Clinical Outcomes of combination antibiotic therapy in Patients with malaria
DOI:
https://doi.org/10.5281/zenodo.22811748Keywords:
malaria, artemisinin-based combination therapy, antibiotic co-therapy, bacteremia, drug resistanceAbstract
Background: Combination therapy is now standard across malaria care: artemisinin-based combinations for falciparum malaria, and, where bacterial infection coexists, combined antimalarial-antibacterial regimens [2,20].
Objective: This review synthesizes outcomes for combination antimalarial therapy in uncomplicated and severe malaria, resistance's impact on that strategy, and combined antimalarial-antibacterial therapy in bacterial co-infection.
Methods: We synthesized trials and meta-analyses of artemisinin combinations, resistance-surveillance studies, and cohorts and trials on bacterial co-infection and antibacterial therapy in malaria patients.
Findings: Artesunate combinations roughly halve treatment failure in uncomplicated malaria [7]; intravenous artesunate lowers severe-malaria mortality versus quinine, from 22% to 15% in adults and roughly 10.9% to 8.5% in children [10,11]; triple combinations extend this where resistance has emerged [18]; and bacterial co-infection, in roughly 6% of severe-malaria children, more than doubles case fatality (24.1% vs 10.2%) despite imprecise clinical criteria for antibacterial cover [20,6].
Conclusions: Combination therapy improves malaria outcomes through distinct mechanisms by scenario; sustained resistance surveillance and better diagnostics for antibacterial targeting will determine whether that benefit holds [16,20].
References
White, N.J., Nosten, F., Looareesuwan, S., Watkins, W.M., Marsh, K., Snow, R.W., et al. (1999) Averting a malaria disaster. Lancet, 353(9164): 1965-1967.
Kremsner, P.G., Krishna, S. (2004) Antimalarial combinations. Lancet, 364(9430): 285-294. DOI: 10.1016/S0140-6736(04)16680-4
Snow, R.W., Guerra, C.A., Noor, A.M., Myint, H.Y., Hay, S.I. (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, 434(7030): 214-217. DOI: 10.1038/nature03342
White, N.J., Pukrittayakamee, S., Hien, T.T., Faiz, M.A., Mokuolu, O.A., Dondorp, A.M. (2014) Malaria. Lancet, 383(9918): 723-735. DOI: 10.1016/S0140-6736(13)60024-0
Berkley, J.A., Bejon, P., Mwangi, T., Gwer, S., Maitland, K., Williams, T.N., et al. (2005) Bacteremia among children admitted to a rural hospital in Kenya. New England Journal of Medicine, 352(1): 39-47. DOI: 10.1056/NEJMoa040275
Nadjm, B., Amos, B., Mtove, G., Ostermann, J., Chonya, S., Wangai, H., et al. (2010) WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. BMJ, 340: c1350. DOI: 10.1136/bmj.c1350
Adjuik, M., Babiker, A., Garner, P., Olliaro, P., Taylor, W., White, N. (2004) Artesunate combinations for treatment of malaria: meta-analysis. Lancet, 363(9402): 9-17. DOI: 10.1016/S0140-6736(03)15162-8
Nosten, F., White, N.J. (2007) Artemisinin-based combination treatment of falciparum malaria. American Journal of Tropical Medicine and Hygiene, 77(6 Suppl): 181-192.
Guerin, P.J., Olliaro, P., Nosten, F., Druilhe, P., Laxminarayan, R., Binka, F., et al. (2002) Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development. Lancet Infectious Diseases, 2(9): 564-573. DOI: 10.1016/S1473-3099(02)00239-6
Dondorp, A., Nosten, F., Stepniewska, K., Day, N., White, N. (2005) Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet, 366(9487): 717-725. DOI: 10.1016/S0140-6736(05)67176-0
Dondorp, A.M., Fanello, C.I., Hendriksen, I.C., Gomes, E., Seni, A., Chhaganlal, K.D., et al. (2010) Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet, 376(9753): 1647-1657. DOI: 10.1016/S0140-6736(10)61924-1
Sinclair, D., Donegan, S., Isba, R., Lalloo, D.G. (2012) Artesunate versus quinine for treating severe malaria. Cochrane Database of Systematic Reviews, 2012(6): CD005967. DOI: 10.1002/14651858.CD005967.pub4
Achan, J., Talisuna, A.O., Erhart, A., Yeka, A., Tibenderana, J.K., Baliraine, F.N., et al. (2011) Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malaria Journal, 10: 144. DOI: 10.1186/1475-2875-10-144
Noedl, H., Se, Y., Schaecher, K., Smith, B.L., Socheat, D., Fukuda, M.M. (2008) Evidence of artemisinin-resistant malaria in western Cambodia. New England Journal of Medicine, 359(24): 2619-2620. DOI: 10.1056/NEJMc0805011
Dondorp, A.M., Nosten, F., Yi, P., Das, D., Phyo, A.P., Tarning, J., et al. (2009) Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine, 361(5): 455-467. DOI: 10.1056/NEJMoa0808859
Ashley, E.A., Dhorda, M., Fairhurst, R.M., Amaratunga, C., Lim, P., Suon, S., et al. (2014) Spread of artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine, 371(5): 411-423. DOI: 10.1056/NEJMoa1314981
Tun, K.M., Imwong, M., Lwin, K.M., Win, A.A., Hlaing, T.M., Hlaing, T., et al. (2015) Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infectious Diseases, 15(4): 415-421. DOI: 10.1016/S1473-3099(15)70032-0
van der Pluijm, R.W., Tripura, R., Hoglund, R.M., Pyae Phyo, A., Lek, D., ul Islam, A., et al. (2020) Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet, 395(10233): 1345-1360. DOI: 10.1016/S0140-6736(20)30552-3
Scott, J.A., Berkley, J.A., Mwangi, I., Ochola, L., Uyoga, S., Macharia, A., et al. (2011) Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. Lancet, 378(9799): 1316-1323. DOI: 10.1016/S0140-6736(11)60888-X
Church, J., Maitland, K. (2014) Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Medicine, 12: 31. DOI: 10.1186/1741-7015-12-31
Bronzan, R.N., Taylor, T.E., Mwenechanya, J., Tembo, M., Kayira, K., Bwanaisa, L., et al. (2007) Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. Journal of Infectious Diseases, 195(6): 895-904.
Bassat, Q., Guinovart, C., Sigauque, B., Aide, P., Sacarlal, J., Nhampossa, T., et al. (2009) Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital. Tropical Medicine & International Health, 14(9): 1011-1019. DOI: 10.1111/j.1365-3156.2009.02326.x
Were, T., Davenport, G.C., Yamo, E.O., Hittner, J.B., Awandare, G.A., Otieno, M.F., et al. (2011) Bacteremia in Kenyan children presenting with malaria. Journal of Clinical Microbiology, 49(2): 671-676. DOI: 10.1128/JCM.01864-10
Maitland, K., Kiguli, S., Opoka, R.O., Engoru, C., Olupot-Olupot, P., Akech, S.O., et al. (2011) Mortality after fluid bolus in African children with severe infection. New England Journal of Medicine, 364(26): 2483-2495. DOI: 10.1056/NEJMoa1101549
Chico, R.M., Pittrof, R., Greenwood, B., Chandramohan, D. (2008) Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy. Malaria Journal, 7: 255. DOI: 10.1186/1475-2875-7-255
Kimani, J., Phiri, K., Kamiza, S., Duparc, S., Ayoub, A., Rojo, R., et al. (2016) Efficacy and safety of azithromycin-chloroquine versus sulfadoxine-pyrimethamine for intermittent preventive treatment of Plasmodium falciparum malaria infection in pregnant women in Africa: an open-label, randomized trial. PLOS ONE, 11(6): e0157045. DOI: 10.1371/journal.pone.0157045
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Giulia Ferrari, et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
