Volume 94, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Most patients with suspected malaria do not receive diagnostic confirmation before beginning antimalarial treatment. We investigated the extent to which uncertainty about malaria diagnosis contributes to patient nonadherence to artemether–lumefantrine (AL) treatment through a randomized controlled trial in central Uganda. Among 1,525 patients purchasing a course of AL at private drug shops, we randomly offered 37.6% a free malaria rapid diagnostic test (RDT) and then assessed adherence through home visits 3 days later. Of these subjects, 68.4% tested positive for malaria and 65.8% adhered overall. Patients who tested positive did not have significantly higher odds of adherence than those who were not offered the test (adjusted odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.734–1.57, = 0.719). Patients who received a positive malaria test had 0.488 fewer pills remaining than those not offered the test (95% CI: −1.02 to 0.043, = 0.072). We found that patients who felt relatively healthy by the second day of treatment had lower odds of completing treatment (adjusted OR: 0.532, 95% CI: 0.394–0.719, < 0.001). Our results suggest that diagnostic testing may not improve artemisinin-based combination therapy adherence unless efforts are made to persuade patients to continue taking the full course of drugs even if symptoms have resolved.


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  1. World Health Organization, 2014. World Malaria Report 2014. Available at: http://www.who.int/malaria/publications/world_malaria_report_2014/en/. Accessed January 11, 2015. [Google Scholar]
  2. Makanga M, Bassat Q, Falade CO, Premji ZG, Krudsood S, Hunt P, Walter V, Beck H-P, Marrast A-C, Cousin M, Rosenthal PJ, , 2011. Efficacy and safety of artemether-lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis. Am J Trop Med Hyg 85: 793804.[Crossref] [Google Scholar]
  3. Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, Talisuna AO, Greenhouse B, Nosten F, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, , 2007. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin Trials 2: e20.[Crossref] [Google Scholar]
  4. Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, , 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 2210.[Crossref] [Google Scholar]
  5. Koram KA, Abuaku B, Duah N, Quashie N, , 2005. Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Trop 95: 194203.[Crossref] [Google Scholar]
  6. Banek K, Lalani M, Staedke SG, Chandramohan D, , 2014. Adherence to artemisinin-based combination therapy for the treatment of malaria: a systematic review of the evidence. Malar J 13: 7.[Crossref] [Google Scholar]
  7. Bruxvoort K, Goodman C, Kachur SP, Schellenberg D, , 2014. How patients take malaria treatment: a systematic review of the literature on adherence to antimalarial drugs. PLoS One 9: e84555.[Crossref] [Google Scholar]
  8. Bruxvoort K, Kalolella A, Cairns M, Festo C, Kenani M, Lyaruu P, Kachur S, Schellenberg D, Goodman C, , 2015. Are Tanzanian patients attending public facilities or private retailers more likely to adhere to artemisinin-based combination therapy? Malar J 14: 87.[Crossref] [Google Scholar]
  9. Novartis, 2010. Coartem: Full Prescribing Information. Available at: http://www.pharma.us.novartis.com/product/pi/pdf/coartem.pdf. [Google Scholar]
  10. Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, De Palacios PI, , 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg 74: 991998. [Google Scholar]
  11. World Health Organization, 2010. Roll Back Malaria Partnership: Economic Costs of Malaria. Available at: http://www.rollbackmalaria.org/cmc_upload/0/000/015/363/RBMInfosheet_10.htm. Accessed February 12, 2015. [Google Scholar]
  12. White NJ, Pongtavornpinyo W, Maude RJ, Saralamba S, Aguas R, Stepniewska K, Lee SJ, Dondorp AM, White LJ, Day NP, , 2009. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance. Malar J 8: 253.[Crossref] [Google Scholar]
  13. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han K-T, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ, Tracking Resistance to Artemisinin Collaboration (TRAC); , 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423.[Crossref] [Google Scholar]
  14. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NPJ, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref] [Google Scholar]
  15. Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NP, White NJ, Anderson TJ, Nosten F, , 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 19601966.[Crossref] [Google Scholar]
  16. White NJ, , 2012. The consequences of artemisinin resistance in falciparum malaria. Malar J 11 (Suppl 1): O36.[Crossref] [Google Scholar]
  17. Bruxvoort K, Festo C, Kalolella A, Cairns M, Lyaruu P, Kenani M, Kachur SP, Goodman C, Schellenberg D, , 2014. Cluster randomized trial of text message reminders to retail staff in Tanzanian drug shops dispensing artemether-lumefantrine: effect on dispenser knowledge and patient adherence. Am J Trop Med Hyg 91: 844853.[Crossref] [Google Scholar]
  18. Raifman JRG, Lanthorn HE, Rokicki S, Fink G, , 2014. The impact of text message reminders on adherence to antimalarial treatment in northern Ghana: a randomized trial. PLoS One 9: e109032.[Crossref] [Google Scholar]
  19. Mubi M, Janson A, Warsame M, Mårtensson A, Källander K, Petzold MG, Ngasala B, Maganga G, Gustafsson LL, Massele A, Tomson G, Premji Z, Björkman A, , 2011. Malaria rapid testing by community health workers is effective and safe for targeting malaria treatment: randomised cross-over trial in Tanzania. PLoS One 6: e19753.[Crossref] [Google Scholar]
  20. Asante KP, Owusu R, Dosoo D, Awini E, Adjei G, Amenga Etego S, Chandramohan D, Owusu-Agyei S, , 2009. Adherence to artesunate-amodiaquine therapy for uncomplicated malaria in rural Ghana: a randomised trial of supervised versus unsupervised drug administration. J Trop Med 2009: 17.[Crossref] [Google Scholar]
  21. Johansson EW, Gething PW, Hildenwall H, Mappin B, Petzold M, Peterson SS, Selling KE, , 2014. Diagnostic testing of pediatric fevers: meta-analysis of 13 national surveys assessing influences of malaria endemicity and source of care on test uptake for febrile children under five years. PLoS One 9: e95483.[Crossref] [Google Scholar]
  22. Littrell M, Gatakaa H, Evance I, Poyer S, Njogu J, Solomon T, Munroe E, Chapman S, Goodman C, Hanson K, Zinsou C, Akulayi L, Raharinjatovo J, Arogundade E, Buyungo P, Mpasela F, Adjibabi C, Agbango J, Ramarosandratana B, Coker B, Rubahika D, Hamainza B, Shewchuk T, Chavasse D, O'Connell KA, , 2011. Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries. Malar J 10: 327.[Crossref] [Google Scholar]
  23. ACT Watch Group, PACE/Uganda, Independent Evaluation Team, 2010. Outlet Survey Report 2010 (Round 3) for the Baseline Independent Evaluation of the Affordable Medicines Facility (AMFm), Uganda. Available at: www.ACTwatch.info. [Google Scholar]
  24. Källander K, Nsungwa-Sabiiti J, Peterson S, , 2004. Symptom overlap for malaria and pneumonia—policy implications for home management strategies. Acta Trop 90: 211214.[Crossref] [Google Scholar]
  25. D'Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, Lengeler C, Cherpillod P, Kaiser L, Genton B, , 2014. Beyond malaria—causes of fever in outpatient Tanzanian children. N Engl J Med 370: 809817.[Crossref] [Google Scholar]
  26. Crump JA, Morrissey AB, Nicholson WL, Massung RF, Stoddard RA, Galloway RL, Ooi EE, Maro VP, Saganda W, Kinabo GD, Muiruri C, Bartlett JA, , 2013. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis 7: e2324.[Crossref] [Google Scholar]
  27. Cohen J, Cox A, Dickens W, Maloney K, Lam F, Fink G, , 2015. Determinants of malaria diagnostic uptake in the retail sector: qualitative analysis from focus groups in Uganda. Malar J 14: 89.[Crossref] [Google Scholar]
  28. Bastiaens GJH, Bousema T, Leslie T, , 2014. Scale-up of malaria rapid diagnostic tests and artemisinin-based combination therapy: challenges and perspectives in sub-Saharan Africa. PLoS Med 11: e1001590.[Crossref] [Google Scholar]
  29. Williams H, Causer L, Metta E, Malila A, O'Reilly T, Abdulla S, Kachur SP, Bloland PB, , 2008. Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients—Tanzania, 2005. Malar J 7: 239.[Crossref] [Google Scholar]
  30. Mukanga D, Tibenderana JK, Kiguli J, Pariyo GW, Waiswa P, Bajunirwe F, Mutamba B, Counihan H, Ojiambo G, Kallander K, , 2010. Community acceptability of use of rapid diagnostic tests for malaria by community health workers in Uganda. Malar J 9: 203.[Crossref] [Google Scholar]
  31. World Health Organization, 2010. Guidelines for the Treatment of Malaria, 2nd edition. Geneva, Switzerland: World Health Organization. [Google Scholar]
  32. Lubell Y, Reyburn H, Mbakilwa H, Mwangi R, Chonya S, Whitty CJM, Mills A, , 2008. The impact of response to the results of diagnostic tests for malaria: cost-benefit analysis. BMJ 336: 202205.[Crossref] [Google Scholar]
  33. Shillcutt S, Morel C, Goodman C, Coleman P, Bell D, Whitty CJM, Mills A, , 2008. Cost-effectiveness of malaria diagnostic methods in sub-Saharan Africa in an era of combination therapy. Bull World Health Organ 86: 101110.[Crossref] [Google Scholar]
  34. Uganda Bureau of Statistics, ICF Macro, 2010. Uganda Malaria Indicator Survey 2009. Calverton, MD: UBOS and ICF Macro. [Google Scholar]
  35. Nabyonga Orem J, Mugisha F, Okui A, Musango L, Kirigia J, , 2013. Health care seeking patterns and determinants of out-of-pocket expenditure for malaria for the children under-five in Uganda. Malar J 12: 175.[Crossref] [Google Scholar]
  36. Laxminarayan R, Gelband H, , 2009. A global subsidy: key to affordable drugs for malaria? Health Aff (Millwood) 28: 949961.[Crossref] [Google Scholar]
  37. Institute of Medicine Arrow KJ, Panosian C, Gelband H, , 2004. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance. , eds. Washington, DC: National Academies Press. [Google Scholar]
  38. StataCorp, 2009. Stata Statistical Software: Release 11. College Station, TX: StataCorp LP. [Google Scholar]
  39. Ashraf N, Berry J, Shapiro JM, , 2010. Can higher prices stimulate product use? Evidence from a field experiment in Zambia. Am Econ Rev 100: 23832413.[Crossref] [Google Scholar]
  40. Cohen J, Dupas P, , 2010. Free distribution or cost-sharing? Evidence from a randomized malaria prevention experiment. Q J Econ 125: 145.[Crossref] [Google Scholar]
  41. World Health Organization, Special Programme for Research and Training in Tropical Diseases, Foundation for Innovative New Diagnostics, Centers for Disease Control and Prevention, 2012. Malaria Rapid Diagnostic Test Performance Results of WHO Product Testing of Malaria RDTs: 4 (2012). Geneva, Switzerland: World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases. Available at: http://apps.who.int/iris/bitstream/10665/77748/1/9789241504720_eng.pdf. Accessed February 14, 2015. [Google Scholar]
  42. Das D, Price RN, Bethell D, Guerin PJ, Stepniewska K, , 2013. Early parasitological response following artemisinin-containing regimens: a critical review of the literature. Malar J 12: 125.[Crossref] [Google Scholar]
  43. Muhindo MK, Kakuru A, Jagannathan P, Talisuna A, Osilo E, Orukan F, Arinaitwe E, Tappero JW, Kaharuza F, Kamya MR, Dorsey G, , 2014. Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated Plasmodium falciparum malaria. Malar J 13: 32.[Crossref] [Google Scholar]
  44. Filmer D, Pritchett LH, , 2001. Estimating wealth effects without expenditure data-or tears: an application to educational enrollments in states of India. Demography 38: 115132. [Google Scholar]
  45. Cohen JL, Yavuz E, Morris A, Arkedis J, Sabot O, , 2012. Do patients adhere to over-the-counter artemisinin combination therapy for malaria? Evidence from an intervention study in Uganda. Malar J 11: 83.[Crossref] [Google Scholar]
  46. Kizito J, Kayendeke M, Nabirye C, Staedke SG, Chandler CI, , 2012. Improving access to health care for malaria in Africa: a review of literature on what attracts patients. Malar J 11: 55.[Crossref] [Google Scholar]
  47. Mbonye AK, Ndyomugyenyi R, Turinde A, Magnussen P, Clarke S, Chandler C, , 2010. The feasibility of introducing rapid diagnostic tests for malaria in drug shops in Uganda. Malar J 9: 367.[Crossref] [Google Scholar]
  48. Odaga J, Sinclair D, Lokong JA, Donegan S, Hopkins H, Garner P, The Cochrane Collaboration, 2014. Rapid diagnostic tests versus clinical diagnosis for managing people with fever in malaria endemic settings. , ed. Cochrane Database of Systematic Reviews. Chichester, United Kingdom: John Wiley and Sons, Ltd. Available at: http://doi.wiley.com/10.1002/14651858.CD008998.pub2. Accessed February 15, 2015. [Google Scholar]
  49. Ikwuobe JO, Faragher BE, Alawode G, Lalloo DG, , 2013. The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria. Malar J 12: 380.[Crossref] [Google Scholar]
  50. Cohen J, Fink G, Maloney K, Berg K, Jordan M, Svoronos T, Aber F, Dickens W, , 2015. Introducing rapid diagnostic tests for malaria to drug shops in Uganda: a cluster-randomized controlled trial. Bull World Health Organ 93: 142151.[Crossref] [Google Scholar]
  51. Chandler CI, Whitty CJ, Ansah EK, , 2010. How can malaria rapid diagnostic tests achieve their potential? A qualitative study of a trial at health facilities in Ghana. Malar J 9: 95.[Crossref] [Google Scholar]
  52. Baltzell K, Elfving K, Shakely D, Ali AS, Msellem M, Gulati S, Mårtensson A, , 2013. Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers' practices in Zanzibar. Malar J 12: 37.[Crossref] [Google Scholar]
  53. Msellem MI, Mårtensson A, Rotllant G, Bhattarai A, Strömberg J, Kahigwa E, Garcia M, Petzold M, Olumese P, Ali A, Björkman A, , 2009. Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar—a crossover validation study. PLoS Med 6: e1000070.[Crossref] [Google Scholar]
  54. Faust C, Zelner J, Brasseur P, Vaillant M, Badiane M, Cisse M, Grenfell B, Olliaro P, , 2015. Assessing drivers of full adoption of test and treat policy for malaria in Senegal. Am J Trop Med Hyg 93: 159167.[Crossref] [Google Scholar]
  55. Gore-Langton GR, Alenwi N, Mungai J, Erupe NI, Eves K, Kimwana FN, Soti D, Akhwale W, Hassan FA, Juma E, Allan R, , 2015. Patient adherence to prescribed artemisinin-based combination therapy in Garissa County, Kenya, after three years of health care in a conflict setting. Malar J 14: 125.[Crossref] [Google Scholar]
  56. Mace KE, Mwandama D, Jafali J, Luka M, Filler SJ, Sande J, Ali D, Kachur SP, Mathanga DP, Skarbinski J, , 2011. Adherence to treatment with artemether-lumefantrine for uncomplicated malaria in rural Malawi. Clin Infect Dis 53: 772779.[Crossref] [Google Scholar]
  57. Lawford H, Zurovac D, O'Reilly L, Hoibak S, Cowley A, Munga S, Vulule J, Juma E, Snow RW, Allan R, , 2011. Adherence to prescribed artemisinin-based combination therapy in Garissa and Bunyala districts, Kenya. Malar J 10: 281.[Crossref] [Google Scholar]
  58. Dunyo S, Sirugo G, Sesay S, Bisseye C, Njie F, Adiamoh M, Nwakanma D, Diatta M, Janha R, Sisay Joof F, Temple B, Snell P, Conway D, Walton R, Cheung YB, Milligan P, , 2011. Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in The Gambia. PLoS One 6: e17371.[Crossref] [Google Scholar]
  59. Kalyango JN, Rutebemberwa E, Karamagi C, Mworozi E, Ssali S, Alfven T, Peterson S, , 2013. High adherence to antimalarials and antibiotics under integrated community case management of illness in children less than five years in eastern Uganda. PLoS One 8: e60481.[Crossref] [Google Scholar]
  60. Kachur SP, Khatib RA, Kaizer E, Fox SS, Abdulla SM, Bloland PB, , 2004. Adherence to antimalarial combination therapy with sulfadoxine-pyrimethamine and artesunate in rural Tanzania. Am J Trop Med Hyg 71: 715722. [Google Scholar]
  61. Ogolla JO, Ayaya SO, Otieno CA, , 2013. Levels of adherence to Coartem© in the routine treatment of uncomplicated malaria in children aged below five years, in Kenya. Iran J Public Health 42: 129133. [Google Scholar]
  62. Lemma H, Löfgren C, San Sebastian M, , 2011. Adherence to a six-dose regimen of artemether-lumefantrine among uncomplicated Plasmodium falciparum patients in the Tigray Region, Ethiopia. Malar J 10: 349.[Crossref] [Google Scholar]
  63. White NJ, van Vugt M, Ezzet F, , 1999. Clinical pharmacokinetics and pharmacodynamics of artemether-lumefantrine. Clin Pharmacokinet 37: 105125.[Crossref] [Google Scholar]

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  • Received : 05 Jun 2015
  • Accepted : 06 Nov 2015
  • Published online : 06 Apr 2016

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