Transfusion‐transmitted malaria masquerading as sickle cell crisis with multisystem organ failure

Maier, Cheryl L.; Gross, Phillip J.; Dean, Christina L.; Chonat, Satheesh; Ip, Andrew; McLemore, Morgan L.; Rassi, Fuad El; Stowell, Sean R.; Josephson, Cassandra D.; Fasano, Ross M.

doi:10.1111/trf.14566

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…In 2015 alone, there were 1186 of such travel-related malaria cases reported to the Center for Disease Control (CDC) [3] and the number of malaria hospitalizations from 2000 to 2014 far exceeded that of other common travel-related illnesses [4]. Additionally, malaria is also a major risk to the blood supply in both endemic and non-endemic countries [5–7].…”

Section: Introductionmentioning

confidence: 99%

Sensitive real-time PCR detection of Plasmodium falciparum parasites in whole blood by erythrocyte membrane protein 1 gene amplification

Grabias

Essuman

Quakyi

et al. 2019

Malar J

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Background Malaria remains a global public health problem responsible for 445,000 deaths in 2016. While microscopy remains the mainstay of malaria diagnosis, highly sensitive molecular methods for detection of low-grade sub-microscopic infections are needed for surveillance studies and identifying asymptomatic reservoirs of malaria transmission. Methods The Plasmodium falciparum genome sequence was analysed to identify high copy number genes that improve P. falciparum parasite detection in blood by RT-PCR. Plasmodium falciparum erythrocyte membrane protein 1 ( Pf EMP1)-specific primers were evaluated for P. falciparum detection in hospital-based microscopically positive dried blood spots and field-acquired whole blood from asymptomatic individuals from Ghana. Results Pf EMP1 outperformed the Pf 18S sequence for amplification-based P. falciparum detection. Pf EMP1 primers exhibited sevenfold higher sensitivity compared to Pf 18S primers for parasite genomic DNA. Probit analysis established a 95% detection threshold of 9.3 parasites/mL for Pf EMP1 compared to 98.2 parasites/mL for Pf 18S primers. The Pf EMP1 primers also demonstrated superior clinical sensitivity, identifying 100% (20/20) of dried blood spot samples and 70% (69/98) of asymptomatic individuals as positive versus 55% (11/20) and 54% (53/98), respectively, for Pf 18S amplification. Conclusions These results establish Pf EMP1 as a novel amplification target for highly sensitive detection of both acute infections from filter paper samples and submicroscopic asymptomatic low-grade infections.

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Section: Introductionmentioning

confidence: 99%

Sensitive real-time PCR detection of Plasmodium falciparum parasites in whole blood by erythrocyte membrane protein 1 gene amplification

Grabias

Essuman

Quakyi

et al. 2019

Malar J

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“…There are risks with RBC transfusion [181], such as transfusion-transmitted malaria (TTM). However, because the risk of TTM is so low in the US, patients with TTM have been successfully treated with RBCX, which exposes them to additional RBC units [182,183]. Importantly, there is only a slight decline in concentrations of anti-malarial drugs after this procedure [184].…”

Section: Manual Et/rbcx For Malariamentioning

confidence: 99%

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells

Jajosky,

Wu,

Jajosky

et al. 2023

TropicalMed

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Plasmodium knowlesi (Pk) causes zoonotic malaria and is known as the “fifth human malaria parasite”. Pk malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with Pk malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with Pk and (2) Pk is often misdiagnosed as P. malariae (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of Pk malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when Pk parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing “sticky” parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special Pk-resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. “Therapeutically-rational exchange transfusion” (T-REX) is proposed in which Pk-resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs—also known as Fy(a-b-) RBCs—could replace the majority of the patient’s circulating normocytes with Pk invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture—in a 24 h Pk asexual life cycle—the released merozoites cannot invade Fy(a-b-) RBCs. When Fy(a-b-) RBC units are scarce (e.g., in Malaysia), clinicians can consider the risks and benefits of transfusing plausibly Pk-resistant RBCs, such as glucose-6-phosphate dehydrogenase deficient (G6PDd) RBCs and Southeast Asian ovalocytes (SAO). Patients typically require a very short recovery time (<1 h) after the procedure. Fy(a-b-) RBCs should have a normal lifespan, while SAO and G6PDd RBCs may have mildly reduced half-lives. Because SAO and G6PDd RBCs come from screened blood donors who are healthy and not anemic, these RBCs have a low-risk for hemolysis and do not need to be removed after the patient recovers from malaria. T-REX could be especially useful if (1) antimalarial medications are not readily available, (2) patients are likely to progress to severe disease, or (3) drug-resistant strains emerge. In conclusion, T-REX is a proposed optimization of manual ET/RBCX that has not yet been utilized but can be considered by physicians to treat Pk malaria patients.

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“…Consequently, TTM is an important complication seen among SCD patients who had received blood transfusion from donors within or originating from malaria endemic countries (40,41). Therefore, SCD patients and their parents should be adequately counseled to strictly comply with their routine anti-malarial chemo-prophylaxis as is usually incorporated in the standard of care for SCD patients who are resident in their native malaria-endemic tropical countries (42).…”

Section: Parametersmentioning

confidence: 99%

Haemoglobin phenotypes and the risk of asymptomatic malaria parasitemia among blood donors in northwest Nigeria: clinical implications in the practice of tropical transfusion medicine

Kani¹,

Ibrahim²,

Habeeb³

et al. 2021

Af J Clin Exp Micro

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Background: In malaria-endemic populations, sickle cell trait (SCT) protects against both severe and non-severe malaria, but inconsistencies exist about protective effect of SCT on asymptomatic malarial parasitemia (AMP). Surprisingly, the effect of Hb-phenotypes on AMP has not been explored among blood donors in Nigeria or other malaria-endemic countries, where risks of AMP and transfusion transmitted malaria (TTM) are high. The objective of this study is to determine risk of AMP with respect to donor Hb-phenotypes (SCT versus HbAA), and elucidate clinical implications of AMP with respect to risk of TTM vis-à-vis the practice of transfusion medicine in Nigeria, and by implication other malaria-endemic tropical countries.Methodology: Analysis of 100 blood donors with AMP (cases) and 100 donors without AMP (controls) was performed. Frequencies of SCT and HbAA (determined by Hb electrophoresis) among cases and controls were compared by X2 -test. Risks of AMP (detected by microscopy) with respect to Hb-phenotypes were expressed as Odds ratios (OR) by case-control logistic regression.Results: In comparison with blood donor without AMP (controls), donors with AMP had lower frequencies of SCT (12% vs 28%, p<0.05) with corresponding higher frequencies of HbAA (88% vs 72%, p<0.05). HbAA is associated with high risk of AMP (OR=2.91, 95%CI: 2.10-3.48, p=0.021), while SCT is associated low risk of AMP (OR=0.49, 95%CI: 0.27-0.73, p=0.032).Conclusion: This finding shows that donor SCT is a surreptitious mitigator of the risk of AMP and TTM in the tropics. Therefore, patients who are selectively transfused with HbAA blood (e. g. neonates and sickle cell disease patients) could be at greater risks of TTM, and such patients need closer post transfusion monitoring. The risk of TTM calls for diligent post transfusion haemovigilance in Nigeria and other malaria endemic tropical countries in Africa Keywords: blood donors, sickle cell trait, asymptomatic malaria parasitemia, transfusion transmitted malaria

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Transfusion‐transmitted malaria masquerading as sickle cell crisis with multisystem organ failure

Cited by 5 publications

References 29 publications

Sensitive real-time PCR detection of Plasmodium falciparum parasites in whole blood by erythrocyte membrane protein 1 gene amplification

Sensitive real-time PCR detection of Plasmodium falciparum parasites in whole blood by erythrocyte membrane protein 1 gene amplification

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells

Haemoglobin phenotypes and the risk of asymptomatic malaria parasitemia among blood donors in northwest Nigeria: clinical implications in the practice of tropical transfusion medicine

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