4:26. doi: 10.12688/wellcomeopenres.14950.1.
    1. Kerkhof K, Sluydts V, Willen L, Kim S, Canier L, Heng S, Tsuboi T, Sochantha T, Sovannaroth S, Ménard D, Coosemans M, Durnez L. Serological markers to measure recent changes in malaria at population level in Cambodia. Malar J. 2016;15(1):529. doi: 10.1186/s12936-016-1576-z.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir