Post-artemisinin delayed hemolysis after oral therapy for P. falciparum infection

Conlon, Christian C.; Stein, Anna; Colombo, Rhonda E; Schofield, Christina

doi:10.1016/j.idcr.2020.e00741

Cited by 11 publications

(10 citation statements)

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“…Another pattern is called persistent PADH, in which a decline in the hemoglobin concentration is found at approximately day 7 after the beginning of artemisinin medication. The anemia remains constant and persists beyond day 14 [ 20 , 24 , 25 ]. Most importantly, other potential causes of hemolytic anemia must be excluded ( Table 1 ).…”

Section: Clinical Features and Laboratory Resultsmentioning

confidence: 99%

“…Hyperparasitemia in severe malaria, with more than 5% of infected erythrocytes, is considered a major risk factor for PADH [ 6 , 14 ]. The occurrence of PADH is most commonly reported with the use of the intravenous form of artemisinin derivatives, but it has also been reported in those treated with oral artemisinin-based combination therapy, intramuscular injection, and the rectal form [ 18 , 19 , 20 ]. Despite the increasing number of PADH cases, with its severity ranging from mild to severe, no fatal outcome has been caused by PADH to date [ 21 ].…”

Section: Epidemiologymentioning

confidence: 99%

“…The etiology of hemolytic anemia can be either idiopathic or secondary to certain causes including medication. Scientists suggested the plausible pathophysiology explained by drug–anti-drug immune complex formation on the red blood cell surface; thus, the production of autoantibodies causes positive DATs and immune hemolytic anemia [ 20 , 37 ].…”

Section: Pathophysiologymentioning

confidence: 99%

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Post-Artesunate Delayed Hemolysis: A Review of Current Evidence

et al. 2023

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Artesunate is the drug of choice for treating patients with severe malaria. Post-artesunate delayed hemolysis (PADH) is an uncommon adverse event from malaria treatment. Most patients with PADH are non-immune travelers. The pathophysiology of PADH is not fully understood, but the most likely mechanism is “pitting”, in which red blood cells carrying dead parasites killed by artesunate’s action are directed to the spleen for clearing the dead parasites. After the cleansing process, these red blood cells re-enter the circulation but with a smaller size and impaired integrity, resulting in a shortened lifespan of 7–21 days. Therefore, most patients with PADH usually present with clinical features of hemolytic anemia 7 days or later after the initiation of artesunate. To date, the benefits of artesunate treatment outweigh its adverse events, and no fatal cases have resulted from PADH. However, the hematological follow-up of patients with malaria treated with artesunate is recommended for clinicians to detect any delayed hemolytic event early and prevent potentially serious consequences.

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Section: Clinical Features and Laboratory Resultsmentioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

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Post-Artesunate Delayed Hemolysis: A Review of Current Evidence

et al. 2023

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“…Postartemisinin delayed hemolysis occurred in 4.8% of 280 US patients presenting 1 to 3 weeks after treatment . Patients should be monitored for this adverse event for 4 weeks posttherapy; rare case reports after oral therapy for treatment of severe falciparum malaria with ACTs have been described . Intravenous quinidine is no longer available for treatment in the US.…”

Section: Prevention and Treatment Of Malariamentioning

confidence: 99%

Diagnosis, Treatment, and Prevention of Malaria in the US

Daily

Minuti

Khan

2022

JAMA

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n 2020, approximately 241 million cases of malaria occurred in 85 countries with endemic malaria. Travelers to these regions are at risk for infection. 1 The number of people with malaria who arrive in the US has increased each year since 1972, from approximately 614 cases in 1972 to an 2161 cases in 2017. 2 Patients with malaria typically present to frontline US health care workers, who need to diagnose and manage this infection. This Review summarizes current evidence regarding the prevention, diagnosis, and treatment of malaria. MethodsWe searched the PubMed and Cochrane Library databases for English-language randomized clinical trials, meta-analyses, systematic reviews, and observational studies of the epidemiology, diagnosis, and treatment of malaria, published from January 2016 to March 2022. References were searched manually for additional relevant publications, including World Health Organization IMPORTANCE Malaria is caused by protozoa parasites of the genus Plasmodium and is diagnosed in approximately 2000 people in the US each year who have returned from visiting regions with endemic malaria. The mortality rate from malaria is approximately 0.3% in the US and 0.26% worldwide. OBSERVATIONS In the US, most malaria is diagnosed in people who traveled to an endemic region. More than 80% of people diagnosed with malaria in the US acquired the infection in Africa. Of the approximately 2000 people diagnosed with malaria in the US in 2017, an estimated 82.4% were adults and about 78.6% were Black or African American. Among US residents diagnosed with malaria, 71.7% had not taken malaria chemoprophylaxis during travel. In 2017 in the US, P falciparum was the species diagnosed in approximately 79% of patients, whereas P vivax was diagnosed in an estimated 11.2% of patients. In 2017 in the US, severe malaria, defined as vital organ involvement including shock, pulmonary edema, significant bleeding, seizures, impaired consciousness, and laboratory abnormalities such as kidney impairment, acidosis, anemia, or high parasitemia, occurred in approximately 14% of patients, and an estimated 0.3% of those receiving a diagnosis of malaria in the US died. P falciparum has developed resistance to chloroquine in most regions of the world, including Africa. First-line therapy for P falciparum malaria in the US is combination therapy that includes artemisinin. If P falciparum was acquired in a known chloroquine-sensitive region such as Haiti, chloroquine remains an alternative option. When artemisinin-based combination therapies are not available, atovaquone-proguanil or quinine plus clindamycin is used for chloroquine-resistant malaria. P vivax, P ovale, P malariae, and P knowlesi are typically chloroquine sensitive, and treatment with either artemisinin-based combination therapy or chloroquine for regions with chloroquine-susceptible infections for uncomplicated malaria is recommended. For severe malaria, intravenous artesunate is first-line therapy. Treatment of mild malaria due to a chloroquine-resistant parasite consists ...

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“…Severe hemolytic anemia requiring transfusion is a well-documented complication encountered within 28 days of therapy initiation by 20–25% of malaria patients treated with parenterally administered Artusenate and it necessitates close clinical monitoring for risk mitigation ( Jauréguiberry et al, 2014 ; Savargaonkar et al, 2020 ). Likewise, severe hemolytic anemia requiring blood transfusions after oral artemisinin therapy has been observed as a rare complication in malaria patients with high parasite loads ( Conlon et al, 2020 ). Based on its overall favorable safety profile, the World Health Organization (WHO) recommends parenteral artesunate for the treatment of severe malaria (WHO) ( WHO, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug

Uckun¹,

Saund²,

Windlass³

et al. 2021

Front. Pharmacol.

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Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.

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Post-artemisinin delayed hemolysis after oral therapy for P. falciparum infection

Cited by 11 publications

References 11 publications

Post-Artesunate Delayed Hemolysis: A Review of Current Evidence

Post-Artesunate Delayed Hemolysis: A Review of Current Evidence

Diagnosis, Treatment, and Prevention of Malaria in the US

Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug

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