Treatment of a patient with severe cerebral malaria during the COVID-19 pandemic in China:A case report

BACKGROUND On June 30,2021,China received certification from the World Health Organization for malaria elimination.However,this certification does not signify the absence of malaria within China.Due to the increasing frequency of international exchanges and collaborations,the threat of imported malaria persists in China.Consequently,the prevention and control of imported malaria have become a primary focus for our country to maintain its malaria elimination status.CASE SUMMARY Herein,we present a case report of a 53-year-old Chinese man who worked in Africa for nearly two years.He was diagnosed with malaria in the Democratic Republic of the Congo between November 19 and November 23,2022.After receiving effective treatment with oral antimalarial drugs,his condition improved,allowing him to return to China.He was later admitted to our hospital on January 12,2023,during the coronavirus disease 2019 pandemic in Huangshi,China.Through a thorough evaluation of the patient's symptoms,clinical signs,imaging and laboratory test results,and epidemiological data,he was rapidly diagnosed with severe cerebral malaria.The patient underwent successful treatment through a series of intensive care unit interventions.CONCLUSION The successful treatment of this imported case of severe cerebral malaria provides a valuable reference for managing patients with similar malaria infections and has significant clinical implications.

Cerebral Malaria: Epidemiological, Clinical and Prognosis Aspects in the Anesthesia-Resuscitation Department CHU Ignace Deen

Objective: To describe the epidemiological, clinical, paraclinical and prognostic aspects of cerebral malaria received in the anesthesia-resuscitation department. Methodology: This was a prospective descriptive type study carried out in the anesthesia-resuscitation department over a period of three (03) months (June 01 to August 31, 2022). All patients admitted for cerebral malaria were included. Sociodemographic, clinical and prognostic parameters were studied. Results: We collected 25 cases out of 105 admitted patients (23.8%). The average age was 27.6 ± 9.5 years with extremes of 11 and 50 years. The sex ratio was 0.7 (M/F). Students and housewives were in the majority, i.e. 52% and 24%. Neurological disorders were found on admission in all patients, dominated by impaired consciousness at 100% followed by convulsion (60%), prostration (44%), confusion (36%) associated with deep coma in (68%). Gross hemoglobinuria was present in (84%) of cases. On the blood count, anemia was present in (70%) of the patients followed by thrombocytopenia in more than half of the cases (60%) and transfusion was necessary in 19 cases. P Falciparum malaria was found in all patients (100%), the average parasite density was 60342.8 ± 30425.6 trophozoites/μl with extremes of 9000 to 100000 trophozoites/μl. All our patients were treated with intravenous injectable artesunate. Transfusion was performed in 76% of our patients. Eighty percent of the patients had benefited from dialysis. High oxygen therapy was performed in (92%) of cases. The average duration of hospitalization was 5.74 ± days with extremes of 1 to 17 days. Mortality was 48%. Conclusion: Cerebral malaria can take different clinical forms, the most important of which is cerebral involvement. Prompt initiation of appropriate resuscitation can reduce mortality.

Interest of Procalcitonin Measurement in Children with Cerebral Malaria in Southern Benin

Introduction: Cerebral malaria is a major complication of the Plasmodium falciparum infection with a high case fatality rate. The objective of this study was to determine the relationship between cerebral malaria and high serum procalcitonin (PCT) level in children. Method: This was a prospective descriptive and analytical cohort study conducted over 12 months, on a series of PCT blood tests in children aged 6 months to 15 years old hospitalized for cerebral malaria in the pediatric wards of four hospitals in southern Benin. The cerebral malaria diagnosis was done based on WHO criteria. Blood samples for PCT measurement were collected on admission, 24 hours and 48 hours after the malaria therapy initiation. Student’s test, Pearson’s chi2 test, Fisher’s test and Kruskal-Wallis test were used where appropriate. For all comparisons the difference was significant when p was less than 5%. Results: Sixty-five children were included in the study with a sex ratio of 1.41. The age group of children under 5 years was the most represented, at 57%. PCT levels were high in 92.3% of children at admission, 90.8% at 24 hours and 84.6% at 48 hours. Forty-nine children had a positive clinical outcome while 16 died (24.6%). PCT levels were generally high over the three days of hospitalization, but higher at admission in case of death (p = 0.000). The association between PCT level and parasitemia at admission was significant (p = 0.04). Conclusion: In the view of the results, blood PCT level measured at admission could be predictive of the disease outcome in children with cerebral malaria.

Interferon-induced protein with tetratricopeptide repeats 1(IFIT1) polymorphism as a genetic marker of cerebral malaria in Thai population

Objective:To know whether the effect of interferon-induced protein with tetratricopeptide repeats(IFIT)1 polymorphism influences the susceptibility of cerebral malaria outcome.Methods:Case-control association study was performed among 314 Thai patients(110 with cerebral malaria and 204 with uncomplicated malaria)infected with Plasmodium falciparum.Genotyping for five tag-single nucleotide polymorphisms of IFIT1 was performed by endpoint genotyping.Results:Genotype frequencies of all tag-SNPs(single nucleotide polymorphisms)showed no association with malaria outcome.However,C allele of rs11203109 was associated with the protection from cerebral malaria(OR=0.62,95%CI=0.38-0.99,P=0.048).Two single nucleotide polymorphisms(rs5786868 and rs57941432)were in linkage disequilibrium with rs11203109.Conclusions:This suggests that our associated single nucleotide polymorphism(rs11203109)might be a genetic marker of cerebral malaria progression in the Thai population.

The Relationship between the Plasmodium Falciparum Clearance and the Clinical Effect of the Case with Cerebral Malaria Treated with Artemisinin

Malaria is 1 mosquito-borne disease,which is most commonly caused by a parasite called Plasmodium falciparum(P.falciparum).Cerebral malaria is the most severe neurological complication presented in

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria

Background Cerebral malaria(CM)is a neuropathology which remains one of the deadliest forms of malaria among African children.The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood.The increasing production of cytokines,chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM,participating in both the amplification of the neuroinflammation phenomenon and its resolution.In this study,we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis.Methods Children presenting with CM(n=70)due to P.falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died.Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients'cerebrospinal fluid to rule out coinfections.Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels,respectively.Data were analysed by univariate analysis using the nonparametric Mann-Whitney U test and Pearson’s Chi2 test.Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors.Results Univariate analysis revealed higher plasma levels of tumour necrosis factor(TNF),interleukin-1beta(IL-1β),IL-10,IL-8,C-X-C motif chemokine ligand 9(CXCL9),granzyme B,and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite(PGEM)in children who died compared to those who survived CM(Mann-Whitney U-test,P-values between 0.03 and<0.0001).The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM(adjusted odd ratio=14.2,P-value=0.002).Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution,including plasma CXCL5,C-C motif chemokine ligand 17(CCL17),CCL22,and urinary 15-F2t-isoprostane.Conclusions The main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion.Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation,endothelium activation and damage,inflammatory and oxidative response.These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria

Cerebral malaria(CM)is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum,in which the destruction of the blood–brain barrier(BBB)is the main cause of death.However,increasing evidence has shown that antimalarial drugs,the current treatment for CM,do little to protect against CM-induced BBB damage.Therefore,a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM.The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation.Here,we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria(eCM).Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells(RBCs)and/or proinflammatory lymphocytes in CNS blood vessels,thereby promoting the disruption of BBB integrity.Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes.Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM,such as limb paralysis,brain vascular leakage,and death.In addition,AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM.Taken together,our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.

Non-traumatic coma in young children in Benin:are viral and bacterial infections gaining ground on cerebral malaria?

Background:While malaria morbidity and mortality have declined since 2000,viral central nervous system infections appear to be an important,underestimated cause of coma in malaria-endemic Eastern Africa.We aimed to describe the etiology of non-traumatic comas in young children in Benin,as well as their management and early outcomes,and to identify factors associated with death.Methods:From March to November 2018,we enrolled all HIV-negative children aged between 2 and 6 years,with a Blantyre Coma Score≤2,in this prospective observational study.Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol,including blood cultures,malaria diagnostics,and cerebrospinal fluid analysis using multiplex PCR.To determine factors associated with death,univariate and multivariate analyses were performed.Results:From 3244 admissions,84 children were included:malaria was diagnosed in 78,eight of whom had a viral or bacterial co-infection.Six children had a non-malarial infection or no identified cause.The mortality rate was 29.8%(25/84),with 20 children dying in the first 24 h.Co-infected children appeared to have a poorer prognosis.Of the 76 children who consulted a healthcare professional before admission,only 5 were prescribed adequate antimalarial oral therapy.Predictors of early death were jaundice or increased bilirubin[odd ratio(OR)=8.6;95% confidential interval(CI):2.03-36.1]and lactate>5 mmol/L(OR=5.1;95%CI:1.49-17.30).Antibiotic use before admission(OR=0.1;95%CI:0.02-0.85)and vaccination against yellow fever(OR=0.2,95%CI:0.05-0.79)protected against mortality.Conclusions:Infections were found in all children who died,and cerebral malaria was by far the most common cause of non-traumatic coma.Missed opportunities to receive early effective antimalarial treatment were common.Other central nervous system infections must be considered in their management.Some factors that proved to be protective against early death were unexpected.

Antigenic variation and cytoadherence of PfEMP1 of Plasmodium falciparum infected erythrocyte from malaria patients

To approve a theoretical basis for the molecular pathogenesis of human cerebral malaria and treatment with prevention Methods The blood samples were collected from 24 patients with cerebral malaria, 143 with falciparum malaria, 34 with vivax malaria and 20 healthy controls from the endemic areas of Yunnan Province, China Using the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) technique, we determined the molecular mass (Mr) of these Plasmodium falciparum (P falciparum) erythrocyte membrane protein 1 (PfEMP1) molecules Results Our findings indicate that higher molecular mass (260?kDa-320?kDa) forms of PfEMP1 were expressed on parasitized erythrocyte (PE) from human cerebral malaria patients Compared with PfEMP1 expressed on PE from human cerebral malaria patients, the expression of PfEMP1 and Plasmodium vivax (P vivax) erythrocyte membrane protein 1 (PvEMP1) on PE from falciparum malaria patients and vivax malaria patients did not have multiple bands of PfEMP1 of ≥260?kDa, but had a PfEMP1 with molecular mass of 240?kDa and a PvEMP1 with molecular mass of 180?kDa band separately Healthy controls expressed an EMP of molecular mass of 140?kDa Conclusion Results confirm the antigenic variation of higher molecular mass of PfEMP1 whose molecular mass is equal to or exceeds 260?kDa-320?kDa on PE of patients with cerebral malaria Our results show that the binding of large antigenic variability PfEMP1 molecular mass of 260?kDa-320?kDa on PE from human cerebral malaria patients with diverse receptor molecules on the endothelial cell (EC) of the cerebral microvessels may be involved in the molecular pathogenesis of cerebral malaria

Insights into Plasmodium and SARS-CoV-2 co-infection driven neurological manifestations

In malaria-endemic regions,people often get exposed to various pathogens simultaneously,generating coinfection scenarios.In such scenarios,overlapping symptoms pose serious diagnostic challenges.The delayed diagnosis may lead to an increase in disease severity and catastrophic events.Recent coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has affected various areas globally,including malaria-endemic regions.The Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored.We present a case report of a previously healthy,middle-aged individual from the malaria-endemic area who suffered SARS-CoV-2 and Plasmodium falciparum co-infection.The patient developed severe disease indications in a short time period.The patient showed neurological symptoms,altered hematological as well as liver-test parameters,and subsequent death in a narrow time span.We hereby discuss the various aspects of this case regarding treatment and hematological parameters.Further,we have put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case.In malaria-endemic regions,due to overlapping symptoms,suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay.The SARS-CoV-2 and Plasmodium co-infection could increase the disease severity in a short time span.In treatment,dexamethasone may not help in severe cases having malaria as well as COVID-19 positive status and needs further exploration.