Skip to main content

Quinine plus clindamycin vs artemether-lumefantrine for treatment of uncomplicated falciparum malaria in western Kenya

We read with interest the comment by Kremsner and Krishna on our paper published on this Journal. The comment correctly points out that we documented an adequate clinical and parasitological response (ACPR) of 44% with quinine plus clindamycin compared with 97% on artemether-lumefantrine assessed on day 28 after starting treatment. We recognize the long-standing research interest by Kremsner and Krishna on the role of clindamycin-based combinations in the treatment of falciparum malaria, demonstrated by their publications. In this comment, Kremsner and Krishna are concerned with the level of ACPR on the quinine plus clindamycin arm in our study. They cite a few of their studies conducted in Gabon and Brazil that evaluated the efficacy of a 3-day course of 12-hourly quinine plus clindamycin treatment for participants with either uncomplicated or severe malaria. In the cited studies, administration of a relatively higher dose of quinine (15 mg/kg bd) combined with a relatively lower dose of clindamycin (7 mg/kg bd) was consistently associated with cure rates of between 88 and 100% (excluding reinfections). They correctly observe that 54% of children treated with quinine plus clindamycin in our study were still parasitaemic on day 3. However, they confirm that the mean parasite clearance with quinine plus clindamycin was slow (48 to 65 h) even in their previous studies and they commonly observed that up to 50% of participants were still parasitaemic on day 3 but “without the need for rescue treatment”. In conclusion, Kremsner and Krishna highlight the continuing need to evaluate non-artemisinin-based combinations for the treatment of uncomplicated malaria using appropriate study designs and correct dosages to avoid exposing participants to undertreatment and possible misinterpretation of the findings.

We do not agree with the statement by Kremsner and Krishna that our study was probably not well-designed, which they have not elaborated. We followed the standard methods for the design of randomized controlled parallel-group clinical trials for assessing the treatment efficacy of anti-malarials [1,2,3,4,5,6]. Specifically, we implemented an open-label, randomized controlled trial to evaluate the efficacy of quinine plus clindamycin vs artemether-lumefantrine for treatment of Kenyan children (under 5 years) with uncomplicated falciparum malaria. We pre-specified the eligibility criteria, endpoints and duration of follow-up in the protocol, supervised the administration of study treatment and used objective outcome measures to assess treatment efficacy. Our results are internally valid as we minimized the possibility of systematic bias by ensuring that our participants had comparable prognosis (by randomization), had comparability of treatments (by using oral 12-hourly treatment for 3 days) and comparability of outcome information (by using hard outcomes) [7]. The possibility of information bias (from attrition) was minimized by intention-to-treat analysis. We are not convinced that we undertreated the participants on the quinine plus clindamycin arm of our study. Lell and Kremsner 2002, reviewed 13 studies (only 3 were in children) that had evaluated the efficacy of quinine (8–12 mg/kg bd) plus clindamycin (5–10 mg/kg bd) in the treatment of adults or children with uncomplicated falciparum malaria and found cure rates of 88–100% [8]. We used a similar range of dosages in our study but found comparatively low cure rates with this regimen. We speculated that the low unexpected cure rates following treatment with quinine plus clindamycin could be explained by the short treatment course (3 days), the low quinine (10 mg/kg bd) dose, a declining quinine efficacy or the slow action of clindamycin. We do not agree with the conclusion of Kremsner and Krishna that persistent parasitaemia at day 3 is not a useful marker for assessing treatment success or failure. In our study, half of the children treated with quinine plus clindamycin were still parasitaemic by day 3 post-treatment. This was not a surprising finding as slow parasite clearance is an expected phenomenon with clindamycin treatment thought to derive from “delayed parasite death” [9]. Delayed clearance of malaria parasites by the third day after treatment has consistently been found to strongly correlate with anti-malarial treatment failure [10,11,12,13].

Overall, all the studies cited by Kremsner and Krishna had methodological flaws, had used a 3-day 12 hourly regimen of quinine plus clindamycin with comparable doses, long mean parasite clearance times but higher cure rates. It is important to note that there were probably spatio-temporal differences in parasite resistance patterns between Gabon and western Kenya. Only one of the cited studies was closely comparable to our study because they used a well-designed study to compare the efficacy of quinine plus clindamycin to an artemisinin-based combination therapy (artesunate plus clindamycin) in the treatment of African children with uncomplicated falciparum malaria [14]. In conclusion, the weight of the available evidence does not support the recommendation of quinine plus clindamycin for the treatment of children with uncomplicated falciparum malaria.


  1. White NJ. The assessment of antimalarial drug efficacy. Trends Parasitol. 2002;18:458–64.

    Article  CAS  Google Scholar 

  2. Guthmann JP, Pinoges L, Checchi F, Cousens S, Balkan S, van Herp M, et al. Methodological issues in the assessment of antimalarial drug treatment: analysis of 13 studies in eight African countries from 2001 to 2004. Antimicrob Agents Chemother. 2006;50:3734–9.

    Article  CAS  Google Scholar 

  3. Stepniewska K, Taylor WR, Mayxay M, Price R, Smithuis F, Guthmann JP, et al. In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up. Antimicrob Agents Chemother. 2004;48:4271–80.

    Article  CAS  Google Scholar 

  4. Stepniewska K, White NJ. Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria. Malar J. 2006;5:127.

    Article  Google Scholar 

  5. Snounou G, Beck HP. The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment. Parasitol Today. 1998;14:462–7.

    Article  CAS  Google Scholar 

  6. Borrmann S, Peto T, Snow RW, Gutteridge W, White NJ. Revisiting the design of phase III clinical trials of antimalarial drugs for uncomplicated Plasmodium falciparum malaria. PLoS Med. 2008;5:e227.

    Article  Google Scholar 

  7. Tijssen JG. Intervention research. Neth J Med. 1995;47:87–92.

    Article  CAS  Google Scholar 

  8. Lell B, Kremsner PG. Clindamycin as an antimalarial drug: review of clinical trials. Antimicrob Agents Chemother. 2002;46:2315–20.

    Article  CAS  Google Scholar 

  9. Burkhardt D, Wiesner J, Stoesser N, Ramharter M, Uhlemann AC, Issifou S, et al. Delayed parasite elimination in human infections treated with clindamycin parallels “delayed death” of Plasmodium falciparum in vitro. Int J Parasitol. 2007;37:777–85.

    Article  CAS  Google Scholar 

  10. Das D, Price RN, Bethell D, Guerin PJ, Stepniewska K. Early parasitological response following artemisinin-containing regimens: a critical review of the literature. Malar J. 2013;12:125.

    Article  CAS  Google Scholar 

  11. Price RN, Dorsey G, Ashley EA, Barnes KI, Baird JK, d’Alessandro U, et al. World Antimalarial Resistance Network I: clinical efficacy of antimalarial drugs. Malar J. 2007;6:119.

    Article  Google Scholar 

  12. Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, et al. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis. 2013;208:2017–24.

    Article  CAS  Google Scholar 

  13. Betson M, Sousa-Figueiredo JC, Atuhaire A, Arinaitwe M, Adriko M, Mwesigwa G, et al. Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment. Parasitology. 2014;141:1880–90.

    Article  CAS  Google Scholar 

  14. Ramharter M, Oyakhirome S, Klein Klouwenberg P, Adégnika AA, Agnandji ST, Missinou MA, et al. Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial. Clin Infect Dis. 2005;40:1777–84.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Charles O. Obonyo.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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 The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Obonyo, C.O., Ogutu, B.R. Quinine plus clindamycin vs artemether-lumefantrine for treatment of uncomplicated falciparum malaria in western Kenya. Malar J 21, 198 (2022).

Download citation

  • Published:

  • DOI: