{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:14:46Z","timestamp":1774066486650,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Outcome of falciparum malaria is largely influenced by the standard of care provided, which in turn depends on the available medical resources. Worldwide, the COVID-19 pandemic has had a major impact on the availability of these resources, even in resource-rich healthcare systems such as Germany\u2019s. The present study aimed to determine the under-explored factors associated with hospital length of stay (LOS) in imported falciparum malaria to identify potential targets for improving management. This retrospective observational study used multivariate Cox proportional hazard regression with time to discharge as an endpoint for adults hospitalized between 2001 and 2015 with imported falciparum malaria in the Charit\u00e9 University Hospital, Berlin. The median LOS of the 535 cases enrolled was 3 days (inter-quartile range, IQR, 3\u20134 days). The likelihood of being discharged by day 3 strongly decreased with severe malaria (hazard ratio, HR, 0.274; 95% Confidence interval, 95%CI: 0.190\u20130.396) and by 40% with each additional presenting complication (HR, 0.595; 95%CI: 0.510\u20130.694). The 55 (10.3%) severe cases required a median LOS of 7 days (IQR, 5\u201312 days). In multivariate analysis, occurrence of shock (adjusted HR, aHR, 0.438; 95%CI 0.220\u20130.873), acute pulmonary oedema or acute respiratory distress syndrome (aHR, 0.450; 95%CI: 0.223\u20130.874), and the need for renal replacement therapy (aHR, 0.170; 95%CI: 0.063\u20130.461) were independently associated with LOS. All patients survived to discharge. This study illustrates that favourable outcomes can be achieved with high-standard care in imported falciparum malaria. Early recognition of disease severity together with targeted supportive care can lead to avoidance of manifest organ failure, thereby potentially decreasing LOS and alleviating pressure on bed capacities.<\/jats:p>","DOI":"10.3390\/microorganisms9091941","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Factors Associated with Prolonged Hospital Length of Stay in Adults with Imported Falciparum Malaria\u2014An Observational Study from a Tertiary Care University Hospital in Berlin, Germany"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8277-8948","authenticated-orcid":false,"given":"Bodo","family":"Hoffmeister","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Clinic-Group Ernst von Bergmann, Potsdam and Bad Belzig, 14806 Bad Belzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nm.3073","article-title":"Malaria biology and disease pathogenesis: Insights for new treatments","volume":"19","author":"Miller","year":"2013","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.pt.2016.11.004","article-title":"EPCR and Malaria Severity: The Center of a Perfect Storm","volume":"33","author":"Bernabeu","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_3","unstructured":"WHO (2014). Guidelines for the Treatment of Malaria, WHO. [3rd ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(05)67176-0","article-title":"Artesunate versus quinine for treatment of severe falciparum malaria: A randomised trial","volume":"366","author":"Dondorp","year":"2005","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1086\/589287","article-title":"The relationship between age and the manifestations of and mortality associated with severe malaria","volume":"47","author":"Dondorp","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/cid\/ciy211","article-title":"A competing-risk approach for modeling length of stay in severe malaria patients in South-East Asia and the implications for planning of hospital services","volume":"67","author":"Keene","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/infdis\/jiz449","article-title":"Associations between restrictive fluid management and renal function and tissue perfusion in adults with severe falciparum malaria: A prospective observational study","volume":"221","author":"Ishioka","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12936-016-1673-z","article-title":"Severe malaria in Europe: An 8-year multi-centre observational study","volume":"16","author":"Kurth","year":"2017","journal-title":"Malar J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13613-020-0634-4","article-title":"Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017","volume":"10","author":"Lebut","year":"2020","journal-title":"Ann. Intensive Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1086\/597258","article-title":"Risk factors for severe disease in adults with falciparum malaria","volume":"48","author":"Phillips","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/S0140-6736(21)00768-6","article-title":"Effects of nurse-to-patient ratio legislation on nurse stuffing and patient mortality, readmissions, and length of stay: A prospective study in a panel of hospitals","volume":"397","author":"McHugh","year":"2021","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1056\/NEJMsb2021088","article-title":"Covid-19-Implications for the helath care system","volume":"383","author":"Blumenthal","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1056\/NEJMsb2005114","article-title":"Fair allocation of scarce medical resources in the time of Covid-19","volume":"382","author":"Emanuel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_14","first-page":"27","article-title":"Impact of the COVID-19 pandemic and associated non-pharmaceutical interventions on other notifiable infectious diseases in Germany: An analysis of national surveillance data during week 1-2016-week-32-2020","volume":"15","author":"Ullrich","year":"2021","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.jclinepi.2004.03.012","article-title":"New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality","volume":"57","author":"Sundararajan","year":"2004","journal-title":"J. Clin. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1186\/s12936-019-3007-4","article-title":"Hypertension is associated with an increased risk for severe imported falciparum malaria: A tertiary care hospital based observational study from Berlin, Germany","volume":"18","author":"Hoffmeister","year":"2019","journal-title":"Malar. J."},{"key":"ref_17","first-page":"2526","article-title":"Acute respiratory distress syndrome: The Berlin Definition","volume":"307","author":"Ranieri","year":"2012","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/trstmh\/trab027","article-title":"\u2018Run the dry\u2019: A retrospective experience with a restrictive fluid management strategy in severe imported falciparum malaria from a tertiary care university hospital in Berlin, Germany","volume":"115","author":"Hoffmeister","year":"2021","journal-title":"Trans. R. Soc Trop. Med. Hyg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Verburg, I.W.M., de Keizer, N.F., de Jonge, E., and Peek, N. (2014). Comparison of regresson methods for modeling intensive care length of stay. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109684"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thabane, L., Mbuagbaw, L., Zhang, S., Samaan, Z., Marcucci, M., Ye, C., Thabane, M., Giangregorio, L., Dennis, B., and Kosa, D. (2013). A tutorial on sensitivity analyses in clinical trials: The what, why, when and how. BMC Med. Res. Metodol., 13.","DOI":"10.1186\/1471-2288-13-92"},{"key":"ref_21","first-page":"431","article-title":"Variable selection\u2014A review and recommendations for the practicing statistician","volume":"60","author":"Heinze","year":"2017","journal-title":"Biomed. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.21037\/atm.2016.03.35","article-title":"Variable selection with stepwise and best subset approaches","volume":"4","author":"Zhang","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1086\/523762","article-title":"Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria","volume":"197","author":"Dondorp","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nm986","article-title":"Differentiating the pathologies of cerebral malaria by postmortem parasite counts","volume":"10","author":"Taylor","year":"2004","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1086\/649928","article-title":"A simple score to predict the outcome of severe malaria in adults","volume":"50","author":"Hanson","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1146\/annurev-pathmechdis-012419-032640","article-title":"New insights into malaria pathogenesis","volume":"15","author":"Moxon","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Plewes, K., Kingston, H.W.F., Ghose, A., Maude, R.J., Herdman, M.T., Leopold, S.J., Ishioka, H., Hasan, M.U., Haider, S., and Alam, S. (2017). Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: An observational study. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2373-1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/QCO.0000000000000419","article-title":"Pathophysiology, clinical presentation, and treatment of coma and acute kidney injury complicating falciparum malaria","volume":"31","author":"Plewes","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/clind\/15.5.874","article-title":"Acute renal failure in patients with severe falciparum malaria","volume":"15","author":"Trang","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17097","DOI":"10.1073\/pnas.0805782105","article-title":"Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria","volume":"105","author":"Yeo","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/infdis\/jit419","article-title":"Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children","volume":"209","author":"Moxon","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1097\/CCM.0b013e31827466d2","article-title":"Fluid resuscitation of adults with severe falciparum malaria: Effects on Acid-base status, renal function, and extravascular lung water","volume":"41","author":"Hanson","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1378\/chest.11-2655","article-title":"Respiratory manifestations of malaria","volume":"142","author":"Taylor","year":"2012","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1186\/s12936-016-1577-y","article-title":"The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles","volume":"15","author":"Marelli","year":"2016","journal-title":"Malar. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/cc7100","article-title":"Clinical review: Critical illness polyneuropathy and myopathy","volume":"12","author":"Hermans","year":"2008","journal-title":"Crit. Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e030793","DOI":"10.1136\/bmjopen-2019-030793","article-title":"Prognostic models for the clinical management of malaria and its complications: A systematic review","volume":"9","author":"Njim","year":"2019","journal-title":"BMJ Open"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1093\/cid\/cix437","article-title":"Obesity and diabetes as risk factors for severe Plasmodium falciparum malaria: Results from a Swedish nationwide study","volume":"65","author":"Wyss","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.tmaid.2014.04.014","article-title":"Risk factors associated with malaria deaths in travellers: A literature review","volume":"13","author":"Luthi","year":"2015","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/cid\/civ575","article-title":"Intravenous artesunate reduces parasite clearance time, duration of intensive care, and hospital treatment in patients with severe malaria in Europe: The TropNet Severe Malaria study","volume":"61","author":"Kurth","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/1475-2875-10-217","article-title":"Laboratory prediction of the requirement for renal replacement in acute falciparum malaria","volume":"10","author":"Hanson","year":"2011","journal-title":"Malar. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"The National Heart, Lung, and Blood Institute Acute respiratory Distress Syndrom (ARDS) Clinical trials Network (2006). Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med., 354, 2564\u20132575.","DOI":"10.1056\/NEJMoa062200"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1164\/rccm.201606-1306OC","article-title":"Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study","volume":"195","author":"Bellani","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Graca, L.A., Gomez Abreu, I., Santos, A.S., Graca, L., Dias, P.F., and Santos, M.L. (2020). Descriptive acute respiratory distress syndrome (ARDS) in adults with imported severe Plasmodium falciparum malaria: A 10 year-study in a Portuguese tertiary care hospital. 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