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Meta-Analysis
. 2023 Oct 10;22(1):306.
doi: 10.1186/s12936-023-04725-w.

Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Parinaz Mehdipour  1 , Megha Rajasekhar  1 , Saber Dini  1 , Sophie Zaloumis  1 , Tesfay Abreha  2 , Ishag Adam  3 , Ghulam Rahim Awab  4   5 , J Kevin Baird  6   7 , Larissa W Brasil  8   9 , Cindy S Chu  7   10 , Liwang Cui  11 , André Daher  12 , Margarete do Socorro M Gomes  13   14 , Lilia Gonzalez-Ceron  15 , Jimee Hwang  16   17 , Harin Karunajeewa  18 , Marcus V G Lacerda  19   20   21 , Simone Ladeia-Andrade  22   23 , Toby Leslie  24   25 , Benedikt Ley  26 , Kartini Lidia  27 , Alejandro Llanos-Cuentas  28 , Rhea J Longley  29   30   31 , Wuelton Marcelo Monteiro  32 , Dhelio B Pereira  33   34 , Komal Raj Rijal  35   36 , Kavitha Saravu  37   38 , Inge Sutanto  39 , Walter R J Taylor  4   7 , Pham Vinh Thanh  40 , Kamala Thriemer  26 , José Luiz F Vieira  41 , Nicholas J White  4   7 , Lina M Zuluaga-Idarraga  42   43 , Philippe J Guerin  7   44   45 , Ric N Price  7   26   46 , Julie A Simpson  1   46 , Robert J Commons  47   48   49 ; WWARN Vivax Adherence Study Group
Collaborators, Affiliations
Meta-Analysis

Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Parinaz Mehdipour et al. Malar J. .

Abstract

Background: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence.

Methods: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis.

Results: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001.

Conclusion: Reduced adherence, including less supervision, increases the risk of vivax recurrence.

Keywords: Adherence; Malaria; Plasmodium vivax; Primaquine; Rate of recurrence; Supervision.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study profile
Fig. 2
Fig. 2
Risk of the first recurrence between days 7 and 90 in patients with adherence by supervision. The shaded areas represent 95% CIs. There were no patients with adherence by supervision between > 50– <90%.
Fig. 3
Fig. 3
Risk of the first recurrence between days 7 and 90 in patients with adherence by total mg/kg dose administered. The shaded areas represent 95% CIs
See this image and copyright information in PMC

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