Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia

Agus Setyadi, Eggi Arguni, Enny Kenangalem, Afdhal Hasanuddin, Daniel A. Lampah, Kamala Thriemer, Nicholas M. Anstey, Paulus Sugiarto, Julie A. Simpson, Ric N. Price, Nicholas M. Douglas, Jeanne R. Poespoprodjo

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    Abstract

    Background: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. 

    Methods: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. 

    Results: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. 

    Conclusions: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.

    Original languageEnglish
    Article number111
    Pages (from-to)1-11
    Number of pages11
    JournalMalaria Journal
    Volume18
    DOIs
    Publication statusPublished - 2 Apr 2019

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    Primaquine
    Vivax Malaria
    Indonesia
    Safety
    Hemolysis
    Accidental Falls
    Glucosephosphate Dehydrogenase Deficiency
    Glucosephosphate Dehydrogenase

    Cite this

    Setyadi, A., Arguni, E., Kenangalem, E., Hasanuddin, A., Lampah, D. A., Thriemer, K., ... Poespoprodjo, J. R. (2019). Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia. Malaria Journal, 18, 1-11. [111]. https://doi.org/10.1186/s12936-019-2745-7
    Setyadi, Agus ; Arguni, Eggi ; Kenangalem, Enny ; Hasanuddin, Afdhal ; Lampah, Daniel A. ; Thriemer, Kamala ; Anstey, Nicholas M. ; Sugiarto, Paulus ; Simpson, Julie A. ; Price, Ric N. ; Douglas, Nicholas M. ; Poespoprodjo, Jeanne R. / Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia. In: Malaria Journal. 2019 ; Vol. 18. pp. 1-11.
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    title = "Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia",
    abstract = "Background: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. Methods: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. Results: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3{\%}) had data available for analysis. In total 1228 (33.4{\%}) infants were aged between 1 and 6 months and 2453 (66.6{\%}) between 6 and 12 months of age. Thirty-three (0.9{\%}) patients received low-dose primaquine (LDP), 174 (4.7{\%}) received high-dose primaquine (HDP), 3432 (93.2{\%}) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25{\%} to less than 5 g/dL was similar in the LDP or HDP groups (4.3{\%}, 1/23) versus the NPQ group (3.5{\%}, 16/461). Three infants (1.4{\%}) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5{\%}) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. Conclusions: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.",
    keywords = "Evaluation, Infants, Plasmodium vivax, Primaquine, Safety",
    author = "Agus Setyadi and Eggi Arguni and Enny Kenangalem and Afdhal Hasanuddin and Lampah, {Daniel A.} and Kamala Thriemer and Anstey, {Nicholas M.} and Paulus Sugiarto and Simpson, {Julie A.} and Price, {Ric N.} and Douglas, {Nicholas M.} and Poespoprodjo, {Jeanne R.}",
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    Setyadi, A, Arguni, E, Kenangalem, E, Hasanuddin, A, Lampah, DA, Thriemer, K, Anstey, NM, Sugiarto, P, Simpson, JA, Price, RN, Douglas, NM & Poespoprodjo, JR 2019, 'Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia', Malaria Journal, vol. 18, 111, pp. 1-11. https://doi.org/10.1186/s12936-019-2745-7

    Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia. / Setyadi, Agus; Arguni, Eggi; Kenangalem, Enny; Hasanuddin, Afdhal; Lampah, Daniel A.; Thriemer, Kamala; Anstey, Nicholas M.; Sugiarto, Paulus; Simpson, Julie A.; Price, Ric N.; Douglas, Nicholas M.; Poespoprodjo, Jeanne R.

    In: Malaria Journal, Vol. 18, 111, 02.04.2019, p. 1-11.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia

    AU - Setyadi, Agus

    AU - Arguni, Eggi

    AU - Kenangalem, Enny

    AU - Hasanuddin, Afdhal

    AU - Lampah, Daniel A.

    AU - Thriemer, Kamala

    AU - Anstey, Nicholas M.

    AU - Sugiarto, Paulus

    AU - Simpson, Julie A.

    AU - Price, Ric N.

    AU - Douglas, Nicholas M.

    AU - Poespoprodjo, Jeanne R.

    PY - 2019/4/2

    Y1 - 2019/4/2

    N2 - Background: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. Methods: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. Results: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. Conclusions: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.

    AB - Background: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. Methods: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. Results: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. Conclusions: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.

    KW - Evaluation

    KW - Infants

    KW - Plasmodium vivax

    KW - Primaquine

    KW - Safety

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    U2 - 10.1186/s12936-019-2745-7

    DO - 10.1186/s12936-019-2745-7

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    AN - SCOPUS:85063767989

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