Abstract
Plasmodium resistance to antimalarial drugs is an obstacle to the elimination of malaria in endemic areas. This situation is particularly dramatic for Africa, which accounts for nearly 92% of malaria cases worldwide. Drug pressure has been identified as a key factor in the emergence of antimalarial drug resistance. Indeed, this pressure is favoured by several factors, including the use of counterfeit forms of antimalarials, inadequate prescription controls, poor adherence to treatment regimens, dosing errors, and the increasing use of other forms of unapproved antimalarials. This resistance has led to the replacement of chloroquine (CQ) by artemisinin-based combination therapies (ACTs) which are likely to become ineffective in the coming years due to the uncontrolled use of Artemisia annua in the sub-Saharan African region for malaria prevention and COVID-19. The use of Artemisia annua for the prevention of malaria and COVID-19 could be an important factor in the emergence of resistance to Artemisinin-based combination therapies.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Background
Malaria is caused by parasites of the Plasmodium species and it is a global public health burden. In 2019, WHO reported 228 million malaria cases and 405,000 deaths worldwide, with a predominance in sub-Saharan Africa [1]. In December 2019, new pneumonia called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features similar to malaria such as fever, was reported in Wuhan, China [2]. COVID-19 rapidly evolved into a global pandemic, declared by the World Health Organization (WHO) on March 11, 2020, as a Public Health Emergency International Concern (PHEIC) [3]. At September 30, 2021, there were more than 234,390,731 confirmed cases in 223 countries and deaths exceeded 4,792,848 [4].
The use of plants for health care is a matter of culture and tradition in Africa [5,6,7,8,9]. It should be noted that for primary health needs, a large part of the African population resorts to traditional medicine, whose remedies mostly come from plant origin [6, 10]. The preference for these remedies is due to their accessibility and their low cost [11, 12]. This use has increased with the emergence of COVID-19. Thus, to prevent this disease, people deliberately use extracts of Artemisia annua (a plant containing artemisinin), which is also used by people to prevent malaria [13, 14]. Malaria is endemic in tropical and subtropical low-income countries, and the inadequate use of antimalarial drugs, especially artemisinin, for malaria prevention and in the context of COVID-19 could lead to an increase of Plasmodium resistance to antimalarial drugs, including artemisinin and its derivatives, thus compromising their efficacy. Therefore, such resistance would affect malaria control in these regions and jeopardize efforts to eliminate malaria by 2030 [15]. Our review focused on the selection factors of Plasmodium resistance to antimalarial drugs and the risk of emergence of resistance to artemisinin and its derivatives due to the empirical use of Artemisia annua in one part, and in another part the need to monitor regularly the efficacy of antimalarial drugs to achieve the goal of malaria elimination in Africa on time.
Selection Factors for Plasmodium Resistance to Antimalarial Drugs
Drug pressure has been identified as a key factor in the emergence of antimalarial drug resistance [16]. Antimalarial drug resistance must be considered in two parts: on the one hand, the initial genetic event that produces the resistant mutant, and on the other hand, the subsequent selection process in which the survival advantage in the presence of the antimalarial drug leads to the preferential transmission and spread of resistance [17]. Indeed, the evolution of antimalarial drug resistance is facilitated by several factors, including the use of counterfeit forms of antimalarial drugs, inadequate controls on prescribing, poor adherence to treatment regimens, incorrect dosing, and the increasing use of other forms of unlicensed antimalarial drugs [18, 19]. This last factor has attracted more attention from WHO in recent years with the deliberate use of Artemisia annua extracts for malaria prevention and COVID-19 [20,21,22,23].
About artemisinin, while this plant is currently cultivated in various regions of African countries, studies have revealed that there is a diversity of Artemisia annua species, and for the same species, the artemisinin content can vary from one region to another depending on the composition of the soils on which these plants are grown [24, 25]. Thus, these Artemisia extracts are likely to exert undesirable drug pressure over a long period of time once their concentrations fall below the critical threshold and may select for resistant parasites [26].
In Africa, the resistance to CQ had led to its replacement by artemisinin-based combination therapies (ACTs) [27,28,29]. This resistance has appeared in Southeast Asia, for all classes of antimalarial drugs and recently for artemisinin, the main component of current antimalarial drugs [16, 30, 31] with an increase in markers of this resistance in African countries [30]. Not only the effects of resistance on morbidity and mortality are generally underestimated [32, 33], but it is also an obstacle to malaria elimination [34, 35].
Resistance of Plasmodium to Artemisinin and Its Derivatives
Artemisinin has been discovered since the early 1970s by Dr. Youyou Tu, the 2015 Nobel Laureate, as an effective drug for the treatment of malaria [36]. Following WHO recommendations, artemisinin-based combination therapies (ACTs) are used for malaria treatment in Africa, because fast-acting artemisinin can immediately reduce parasitaemia, allowing the remaining parasites to be eliminated with a long-acting partner drug [37]. Although recent studies have confirmed the existence of artemisinin resistance in P. falciparum [38], artemisinin and its derivatives have nonetheless made progress in the treatment of malaria and have made quinolones as a secondary treatment option in most countries of the world [38, 39].
Since 2014, mutations in the "helix" region of a P. falciparum Kelch protein (encoded by the kelch13 gene) have been identified as molecular markers of artemisinin resistance based on their association with the slow clearance phenotype [40].
In Asia, 36.5% of K13 mutations were distributed in two areas, one in Cambodia, Vietnam and Laos, and the other in western Thailand, Myanmar and China [41].
In Africa, non-synonymous mutations are still rare and very diverse. Non-synonymous K13 mutations have been reported in Angola, Burkina Faso, Cameroon, Central African Republic, Comoros, Congo, Ivory Coast, Democratic Republic of Congo, Equatorial Guinea, Ethiopia, Gabon, Gambia, Kenya, Liberia, Madagascar, Malawi, Mali, Mozambique, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, Togo, Uganda and Zambia [42]. However, a recent study in Uganda found an association between K13 mutations and delayed parasite clearance in subjects treated with artesunate, a soluble arteminisin derivative [30].
In Togo, 1.8% of K13 mutations were identified in three sentinel sites monitoring antimalarial efficacy in 2013 [40]. Although K13 helix mutations associated with artemisinin resistance have been found in Tanzania and Uganda [30, 41], there is no evidence of emerging resistance to artemisinin and its derivatives associated with K13 mutations in Togo in particular [40].
Furthermore, immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites [43]. Most malaria infections are genetically diverse [44,45,46,47], and this diversity increases in areas of high transmission where hosts experience frequent and overlapping infections [48,49,50,51]. In a multi-infected host, different lineages compete for the same resources while being subject to specific and non-specific immune regulation. When drug-resistant and drug-sensitive parasites are present in the same host, the sensitive lineages can suppress the growth and transmission of the resistant lineages [52,53,54]. However, reduced malaria transmission decreases naturally acquired immunity, which may influence the emergence of artemisinin-resistant phenotypes and genotypes of Plasmodium falciparum over time [55]. It is important to understand how changing transmission and immunity could impact the emergence of artemisinin resistance, especially as increased malaria control and elimination activities may improve the immunological conditions for the expansion of artemisinin-resistant P. falciparum [56].
To ensure that the current COVID-19 pandemic does not result in a major upsurge in malaria cases, derailing sub-Saharan Africa elimination efforts, it is critical that the recommended malaria case management practices and procedures are closely monitored [57].
Use of Domestic Artemisinin for the Treatment of COVID-19
The effective antimalarial drugs recommended by the WHO are made from artemisinin isolated from Artemisia annua [58]. Thus, populations especially in malaria-endemic areas empirically use infusions of Artemisia annua leaves to prevent or treat malaria [59]. While its active ingredient (artemisinin) content is dependent on geo-climatic factors and season [60], it is currently planted in several countries for domestic use against malaria [61].
With the emergence of COVID-19 pandemic, many populations have illegally adopted Artemisia annua for the prevention and treatment of COVID-19, despite WHO calls against its use without proper scientific approval [20,21,22,23]. For example, Madagascar has used a tonic (Covid Organic) from Artemisia annua as a potential remedy for COVID-19 [62]. Unfortunately, no studies to date have elucidated the interactions of artemisinin on the angiotensin-converting enzyme 2 (ACE2) receptor, which is known to be the critical cellular binding receptor for SARS-CoV-2 [63], although studies have demonstrated the anti-inflammatory potential of high-dose artesunate in the context of COVID-19 [64, 65]. This may partially justify the rejection of some institutions such as WHO to allow artemisinin as a cure for COVID-19 [23].
Impact of Plasmodium Resistance to Antimalarial Drugs on the Achievement of the New Malaria Strategy Plan
Remarkable advances in malaria control in recent years have been partially wiped out by the COVID-19 pandemic [66]. Therefore, WHO recommends attention to malaria interventions while responding to the pandemic to avoid the unintended consequences of SARS-CoV-2 on malaria in Africa [3]. Although medicinal plants such as Artemisia annua are considered as possible treatments for COVID-19, its use has been discouraged by the WHO, due to lack of data on the efficacy of the extracts and lack of safety information [67,68,69]. In fact, its use could potentiate the development of resistance to ACTs, especially in Africa where the malaria burden remains the highest [1].
However, resistance has been shown to occur primarily during the ring stage of parasite development due to multiple forms of mutations in the Kelch PF3D7_1343700 (K13-propeller) helix domain on chromosome 13 [70]. Mutations in the K13-propeller lead to an increase in phosphatidylinositol-3-kinase (PfPI3K), which is required to mediate cell signalling and survival [71]. The latter leads to vesicle expansion that increases engagement in the unfolded protein response (UPR) [72]. Vesicle expansion (rather than increasing individual genetic determinants of UPR) effectively induces artemisinin resistance, presumably by promoting "proteostasis" (protein translation coupled with proper protein folding and vesicle remodelling) to mitigate artemisinin-induced proteinopathy (death due to abnormal overall protein toxicity) [73]. This may jeopardize malaria elimination plans in African countries and other malaria-prone regions, as artemisinin monotherapy and especially low-dose artemisinin monotherapy could lead to the spreading of the Kelch13-positive strains in Africa [74]. While resistance to most malaria drugs (amodiaquine, lumefantrine, mefloquine and sulfadoxine–pyrimethamine) has already been well demonstrated [74, 75], the uncontrolled use of artemisinin-based drugs could be a factor for the emergence of resistance in the coming years [76]. Following the pattern of CQ resistance, Plasmodium may become increasingly resistant to artemisinin in the coming years.
Furthermore, although control strategies for COVID-19 have been significantly improved by vaccination [77, 78], malaria control strategies are disrupted, particularly in low-resource settings where clinical facilities are extremely limited [66]. Thus, controlling COVID-19 is a global challenge. Malaria elimination would be effective if efforts against COVID-19 were also engaged in the fight against malaria, which causes more than 400,000 deaths per year in Africa, with children being the most affected [1, 79,80,81]. Given that the burden of malaria is highest in low-income tropical countries that have little capacity to fund malaria control and elimination programmes, malaria control in these regions is likely to be hampered in a few years by the spreading of the Kelch13-positive strains. To verify this hypothesis and to trace this potential risk, it would be good to set up regular monitoring sites in all African countries to detect in time any suspicious increase of molecular markers or its appearance, so as to be able to act quickly to prevent its propagation to other regions of the world.
Conclusion
Plasmodium resistance to antimalarial drugs is an obstacle in the fight against malaria. The resistance to ACTs especially could be potentiated by the use of Artemisia annua for the prevention and treatment of malaria and COVID-19. Although COVID-19 has a collateral impact in Africa, this pandemic could be an important factor in the emergence of TCA resistance. Therefore, more concerted efforts are needed to defeat these two diseases.
Change history
13 January 2022
A Correction to this paper has been published: https://doi.org/10.1007/s11686-021-00516-y
References
WHO (2019) World Malaria Report 2019. World Health Organization. https://www.who.int/malaria/publications/world-malaria-report-2019/en/. Accessed April 21, 2021
Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271–280. https://doi.org/10.1016/j.cell.2020.1002.1052
WHO (2020) Tailoring Malaria Interventions in the COVID-19 Response. Geneva: WHO. https://www.who.int/malaria/publications/atoz/tailoring-malaria-interventions-covid-19.pdf?ua=11. Accessed May 15, 2021
Worldometer (2021) Reported Cases and Deaths by Country or Territory. https://www.worldometers.info/coronavirus/. Accessed September 30, 2021
Jeruto P, Lukhoba C, Ouma G, Otieno D, Mutai C (2008) An ethnobotanical study of medicinal plants used by the Nandi people in Kenya. J Ethnopharmacol 116(2):370–376. https://doi.org/10.1016/j.jep.2007.11.1041
Tchacondo T, Karou SD, Batawila K, Agban A, Ouro-Bang’na K, Anani KT, Gbeassor M, de Souza C (2011) Herbal remedies and their adverse effects in Tem tribe traditional medicine in Togo. AJTCAM 8(1):45–60. https://doi.org/10.4314/ajtcam.v4318i4311.60522
Abdullahi AA (2011) Trends and challenges of traditional medicine in Africa. AJTCAM 8(5):115–123. https://doi.org/10.4314/ajtcam.v8i5S.5
Quiroz D, van Andel T (2018) The cultural importance of plants in Western African religions. Econ Bot 72(3):251–262. https://doi.org/10.1007/s12231-018-9410-x
Towns AM, Mengue Eyi S, van Andel T (2014) Traditional medicine and childcare in Western Africa: mothers’ knowledge, folk illnesses, and patterns of healthcare-seeking behavior. PLoS ONE 9(8):e105972. https://doi.org/10.1371/journal.pone.0105972
Karou SD, Tchacondo T, Ouattara L, Anani K, Savadogo A, Agbonon A, Attaia MB, de Souza C, Sakly M, Simpore J (2011) Antimicrobial, antiplasmodial, haemolytic and antioxidant activities of crude extracts from three selected Togolese medicinal plants. Asian Pac J Trop Med 4(10):808–813
Chali BU, Hasho A, Koricha NB (2021) Preference and practice of traditional medicine and associated factors in Jimma Town, Southwest Ethiopia. Evid Based Complement Alternat Med. https://doi.org/10.1155/2021/9962892
Welz AN, Emberger-Klein A, Menrad K (2018) Why people use herbal medicine: insights from a focus-group study in Germany. BMC Complement Altern Med 18(1):92. https://doi.org/10.1186/s12906-018-2160-6
Nair MS, Huang Y, Fidock DA, Polyak SJ, Wagoner J, Towler MJ, Weathers PJ (2021) Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants. BioRxiv 2008:425825
Septembre-Malaterre A, Lalarizo Rakoto M, Marodon C, Bedoui Y, Nakab J, Simon E, Hoarau L, Savriama S, Strasberg D, Guiraud P et al (2020) Artemisia annua, a traditional plant brought to light. Int J Mol Sci 21(14):4986
WHO (2015) Global Technical Strategy for Malaria 2016–2030. http://apps.who.int/iris/bitstream/handle/10665/176712/9789241564991_eng.pdf?sequence=9789241564991. Accessed April 21, 2021
Stokes BH, Dhingra SK, Rubiano K, Mok S, Straimer J, Gnädig NF, Deni I, Schindler KA, Bath JR, Ward KE et al (2021) Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness. Elife 10:e66277
Day N, Pham T, Phan T, Dinh X, Pham P, Ly V, Tran T, Nguyen T, Bethell DB, Nguyan H (1996) Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria. Blood 88(12):4694–4700 (PMID: 8977263)
Wernsdorfer WH (1991) The development and spread of drug-resistant malaria. Parasitol Today 7(11):297–303. https://doi.org/10.1016/0169-4758(91)90262-m
Wernsdorfer WH (1994) Epidemiology of drug resistance in malaria. Acta Trop 56(2–3):143–156. https://doi.org/10.1016/0001-706x(94)90060-4
Cao R, Hu H, Li Y, Wang X, Xu M, Liu J, Zhang H, Yan Y, Zhao L, Li W et al (2020) Anti-SARS-CoV-2 potential of Artemisinins In Vitro. ACS Infect Dis 6(9):2524–2531
Gendrot M, Duflot I, Boxberger M, Delandre O, Jardot P, Le Bideau M, Andreani J, Fonta I, Mosnier J, Rolland C et al (2020) Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: in vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate. Int J Infect Dis 99:437–440
Li G, Yuan M, Li H, Deng C, Wang Q, Tang Y, Zhang H, Yu W, Xu Q, Zou Y et al (2020) Safety and efficacy of Artemisinin-Piperaquine for treatment of COVID-19: an open-label, non-randomized, and controlled trial. Int J Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2020.106216
Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C (2020) Cytokine storm in COVID-19: the current evidence and treatment strategies. Front Immunol 11:1708. https://doi.org/10.3389/fimmu.2020.01708
Wetzstein HY, Porter JA, Janick J, Ferreira JFS, Mutui TM (2018) Selection and clonal propagation of high Artemisinin Genotypes of Artemisia annua. Front Plant Sci. https://doi.org/10.3389/fpls.2018.00358
Mannan A, Ahmed I, Arshad W, Asim MF, Qureshi RA, Hussain I, Mirza B (2010) Survey of artemisinin production by diverse Artemisia species in northern Pakistan. Malar J 9(1):310. https://doi.org/10.1186/1475-2875-9-310
Watkins W, Mberu E, Winstanley P, Plowe C (1997) The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses. J Parasitology Today 13(12):459–464
Mutabingwa T, Nzila A, Mberu E, Nduati E, Winstanley P, Hills E, Watkins W (2001) Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania. Lancet 358(9289):1218–1223
Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B (2003) Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet 361(9364):1174–1181
Plowe CV, Kublin JG, Dzinjalamala FK, Kamwendo DS, Chimpeni P, Molyneux ME (2004) Taylor TE (2004) Sustained clinical efficacy of sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Malawi after 10 years as first line treatment: five year prospective study. BMJ 328(7439):545
Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, Opio W, Emoto S, Anywar DA, Kimura E et al (2021) Evidence of Artemisinin-resistant malaria in Africa. N Engl J Med 385(13):1163–1171. https://doi.org/10.1056/NEJMoa2101746
Rosenthal PJ (2021) Has artemisinin resistance emerged in Africa? Lancet Infect Dis 21(8):1056–1057. https://doi.org/10.1016/S1473-3099(21)00168-7
Trape J-F, Pison G, Preziosi M-P, Enel C, du Loû AD, Delaunay V, Samb B, Lagarde E, Molez J-F, Simondon F (1998) Impact of chloroquine resistance on malaria mortality. Comptes Rendus de l’Académie des Sciences-Series III-Sciences de la Vie 321(8):689–697
White N (1999) Antimalarial drug resistance and combination chemotherapy. Philos Trans R Soc Lond B Biol Sc 354(1384):739–749. https://doi.org/10.1098/rstb.1999.0426
Bazie VB, Ouattara AK, Sagna T, Compaore TR, Soubeiga ST, Sorgho PA, Yonli AT, Simpore J (2020) Resistance of Plasmodium falciparum to Sulfadoxine-Pyrimethamine (Dhfr and Dhps) and Artemisinin and Its Derivatives (K13): A Major Challenge for Malaria Elimination in West Africa. J Biosci Med 8:82–95. https://doi.org/10.4236/jbm.2020.82007
Tang Y-Q, Ye Q, Huang H, Zheng W-Y (2020) An overview of available antimalarials: discovery, mode of action and drug resistance. J Curr Mol Med 20(8):583–592
Su X-Z, Miller LH (2015) The discovery of artemisinin and the Nobel Prize in physiology or medicine. Sci China Life Sci 58(11):1175–1179
Ashley EA, Stepniewska K, Lindegårdh N, McGready R, Annerberg A, Hutagalung R, Singtoroj T, Hla G, Brockman A, Proux S et al (2007) Pharmacokinetic study of artemether–lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant P. falciparum malaria. Trop Med Int Health 12(2):201–208. https://doi.org/10.1111/j.1365-3156.2006.01785.x
Tilley L, Straimer J, Gnädig NF, Ralph SA, Fidock DA (2016) Artemisinin action and resistance in Plasmodium falciparum. Trends Parasitol 32(9):682–696. https://doi.org/10.1016/j.pt.2016.05.010
McIntosh HM, Olliaro P (2000) Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev 1998(2):CD000527
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, Kim S, Duru V, Bouchier C, Ma L (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. J Nature 505(7481):50–55. https://doi.org/10.1038/nature12876
Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, Rahim-Awab G, Barnadas C, Berry A, Boum Y et al (2016) A worldwide Map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med 374(25):2453–2464. https://doi.org/10.1056/NEJMoa1513137
WHO (2016) Artemisinin and artemisinin-based combination therapy resistance. Global Malaria Programme. http://apps.who.int/iris/bitstream/handle/10665/208820/WHO_HTM_GMP_202016.208825_eng.pdf?sequence=208821. Accessed May 18,2021
Ataide R, Ashley EA, Powell R, Chan J-A, Malloy MJ, O’Flaherty K, Takashima E, Langer C, Tsuboi T, Dondorp AM et al (2017) Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort. Proc Natl Acad Sci USA 114(13):3515–3520
Tanner M, Beck HP, Felger I, Smith T (1999) The epidemiology of multiple plasmodium falciparum infections. 1. General introduction. Trans R Soc Trop Med Hyg 93(Suppl 1):1–2. https://doi.org/10.1016/s0035-9203(1099)90319-x
Ae IE, ElGhazali G, A-Elgadir TM, Hamad AA, Babiker HA, Elbashir MI, Giha HA (2007) Allelic polymorphism of MSP2 gene in severe P falciparum malaria in an area of low and seasonal transmission. Parasitol Res 102(1):29–34
Babiker HA, Creasey AM, Fenton B, Bayoumi RA, Arnot DE, Walliker D (1991) Genetic diversity of Plasmodium falciparum in a village in eastern Sudan. 1. Diversity of enzymes, 2D-PAGE proteins and antigens. Trans R Soc Trop Med Hyg 85(5):572–577
Paul RE, Hackford I, Brockman A, Muller-Graf C, Price R, Luxemburger C, White NJ, Nosten F, Day KP (1998) Transmission intensity and Plasmodium falciparum diversity on the northwestern border of Thailand. Am J Trop Med Hyg 58(2):195–203
Babiker HA, Lines J, Hill WG, Walliker D (1997) Population structure of Plasmodium falciparum in villages with different malaria endemicity in east Africa. Am J Trop Med Hyg 56(2):141–147. https://doi.org/10.4269/ajtmh.1997.56.141
Arnot D (1998) Unstable malaria in Sudan: the influence of the dry season Clone multiplicity of Plasmodium falciparum infections in individuals exposed to variable levels of disease transmission. Trans R Soc Trop Med Hyg 92(6):580–585
Juliano JJ, Porter K, Mwapasa V, Sem R, Rogers WO, Ariey F, Wongsrichanalai C, Read A, Meshnick SR (2010) Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing. Procd Natl Acad Sci 107(46):20138–20143. https://doi.org/10.1073/pnas.1007068107
Mideo N, Bailey JA, Hathaway NJ, Ngasala B, Saunders DL, Lon C, Kharabora O, Jamnik A, Balasubramanian S, Björkman A et al (2016) A deep sequencing tool for partitioning clearance rates following antimalarial treatment in polyclonal infections. Evol Med Public Health 6(1):21–36. https://doi.org/10.1093/emph/eov1036
Wargo AR, Huijben S, de Roode JC, Shepherd J, Read AF (2007) Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model. Proc Natl Acad Sci USA 104(50):19914–19919. https://doi.org/10.1073/pnas.0707766104
de Roode JC, Helinski ME, Anwar MA, Read AF (2005) Dynamics of multiple infection and within-host competition in genetically diverse malaria infections. Am Nat 166(5):531–542. https://doi.org/10.1086/491659
Bushman M, Morton L, Duah N, Quashie N, Abuaku B, Koram KA, Dimbu PR, Plucinski M, Gutman J, Lyaruu P et al (2016) Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum. Proc Biol Sci 283(1826):20153038
Fowkes FJ, Boeuf P, Beeson JGJP (2016) Immunity to malaria in an era of declining malaria transmission. Parasitology 143(2):139–153. https://doi.org/10.1017/S0031182015001249
Ataíde R, Powell R, Moore K, McLean A, Phyo AP, Nair S, White M, Anderson TJ, Beeson JG, Simpson JA et al (2017) Declining transmission and immunity to malaria and emerging artemisinin resistance in Thailand: a longitudinal study. J Infect Dis 216(6):723–731. https://doi.org/10.1093/infdis/jix1371
Raman J, Barnes KI, Baker L, Blaylock M, Blumberg L, Frean J, Misiani E, Ukpe IS (2020) Maintaining focus on administering effective malaria treatment during the COVID-19 pandemic. S Afr Med J 111(1):13–16. https://doi.org/10.7196/SAMJ.2020.v111i11.15289
WHO (2011) Global Fund Malaria Proposal Development: WHO Policy Brief - WHO/GMP. World Health Organization. https://www.who.int/malaria/publications/atoz/malaria_gf_proposal_who_policy_fr.pdf . Accessed May 7, 2021
Elfawal MA (2014) Dried whole plant Artemisia annua as a novel antimalarial therapy. Dr Diss. https://doi.org/10.7275/6028909.0
Khan SM, Page S, Ahmad H, Harper D (2013) Identifying plant species and communities across environmental gradients in the Western Himalayas: Method development and conservation use. Ecol Inform 14:99–103. https://doi.org/10.1016/j.ecoinf.2012.11.010
Isah T (2019) Stress and defense responses in plant secondary metabolites production. Biol Res 52:39. https://doi.org/10.1186/s40659-019-0246-3
Finnan D (2020) Artemisia: Madagascar's Coronavirus Cure or Covid-19 Quackery? http://www.rfi.fr/en/africa/20200505-artemisia-madagascar-s-coronavirus-cure-or-covid-20200519-quackery-covid-organics-malaria. Accessed May 18, 2021
Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798):270–273
Fuzimoto AD (2021) An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment. J Integr Med 19(5):375–388. https://doi.org/10.1016/j.joim.2021.07.003
Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, Kamarulzaman A, Sall A, Kremsner P (2020) Repurposing antimalarials to tackle the COVID-19 pandemic. Trends Parasitol 37(1):8–11. https://doi.org/10.1016/j.pt.2020.10.003
Global Fund (2020) Mitigating the impact of COVID-19 in countries affected by HIV, tuberculosis, and malaria. The Global Fund to Fight AIDS, Tuberculosis and Malaria. https://www.theglobalfund.org/fr/covid-19-plan/. Accessed May 15, 2021
WHO (2012) WHO Position Statement: Effectiveness of Non-Pharmaceutical Forms of Artemisia Annua Against Malaria. Geneva: World Health Organization. https://www.who.int/malaria/position_statement_herbal_remedy_artemisia_annua_l.pdf. Accessed May 5, 2021
WHO (2021) WHO supports scientifically-proven traditional medicine. https://www.afro.who.int/news/who-supports-scientifically-proven-traditional-medicine?gclid=Cj0KCQjwtMCKBhDAARIsAG-2Eu8R-nmBrnzewl12uygbtpgouFYKHVZXj19zeIdk17CSVRHJn-17a11Fw16QaArtREALw_wcB. Acceced, 26th september 2021
Kapepula PM, Kabengele JK, Kingombe M, Van Bambeke F, Tulkens PM, Sadiki Kishabongo A, Decloedt E, Zumla A, Tiberi S, Suleman F et al (2020) Artemisia Spp. derivatives for COVID-19 treatment: anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials. Am J Trop Med Hyg 103(3):960–964. https://doi.org/10.4269/ajtmh.20-0820
Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B et al (2013) Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 13(12):1043–1049
Mok S, Ashley EA, Ferreira PE, Zhu L, Lin Z, Yeo T, Chotivanich K, Imwong M, Pukrittayakamee S, Dhorda M et al (2015) Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science 347(6220):431–435. https://doi.org/10.1126/science.1260403
Suresh N, Haldar K (2018) Mechanisms of artemisinin resistance in Plasmodium falciparum malaria. Curr Opin Pharmacol 42:46–54. https://doi.org/10.1016/j.coph.2018.1006.1003
Bhattacharjee S, Coppens I, Mbengue A, Suresh N, Ghorbal M, Slouka Z, Safeukui I, Tang HY, Speicher DW, Stahelin RV et al (2018) Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance. Blood 131(11):1234–1247
Sibley CH, Hyde JE, Sims PFG, Plowe CV, Kublin JG, Mberu EK (2001) Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17:570–571
Picot S, Olliaro P, De Monbrison F, Bienvenu AL, Price RN, Ringwald P (2009) A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar J 8:1–15. https://doi.org/10.1186/1475-2875-1188-1189
Prodines B, Dormoi J, Briolant S, Bogreau H, Rogier C (2010) La résistance aux antipaludiques. Rev Francoph Des Lab 422:51–62. https://doi.org/10.1016/S1773-35X(10)70510-4
Mohammadi A, Mollalo A, Bergquist R, Kiani B (2021) Measuring COVID-19 vaccination coverage: an enhanced age-adjusted two-step floating catchment area model. Infect Dis Poverty 10(1):118
Estadilla CDS, Uyheng J, de Lara-Tuprio EP, Teng TR, Macalalag JMR, Estuar MRJE (2021) Impact of vaccine supplies and delays on optimal control of the COVID-19 pandemic: mapping interventions for the Philippines. Infect Dis Poverty 10(1):107
WHO (2014) WHO severe malaria. Trop Med Int Health 19:7–131
Dhochak N, Singhal T, Kabra SK, Lodha R (2020) Pathophysiology of COVID-19: why children fare better than adults? Indian J Pediatr 14:1–10. https://doi.org/10.1007/s12098-12020-03322-y
Kindzeka M (2021) COVID-19 Frightens Malaria Patients in Cameroon. 2020. https://www.voanews.com/science-health/covid-19-frightens-malaria-patients-cameroon. Accessed November 15, 2021
Author information
Authors and Affiliations
Contributions
EA, AMD and CTN contributed to the design of the study and analysed the research data. TB, TT, KDK, KY and TA provided additional articles related to the topic. EA, AMD and CTN wrote the review which was then read and approved by all the other authors.
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
he original online version of this article was revised: The copyright holder for this article was incorrectly given as 'The Author(s), under exclusive licence to The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences' but should have been 'The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences'. The original article has been corrected.
Rights and permissions
About this article
Cite this article
Ataba, E., Dorkenoo, A.M., Nguepou, C.T. et al. Potential Emergence of Plasmodium Resistance to Artemisinin Induced by the Use of Artemisia annua for Malaria and COVID-19 Prevention in Sub-African Region. Acta Parasit. 67, 55–60 (2022). https://doi.org/10.1007/s11686-021-00489-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11686-021-00489-y