Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

Stepniewska, Kasia; Allen, Elizabeth N.; Humphreys, Georgina S.; Poirot, Eugenie; Craig, Elaine; Kennon, Kalynn; Yilma, Daniel; Bousema, Teun; Guerin, Philippe J.; White, Nicholas J.; Price, Ric N.; Raman, Jaishree; Martensson, Andreas; Mwaiswelo, Richard O.; Bancone, Germana; Bastiaens, Guido J. H.; Bjorkman, Anders; Brown, Joelle M.; D’Alessandro, Umberto; Dicko, Alassane A.; El-Sayed, Badria; Elzaki, Salah-Eldin; Eziefula, Alice C.; Gonçalves, Bronner P.; Hamid, Muzamil Mahdi Abdel; Kaneko, Akira; Kariuki, Simon; Khan, Wasif; Kwambai, Titus K.; Ley, Benedikt; Ngasala, Billy E.; Nosten, Francois; Okebe, Joseph; Samuels, Aaron M.; Smit, Menno R.; Stone, Will J. R.; Sutanto, Inge; Ter Kuile, Feiko; Tine, Roger C.; Tiono, Alfred B.; Drakeley, Chris J.; Gosling, Roly; Stergachis, Andy; Barnes, Karen I.; Chen, Ingrid

doi:10.1186/s12916-022-02504-z

Table 2 Baseline characteristics of patients included in the analysis

From: Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

	Primaquine		No primaquine		All
	N	n [%] or median [range]	N	n [%] or median [range]	N	n [%] or median [range]
Sex: male	5127	2912 [56.8]	1277	723 [56.6]	6404	3638 [56.8]
Age	5129	10.0 [0.5–91.0]	1277	11.0 [1.0–84.0]	6406	10.0 [0.5–91.0]
Age category
< 5 years	5129	985 [19.2]	1277	213 [16.7]	6406	1198 [18.7]
5–11 years	5129	1865 [36.4]	1277	429 [33.6]	6406	2294 [35.8]
12+ years	5129	2279 [44.4]	1277	635 [49.7]	6406	2914 [45.5]
WAZ score^a	663	− 0.5 [− 5.8–4.0]	163	− 0.6 [− 3.8–2.5]	826	− 0.5 [− 5.8–4.0]
Underweight^a	663	74 [11.2]	163	23 [14.1]	826	97 [11.7]
Pf Malaria status^b
No	5129	1477 [28.8]	1277	175 [13.7]	6406	1652 [25.8]
Yes	5129	1820 [35.5]	1277	1026 [80.3]	6406	2846 [44.4]
Unknown	5129	1832 [35.7]	1277	76 [6.0]	6406	1908 [29.8]
G6PD status: deficient	4442	309 [7.0]	1099	75 [6.8]	5541	384 [6.9]
Pf parasite count (× 10³/μL)	1672	6.3 [0.012–1292]	978	6.7 [0.009–432]	2650	6.5 [0.009–1292]
Hyperparasiteamia^c	1672	112 [6.7]	978	35 [3.6]	2650	147 [5.6]
Temperature (°C)	3731	36.9 [34.1–40.3]	1020	37.0 [34.0–40.5]	4751	36.9 [34.0–40.5]
Fever^d	3732	523 [14.0]	1021	404 [39.6]	4753	927 [19.5]
Hb (g/dL)	3381	11.9 [6.0–20.8]	1259	11.9 [5.1–18.4]	4640	11.9 [5.1–20.8]
Anaemia^e
No	3381	2938 [86.9]	1259	1052 [83.6]	4640	3990 [86.0]
Severe	3381	1 [0.0]	1259	34 [2.7]	4640	35 [0.8]
Moderate	3381	442 [13.1]	1259	173 [13.7]	4640	615 [13.3]
Transmission intensity^f
Low	5129	3970 [77.4]	1277	897 [70.2]	6406	4867 [76.0]
Moderate	5129	665 [13.0]	1277	205 [16.1]	6406	870 [13.6]
High	5129	494 [9.6]	1277	175 [13.7]	6406	669 [10.4]
Region
Africa	5129	3083 [60.1]	1277	1098 [86.0]	6406	4181 [65.3]
Asia	5129	2046 [39.9]	1277	179 [14.0]	6406	2225 [34.7]
ACT
AL	5129	1094 [21.3]	1277	469 [36.7]	6406	1563 [24.4]
AP	5129	286 [5.6]	1277	5 [0.4]	6406	291 [4.5]
ASAQ	5129	45 [0.9]	1277	47 [3.7]	6406	92 [1.4]
ASSP	5129	1006 [19.6]	1277	272 [21.3]	6406	1278 [20.0]
DP	5129	2698 [52.6]	1277	484 [37.9]	6406	3182 [49.7]
Primaquine dose (mg/kg)	5129	0.3 [0.05–1.9]
Primaquine target dose (mg/kg)	5129	613 [12.0]
< 0.25
0.25	5129	2540 [49.5]
> 0.25	5129	1976 [38.5]
Day of primaquine administration based on ACT regimen
0	5129	848 [16.5]
1	5129	1737 [33.9]
2	5129	2231 [43.5]
3	5129	313 [6.1]

ACT artemisinin combination therapy, AL artemether-lumefnantrine, AP artemisinin-piperaquine, ASAQartesunate-amodiaquine, ASSP artesunate-sulfadoxine-pyrimethamine, DP dihydroartemisinin-piperaquine. Pf Plasmodium falciparum, PQ primaquine
^aEvaluated in children < 5 years of age, WAZ weight-for-age z-score, underweight is defined as WAZ score < − 2
^bNon-detectable malaria includes community participants in the MDA studies (n = 1017) and study participants who were positive for malaria or had detectable gametocytes at screening (n = 635), and unknown malaria includes not tested community participants from MDA studies (n = 1848) and study participants who were positive for malaria or had detectable gametocytes at screening (n = 60)
^cDefined as parasitaemia < 100,000/μL
^dDefined as temperature > 37.5 °C or history of fever
^eSevere anaemia defined as Hb < 7 g/dL, moderate anaemia defined as 7 g/dL < Hb < 10 g/dL
^f Transmission intensity defined based on estimates of P. falciparum prevalence rate (PfPR), assuming low transmission for study sites with a PfPR < 0.15, moderate transmission if PfPR 0.15 to < 0.40, and high transmission if PfPR ≥ 0.40

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