Abstract
The advancement of malaria control is significant; yet, the presence of drug-resistant malarial parasites remains an issue. In Pakistan, nearly one million malaria cases occur each year. A prospective, observational, cohort study was conducted among 354 malaria patients in Karachi, Pakistan. By Day 28, recurrent Plasmodium vivax infection occurred in 10/98 (10.2%) of participants receiving chloroquine (CQ) monotherapy, 17/84 (20.2%) receiving artemether–lumefantrine (AL) monotherapy, 1/93 (1.1%) receiving CQ plus primaquine (CQ + PQ), and 3/79 (3.8%) receiving AL plus primaquine (AL + PQ). The corresponding Kaplan–Meier cumulative incidence estimates at Day 28 were 13.4% (95% CI 5.6–21.2), 24.5% (95% CI 14.3–34.7), 1.5% (95% CI 0.0–4.4), and 5.3% (95% CI 0.0–11.2), respectively. By the end of six months of follow-up, observed recurrence was 15/98 (15.3%) for CQ, 27/84 (32.2%) for AL, 1/93 (1.1%) for CQ + PQ, and 5/79 (6.3%) for AL + PQ; Kaplan–Meier cumulative incidence estimates were 21.0% (95% CI 11.0–31.0), 39.1% (95% CI 26.7–51.4), 1.5% (95% CI 0.0–4.4), and 10.0% (95% CI 1.6–18.4), respectively. In unadjusted Cox proportional hazards models, AL monotherapy was associated with a higher hazard of recurrence than CQ monotherapy, while primaquine-containing regimens showed lower recurrence hazards than the corresponding monotherapies during follow-up.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
References
Rao, S. S., Vaidya, K. A. & Sharma, A. K. An observational study comparing the effects of chloroquine and Artemisinin-Based combination therapy on hematological recovery in patients with plasmodium Vivax malaria. Cureus 15 (10), e47127 (2023).
Ameja, C., Ogbe, P., Ibubeleye, V. & Georgewill, U. Evaluation of the Efficacy of Artemether/Lumefantrine/Doxycycline Combination against Plasmodium berghei in Mice. EAS J. Parasitol. Infect. Dis. 5, 36–42. https://doi.org/10.36349/easjpid.2023.v05i04.001 (2023).
Tabassum, S. et al. Reflections on the surge in malaria cases after unprecedented flooding in Pakistan-A commentary. Health Sci. Rep. 6 (10), e1620 (2023).
Jabeen, A., Ansari, J. A., Ikram, A., Khan, M. A. & Safdar, M. Impact of climate change on the epidemiology of vector-borne diseases in Pakistan. Global Biosecur. ;4(1). (2022).
WHO. World malaria report 2024 [Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2024/questions-and-answers#:~:text=This%20year’s%20report%20shows%20an,increasing%20or%20decreasing%20%E2%80%93%20remain%20uncertain
Killeen, G. F. et al. Going beyond personal protection against mosquito bites to eliminate malaria transmission: population suppression of malaria vectors that exploit both human and animal blood. BMJ Glob Health. 2 (2), e000198 (2017).
Chen, L. H., Wilson, M. E. & Schlagenhauf, P. Controversies and misconceptions in malaria chemoprophylaxis for travelers. JAMA 297 (20), 2251–2263 (2007).
Daily, J. P., Minuti, A. & Khan, N. Diagnosis, Treatment, and prevention of malaria in the US: A review. JAMA 328 (5), 460–471 (2022).
Larréché, S. et al. Sensitivity of parasitological tests in imported plasmodium Vivax malaria in adults and impact of chemoprophylaxis and attack type. J. Travel Med. 21 (3), 195–200 (2014).
Daily, J. P., Parikh, S. & Malaria N. Engl. J. Med. ;392(13):1320–1333. (2025).
Olliaro, P. L. et al. Implications of plasmodium Vivax biology for Control, Elimination, and research. Am. J. Trop. Med. Hyg. 95 (6 Suppl), 4–14 (2016).
Kojom Foko, L. P., Arya, A., Sharma, A. & Singh, V. Epidemiology and clinical outcomes of severe plasmodium Vivax malaria in India. J. Infect. 82 (6), 231–246 (2021).
Geleta, G. & Ketema, T. Severe malaria associated with plasmodium falciparum and P. vivax among children in Pawe Hospital, Northwest Ethiopia. Malar. Res. Treat. 2016 (1), 1240962 (2016).
Ketema, T. & Bacha, K. Plasmodium Vivax associated severe malaria complications among children in some malaria endemic areas of Ethiopia. BMC Public. Health. 13 (1), 637 (2013).
Demissie, Y. & Ketema, T. Complicated malaria symptoms associated with plasmodium Vivax among patients visiting health facilities in Mendi town, Northwest Ethiopia. BMC Infect. Dis. 16 (1), 436 (2016).
Malik, M., Hussain, A., Hassali, M. A. & Shafie, A. A. Standard treatment guidelines for malaria: challenges in its implementation in Islamabad (federal capital) and Rawalpindi (twin city), Pakistan. Saudi Pharm. J. 21 (1), 123–124 (2013).
The effect of dose on the antimalarial efficacy. Of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data. Lancet Infect. Dis. 15 (6), 692–702 (2015).
World Health, O. WHO guidelines for malaria, 13 July 2021. Geneva: World Health Organization; Contract No.: WHO/UCN/GMP/2021.01 Rev.1. (2021) 2021.
Senn, N. et al. Effectiveness of Artemether/Lumefantrine for the treatment of uncomplicated plasmodium Vivax and P. falciparum malaria in young children in Papua new Guinea. Clin. Infect. Dis. 56 (10), 1413–1420 (2013).
Price, R. N. et al. Global extent of chloroquine-resistant plasmodium vivax: a systematic review and meta-analysis. Lancet Infect. Dis. 14 (10), 982–991 (2014).
Waheed, A. A. et al. Vivax malaria and chloroquine resistance: a neglected disease as an emerging threat. Malar. J. 14, 146 (2015).
White, N. J. Determinants of relapse periodicity in plasmodium Vivax malaria. Malar. J. 10 (1), 297 (2011).
Beutler, E. A series of new screening procedures for pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency, and glutathione reductase deficiency. Blood 28 (4), 553–562 (1966).
News, M-P-R-D-O. Malaria - Pakistan. (2022).
Disease Outbreak News. Malaria - Pakistan [press release]. (2022).
Abanyie, F. A., Arguin, P. M. & Gutman, J. State of malaria diagnostic testing at clinical laboratories in the united States, 2010: a nationwide survey. Malar. J. 10, 340 (2011).
Wilson, M. L. Malaria rapid diagnostic tests. Clin. Infect. Dis. 54 (11), 1637–1641 (2012).
Muhammad, S. et al. Therapeutic efficacy of chloroquine vs Artemether/lumefantrine combination in Vivax malaria in Nowshera and surroundings. Med. Forum Monthly. 33, 53 (2023).
Abreha, T. et al. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of plasmodium Vivax infection in ethiopia: A randomized controlled trial. PLoS Med. 14 (5), e1002299 (2017).
John, G. K. et al. Primaquine radical cure of plasmodium vivax: a critical review of the literature. Malar. J. 11 (1), 280 (2012).
Groger, M. et al. Prospective clinical trial assessing Species-Specific efficacy of Artemether-Lumefantrine for the treatment of plasmodium malariae, plasmodium ovale, and mixed plasmodium malaria in Gabon. Antimicrob. Agents Chemother. 62(3), e01758-17. https://doi.org/10.1128/AAC.01758-17 (2018).
Assefa, A. et al. Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated plasmodium Vivax infection in Ethiopia. Malar. J. 21 (1), 359 (2022).
Zaman, N. et al. Incidence of malarial infection and response to antimalarial drugs at districts lower dir and swat of Khyber Pakhtunkhwa, Pakistan. Dialogues Health. 1, 100035 (2022).
Khan, M. I. et al. Malaria prevalence in pakistan: A systematic review and meta-analysis (2006–2021). Heliyon 9 (4), e15373 (2023).
Khan, A., Godil, F. J. & Naseem, R. Chloroquine-resistant plasmodium Vivax in pakistan: an emerging threat. Lancet Glob Health. 4 (11), e790 (2016).
Getachew, S. et al. Chloroquine efficacy for plasmodium Vivax malaria treatment in Southern Ethiopia. Malar. J. 14, 525 (2015).
Yohannes, A. M., Teklehaimanot, A., Bergqvist, Y. & Ringwald, P. Confirmed Vivax resistance to chloroquine and effectiveness of artemether-lumefantrine for the treatment of Vivax malaria in Ethiopia. Am. J. Trop. Med. Hyg. 84 (1), 137–140 (2011).
Ahmad, S. S., Rahi, M. & Sharma, A. Relapses of plasmodium Vivax malaria threaten disease elimination: time to deploy tafenoquine in India? BMJ Glob. Health. 6(2), e004558. https://doi.org/10.1136/bmjgh-2020-004558 (2021).
Leslie, T. et al. Compliance with 14-day primaquine therapy for radical cure of Vivax malaria–a randomized placebo-controlled trial comparing unsupervised with supervised treatment. Trans. R Soc. Trop. Med. Hyg. 98 (3), 168–173 (2004).
Douglas, N. M. et al. Major burden of severe anemia from non-falciparum malaria species in Southern papua: a hospital-based surveillance study. PLoS Med. 10 (12), e1001575 (2013). discussion e.
Bruxvoort, K., Goodman, C., Kachur, S. P. & Schellenberg, D. How patients take malaria treatment: a systematic review of the literature on adherence to antimalarial drugs. PLoS One. 9 (1), e84555 (2014).
Acknowledgements
There is no funding body for this research.
Funding
No funding.
Author information
Authors and Affiliations
Contributions
Sidra Khan/Syed HM Zaidi: Conceptualization, writing original draft; Jamil Muqtadir: Writing Reviewing and editing; Kashif Ayoob/Bhagwan Das: Software, Data curation; Syed Ali Abbas: Resources, visualization; Ahmed Wahab/FNU Sameeullah: Methodology, validation; Ejaz A. Vohra: Formal analysis, project administration, supervision.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Khan, S., Muqtadir, J., Abbas, S.A. et al. Efficacy of artemether lumefantrine vs chloroquine for the treatment of Plasmodium Vivax infection in Pakistan. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38713-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-38713-2