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Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Research

Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa

Authors: Hannah C. Slater, Jamie T. Griffin, Azra C. Ghani, Lucy C. Okell

Published in: Malaria Journal | Issue 1/2016

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Abstract

Background

Artemisinin and partner drug resistant malaria parasites have emerged in Southeast Asia. If resistance were to emerge in Africa it could have a devastating impact on malaria-related morbidity and mortality. This study estimates the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge.

Methods

Using data from Asia and Africa, five possible artemisinin and partner drug resistance scenarios are characterized. An individual-based malaria transmission model is used to estimate the impact of each resistance scenario on clinical incidence and parasite prevalence across Africa. Artemisinin resistance is characterized by slow parasite clearance and partner drug resistance is associated with late clinical failure or late parasitological failure.

Results

Scenarios with high levels of recrudescent infections resulted in far greater increases in clinical incidence compared to scenarios with high levels of slow parasite clearance. Across Africa, it is estimated that artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7 % increase in cases compared to a scenario with no resistance. A scenario with high levels of slow clearance but no recrudescence resulted in an additional 10 million additional cases over the same period.

Conclusion

Artemisinin resistance is potentially a more pressing concern than partner drug resistance due to the lack of viable alternatives. However, it is predicted that a failing partner drug will result in greater increases in malaria cases and morbidity than would be observed from artemisinin resistance only.
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Literature
2.
go back to reference Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.PubMedPubMedCentralCrossRef Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411–23.PubMedPubMedCentralCrossRef
3.
go back to reference Dondorp AM, Ringwald P. Artemisinin resistance is a clear and present danger. Trends Parasitol. 2013;29:359–60.PubMedCrossRef Dondorp AM, Ringwald P. Artemisinin resistance is a clear and present danger. Trends Parasitol. 2013;29:359–60.PubMedCrossRef
4.
go back to reference Naidoo I, Roper C. Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends Parasitol. 2010;26:447–56.PubMedCrossRef Naidoo I, Roper C. Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends Parasitol. 2010;26:447–56.PubMedCrossRef
5.
go back to reference Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–5.PubMedCrossRef Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–5.PubMedCrossRef
6.
go back to reference Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, et al. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis. 2015;211:670–9.PubMedCrossRef Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, et al. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis. 2015;211:670–9.PubMedCrossRef
7.
go back to reference Talundzic E, Okoth SA, Congpuong K, Plucinski MM, Morton L, Goldman IF, et al. Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign. PLoS Pathog. 2015;11:e1004789.PubMedPubMedCentralCrossRef Talundzic E, Okoth SA, Congpuong K, Plucinski MM, Morton L, Goldman IF, et al. Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign. PLoS Pathog. 2015;11:e1004789.PubMedPubMedCentralCrossRef
8.
go back to reference Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2015;211:680–8.PubMedCrossRef Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2015;211:680–8.PubMedCrossRef
9.
go back to reference Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, et al. K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis. 2015;211:1352–5.PubMed Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, et al. K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis. 2015;211:1352–5.PubMed
10.
go back to reference Lubell Y, Dondorp A, Guerin P, Drake T, Meek S, Ashley E, et al. Artemisinin resistance—modelling the potential human and economic costs. Malar J. 2014;13:452.PubMedPubMedCentralCrossRef Lubell Y, Dondorp A, Guerin P, Drake T, Meek S, Ashley E, et al. Artemisinin resistance—modelling the potential human and economic costs. Malar J. 2014;13:452.PubMedPubMedCentralCrossRef
11.
go back to reference Flegg J, Guerin P, White N, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J. 2011;10:339.PubMedPubMedCentralCrossRef Flegg J, Guerin P, White N, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J. 2011;10:339.PubMedPubMedCentralCrossRef
12.
go back to reference Krishna S, Kremsner PG. Antidogmatic approaches to artemisinin resistance: reappraisal as treatment failure with artemisinin combination therapy. Trends Parasitol. 2013;29:313–7.PubMedCrossRef Krishna S, Kremsner PG. Antidogmatic approaches to artemisinin resistance: reappraisal as treatment failure with artemisinin combination therapy. Trends Parasitol. 2013;29:313–7.PubMedCrossRef
13.
go back to reference Griffin JT, Hollingsworth TD, Okell LC, Churcher TS, White M, Hinsley W, et al. Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLoS Med. 2010;7:e1000324.PubMedPubMedCentralCrossRef Griffin JT, Hollingsworth TD, Okell LC, Churcher TS, White M, Hinsley W, et al. Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLoS Med. 2010;7:e1000324.PubMedPubMedCentralCrossRef
14.
go back to reference Griffin JT, Ferguson NM, Ghani AC. Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat Commun. 2014;5:3136.PubMedPubMedCentralCrossRef Griffin JT, Ferguson NM, Ghani AC. Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat Commun. 2014;5:3136.PubMedPubMedCentralCrossRef
15.
go back to reference Francis D, Nsobya SL, Talisuna A, Yeka A, Kamya MR, Machekano R, et al. Geographic differences in antimalarial drug efficacy in Uganda are explained by differences in endemicity and not by known molecular markers of drug resistance. J Infect Dis. 2006;193:978–86.PubMedCrossRef Francis D, Nsobya SL, Talisuna A, Yeka A, Kamya MR, Machekano R, et al. Geographic differences in antimalarial drug efficacy in Uganda are explained by differences in endemicity and not by known molecular markers of drug resistance. J Infect Dis. 2006;193:978–86.PubMedCrossRef
16.
go back to reference Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, et al. Efficacy of dihydroartemisinin–piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother. 2013;57:818–26.PubMedPubMedCentralCrossRef Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, et al. Efficacy of dihydroartemisinin–piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother. 2013;57:818–26.PubMedPubMedCentralCrossRef
17.
go back to reference Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, et al. Dihydroartemisinin–piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015;15:683–91.PubMedCrossRef Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, et al. Dihydroartemisinin–piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015;15:683–91.PubMedCrossRef
18.
go back to reference Bethell D, Se Y, Lon C, Tyner S, Saunders D, Sriwichai S, et al. Artesunate dose escalation for the treatment of uncomplicated malaria in a region of reported artemisinin resistance: a randomized clinical trial. PLoS One. 2011;6:e19283.PubMedPubMedCentralCrossRef Bethell D, Se Y, Lon C, Tyner S, Saunders D, Sriwichai S, et al. Artesunate dose escalation for the treatment of uncomplicated malaria in a region of reported artemisinin resistance: a randomized clinical trial. PLoS One. 2011;6:e19283.PubMedPubMedCentralCrossRef
19.
go back to reference Naidoo I, Roper C. Mapping ‘partially resistant’, ‘fully resistant’, and ‘super resistant’ malaria. Trends Parasitol. 2013;29:505–15.PubMedCrossRef Naidoo I, Roper C. Mapping ‘partially resistant’, ‘fully resistant’, and ‘super resistant’ malaria. Trends Parasitol. 2013;29:505–15.PubMedCrossRef
20.
go back to reference Griffin JT, Hollingsworth TD, Reyburn H, Drakeley CJ, Riley EM, Ghani AC. Gradual acquisition of immunity to severe malaria with increasing exposure. Proc R Soc Lond B Biol Sci. 2015;282:20142657.CrossRef Griffin JT, Hollingsworth TD, Reyburn H, Drakeley CJ, Riley EM, Ghani AC. Gradual acquisition of immunity to severe malaria with increasing exposure. Proc R Soc Lond B Biol Sci. 2015;282:20142657.CrossRef
21.
23.
go back to reference Gething P, Patil A, Smith D, Guerra C, Elyazar I, Johnston G, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.PubMedPubMedCentralCrossRef Gething P, Patil A, Smith D, Guerra C, Elyazar I, Johnston G, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.PubMedPubMedCentralCrossRef
24.
go back to reference Cairns M, Roca-Feltrer A, Garske T, Wilson AL, Diallo D, Milligan PJ, et al. Estimating the potential public health impact of seasonal malaria chemoprevention in African children. Nat Commun. 2012;3:881.PubMedPubMedCentralCrossRef Cairns M, Roca-Feltrer A, Garske T, Wilson AL, Diallo D, Milligan PJ, et al. Estimating the potential public health impact of seasonal malaria chemoprevention in African children. Nat Commun. 2012;3:881.PubMedPubMedCentralCrossRef
25.
go back to reference Flaxman AD, Fullman N, Otten MW Jr, Menon M, Cibulskis RE, Ng M, et al. Rapid scaling up of insecticide-treated bed net coverage in Africa and its relationship with development assistance for health: a systematic synthesis of supply, distribution, and household survey data. PLoS Med. 2010;7:e1000328.PubMedPubMedCentralCrossRef Flaxman AD, Fullman N, Otten MW Jr, Menon M, Cibulskis RE, Ng M, et al. Rapid scaling up of insecticide-treated bed net coverage in Africa and its relationship with development assistance for health: a systematic synthesis of supply, distribution, and household survey data. PLoS Med. 2010;7:e1000328.PubMedPubMedCentralCrossRef
26.
go back to reference Cohen JM, Woolsey AM, Sabot OJ, Gething PW, Tatem AJ, Moonen B. Optimizing investments in malaria treatment and diagnosis. Science. 2012;338:612–4.PubMedCrossRef Cohen JM, Woolsey AM, Sabot OJ, Gething PW, Tatem AJ, Moonen B. Optimizing investments in malaria treatment and diagnosis. Science. 2012;338:612–4.PubMedCrossRef
27.
go back to reference WHO. World malaria report 2012. Geneva: World Health Organization; 2012. WHO. World malaria report 2012. Geneva: World Health Organization; 2012.
28.
go back to reference Mohammed A, Ndaro A, Kalinga A, Manjurano A, Mosha J, Mosha D, et al. Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania. Malar J. 2013;12:415.PubMedPubMedCentralCrossRef Mohammed A, Ndaro A, Kalinga A, Manjurano A, Mosha J, Mosha D, et al. Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania. Malar J. 2013;12:415.PubMedPubMedCentralCrossRef
29.
go back to reference van Schalkwyk DA, Sutherland CJ. Malaria resistance to non-artemisinin partner drugs: how to reACT. Lancet Infect Dis. 2015;15:621–3.PubMedCrossRef van Schalkwyk DA, Sutherland CJ. Malaria resistance to non-artemisinin partner drugs: how to reACT. Lancet Infect Dis. 2015;15:621–3.PubMedCrossRef
Metadata
Title
Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa
Authors
Hannah C. Slater
Jamie T. Griffin
Azra C. Ghani
Lucy C. Okell
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-015-1075-7

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