Recrudescent severe malaria due to Plasmodium falciparum following treatment in a Taiwanese patient: a case report

Recrudescent severe malaria due to Plasmodium falciparum following treatment in a Taiwanese patient: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Recrudescent severe malaria due to Plasmodium falciparum following treatment in a Taiwanese patient: a case report Yu-Chuan Tseng, Meng-Yu Cheng, Peter Bor-Chian Lin, Shih-Fen Hsu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7000518/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2025 Read the published version in Malaria Journal → Version 1 posted 14 You are reading this latest preprint version Abstract Background Severe malaria caused by Plasmodium falciparum remains a life-threatening disease, particularly in non-immune individuals returning from endemic regions. While prompt treatment can usually achieve parasite clearance, recrudescence after initial recovery is rare and presents unique diagnostic and management challenges. This report documents a case of recrudescent severe malaria in a Taiwanese traveler, highlighting clinical complexities related to organ support and altered drug pharmacokinetics. Case presentation A previously healthy 66-year-old Taiwanese man developed fever, vomiting, diarrhea, and jaundice shortly after returning from multiple Central African countries with high malaria prevalence. His condition rapidly deteriorated to multi-organ failure, including acute kidney injury, liver failure, thrombocytopenia, and respiratory distress. Blood smear microscopy revealed a high parasitemia (20%) due to P. falciparum , which was confirmed by real-time PCR. Management and outcome The patient received intravenous artesunate and oral artemether-lumefantrine, in addition to hemodialysis and plasma exchange as supportive therapies. Initial treatment achieved parasite clearance and clinical improvement. However, four weeks later, the patient experienced recrudescence with recurrent fever, anemia, and return of parasitemia. The therapeutic regimen was then revised to intravenous artesunate combined with doxycycline and clindamycin, followed by oral artemether-lumefantrine. This approach led to successful parasite clearance within two weeks and complete recovery, with no further recurrence observed during follow-up. Conclusions This case highlights that even with prompt, guideline-based therapy, severe P. falciparum malaria in non-immune individuals can relapse, especially when organ failure and interventions such as plasma exchange may alter drug efficacy. Enhanced clinical vigilance, laboratory monitoring, and multidisciplinary care are essential for management. Reporting such rare recrudescent cases supports clinical awareness, informs best practice, and strengthens public health preparedness in low-incidence regions. Recrudescence Malaria Plasmodium falciparum Schizont Plasma exchange therapy Figures Figure 1 Figure 2 Background Severe malaria caused by Plasmodium falciparum remains a major global health challenge, particularly for non-immune individuals returning from endemic regions. The disease may rapidly progress to multi-organ failure and carries a high mortality risk if not diagnosed and treated promptly. In non-endemic areas, its rarity and diverse clinical manifestations further complicate timely diagnosis. High parasitemia (> 2% in non-immune patients) is a key diagnostic criterion for severe malaria and is associated with an increased risk of complications such as acute kidney injury, liver failure, and severe systemic inflammation. In P. falciparum malaria, the risk of vital organ dysfunction rises with parasite density. In low-transmission settings where individuals generally lack pre-existing immunity, mortality rises sharply when parasite density exceeds 100,000 parasites/µL—approximately 2% parasitemia [ 1 ]. Current guidelines from the World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (U.S. CDC) recommend prompt parenteral artemisinin-based therapy, sometimes with adjunctive agents, as the mainstay of treatment. However, recrudescence remains a concern, particularly in patients with complicated courses or those undergoing interventions such as dialysis or plasma exchange, which may alter drug pharmacokinetics and therapeutic efficacy. Here, we describe a case of severe falciparum malaria in a Taiwanese traveler returning from Central Africa, complicated by multi-organ failure and recrudescence after standard treatment. The aim of this report is to highlight the clinical complexity and therapeutic challenges of managing severe imported malaria, and to underscore the need for individualized monitoring and treatment adjustment, especially in patients receiving organ support. Case presentation A previously healthy 66-year-old Taiwanese man with no history of chronic disease participated alone in a group tour across multiple Central African countries, including malaria-endemic regions such as Equatorial Guinea, Cameroon, and São Tomé and Príncipe. Upon returning to Taiwan on March 21, 2025, he developed fatigue, vomiting, diarrhea, and jaundice, and initially sought treatment at a local clinic before resting at home. On March 25, his symptoms worsened with chills, oliguria, and generalized malaise. Laboratory tests at a regional healthcare facility revealed abnormal liver function, prompting referral to the emergency department of China Medical University Hospital. Initial emergency department evaluation indicated severe hepatic and renal dysfunction alongside systemic inflammatory response. Given the patient's recent international travel and clinical presentation, airborne infectious disease was suspected, and the patient was admitted to an isolation ward. Several infectious diseases were considered in the differential diagnosis, including malaria, yellow fever, Ebola virus disease, hantavirus infection, and leptospirosis. Follow-up laboratory results on March 26 revealed progressive elevation of liver enzymes, including aspartate aminotransferase at 343 U/L (reference range, 5–34 U/L) and alanine aminotransferase at 365 U/L (5–40 U/L); hyperbilirubinemia, with total bilirubin at 17.97 mg/dL (0.2–1.3 mg/dL) and direct bilirubin at 13.49 mg/dL (0.0–0.4 mg/dL); deteriorating renal function, indicated by elevated creatinine at 2.49 mg/dL (0.6–1.3 mg/dL) and a reduced estimated glomerular filtration rate of 26 mL/min/1.73 m², consistent with severe renal impairment; elevated blood urea nitrogen at 40 mg/dL (5–26 mg/dL); elevated lactate dehydrogenase at 599 U/L (98–192 U/L); marked inflammation, indicated by elevated high-sensitivity C-reactive protein at 23.66 mg/dL (< 1.0 mg/dL); hypoalbuminemia, with albumin at 3.0 g/dL (3.8–5.3 g/dL); hyponatremia, with sodium at 132 mmol/L (135–147 mmol/L); and hypocalcemia, with calcium at 7.5 mg/dL (8.6–10.3 mg/dL). These results indicated acute multi-organ failure consistent with severe malaria. Additionally, severe thrombocytopenia was observed, with a platelet count of less than 10,000/µL (130,000–400,000/µL), hemoglobin at 15 g/dL (male 13.7–17.0 g/dL) and Plasmodium -infected erythrocytes were identified on blood smears. These findings confirmed the diagnosis of severe malaria complicated by acute kidney injury, liver failure, and thrombocytopenia. On March 26, the patient was transferred to the intensive care unit due to respiratory distress. The Taiwan Centers for Disease Control (Taiwan CDC) confirmed via microscopy a high parasitemia (20%) of P. falciparum. Representative microscopic images of ring forms and trophozoites from the initial episode are shown in Figs. 1 A and 1 B. Intravenous artesunate treatment was initiated immediately upon medication arrival from the Taiwan CDC. On March 27, molecular testing using real-time PCR confirmed P. falciparum infection without mixed-species involvement (sample 1, S1; Fig. 2 A and 2 B). Amplification of Internal Control (IC) and Pan- Plasmodium targets validated DNA extraction and Plasmodium spp. presence (Fig. 2 A). Species-specific amplification confirmed P. falciparum ( P.f. S1) infection, without detecting P. vivax , P. malariae , P. ovale , or P. knowlesi (Fig. 2 B). The primers and probes used for Plasmodium spp. detection were provided by the Taiwan CDC and are listed in Table 1 . After confirmation of P. falciparum malaria, testing for yellow fever—given the patient’s prior vaccination history—and for Ebola virus disease—due to the absence of severe bleeding—was not pursued. Serologic antibody testing for hantavirus and leptospirosis was performed, and both yielded negative results. Artesunate treatment (168 mg intravenously at 0, 12, and 24 hours, then daily until parasitemia < 1%) was administered from March 26–28, followed by oral artemether/lumefantrine (20/120 mg, 4 tablets at 0, 8, 12 hours, then every 12 hours for two additional days) [ 2 , 3 ]. Table 1 Sequences of primers and probes used for real-time quantitative PCR detection of Plasmodium spp. Primers and probes Primers and probes (5’-3’) Product size (bp) Real-time PCR for Plasmodium spp. Pan-F GTT AAG GGA GTG AAG ACG ATC AGA TA 157 Pan-R AAC CCA AAG ACT TTG ATT TCT CAT AAG Pan-spp-probe FAM-TCG TAA TCT TAA CCA TAA AC-MGBNFQ Pv-F CGC TTC TAG CTT AAT CCA CAT AAC TG 142 Pv-R AAT TTA CTC AAA GTA ACA AGG ACT TCC AAG Pv-probe VIC-CGC ATT TTG CTA TTA TGT-MGBNFQ Pm-F AGT TAA GGG AGT GAA GAC GAT CAG A 166 Pm-R CAA CCC AAA GAC TTT GAT TTC TCA TAA Pm-probe FAM-ATG AGT GTT TCT TTT AGA TAG C-MGBNFQ Pf-F ATT GCT TTT GAG AGG TTT TGT TAC TTT 95 Pf-R GCT GTA GTA TTC AAA CAC AAT GAA CTC AA Pf-probe FAM-CAT AAC AGA CGG GTA GTC AT-MGBNFQ Po-F CCG ACT AGG TTT TGG ATG AAA GAT TTT T 114 Po-R CAA CCC AAA GAC TTT GAT TTC TCA TAA Po-probe VIC-CGA AAG GAA TTT TCT TAT T-MGBNFQ Pk 17-F CCT TTC CTT CCA TTC TAC GTA ACC 123 Pk 17-R GAC GTC GAG AAG TGG GTT CA Pk-probe FAM-CAG CCA ACA ACA CTT ACA-MGBNFQ Real-time PCR for internal control RnaseP-F AGA TTT GGA CCT GCG AGC G 130 RnaseP-R GAG CGG CTG TCT CCA CAA GT RnaseP Probe FAM-TTC TGA CCT GAA GGC TCT GCG CG-BBQ Due to acute kidney injury complicated by lactic acidosis and oliguria, continuous veno-venous hemofiltration (March 26–30), sustained low-efficiency dialysis (March 31–April 14), and hemodialysis (April 16–May 2) were performed. Plasma exchange was also administered due to acute liver failure and suspected thrombotic microangiopathy (March 31–April 9). Despite initial parasitic clearance, malaria recrudesced in mid-April, evidenced by fever and anemia, with a platelet count of 48,000/µL and hemoglobin at 6.5 g/dL. Blood smears on April 25 revealed the presence of P. falciparum ring forms, trophozoites, schizonts, and gametocytes, including both a macrogametocyte (female) and a microgametocyte (male), as shown in Fig. 1 C–F. A blood sample (sample 2, S2) was also submitted to the Taiwan CDC for real-time PCR testing, which again confirmed P. falciparum mono-infection without evidence of mixed-species involvement (Fig. 2 B), further supporting the diagnosis of recrudescence. Given concerns about drug resistance [ 4 – 6 ], alterations in pharmacokinetics due to dialysis and plasma exchange, and lack of intravenous quinine availability in Taiwan, the therapeutic regimen was adjusted according to international guidelines. The patient received intravenous artesunate (168 mg at 0, 12, and 24 hours, then daily), combined with oral doxycycline (100 mg twice daily) and intravenous clindamycin (900 mg every 8 hours) from April 25–May 1 [ 1 , 7 ]. Subsequent therapy included oral artemether/lumefantrine (May 2–5) alongside doxycycline and clindamycin. Parasitemia was cleared successfully by May 6, with no relapse or clinical recurrence observed over a subsequent six-week follow-up, demonstrating effective and stable therapeutic outcomes. Discussion According to international guidelines, high parasitemia is a key criterion for severe P. falciparum malaria. The WHO considers parasitemia > 2% significant in non-immune individuals [ 1 ], whereas the U.S. CDC defines severe malaria as parasitemia ≥ 5% [ 3 ] or the presence of one or more clinical features, including impaired consciousness, prostration, multiple convulsions, acidosis, hypoglycemia, severe anemia (hemoglobin < 7 g/dL), acute kidney injury, jaundice (with at least one other severe feature), pulmonary edema or acute respiratory distress syndrome, abnormal bleeding or disseminated intravascular coagulation, and circulatory collapse or shock [ 1 , 3 , 8 – 10 ]. In this case, the patient exhibited a parasitemia level exceeding 20%, accompanied by acute hepatic and renal failure, respiratory failure, and impaired consciousness—fulfilling the diagnostic criteria for severe malaria. According to Yadav et al., among 59 patients with P. falciparum infection, 57 (96.6%) had thrombocytopenia and 48 (81.4%) had anemia [ 11 ]. Similarly, Elkhalifa et al. reported that among 192 patients, 72.4% exhibited thrombocytopenia and 60.4% had anemia [ 12 ]. However, direct data on patients presenting with thrombocytopenia in the absence of anemia were not available in the reviewed literature. Notably, our patient initially presented with profound thrombocytopenia (platelet count < 10,000/µL) while maintaining a normal hemoglobin level (15 g/dL), representing a rare manifestation of P. falciparum infection. At recrudescence, however, the patient developed both thrombocytopenia (platelet count 48,000/µL) and marked anemia (hemoglobin 6.5 g/dL), consistent with the typical findings reported in the literature. Recrudescence of P. falciparum refers to the recurrence of symptoms due to incomplete parasite clearance after initial infection, with a small number of parasites persisting and proliferating in the bloodstream weeks to months later. This often results from inadequate therapy or suboptimal drug concentrations. Erythrocytes infected with mature trophozoites and schizonts develop knob-like structures and express PfEMP1, which binds to adhesion molecules on postcapillary venule endothelium, enabling schizonts to mature within the deep microvasculature—a process known as deep-vascular schizogony or sequestration, and a key mechanism underlying recrudescence. [ 13 – 16 ]. Clinically, the presence of mature schizonts in peripheral blood indicates a critical stage of illness [ 17 ]; however, the level of parasitemia observed in peripheral blood often underestimates the true severity of infection in P. falciparum malaria, and severe disease cannot be ruled out even when parasitemia is not high [ 18 ]. In this case, although mature schizonts were not initially observed on peripheral smears, the patient rapidly progressed to multi-organ failure, later exhibiting both mature schizonts and high parasitemia, which confirmed disease deterioration and the mechanism of recrudescence. This highlights the necessity of integrating clinical findings with microscopy results for accurate assessment. According to data from the Taiwan CDC, sixteen imported cases of P. falciparum malaria were reported in Taiwan between 2020 and 2025, including two fatalities. Notably, the present case was the only one to develop clinical recrudescence following treatment, underscoring the exceptional rarity of such an event in Taiwan. During the same period, there were nine cases of P. vivax malaria (including two relapses), one case of P. malariae , one case of P. ovale , and one case of mixed P. falciparum and P. vivax infection [ 19 ]. At admission, this patient already presented with acute kidney injury, lactic acidosis, and oliguria, requiring continuous veno-venous hemofiltration, sustained low-efficiency dialysis, and hemodialysis. Due to acute liver failure and suspected microvascular thrombosis, multiple sessions of plasma exchange were also performed to mitigate organ damage. Although initial therapy resulted in parasite clearance, clinical recrudescence developed. Possible causes include incomplete clearance of blood-stage parasites during initial therapy, sequestration of schizonts within the deep microvasculature (not detectable on peripheral smear), decreased drug concentrations due to poor absorption, concurrent dialysis and plasma exchange, or the presence of drug-resistant parasites [ 1 , 20 , 21 ]. In accordance with World Health Organization guidelines, artesunate in combination with antibiotics was used for seven days, along with renal and hepatic replacement therapies for supportive care. This case demonstrated severe manifestations and is the first documented instance of recrudescent P. falciparum malaria in Taiwan following standard therapy, highlighting its clinical uniqueness and management challenges. It underscores the need for vigilance regarding multi-organ complications and the risk of recrudescence in severe malaria. Conclusion This case demonstrates that even with prompt, guideline-adherent therapy, severe P. falciparum malaria in non-immune individuals can be complicated by recrudescence—particularly when multiple organ failure and interventions such as plasma exchange may influence drug pharmacokinetics and treatment efficacy. It also underscores the necessity for heightened clinical vigilance, close laboratory monitoring, and interdisciplinary care when treating severe imported malaria with multi-organ involvement. Reporting such rare recrudescent cases is crucial for improving clinical awareness, refining treatment protocols, and informing public health preparedness in settings with low malaria incidence. Abbreviations WHO World Health Organization U.S. CDC United States Centers for Disease Control and Prevention Taiwan CDC Taiwan Centers for Disease Control Pan Pan-Plasmodium IC internal control Ct cycle threshold P.f . P. falciparum P.v P. vivax P.m P. malariae P.o. P. ovale P.k. P. knowlesi Declarations Author contributions YCT and MYC contributed to the conception and design of the study. SFH, JJH, and YCS were responsible for data acquisition. YCT, MYC, CTH, and PRH analyzed and/or interpreted the data. YCT, MYC, and PBL drafted the manuscript. MWH, CTH, and PRH critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript. Funding This work was supported by the China Medical University Hospital and Taiwan Centers for Disease Control without grant funding. Data availability The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The need for ethical approval was waived. Informed consent Before preparing the case report, the patient provided written informed consent to write the case and be published. Competing interest The authors declare that they have no competing interests. Acknowledgements We would like to thank Fang-Tzy Wu from Taiwan Centers for Disease Control for critical comments on the manuscript. Author details 1 Department of Laboratory Medicine, China Medical University Hospital, Taichung, China Medical University, Taiwan. 2 Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. 3 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, China Medical University, Taiwan. 4 Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University in St. Louis, Missouri, United States. 5 Taiwan Centers for Disease Control, Taipei City, Taiwan. References World Health Organization. WHO guidelines for malaria. Geneva: World Health Organization; 2024. https://www.who.int/publications/i/item/guidelines-for-malaria. Sanford Guide. Antimicrobial stewardship. Sperryville, VA: Antimicrobial Therapy, Inc.; 2025. https://www.sanfordguide.com. US Centers for Disease Control and Prevention. Clinical guidance: Malaria diagnosis & treatment in the US. Atlanta, GA: US Centers for Disease Control and Prevention; 2024. https://www.cdc.gov/malaria/hcp/clinical-guidance/treatment-of-severe-malaria.html. Tripathi J, Stoklasa M, Nayak S, En Low K, Qian Hui Lee E, Duong Tien QH, et al. The artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular quiescence/senescence and drug resilience. Nat Commun. 2024;15:7485. Krishna S, Kremsner PG. Antidogmatic approaches to artemisinin resistance: reappraisal as treatment failure with artemisinin combination therapy. Trends Parasitol. 2013;29:313-7. Ndiaye M, Diouf M, Mhamadi M, Djigal A, Manga IA, Sene C, et al. P. falciparum genetic markers associated with drug resistance from patients with treatment failure in the Southern part of Senegal in 2017. Int J Mol Epidemiol Genet. 2024;15:22-30. UK Health Security Agency. UK Malaria Expert Advisory Group interim guidance. London: UK Health Security Agency; 2025. https://www.gov.uk/government/publications/management-of-treatment-failure-recrudescence-in-falciparum-malaria. White NJ. Severe malaria. Malar J. 2022;21:284. Daily JP, Parikh S. Malaria. N Engl J Med. 2025;392:1320-33. Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376:1647-57. Yadav RK, Kumar S. To study hematological profile in malaria patients. Int J Adv Med. 2017;4:707-12. Elkhalifa AME, Abdul-Ghani R, Tamomh AG, Eltaher NE, Ali NY, Ali MM, et al. Hematological indices and abnormalities among patients with uncomplicated falciparum malaria in Kosti city of the White Nile state, Sudan: a comparative study. BMC Infect Dis. 2021;21:507. Taiwan Centers for Disease Control. Malaria. Taipei: Taiwan Centers for Disease Control; 2025. https://www.cdc.gov.tw/File/Get/3f3ua7S2RYlrceZhD286yw. Dondorp AM, Nyanoti M, Kager PA, Mithwani S, Vreeken J, Marsh K. The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion. Trans R Soc Trop Med Hyg. 2002;96:282-6. Smith JD. The role of PfEMP1 adhesion domain classification in Plasmodium falciparum pathogenesis research. Mol Biochem Parasitol. 2014;195:82-7. Chan JA, Stanisic DI, Duffy MF, Robinson LJ, Lin E, Kazura JW, et al. Patterns of protective associations differ for antibodies to P. falciparum -infected erythrocytes and merozoites in immunity against malaria in children. Eur J Immunol. 2017;47:2124-36. Lasonder E, Green JL, Grainger M, Langsley G, Holder AA. Extensive differential protein phosphorylation as intraerythrocytic Plasmodium falciparum schizonts develop into extracellular invasive merozoites. Proteomics. 2015;15:2716-29. Daily JP, Minuti A, Khan N. Diagnosis, treatment, and prevention of Malaria in the US: a review. JAMA. 2022;328:460-71. Taiwan Centers for Disease Control. Statistical data on confirmed cases of legally designated infectious diseases imported from abroad. Taipei: Taiwan Centers for Disease Control; 2025. https://www.cdc.gov.tw/Category/Page/5Q6qrh5kM6TnpnRpy3XDfQ. Lin J, Huang X, Qin G, Zhang S, Sun W, Wang Y, et al. Manual exchange transfusion for severe imported falciparum malaria: a retrospective study. Malar J. 2018;17:32. Zaw MT, Lin Z, Emran NA. Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion. J Microbiol Immunol Infect. 2020;53:676-81. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7000518","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":482459252,"identity":"147973c9-8e27-40ef-bae1-b560f2ca80f1","order_by":0,"name":"Yu-Chuan Tseng","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu-Chuan","middleName":"","lastName":"Tseng","suffix":""},{"id":482459254,"identity":"f112dc3a-4d9a-4e18-95d3-2c3c0a0ea86d","order_by":1,"name":"Meng-Yu Cheng","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Meng-Yu","middleName":"","lastName":"Cheng","suffix":""},{"id":482459256,"identity":"a9691b8a-d486-40b1-aab0-864aa8195399","order_by":2,"name":"Peter Bor-Chian Lin","email":"","orcid":"","institution":"Washington University in St. Louis","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"Bor-Chian","lastName":"Lin","suffix":""},{"id":482459258,"identity":"da8ccb87-85d8-43b1-8cd7-0498a73a9d5d","order_by":3,"name":"Shih-Fen Hsu","email":"","orcid":"","institution":"Center for Disease Control","correspondingAuthor":false,"prefix":"","firstName":"Shih-Fen","middleName":"","lastName":"Hsu","suffix":""},{"id":482459260,"identity":"582a08d7-82e1-4814-b353-53384441b83f","order_by":4,"name":"Jen-Jen Hsu","email":"","orcid":"","institution":"Center for Disease Control","correspondingAuthor":false,"prefix":"","firstName":"Jen-Jen","middleName":"","lastName":"Hsu","suffix":""},{"id":482459261,"identity":"1cf54989-c9ff-44e9-a1d5-8860ce6c7f5b","order_by":5,"name":"Yi-Cheng Shen","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Cheng","middleName":"","lastName":"Shen","suffix":""},{"id":482459262,"identity":"e3d12f93-dc43-423b-b4d8-53f703c12f14","order_by":6,"name":"Mao-Wang Ho","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mao-Wang","middleName":"","lastName":"Ho","suffix":""},{"id":482459263,"identity":"b032607e-8fb0-42e1-ad42-033146943eab","order_by":7,"name":"Chiung-Tzu Hsiao","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chiung-Tzu","middleName":"","lastName":"Hsiao","suffix":""},{"id":482459264,"identity":"a08d4c65-c6e6-4570-af18-dd18f535b303","order_by":8,"name":"Po-Ren Hsueh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIiWNgGAWjYBACAygtByIOPCBFizFYSwIpWhIbQCRRWsz5zx58XFFxJ31+2OGHQFvs5HQbCGixnJGXbHjmzLPcjbfTDIBako3NDhBy2A0eM8nGtsO5G2cngLQcSNxGUMv5M0At/w6nG85O/0CklgM5QC0NhxPkpXOIteUG0C8Nxw4bbpDOKTiQYECMX86fPfiwoeawvPzs9M0fPlTYyRHUwsDAA3MhmCSoHEmLfANRqkfBKBgFo2AkAgDfr0mp+bSFjAAAAABJRU5ErkJggg==","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Po-Ren","middleName":"","lastName":"Hsueh","suffix":""}],"badges":[],"createdAt":"2025-06-29 03:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7000518/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7000518/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12936-025-05581-6","type":"published","date":"2025-10-09T15:57:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86422170,"identity":"a837b191-d44d-48cb-b652-90b8b753651f","added_by":"auto","created_at":"2025-07-10 12:56:57","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":246417,"visible":true,"origin":"","legend":"\u003cp\u003ePeripheral blood thin smears showing \u003cem\u003ePlasmodium falciparum\u003c/em\u003eat different developmental stages.\u003c/p\u003e\n\u003cp\u003e(A) Wright-Giemsa-stained smear from the initial episode (March 26, 2025), showing ring forms (orange arrows).\u003c/p\u003e\n\u003cp\u003e(B) Liu’s-stained smear from the same episode showing ring forms and trophozoites (black arrows).\u003c/p\u003e\n\u003cp\u003e(C–F) Smears of samples obtained from the recrudescence episode (April 25, 2025):\u003c/p\u003e\n\u003cp\u003e(C) Ring forms and trophozoites (black and orange arrows);\u003c/p\u003e\n\u003cp\u003e(D) A schizont (red arrow);\u003c/p\u003e\n\u003cp\u003e(E) Trophozoites and a macrogametocyte (female; green arrow); and\u003c/p\u003e\n\u003cp\u003e(F) A microgametocyte (male; green arrow) in infected red blood cells.\u003c/p\u003e\n\u003cp\u003e(Optical microscope magnification, 1000×)\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7000518/v1/e5f4f234c2e6c0458e6296a5.jpg"},{"id":86421048,"identity":"606ed43e-19bb-499c-9a01-a7d74ad4beb9","added_by":"auto","created_at":"2025-07-10 12:48:57","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":242889,"visible":true,"origin":"","legend":"\u003cp\u003eReal-time PCR results obtained from (A) the initial episode (sample 1, S1; March 26, 2025), and from (B) the recrudescence episode (sample 2, S2; April 25, 2025). \u003cem\u003ePlasmodium falciparum\u003c/em\u003e (\u003cem\u003eP.f.\u003c/em\u003e) was detected in both samples (S1 and S2) without evidence of mixed-species infection. (C) Species-specific PCR results for both time points. Cycle threshold (Ct) values indicate positive amplification for internal control (IC), Pan-\u003cem\u003ePlasmodium\u003c/em\u003e (Pan), and \u003cem\u003eP. falciparum\u003c/em\u003e (\u003cem\u003eP.f.\u003c/em\u003e) targets, while no amplification was observed for \u003cem\u003eP. vivax\u003c/em\u003e (\u003cem\u003eP.v.\u003c/em\u003e), \u003cem\u003eP. malariae\u003c/em\u003e (\u003cem\u003eP.m.\u003c/em\u003e), \u003cem\u003eP. ovale\u003c/em\u003e (\u003cem\u003eP.o.\u003c/em\u003e), or \u003cem\u003eP. knowlesi\u003c/em\u003e (\u003cem\u003eP.k.\u003c/em\u003e). Negative and positive controls validate assay performance and specificity.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7000518/v1/ee729f3f4f9493a79b5ff41d.jpg"},{"id":93419639,"identity":"66faa534-912e-40f8-8370-9ed14afb7101","added_by":"auto","created_at":"2025-10-13 16:05:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1062012,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7000518/v1/a5178bce-59a2-4507-8304-ee3b26090dbc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Recrudescent severe malaria due to Plasmodium falciparum following treatment in a Taiwanese patient: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eSevere malaria caused by \u003cem\u003ePlasmodium falciparum\u003c/em\u003e remains a major global health challenge, particularly for non-immune individuals returning from endemic regions. The disease may rapidly progress to multi-organ failure and carries a high mortality risk if not diagnosed and treated promptly. In non-endemic areas, its rarity and diverse clinical manifestations further complicate timely diagnosis.\u003c/p\u003e\u003cp\u003eHigh parasitemia (\u0026gt;\u0026thinsp;2% in non-immune patients) is a key diagnostic criterion for severe malaria and is associated with an increased risk of complications such as acute kidney injury, liver failure, and severe systemic inflammation. In \u003cem\u003eP. falciparum\u003c/em\u003e malaria, the risk of vital organ dysfunction rises with parasite density. In low-transmission settings where individuals generally lack pre-existing immunity, mortality rises sharply when parasite density exceeds 100,000 parasites/\u0026micro;L\u0026mdash;approximately 2% parasitemia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Current guidelines from the World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (U.S. CDC) recommend prompt parenteral artemisinin-based therapy, sometimes with adjunctive agents, as the mainstay of treatment. However, recrudescence remains a concern, particularly in patients with complicated courses or those undergoing interventions such as dialysis or plasma exchange, which may alter drug pharmacokinetics and therapeutic efficacy.\u003c/p\u003e\u003cp\u003eHere, we describe a case of severe falciparum malaria in a Taiwanese traveler returning from Central Africa, complicated by multi-organ failure and recrudescence after standard treatment. The aim of this report is to highlight the clinical complexity and therapeutic challenges of managing severe imported malaria, and to underscore the need for individualized monitoring and treatment adjustment, especially in patients receiving organ support.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA previously healthy 66-year-old Taiwanese man with no history of chronic disease participated alone in a group tour across multiple Central African countries, including malaria-endemic regions such as Equatorial Guinea, Cameroon, and S\u0026atilde;o Tom\u0026eacute; and Pr\u0026iacute;ncipe. Upon returning to Taiwan on March 21, 2025, he developed fatigue, vomiting, diarrhea, and jaundice, and initially sought treatment at a local clinic before resting at home.\u003c/p\u003e\u003cp\u003eOn March 25, his symptoms worsened with chills, oliguria, and generalized malaise. Laboratory tests at a regional healthcare facility revealed abnormal liver function, prompting referral to the emergency department of China Medical University Hospital. Initial emergency department evaluation indicated severe hepatic and renal dysfunction alongside systemic inflammatory response. Given the patient's recent international travel and clinical presentation, airborne infectious disease was suspected, and the patient was admitted to an isolation ward. Several infectious diseases were considered in the differential diagnosis, including malaria, yellow fever, Ebola virus disease, hantavirus infection, and leptospirosis. Follow-up laboratory results on March 26 revealed progressive elevation of liver enzymes, including aspartate aminotransferase at 343 U/L (reference range, 5\u0026ndash;34 U/L) and alanine aminotransferase at 365 U/L (5\u0026ndash;40 U/L); hyperbilirubinemia, with total bilirubin at 17.97 mg/dL (0.2\u0026ndash;1.3 mg/dL) and direct bilirubin at 13.49 mg/dL (0.0\u0026ndash;0.4 mg/dL); deteriorating renal function, indicated by elevated creatinine at 2.49 mg/dL (0.6\u0026ndash;1.3 mg/dL) and a reduced estimated glomerular filtration rate of 26 mL/min/1.73 m\u0026sup2;, consistent with severe renal impairment; elevated blood urea nitrogen at 40 mg/dL (5\u0026ndash;26 mg/dL); elevated lactate dehydrogenase at 599 U/L (98\u0026ndash;192 U/L); marked inflammation, indicated by elevated high-sensitivity C-reactive protein at 23.66 mg/dL (\u0026lt;\u0026thinsp;1.0 mg/dL); hypoalbuminemia, with albumin at 3.0 g/dL (3.8\u0026ndash;5.3 g/dL); hyponatremia, with sodium at 132 mmol/L (135\u0026ndash;147 mmol/L); and hypocalcemia, with calcium at 7.5 mg/dL (8.6\u0026ndash;10.3 mg/dL). These results indicated acute multi-organ failure consistent with severe malaria. Additionally, severe thrombocytopenia was observed, with a platelet count of less than 10,000/\u0026micro;L (130,000\u0026ndash;400,000/\u0026micro;L), hemoglobin at 15 g/dL (male 13.7\u0026ndash;17.0 g/dL) and \u003cem\u003ePlasmodium\u003c/em\u003e-infected erythrocytes were identified on blood smears. These findings confirmed the diagnosis of severe malaria complicated by acute kidney injury, liver failure, and thrombocytopenia.\u003c/p\u003e\u003cp\u003eOn March 26, the patient was transferred to the intensive care unit due to respiratory distress. The Taiwan Centers for Disease Control (Taiwan CDC) confirmed via microscopy a high parasitemia (20%) of \u003cem\u003eP. falciparum.\u003c/em\u003e Representative microscopic images of ring forms and trophozoites from the initial episode are shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB. Intravenous artesunate treatment was initiated immediately upon medication arrival from the Taiwan CDC. On March 27, molecular testing using real-time PCR confirmed \u003cem\u003eP. falciparum\u003c/em\u003e infection without mixed-species involvement (sample 1, S1; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Amplification of Internal Control (IC) and Pan-\u003cem\u003ePlasmodium\u003c/em\u003e targets validated DNA extraction and \u003cem\u003ePlasmodium\u003c/em\u003e spp. presence (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Species-specific amplification confirmed \u003cem\u003eP. falciparum\u003c/em\u003e (\u003cem\u003eP.f.\u003c/em\u003e S1) infection, without detecting \u003cem\u003eP. vivax\u003c/em\u003e, \u003cem\u003eP. malariae\u003c/em\u003e, \u003cem\u003eP. ovale\u003c/em\u003e, or \u003cem\u003eP. knowlesi\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The primers and probes used for \u003cem\u003ePlasmodium\u003c/em\u003e spp. detection were provided by the Taiwan CDC and are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. After confirmation of \u003cem\u003eP. falciparum\u003c/em\u003e malaria, testing for yellow fever\u0026mdash;given the patient\u0026rsquo;s prior vaccination history\u0026mdash;and for Ebola virus disease\u0026mdash;due to the absence of severe bleeding\u0026mdash;was not pursued. Serologic antibody testing for hantavirus and leptospirosis was performed, and both yielded negative results. Artesunate treatment (168 mg intravenously at 0, 12, and 24 hours, then daily until parasitemia\u0026thinsp;\u0026lt;\u0026thinsp;1%) was administered from March 26\u0026ndash;28, followed by oral artemether/lumefantrine (20/120 mg, 4 tablets at 0, 8, 12 hours, then every 12 hours for two additional days) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSequences of primers and probes used for real-time quantitative PCR detection of \u003cem\u003ePlasmodium\u003c/em\u003e spp.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimers and probes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePrimers and probes (5\u0026rsquo;-3\u0026rsquo;)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eProduct size (bp)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eReal-time PCR for \u003cem\u003ePlasmodium\u003c/em\u003e spp.\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePan-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGTT AAG GGA GTG AAG ACG ATC AGA TA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e157\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePan-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAAC CCA AAG ACT TTG ATT TCT CAT AAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePan-spp-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFAM-TCG TAA TCT TAA CCA TAA AC-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePv-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCGC TTC TAG CTT AAT CCA CAT AAC TG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePv-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAAT TTA CTC AAA GTA ACA AGG ACT TCC AAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePv-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVIC-CGC ATT TTG CTA TTA TGT-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePm-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAGT TAA GGG AGT GAA GAC GAT CAG A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e166\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePm-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCAA CCC AAA GAC TTT GAT TTC TCA TAA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePm-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFAM-ATG AGT GTT TCT TTT AGA TAG C-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePf-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eATT GCT TTT GAG AGG TTT TGT TAC TTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePf-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGCT GTA GTA TTC AAA CAC AAT GAA CTC AA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePf-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFAM-CAT AAC AGA CGG GTA GTC AT-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePo-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCCG ACT AGG TTT TGG ATG AAA GAT TTT T\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePo-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCAA CCC AAA GAC TTT GAT TTC TCA TAA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePo-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVIC-CGA AAG GAA TTT TCT TAT T-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePk 17-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCCT TTC CTT CCA TTC TAC GTA ACC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e123\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePk 17-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGAC GTC GAG AAG TGG GTT CA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePk-probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFAM-CAG CCA ACA ACA CTT ACA-MGBNFQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eReal-time PCR for internal control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRnaseP-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAGA TTT GGA CCT GCG AGC G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRnaseP-R\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGAG CGG CTG TCT CCA CAA GT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRnaseP Probe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFAM-TTC TGA CCT GAA GGC TCT GCG CG-BBQ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDue to acute kidney injury complicated by lactic acidosis and oliguria, continuous veno-venous hemofiltration (March 26\u0026ndash;30), sustained low-efficiency dialysis (March 31\u0026ndash;April 14), and hemodialysis (April 16\u0026ndash;May 2) were performed. Plasma exchange was also administered due to acute liver failure and suspected thrombotic microangiopathy (March 31\u0026ndash;April 9).\u003c/p\u003e\u003cp\u003eDespite initial parasitic clearance, malaria recrudesced in mid-April, evidenced by fever and anemia, with a platelet count of 48,000/\u0026micro;L and hemoglobin at 6.5 g/dL. Blood smears on April 25 revealed the presence of \u003cem\u003eP. falciparum\u003c/em\u003e ring forms, trophozoites, schizonts, and gametocytes, including both a macrogametocyte (female) and a microgametocyte (male), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC\u0026ndash;F. A blood sample (sample 2, S2) was also submitted to the Taiwan CDC for real-time PCR testing, which again confirmed \u003cem\u003eP. falciparum\u003c/em\u003e mono-infection without evidence of mixed-species involvement (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), further supporting the diagnosis of recrudescence. Given concerns about drug resistance [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], alterations in pharmacokinetics due to dialysis and plasma exchange, and lack of intravenous quinine availability in Taiwan, the therapeutic regimen was adjusted according to international guidelines. The patient received intravenous artesunate (168 mg at 0, 12, and 24 hours, then daily), combined with oral doxycycline (100 mg twice daily) and intravenous clindamycin (900 mg every 8 hours) from April 25\u0026ndash;May 1 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Subsequent therapy included oral artemether/lumefantrine (May 2\u0026ndash;5) alongside doxycycline and clindamycin. Parasitemia was cleared successfully by May 6, with no relapse or clinical recurrence observed over a subsequent six-week follow-up, demonstrating effective and stable therapeutic outcomes.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAccording to international guidelines, high parasitemia is a key criterion for severe \u003cem\u003eP. falciparum\u003c/em\u003e malaria. The WHO considers parasitemia\u0026thinsp;\u0026gt;\u0026thinsp;2% significant in non-immune individuals [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], whereas the U.S. CDC defines severe malaria as parasitemia\u0026thinsp;\u0026ge;\u0026thinsp;5% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] or the presence of one or more clinical features, including impaired consciousness, prostration, multiple convulsions, acidosis, hypoglycemia, severe anemia (hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;7 g/dL), acute kidney injury, jaundice (with at least one other severe feature), pulmonary edema or acute respiratory distress syndrome, abnormal bleeding or disseminated intravascular coagulation, and circulatory collapse or shock [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this case, the patient exhibited a parasitemia level exceeding 20%, accompanied by acute hepatic and renal failure, respiratory failure, and impaired consciousness\u0026mdash;fulfilling the diagnostic criteria for severe malaria.\u003c/p\u003e\u003cp\u003eAccording to Yadav et al., among 59 patients with \u003cem\u003eP. falciparum\u003c/em\u003e infection, 57 (96.6%) had thrombocytopenia and 48 (81.4%) had anemia [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Similarly, Elkhalifa et al. reported that among 192 patients, 72.4% exhibited thrombocytopenia and 60.4% had anemia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, direct data on patients presenting with thrombocytopenia in the absence of anemia were not available in the reviewed literature. Notably, our patient initially presented with profound thrombocytopenia (platelet count\u0026thinsp;\u0026lt;\u0026thinsp;10,000/\u0026micro;L) while maintaining a normal hemoglobin level (15 g/dL), representing a rare manifestation of \u003cem\u003eP. falciparum\u003c/em\u003e infection. At recrudescence, however, the patient developed both thrombocytopenia (platelet count 48,000/\u0026micro;L) and marked anemia (hemoglobin 6.5 g/dL), consistent with the typical findings reported in the literature.\u003c/p\u003e\u003cp\u003eRecrudescence of \u003cem\u003eP. falciparum\u003c/em\u003e refers to the recurrence of symptoms due to incomplete parasite clearance after initial infection, with a small number of parasites persisting and proliferating in the bloodstream weeks to months later. This often results from inadequate therapy or suboptimal drug concentrations. Erythrocytes infected with mature trophozoites and schizonts develop knob-like structures and express PfEMP1, which binds to adhesion molecules on postcapillary venule endothelium, enabling schizonts to mature within the deep microvasculature\u0026mdash;a process known as deep-vascular schizogony or sequestration, and a key mechanism underlying recrudescence. [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Clinically, the presence of mature schizonts in peripheral blood indicates a critical stage of illness [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]; however, the level of parasitemia observed in peripheral blood often underestimates the true severity of infection in \u003cem\u003eP. falciparum\u003c/em\u003e malaria, and severe disease cannot be ruled out even when parasitemia is not high [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this case, although mature schizonts were not initially observed on peripheral smears, the patient rapidly progressed to multi-organ failure, later exhibiting both mature schizonts and high parasitemia, which confirmed disease deterioration and the mechanism of recrudescence. This highlights the necessity of integrating clinical findings with microscopy results for accurate assessment.\u003c/p\u003e\u003cp\u003eAccording to data from the Taiwan CDC, sixteen imported cases of \u003cem\u003eP. falciparum\u003c/em\u003e malaria were reported in Taiwan between 2020 and 2025, including two fatalities. Notably, the present case was the only one to develop clinical recrudescence following treatment, underscoring the exceptional rarity of such an event in Taiwan. During the same period, there were nine cases of \u003cem\u003eP. vivax\u003c/em\u003e malaria (including two relapses), one case of \u003cem\u003eP. malariae\u003c/em\u003e, one case of \u003cem\u003eP. ovale\u003c/em\u003e, and one case of mixed \u003cem\u003eP. falciparum\u003c/em\u003e and \u003cem\u003eP. vivax\u003c/em\u003e infection [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. At admission, this patient already presented with acute kidney injury, lactic acidosis, and oliguria, requiring continuous veno-venous hemofiltration, sustained low-efficiency dialysis, and hemodialysis. Due to acute liver failure and suspected microvascular thrombosis, multiple sessions of plasma exchange were also performed to mitigate organ damage. Although initial therapy resulted in parasite clearance, clinical recrudescence developed. Possible causes include incomplete clearance of blood-stage parasites during initial therapy, sequestration of schizonts within the deep microvasculature (not detectable on peripheral smear), decreased drug concentrations due to poor absorption, concurrent dialysis and plasma exchange, or the presence of drug-resistant parasites [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In accordance with World Health Organization guidelines, artesunate in combination with antibiotics was used for seven days, along with renal and hepatic replacement therapies for supportive care. This case demonstrated severe manifestations and is the first documented instance of recrudescent \u003cem\u003eP. falciparum\u003c/em\u003e malaria in Taiwan following standard therapy, highlighting its clinical uniqueness and management challenges. It underscores the need for vigilance regarding multi-organ complications and the risk of recrudescence in severe malaria.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case demonstrates that even with prompt, guideline-adherent therapy, severe \u003cem\u003eP. falciparum\u003c/em\u003e malaria in non-immune individuals can be complicated by recrudescence\u0026mdash;particularly when multiple organ failure and interventions such as plasma exchange may influence drug pharmacokinetics and treatment efficacy. It also underscores the necessity for heightened clinical vigilance, close laboratory monitoring, and interdisciplinary care when treating severe imported malaria with multi-organ involvement. Reporting such rare recrudescent cases is crucial for improving clinical awareness, refining treatment protocols, and informing public health preparedness in settings with low malaria incidence.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eWHO World Health Organization\u003c/p\u003e\u003cp\u003eU.S. CDC United States Centers for Disease Control and Prevention\u003c/p\u003e\u003cp\u003eTaiwan CDC Taiwan Centers for Disease Control\u003c/p\u003e\u003cp\u003ePan Pan-Plasmodium\u003c/p\u003e\u003cp\u003eIC internal control\u003c/p\u003e\u003cp\u003eCt cycle threshold\u003c/p\u003e\u003cp\u003e\u003cem\u003eP.f\u003c/em\u003e. \u003cem\u003eP. falciparum\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eP.v P. vivax\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eP.m P. malariae\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eP.o. P. ovale\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eP.k. P. knowlesi\u003c/em\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYCT and MYC contributed to the conception and design of the study. SFH, JJH, and YCS were responsible for data acquisition. YCT, MYC, CTH, and PRH analyzed and/or interpreted the data. YCT, MYC, and PBL drafted the manuscript. MWH, CTH, and PRH critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the China Medical University Hospital and Taiwan Centers for Disease Control without grant funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe need for ethical approval was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore preparing the case report, the patient provided written informed consent to write the case and be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Fang-Tzy Wu from Taiwan Centers for Disease Control for critical comments on the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Laboratory Medicine, China Medical University Hospital, Taichung, China Medical University, Taiwan. \u003csup\u003e2\u003c/sup\u003eDivision of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. \u003csup\u003e3\u003c/sup\u003eDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, China Medical University, Taiwan.\u003csup\u003e4\u003c/sup\u003eDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u0026apos;s Disease Research Center, Washington University in St. Louis, Missouri, United States.\u003csup\u003e5\u003c/sup\u003eTaiwan Centers for Disease Control, Taipei City, Taiwan.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. 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Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376:1647-57.\u003c/li\u003e\n\u003cli\u003eYadav RK, Kumar S. To study hematological profile in malaria patients. Int J Adv Med. 2017;4:707-12.\u003c/li\u003e\n\u003cli\u003eElkhalifa AME, Abdul-Ghani R, Tamomh AG, Eltaher NE, Ali NY, Ali MM, et al. Hematological indices and abnormalities among patients with uncomplicated falciparum malaria in Kosti city of the White Nile state, Sudan: a comparative study. BMC Infect Dis. 2021;21:507.\u003c/li\u003e\n\u003cli\u003eTaiwan Centers for Disease Control. Malaria. Taipei: Taiwan Centers for Disease Control; 2025. https://www.cdc.gov.tw/File/Get/3f3ua7S2RYlrceZhD286yw.\u003c/li\u003e\n\u003cli\u003eDondorp AM, Nyanoti M, Kager PA, Mithwani S, Vreeken J, Marsh K. The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion. Trans R Soc Trop Med Hyg. 2002;96:282-6.\u003c/li\u003e\n\u003cli\u003eSmith JD. The role of PfEMP1 adhesion domain classification in \u003cem\u003ePlasmodium falciparum\u003c/em\u003e pathogenesis research. Mol Biochem Parasitol. 2014;195:82-7.\u003c/li\u003e\n\u003cli\u003eChan JA, Stanisic DI, Duffy MF, Robinson LJ, Lin E, Kazura JW, et al. Patterns of protective associations differ for antibodies to \u003cem\u003eP. falciparum\u003c/em\u003e-infected erythrocytes and merozoites in immunity against malaria in children. Eur J Immunol. 2017;47:2124-36.\u003c/li\u003e\n\u003cli\u003eLasonder E, Green JL, Grainger M, Langsley G, Holder AA. Extensive differential protein phosphorylation as intraerythrocytic \u003cem\u003ePlasmodium falciparum\u003c/em\u003e schizonts develop into extracellular invasive merozoites. Proteomics. 2015;15:2716-29.\u003c/li\u003e\n\u003cli\u003eDaily JP, Minuti A, Khan N. Diagnosis, treatment, and prevention of Malaria in the US: a review. JAMA. 2022;328:460-71.\u003c/li\u003e\n\u003cli\u003eTaiwan Centers for Disease Control. Statistical data on confirmed cases of legally designated infectious diseases imported from abroad. Taipei: Taiwan Centers for Disease Control; 2025. https://www.cdc.gov.tw/Category/Page/5Q6qrh5kM6TnpnRpy3XDfQ.\u003c/li\u003e\n\u003cli\u003eLin J, Huang X, Qin G, Zhang S, Sun W, Wang Y, et al. Manual exchange transfusion for severe imported falciparum malaria: a retrospective study. Malar J. 2018;17:32.\u003c/li\u003e\n\u003cli\u003eZaw MT, Lin Z, Emran NA. Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in \u003cem\u003ePlasmodium falciparum\u003c/em\u003e in Greater Mekong Subregion. J Microbiol Immunol Infect. 2020;53:676-81.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Recrudescence, Malaria, Plasmodium falciparum, Schizont, Plasma exchange therapy","lastPublishedDoi":"10.21203/rs.3.rs-7000518/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7000518/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSevere malaria caused by \u003cem\u003ePlasmodium falciparum\u003c/em\u003e remains a life-threatening disease, particularly in non-immune individuals returning from endemic regions. While prompt treatment can usually achieve parasite clearance, recrudescence after initial recovery is rare and presents unique diagnostic and management challenges. This report documents a case of recrudescent severe malaria in a Taiwanese traveler, highlighting clinical complexities related to organ support and altered drug pharmacokinetics.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e\u003cp\u003eA previously healthy 66-year-old Taiwanese man developed fever, vomiting, diarrhea, and jaundice shortly after returning from multiple Central African countries with high malaria prevalence. His condition rapidly deteriorated to multi-organ failure, including acute kidney injury, liver failure, thrombocytopenia, and respiratory distress. Blood smear microscopy revealed a high parasitemia (20%) due to \u003cem\u003eP. falciparum\u003c/em\u003e, which was confirmed by real-time PCR.\u003c/p\u003e\u003ch2\u003eManagement and outcome\u003c/h2\u003e\u003cp\u003eThe patient received intravenous artesunate and oral artemether-lumefantrine, in addition to hemodialysis and plasma exchange as supportive therapies. Initial treatment achieved parasite clearance and clinical improvement. However, four weeks later, the patient experienced recrudescence with recurrent fever, anemia, and return of parasitemia. The therapeutic regimen was then revised to intravenous artesunate combined with doxycycline and clindamycin, followed by oral artemether-lumefantrine. This approach led to successful parasite clearance within two weeks and complete recovery, with no further recurrence observed during follow-up.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis case highlights that even with prompt, guideline-based therapy, severe \u003cem\u003eP. falciparum\u003c/em\u003e malaria in non-immune individuals can relapse, especially when organ failure and interventions such as plasma exchange may alter drug efficacy. Enhanced clinical vigilance, laboratory monitoring, and multidisciplinary care are essential for management. Reporting such rare recrudescent cases supports clinical awareness, informs best practice, and strengthens public health preparedness in low-incidence regions.\u003c/p\u003e","manuscriptTitle":"Recrudescent severe malaria due to Plasmodium falciparum following treatment in a Taiwanese patient: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-10 12:48:53","doi":"10.21203/rs.3.rs-7000518/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-24T02:02:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-18T03:22:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-15T07:12:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-12T14:28:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157427178559976501178874609313481923519","date":"2025-07-10T10:01:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236159330486608880881650336888686850719","date":"2025-07-10T05:32:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-08T14:46:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182744998791734939844380388696255662081","date":"2025-07-08T08:04:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333639211951653352146473629828272371014","date":"2025-07-08T07:42:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204008548957325600923670333919606296226","date":"2025-07-08T01:10:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-08T00:59:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-30T07:52:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-30T07:51:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2025-06-29T03:41:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e0f2e1c-e4e8-4968-b746-251d81bd4e17","owner":[],"postedDate":"July 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-13T15:59:57+00:00","versionOfRecord":{"articleIdentity":"rs-7000518","link":"https://doi.org/10.1186/s12936-025-05581-6","journal":{"identity":"malaria-journal","isVorOnly":false,"title":"Malaria Journal"},"publishedOn":"2025-10-09 15:57:16","publishedOnDateReadable":"October 9th, 2025"},"versionCreatedAt":"2025-07-10 12:48:53","video":"","vorDoi":"10.1186/s12936-025-05581-6","vorDoiUrl":"https://doi.org/10.1186/s12936-025-05581-6","workflowStages":[]},"version":"v1","identity":"rs-7000518","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7000518","identity":"rs-7000518","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}