Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

Kasia Stepniewska; Georgina S. Humphreys; Bronner P. Gonçalves; Elaine Craig; Roly Gosling; Philippe J. Guerin; Ric N. Price; Karen I. Barnes; Jaishree Raman; Menno R. Smit; Umberto D'Alessandro; Will J.R. Stone; Anders Bjorkman; Aaron M. Samuels; Maria I. Arroyo-Arroyo; Guido J.H. Bastiaens; Joelle M. Brown; Alassane Dicko; Badria B. El-Sayed; Salah Eldin G. Elzaki; Alice C. Eziefula; Simon Kariuki; Titus K. Kwambai; Amanda E. Maestre; Andreas Martensson; Dominic Mosha; Richard O. Mwaiswelo; Billy E. Ngasala; Joseph Okebe; Michelle E. Roh; Patrick Sawa; Alfred B. Tiono; Ingrid Chen; Chris J. Drakeley; Teun Bousema

doi:10.1093/infdis/jiaa498

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

Kasia Stepniewska, Georgina S. Humphreys, Bronner P. Gonçalves, Elaine Craig, Roly Gosling, Philippe J. Guerin, Ric N. Price, Karen I. Barnes, Jaishree Raman, Menno R. Smit, Umberto D'Alessandro, Will J.R. Stone, Anders Bjorkman, Aaron M. Samuels, Maria I. Arroyo-Arroyo, Guido J.H. Bastiaens, Joelle M. Brown, Alassane Dicko, Badria B. El-Sayed, Salah Eldin G. ElzakiAlice C. Eziefula, Simon Kariuki, Titus K. Kwambai, Amanda E. Maestre, Andreas Martensson, Dominic Mosha, Richard O. Mwaiswelo, Billy E. Ngasala, Joseph Okebe, Michelle E. Roh, Patrick Sawa, Alfred B. Tiono, Ingrid Chen, Chris J. Drakeley, Teun Bousema

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

Background

Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.

Methods

An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.

Results

In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.

Conclusion

Primaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Original language	English
Pages (from-to)	1215-1226
Number of pages	12
Journal	Journal of Infectious Diseases
Volume	225
Issue number	7
Early online date	11 Aug 2020
DOIs	https://doi.org/10.1093/infdis/jiaa498
Publication status	Published - 1 Apr 2022

Keywords

gametocytemia
Plasmodium falciparum
single low-dose primaquine

Access to Document

10.1093/infdis/jiaa498Licence: CC BY

Jiaa498Accepted author manuscript, 1.14 MBLicence: CC BY

Cite this

Stepniewska, K., Humphreys, G. S., Gonçalves, B. P., Craig, E., Gosling, R., Guerin, P. J., Price, R. N., Barnes, K. I., Raman, J., Smit, M. R., D'Alessandro, U., Stone, W. J. R., Bjorkman, A., Samuels, A. M., Arroyo-Arroyo, M. I., Bastiaens, G. J. H., Brown, J. M., Dicko, A., El-Sayed, B. B., ... Bousema, T. (2022). Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis. Journal of Infectious Diseases, 225(7), 1215-1226. https://doi.org/10.1093/infdis/jiaa498

@article{aee80394f4d74180b605be856c976b64,

title = "Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis",

abstract = "BackgroundSince the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.MethodsAn individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.ResultsIn 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95\%CI 0.17-0.28 and OR=0.12; 95\%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.ConclusionPrimaquine{\textquoteright}s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.",

keywords = "gametocytemia, Plasmodium falciparum, single low-dose primaquine",

author = "Kasia Stepniewska and Humphreys, \{Georgina S.\} and Gon{\c c}alves, \{Bronner P.\} and Elaine Craig and Roly Gosling and Guerin, \{Philippe J.\} and Price, \{Ric N.\} and Barnes, \{Karen I.\} and Jaishree Raman and Smit, \{Menno R.\} and Umberto D'Alessandro and Stone, \{Will J.R.\} and Anders Bjorkman and Samuels, \{Aaron M.\} and Arroyo-Arroyo, \{Maria I.\} and Bastiaens, \{Guido J.H.\} and Brown, \{Joelle M.\} and Alassane Dicko and El-Sayed, \{Badria B.\} and Elzaki, \{Salah Eldin G.\} and Eziefula, \{Alice C.\} and Simon Kariuki and Kwambai, \{Titus K.\} and Maestre, \{Amanda E.\} and Andreas Martensson and Dominic Mosha and Mwaiswelo, \{Richard O.\} and Ngasala, \{Billy E.\} and Joseph Okebe and Roh, \{Michelle E.\} and Patrick Sawa and Tiono, \{Alfred B.\} and Ingrid Chen and Drakeley, \{Chris J.\} and Teun Bousema",

year = "2022",

month = apr,

day = "1",

doi = "10.1093/infdis/jiaa498",

language = "English",

volume = "225",

pages = "1215--1226",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "7",

}

Stepniewska, K, Humphreys, GS, Gonçalves, BP, Craig, E, Gosling, R, Guerin, PJ, Price, RN, Barnes, KI, Raman, J, Smit, MR, D'Alessandro, U, Stone, WJR, Bjorkman, A, Samuels, AM, Arroyo-Arroyo, MI, Bastiaens, GJH, Brown, JM, Dicko, A, El-Sayed, BB, Elzaki, SEG, Eziefula, AC, Kariuki, S, Kwambai, TK, Maestre, AE, Martensson, A, Mosha, D, Mwaiswelo, RO, Ngasala, BE, Okebe, J, Roh, ME, Sawa, P, Tiono, AB, Chen, I, Drakeley, CJ & Bousema, T 2022, 'Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis', Journal of Infectious Diseases, vol. 225, no. 7, pp. 1215-1226. https://doi.org/10.1093/infdis/jiaa498

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis. / Stepniewska, Kasia; Humphreys, Georgina S.; Gonçalves, Bronner P. et al.
In: Journal of Infectious Diseases, Vol. 225, No. 7, 01.04.2022, p. 1215-1226.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

AU - Stepniewska, Kasia

AU - Humphreys, Georgina S.

AU - Gonçalves, Bronner P.

AU - Craig, Elaine

AU - Gosling, Roly

AU - Guerin, Philippe J.

AU - Price, Ric N.

AU - Barnes, Karen I.

AU - Raman, Jaishree

AU - Smit, Menno R.

AU - D'Alessandro, Umberto

AU - Stone, Will J.R.

AU - Bjorkman, Anders

AU - Samuels, Aaron M.

AU - Arroyo-Arroyo, Maria I.

AU - Bastiaens, Guido J.H.

AU - Brown, Joelle M.

AU - Dicko, Alassane

AU - El-Sayed, Badria B.

AU - Elzaki, Salah Eldin G.

AU - Eziefula, Alice C.

AU - Kariuki, Simon

AU - Kwambai, Titus K.

AU - Maestre, Amanda E.

AU - Martensson, Andreas

AU - Mosha, Dominic

AU - Mwaiswelo, Richard O.

AU - Ngasala, Billy E.

AU - Okebe, Joseph

AU - Roh, Michelle E.

AU - Sawa, Patrick

AU - Tiono, Alfred B.

AU - Chen, Ingrid

AU - Drakeley, Chris J.

AU - Bousema, Teun

PY - 2022/4/1

Y1 - 2022/4/1

N2 - BackgroundSince the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.MethodsAn individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.ResultsIn 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.ConclusionPrimaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

AB - BackgroundSince the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.MethodsAn individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.ResultsIn 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.ConclusionPrimaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

KW - gametocytemia

KW - Plasmodium falciparum

KW - single low-dose primaquine

U2 - 10.1093/infdis/jiaa498

DO - 10.1093/infdis/jiaa498

M3 - Article

SN - 0022-1899

VL - 225

SP - 1215

EP - 1226

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 7

ER -

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

Abstract

Keywords

Access to Document

Fingerprint

Cite this