A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Autoři: Beatriz Galatas aff001;  Francisco Saúte aff002;  Helena Martí-Soler aff001;  Caterina Guinovart aff001;  Lidia Nhamussua aff002;  Wilson Simone aff002;  Humberto Munguambe aff002;  Camilo Hamido aff002;  Júlia Montañà aff001;  Olinda Muguande aff003;  Francois Maartens aff004;  Fabião Luis aff002;  Krijn Paaijmans aff001;  Alfredo Mayor aff001;  Quique Bassat aff001;  Clara Menéndez aff001;  Eusebio Macete aff002;  Regina Rabinovich aff001;  Pedro L. Alonso aff001;  Baltazar Candrinho aff010;  Pedro Aide aff002
Působiště autorů: ISGlobal, Hospital Clínic—Universitat de Barcelona, Barcelona, Spain aff001;  Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique aff002;  Fundação para o Desenvolvimento da Comunidade, Maputo, Mozambique aff003;  Good Bye Malaria, Johannesburg, South Africa aff004;  School of Life Sciences, Center for Evolution and Medicine, Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, United States of America aff005;  CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain aff006;  ICREA, Pg. Lluis Companys 23, Barcelona, Spain aff007;  National Institute of Health, Ministry of Health, Maputo, Mozambique aff008;  Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America aff009;  National Malaria Control Program, Ministry of Health, Maputo, Mozambique aff010
Vyšlo v časopise: A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study. PLoS Med 17(8): e32767. doi:10.1371/journal.pmed.1003227
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1003227



Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique.

Methods and findings

A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015–2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017–June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%–72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study—malaria prevalence and incidence—at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0–11.8) in May 2015 to 2.6% (95% CI 2.0–3.4), representing a 71.3% (95% CI 71.1–71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9–2.2) after phase II. This represented an 84.7% (95% CI 81.4–87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5–77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short pre-intervention period.


In this study, we observed that the interventions deployed during the Magude project fell short of interrupting P. falciparum transmission with the coverages achieved. While new tools and strategies may be required to eventually achieve malaria elimination in stable transmission areas of sub-Saharan Africa, this project showed that innovative mixes of interventions can achieve large reductions in disease burden, a necessary step in the pathway towards elimination.

Trial registration

ClinicalTrials.gov NCT02914145.

Klíčová slova:

Census – Drug administration – Epidemiology – Malaria – Malarial parasites – Mozambique – Parasitic diseases – Pregnancy


1. Ministério da Saúde (MISAU), Instituto Nacional de Estatística (INE), ICF Internacional. Inquérito de Indicadores de Imunização, Malária e HIV/SIDA em Moçambique 2015. Survey of Indicators on Immunization, Malaria and HIV/AIDS in Mozambique. Rockville, Maryland, EUA: INS, INE e ICF International; 2015. Available from: https://dhsprogram.com/pubs/pdf/AIS12/AIS12.pdf

2. Griffin JT, Bhatt S, Sinka ME, Gething PW, Lynch M, Patouillard E, et al. Potential for reduction of burden and local elimination of malaria by reducing Plasmodium falciparum malaria transmission: a mathematical modelling study. Lancet Infect Dis. 2016;16:465–72. doi: 10.1016/S1473-3099(15)00423-5 26809816

3. Alonso P, Noor AM. The global fight against malaria is at crossroads. The Lancet. 2017;390:2532–4.

4. Arroz JAH. Increase in cases of malaria in Mozambique, 2014: epidemic or new endemic pattern? Rev Saúde Pública. 2016;50.

5. Moonasar D, Maharaj R, Kunene S, Candrinho B, Saute F, Ntshalintshali N, et al. Towards malaria elimination in the MOSASWA (Mozambique, South Africa and Swaziland) region. Malar J. 2016;15.

6. Sharp BL, Kleinschmidt I, Streat E, Maharaj R, Barnes KI, Durrheim DN, et al. Seven years of regional malaria control collaboration—Mozambique, South Africa, and Swaziland. Am J Trop Med Hyg. 2007;76:42–47. 17255227

7. World Health Organization, Global Malaria Programme. Global technical strategy for malaria, 2016–2030. 2015 [cited 2020 Jul 30]. Available from: https://www.who.int/malaria/areas/global_technical_strategy/en/

8. World Health Organization (WHO). Eliminating Malaria. World Health Organization; 2016 [cited 2020 Jul 30]. Available from: https://www.who.int/malaria/publications/atoz/eliminating-malaria/en/

9. Aide P, Candrinho B, Galatas B, Munguambe K, Guinovart C, Luis F, et al. Setting the scene and generating evidence for malaria elimination in Southern Mozambique. Malar J. 2019;18:190. doi: 10.1186/s12936-019-2832-9 31170984

10. Kloke RG, Nhamahanga E, Hunt RH, Coetzee M. Vectorial status and insecticide resistance of Anopheles funestus from a sugar estate in southern Mozambique. Parasit Vectors. 2011;4:16. doi: 10.1186/1756-3305-4-16 21306631

11. Aranda C, Aponte JJ, Saute F, Casimiro S, Pinto J, Sousa C, et al. Entomological characteristics of malaria transmission in Manhiça, a rural area in southern Mozambique. J Med Entomol. 2005;42:180–6. doi: 10.1093/jmedent/42.2.180 15799528

12. Cuamba N, Morgan JC, Irving H, Steven A, Wondji CS. High Level of Pyrethroid Resistance in an Anopheles funestus Population of the Chokwe District in Mozambique. PLoS ONE. 2010;5:e11010. doi: 10.1371/journal.pone.0011010 20544036

13. Glunt KD, Abílio AP, Bassat Q, Bulo H, Gilbert AE, Huijben S, et al. Long-lasting insecticidal nets no longer effectively kill the highly resistant Anopheles funestus of southern Mozambique. Malar J. 2015;14:298. doi: 10.1186/s12936-015-0807-z 26242977

14. Salvador C, Rafael B, Matsinhe F, Candrinho B, Muthemba R, De Carvalho E, et al. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria at sentinel sites in Mozambique, 2015. Acta Trop. 2017;171:146–50. doi: 10.1016/j.actatropica.2017.03.032 28373036

15. Galatas B, Nhacolo A, Martí-Soler H, Munguambe H, Jamise E, Guinovart C, et al. Demographic and health community-based surveys to inform a malaria elimination project in Magude district, southern Mozambique. BMJ Open. 2020;10:e033985. doi: 10.1136/bmjopen-2019-033985 32371510

16. Arroz JAH, Candrinho B, Pedro S, Mathe G, da Silva M, Tsabete S, et al. Planning and implementation of a countrywide campaign to deliver over 16 million long-lasting insecticidal nets in Mozambique. Malar J. 2018;17.

17. Swysen C, Bruls M, Oyakhirome S, Drakeley C, Okech B, Carter T, et al. Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine. Malar J. 2011;10:223. doi: 10.1186/1475-2875-10-223 21816032

18. Brady OJ, Slater HC, Pemberton-Ross P, Wenger E, Maude RJ, Ghani AC, et al. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. Lancet Glob Health. 2017;5:E680–7. doi: 10.1016/S2214-109X(17)30220-6 28566213

19. Naimi B. rts: Raster Time Series Analysis. R package version 1.0–45. 2018 [cited 2020 Jul 30]. Available from: https://cran.r-project.org/web/packages/rts/rts.pdf

20. Funk C, Peterson P, Landsfeld M, Pedreros D, Verdin J, Shukla S, et al. The climate hazards infrared precipitation with stations—a new environmental record for monitoring extremes. Sci Data. 2015;2:150066. doi: 10.1038/sdata.2015.66 26646728

21. Linden A. Conducting interrupted time-series analysis for single- and multiple-group comparisons. Stata J. 2015;15:480–500.

22. Poirot E, Skarbinski J, Sinclair D, Kachur SP, Slutsker L, Hwang J. Mass drug administration for malaria. Cochrane Infectious Diseases Group, editor. Cochrane Database Syst Rev. 2013;12:CD009946.

23. von Seidlein L, Greenwood BM. Mass administrations of antimalarial drugs. Trends Parasitol. 2003;19:452–60. doi: 10.1016/j.pt.2003.08.003 14519583

24. Cui J, Qian G. Selection of Working Correlation Structure and Best Model in GEE Analyses of Longitudinal Data. Commun Stat—Simul Comput. 2007;36:987–96.

25. R Core Team. R: A language and environment for statistical computing. Vienna, Austria; 2013 [cited 2020 Jul 30]. Available from: http://softlibre.unizar.es/manuales/aplicaciones/r/fullrefman.pdf

26. Chan XHS, Win YN, Mawer LJ, Tan JY, Brugada J, White NJ. Risk of sudden unexplained death after use of dihydroartemisinin–piperaquine for malaria: a systematic review and Bayesian meta-analysis. Lancet Infect Dis. 2018;18:913–23. doi: 10.1016/S1473-3099(18)30297-4 29887371

27. Smith DL, Guerra CA, Snow RW, Hay SI. Standardizing estimates of the Plasmodium falciparum parasite rate. Malar J. 2007;6:131. doi: 10.1186/1475-2875-6-131 17894879

28. Eisele TP, Bennett A, Silumbe K, Finn TP, Chalwe V, Kamuliwo M, et al. Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial. J Infect Dis. 2016;214:1831–9. doi: 10.1093/infdis/jiw416 27923947

29. Deng C, Huang B, Wang Q, Wu W, Zheng S, Zhang H, et al. Large-scale Artemisinin-Piperaquine Mass Drug Administration With or Without Primaquine Dramatically Reduces Malaria in a Highly Endemic Region of Africa. Clin Infect Dis. 2018;67:1670–6. doi: 10.1093/cid/ciy364 29846536

30. Morris U, Msellem MI, Mkali H, Islam A, Aydin-Schmidt B, Jovel I, et al. 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 Med. 2018;16:215. doi: 10.1186/s12916-018-1202-8 30526588

31. Gerardin J, Bever CA, Bridenbecker D, Hamainza B, Silumbe K, Miller JM, et al. Effectiveness of reactive case detection for malaria elimination in three archetypical transmission settings: a modelling study. Malar J. 2017;16:248. doi: 10.1186/s12936-017-1903-z 28606143

32. Selvaraj P, Wenger EA, Gerardin J. Seasonality and heterogeneity of malaria transmission determine success of interventions in high-endemic settings: a modeling study. BMC Infect Dis. 2018;18:413. doi: 10.1186/s12879-018-3319-y 30134861

33. Stuckey EM, Miller JM, Littrell M, Chitnis N, Steketee R. Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia’s southern province: a simulation study. Malar J. 2016;15:148. doi: 10.1186/s12936-016-1202-0 26957364

34. Nosten F, White NJ. Artemisinin-based combination treatment of falciparum malaria. Am J Trop Med Hyg. 2007;77:181–192. 18165491

35. Gerardin J, Bertozzi-Villa A, Eckhoff PA, Wenger EA. Impact of mass drug administration campaigns depends on interaction with seasonal human movement. Int Health. 2018;10:252–7. doi: 10.1093/inthealth/ihy025 29635471

36. Smith JL, Auala J, Haindongo E, Uusiku P, Gosling R, Kleinschmidt I, et al. Malaria risk in young male travellers but local transmission persists: a case–control study in low transmission Namibia. Malar J. 2017;16:70. doi: 10.1186/s12936-017-1719-x 28187770

37. Slater HC, Ross A, Felger I, Hofmann NE, Robinson L, Cook J, et al. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density. Nat Commun. 2019;10:140. doi: 10.1038/s41467-018-08059-z 30635559

38. Galatas B, Martí-Soler H, Nhamussua L, Cisteró P, Aide P, Saute F, et al. Dynamics of Afebrile Plasmodium falciparum Infections in Mozambican Men. Clin Infect Dis. 2018;67:1045–52. doi: 10.1093/cid/ciy219 29546346

39. Killeen GF. Characterizing, controlling and eliminating residual malaria transmission. Malar J. 2014;13:330. doi: 10.1186/1475-2875-13-330 25149656

40. Mwesigwa J, Achan J, Affara M, Wathuo M, Worwui A, Mohammed NI, et al. Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study. Clin Infect Dis. 2018;69:278–86.

41. Molineaux L, Gramiccia G. The Garki Project. World Health Organization; 1980.

42. Cheah PY, White NJ. Antimalarial mass drug administration: ethical considerations. Int Health. 2016;8:235–8. doi: 10.1093/inthealth/ihw027 27481834

43. World Health Organization. WHO Evidence Review Group on the cardiotoxicity of antimalarials. World Health Organization, Geneva; 2017 [cited 2020 Jul 30]. Available from: https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxicity-report-session2.pdf?ua=1

44. Cirera L, Galatas B, Alonso S, Paaijmans K, Mamuquele M, Martí-Soler H, et al. Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control. PLoS ONE. Public Library of Science; 2020;15:e0235631. doi: 10.1371/journal.pone.0235631 32628741

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