Malaria grave en unidad de cuidados intensivos: Reporte de un caso de una especie no endémica en Norte de Santander, Colombia

Introduction: Malaria is a vector-borne infectious disease which is predominant in tropical and subtropical regions. There are 5 serotypes of Plasmodium, in Colombia there are two serotypes for endemic malaria, P. vivax and P. falciparum. North of Santander is an endemic area for P. vivax. Objective: To show a case of severe malaria caused by P. falciparum, with a brief description of the pathophysiological aspects of severe malaria and the advent of new antimalarial therapies. Case Presentation: A 45-year-old male patient from an endemic region with P. falciparum, who was admitted due to nonspecific febrile symptoms, severe thrombocytopenia, impaired renal and hepatic functions with deterioration of his general condition. He is transferred to the intensive care unit as a dialytic urgency. Severe malaria due to P. falciparum was diagnosed, he is treated with antimalarial medication, and a possible coinfection is reported for the dengue virus due to a positive immunoglobulin M (IgM) result, so he receives a renal replacement therapy. The case is contextualized in a vicious circle of organ dysfunction, which is structured between renal failure and acute respiratory failure with an increased vascular permeability and refractory hypoxemia; despite the therapeutic effort, the patient dies due to multiple organ failures, and severe malaria. Conclusions: Malaria is a problem in the public health area. This case corresponds to imported malaria because this serotype has not been identified yet in the department of North of Santander. [Ortiz-Ruiz G, Urbina-Contreras ZE, Lamos-Duarte AF, Ferreira MF, García-Zambrano F. Severe Malaria in the Intensive Care Unit: The report of a Case of a Non-Endemic Species in North of Santander, Colombia. MedUNAB 2017-2018; 20(3): 383-392].Introducción: La malaria es una enfermedad infecciosa vectorial de predominio en regiones tropicales y subtropicales. Existen 5 serotipos de Plasmodium, en Colombia se encuentran dos serotipos para malaria endémica, P. vivax y P. falciparum. Norte de Santander es una zona endémica para P. vivax. Objetivo: Presentación de un caso de  malaria grave importada por P. falciparum, con una breve descripción de los aspectos fisiopatológicos de la malaria grave y los advenimientos de las nuevas terapias antipalúdicas. Presentación del caso: Paciente masculino de 45 años procedente de una región endémica para P. falciparum, que ingresó por cuadro febril inespecífico, trombocitopenia severa, alteración de la función renal y hepática con deterioro de su estado general. Es trasladado a la unidad de cuidados intensivos como urgencia dialítica, se diagnóstica malaria grave por P. falciparum, es tratado con antimaláricos y se reporta posible coinfección para el virus del dengue por inmunoglobulina M positiva (IgM), recibe terapia de reemplazo renal. Se contextualiza bajo un círculo vicioso en la disfunción de órganos, estructurado entre la insuficiencia renal y la insuficiencia respiratoria aguda con incremento de la permeabilidad vascular e hipoxemia refractaria, pese al esfuerzo terapéutico fallece por falla orgánica múltiple, por malaria grave. Conclusiones: La malaria es un problema en el área de salud pública, en nuestro caso corresponde a una malaria importada ya que en el departamento de Norte de Santander no se ha identificado dicho serotipo. [Ortiz-Ruiz G, Urbina-Contreras ZE, Lamos-Duarte AF, Ferreira MF, García-Zambrano F. Malaria grave en unidad de cuidados intensivos: Reporte de un caso de una especie no endémica en Norte de Santander, Colombia. MedUNAB 2017-2018; 20(3): 383-392]

Laboratory prediction of the requirement for renal replacement in acute falciparum malaria

BACKGROUND: Acute renal failure is a common complication of severe malaria in adults, and without renal replacement therapy (RRT), it carries a poor prognosis. Even when RRT is available, delaying its initiation may increase mortality. Earlier identification of patients who will need RRT may improve outcomes. METHOD: Prospectively collected data from two intervention studies in adults with severe malaria were analysed focusing on laboratory features on presentation and their association with a later requirement for RRT. In particular, laboratory indices of acute tubular necrosis (ATN) and acute kidney injury (AKI) that are used in other settings were examined. RESULTS: Data from 163 patients were available for analysis. Whether or not the patients should have received RRT (a retrospective assessment determined by three independent reviewers) was used as the reference. Forty-three (26.4%) patients met criteria for dialysis, but only 19 (44.2%) were able to receive this intervention due to the limited availability of RRT. Patients with impaired renal function on admission (creatinine clearance < 60 ml/min) (n = 84) had their laboratory indices of ATN/AKI analysed. The plasma creatinine level had the greatest area under the ROC curve (AUC): 0.83 (95% confidence interval 0.74-0.92), significantly better than the AUCs for, urinary sodium level, the urea to creatinine ratio (UCR), the fractional excretion of urea (FeUN) and the urinary neutrophil gelatinase-associated lipocalcin (NGAL) level. The AUC for plasma creatinine was also greater than the AUC for blood urea nitrogen level, the fractional excretion of sodium (FeNa), the renal failure index (RFI), the urinary osmolality, the urine to plasma creatinine ratio (UPCR) and the creatinine clearance, although the difference for these variables did not reach statistical significance. CONCLUSIONS: In adult patients with severe malaria and impaired renal function on admission, none of the evaluated laboratory indices was superior to the plasma creatinine level when used to predict a later requirement for renal replacement therapy

Heme Mediated STAT3 Activation in Severe Malaria

The mortality of severe malaria [cerebral malaria (CM), severe malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)] remains high despite the availability associated with adequate treatments. Recent studies in our laboratory and others have revealed a hitherto unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3 interactions are directly involved in the pathogenesis of CM and fatal disease, the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and regulated under these conditions is still unknown. We therefore tested the hypothesis that these factors share common signaling pathways and may be mutually regulated.We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and STAT3 in CM pathogenesis utilizing a well established experimental cerebral malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among them in CRL-2581, a murine endothelial cell line.The results demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO-1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3 signaling.Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3 molecules as well as related signaling pathways play very important roles in the pathogenesis of severe malaria. We conclude that these factors are mutually regulated and provide new opportunities to develop potential novel therapeutic targets that could be used to supplement traditional prophylactics and treatments for malaria and improve clinical outcomes while reducing malaria mortality. Our ultimate goal is to develop novel therapies targeting Heme or CXCL10-related biological signaling molecules associated with development of fatal malaria

Joseph Franz Barwirsch levele Lukács Györgynek

_Background:_ Acute kidney injury (AKI) is a frequently encountered complication of imported Plasmodium falciparum infection. Markers of structural kidney damage have been found to detect AKI earlier than serum creatinine-based prediction models but have not yet been evaluated in imported malaria. This pilot study aims to explore the predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with imported P. falciparum infection. _Methods:_ Thirty-nine patients with imported falciparum malaria from the Rotterdam Malaria Cohort with available serum and urine samples at presentation were included. Ten of these patients met the criteria for severe malaria. The predictive performance of NGAL and KIM-1 as markers for AKI was compared with that of serum creatinine. _Results:_ Six of the 39 patients (15 %) developed AKI. Serum and urine NGAL and urine KIM-1 were all found to have large areas under the receiver operating characteristics curves (AUROC) for predicting AKI. Urine NGAL was found to have an excellent performance with positive predictive value (PPV) of 1.00 (95 % CI 0.54-1.00), a negative predictive value (NPV) of 1.00 (95 % CI 0.89-1.00) and an AUROC of 1.00 (95 % CI 1.00-1.00). _Conclusion:_ A good diagnostic performance of NGAL and KIM-1 for AKI was found. Particularly, urine NGAL was found to have an excellent predictive performance. Larger studies are needed to demonstrate whether these biomarkers are superior to serum creatinine as predictors for AKI in P. falciparum malaria