Delayed Hemolytic Anemia after Treatment with Artesunate: Case Report and Literature Review

Salehi, Mohammadreza; Masoumi-Asl, Hosein; Assarian, Mehrdad; Khoshnam‐Rad, Niloofar; Haghi, Afsaneh Motevalli; Nikbakht, Mehran; Khalili, Hossein

doi:10.2174/1574886313666181109150157

Cited by 10 publications

(5 citation statements)

References 25 publications

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“…Artemisinin drugs and derivatives are known to kill malaria parasites by inducing oxidative stress following the activation of the peroxide bridge, which generates reactive metabolites that cause hemolysis [33]. Additionally, artemisinininduced and post-artemisinin-delayed hemolysis have been reported [34,35]. This nding is consistent with other reports on artemisinin-induced hemolysis in PbANKA-infected mice [36][37][38].…”

Section: Discussionsupporting

confidence: 86%

In vivo antimalarial activity of Cyperus rotundus and its combination with dihydroartemisinin against Plasmodium berghei

Ounjaijean,

Lektip,

Somsak

2023

Preprint

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Background The increase in the number of drug-resistant Plasmodium species continues to be a serious public health concern. Therefore, identification of potential novel antimalarial drugs derived from therapeutic plants could help solve this issue. This study investigated whether Cyperus rotundus aqueous crude extract (CRE) and its combination with dihydroartemisinin (DHA) were effective against Plasmodium berghei ANKA-infected mice. Methods CRE was prepared from C. rotundus rhizomes and evaluated in acute and subacute toxicity tests on BALB/c mice. The antimalarial effectiveness of CRE was assessed at 100, 200, and 400 mg/kg in a 4-day suppressive test with curative and prophylactic testing and measurement of packed cell volume (PCV), body weight (BW), rectal temperature, and mean survival time (MST). Results Following acute and subacute treatment, CRE caused no harmful effects or mortality in mice. When compared with that in the untreated control, infected mice administered with 400 mg/kg of CRE in a 4-day suppressive test exhibited the strongest antimalarial activity (55.30% inhibition) with prolonged MST. However, curative and prophylactic assays did not reveal CRE to have antimalarial activity. In comparison with that achieved with the single therapy, the combination of DHA and CRE at ED50/2 (1 and 200 mg/kg, respectively) produced considerable antimalarial activity at 90.08% inhibition with synergism (combination index = 0.21701). For the other parameters, CRE administration prevented malarial-induced changes in PCV, BW, and rectal temperature. Conclusions CRE treatment significantly inhibited malaria in the 4-day suppressive test, and CRE combined with DHA had a synergistic antimalarial effect.

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Section: Discussionsupporting

confidence: 86%

In vivo antimalarial activity of Cyperus rotundus and its combination with dihydroartemisinin against Plasmodium berghei

Ounjaijean,

Lektip,

Somsak

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Artemisinin drugs and derivatives are known to kill malaria parasites by inducing oxidative stress following the activation of the peroxide bridge, which generates reactive metabolites that cause hemolysis [33]. In addition, artemisinin-induced and postartemisinin-delayed hemolysis have been reported [34,35]. Tis fnding is consistent with other reports on artemisinin-induced hemolysis in PbANKA-infected mice [36][37][38].…”

Section: Discussionsupporting

confidence: 86%

In Vivo Antimalarial Activity of Cyperus rotundus and Its Combination with Dihydroartemisinin against Plasmodium berghei

Ounjaijean,

Lektip,

Somsak

2024

Advances in Pharmacological and Pharmaceutical Sciences

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Background. The increase in the number of drug-resistant Plasmodium species continues to be a serious public health concern. Therefore, identification of the potential novel antimalarial drugs derived from therapeutic plants could help solve this issue. This study investigated whether Cyperus rotundus aqueous crude extract (CRE) and its combination with dihydroartemisinin (DHA) were effective against Plasmodium berghei ANKA-infected mice. Methods. CRE was prepared from C. rotundus rhizomes and evaluated using acute and subacute toxicity tests on BALB/c mice. The antimalarial effectiveness of CRE was assessed at 100, 200, and 400 mg/kg in a 4-day suppressive test with curative and prophylactic testing and measurement of packed cell volume (PCV), body weight (BW), rectal temperature, and mean survival time (MST). Results. Following acute and subacute treatment, CRE caused no harmful effects or mortality in mice. When compared with that in the untreated control, infected mice administered with 400 mg/kg of CRE in a 4-day suppressive test exhibited the strongest antimalarial activity (55.30% inhibition) with prolonged MST. However, curative and prophylactic assays did not reveal CRE to have antimalarial activity. In comparison with that achieved with the single therapy, the combination of DHA and CRE at ED50/2 (1 and 200 mg/kg, respectively) produced considerable antimalarial activity at 90.08% inhibition with synergism (combination index = 0.21701). For the other parameters, CRE administration prevented malarial-induced changes in PCV, BW, and rectal temperature. Conclusions. CRE treatment significantly inhibited malaria in the 4-day suppressive test, and CRE combined with DHA had a synergistic antimalarial effect.

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“…New drug combinations for severe malaria will need to have a safety and tolerability profile at least as good as that of artesunate. The main safety issue with artesunate is delayed haemolytic anaemia, which is observed particularly among non-immune travellers and young children with high parasitaemia [ 62 , 63 ]. Artesunate has a dose limiting adverse event of neutropenia which precludes the use of higher doses to overcome any clinical impact of artemisinin partial resistance [ 64 , 65 ].…”

Section: Updating the Tpp For New Severe Malaria Therapeuticsmentioning

confidence: 99%

Defining the next generation of severe malaria treatment: a target product profile

Achan,

Barry,

Leroy

et al. 2024

Malar J

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Background Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.

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Delayed Hemolytic Anemia after Treatment with Artesunate: Case Report and Literature Review

Cited by 10 publications

References 25 publications

In vivo antimalarial activity of Cyperus rotundus and its combination with dihydroartemisinin against Plasmodium berghei

In vivo antimalarial activity of Cyperus rotundus and its combination with dihydroartemisinin against Plasmodium berghei

In Vivo Antimalarial Activity of Cyperus rotundus and Its Combination with Dihydroartemisinin against Plasmodium berghei

Defining the next generation of severe malaria treatment: a target product profile

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