Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by Plasmodium falciparum

BACKGROUND Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.

Manejo clínico-terapéutico de la malaria grave

La malaria representa un grave problema de salud pública en el país, por su morbilidad y mortalidad. Es importante conocer la patogenia y las manifestaciones clínicas de la malaria grave, en especial revisar el ciclo biológico del parásito, ya que la enfermedad comienza con la ruptura del esquizonte maduro, siendo las primeras manifestaciones clínicas: fiebre y anemia. La infección por Plasmodium falciparum es más severa y es mediada por el fenómeno de secuestro en la microvasculatura venosa profunda, mientras que Plasmodium vivax causa una enfermedad debilitante, rara vez mortal, pero en oportunidades se presentan manifestaciones graves que causan la muerte del paciente. Malaria grave se define por la presencia de signos clínicos y de laboratorio de disfunción de órganos vitales como sistema nervioso central, riñón, gastrointestinal, vías respiratorias y alteraciones hemodinámicas; la cual requiere el rápido reconocimiento de la enfermedad y del grado de severidad. Se debe hacer un manejo de índole general y prestar especial atención a la terapia antimalárica oportuna con Artesunato, primera línea en malaria grave, o Arthemeter o Quinina con Clindamicina según los protocolos nacionales e internacionales, para lograr una evolución satisfactoria. En consecuencia, es un reto enfrentar esta entidad y obliga a la constante actualización en las diferentes opciones cónsonas con las diferentes especies de Plasmodium patógeno.

Malaria represents a serious public health problem in the country, due to its morbidity and mortality. It is of most importance to know the pathogenesis and clinical manifestations of severe malaria, particularly to review the biological cycle of the parasite. The disease begins with the rupture of the mature schizont, with the first clinical manifestations being fever and anemia. Plasmodium falciparum infection is more severe and is mediated by the phenomenon of sequestration in the deep venous microvasculature, while Plasmodium vivax causes a debilitating disease, rarely fatal, but sometimes serious manifestations occur that cause the death of the patient. Severe malaria is defined by the presence of clinical and laboratory signs of dysfunction of vital organs such as the central nervous system, kidney, gastrointestinal, respiratory tract, and pathological hemodynamic changes that requires rapid disease recognition and degree of severity. General management and timely antimalarial therapy with Artesunate, first line in severe malaria, or Arthemeter, or Quinine with Clindamycin following national and international protocols, achieve a favorable outcome. Consequently, it is a challenge to face this entity and requires constant updating in the different options consistent with the different species of pathogenic Plasmodium.

Malaria cerebral con pancitopenia por plasmodium vivax en la amazonía peruana: reporte de caso / Plasmodium vivax cerebral malaria with pancytopenia in the peruvian amazon: case report

RESUMEN Plasmodium vivax es la especie más común en la Amazonía peruana y ocasiona el 81% del total de casos de malaria. Presentamos el caso de un paciente adulto varón con malaria cerebral por Plasmodium vivax, que inicia con malestar general y fiebre, luego presenta convulsiones más de dos veces al día con pérdida de consciencia y limitación funcional motora. Se le realiza gota gruesa donde se observa trofozoítos de Plasmodium vivax y depresión de las tres series sanguíneas. Se inicia tratamiento con artesunato y clindamicina por cinco días, se le transfunde un paquete globular, y continua con primaquina por siete días. El paciente muestra mejoría clínica con secuela neurológica en extremidad inferior izquierda.

ABSTRACT Plasmodium vivax causes 81% of all malaria cases and is the most common species in the Peruvian Amazon. We present the case of a male patient with cerebral malaria caused by Plasmodium vivax, who had general malaise and fever, and then presented seizures more than twice a day with loss of consciousness and motor functional limitation. Plasmodium vivax trophozoites were detected by thick blood smear, besides, we also observed low counts of all three blood cell types. Treatment began with artesunate and clindamycin for five days, then one unit of packed red blood cells was transfused; treatment continued with primaquine for seven days. The patient showed clinical improvement with neurological sequelae in one lower limb.

Non invasive tests for diagnosis of parasitic infections of CNS

Central nervous system (CNS) infections are among the most devastating diseases with high mortality and morbidity. In the pre-human immunodeficiency virus (HIV) era, the occurrence of CNS infections was very infrequent. However, in the past four decades or so, with a global increase in the immunocompromised population, the incidence of opportunistic infections of the CNS has changed. This includes a global increase in the incidence of parasitic infections such as Toxoplasma gondii. Infections such as neurocysticercosis and cerebral malaria are quite prevalent in developing countries. Early diagnosis of these infections is crucial for instituting accurate therapy and preventing mortality and morbidity. Despite advances in neuroimaging techniques, laboratory diagnosis remains the mainstay for confirmation of diagnosis. We present an update on the noninvasive tests available for laboratory diagnosis of parasitic infections of the CNS.

BRAIN MALARIA: PRESENTATION OF A CASE AND REVIEW OF THE LITERATURE

Malaria is a zoonotic disease caused by protozoa of the genus Plasmodium, acquired through the bite of a female of the Anopheles mosquito genus. The initial symptoms of malaria are usually non-speci?c, presenting with fever, moderate to severe dehydration, tachycardia and tachypnea, with systolic blood pressure usually within normal ranges and in some cases with headache, nausea and vomiting. The clinical diagnosis can be con?rmed by the presence of malarial retinopathy or the presence of parasites in at least 20% of the capillaries in the histopathological study of the brain. The drugs of choice are those derived from artemisinin, artesunate and quinine. We present a case of severe malaria with brain involvement.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Clinical and haematological determinants of outcome among children with cerebral malaria in a tertiary centre in Nigeria

Background: Many clinical and haematological changes occur as a result of severe malaria, of which cerebral malaria (CM) is a common entity. These changes affect virtually all organs and systems of the body. We identify various clinical and haematological determinants of outcome in CM so as to institute proactive management of such children.Methods: All children who met World Health Organization (WHO) diagnostic criteria for CM over 8 month-period were prospectively studied. The presenting symptoms and its duration, detailed physical examination and laboratory parameters were obtained. Logistic regression was employed to determine the prognostic significance of various clinical and laboratory parameters. Outcome indicators were full recovery, alive with neurological sequelae or death of the children. Results: Of the 892 children admitted into the Children Emergency Unit (CEU) over the study period, 50 (5.6%) had CM with M: F ratio of 1:1 and age range of 6 months to 12 years. Sixty percent were aged less than 5 years. The defining symptoms were fever (100%), coma (100%) and convulsion (98%). Forty-one (82%) patients survived, while nine (18%) died. Of the 41 survivors, 30 (73.2%) recovered fully, while 11 (26.8%) had neurological deficits at discharge. Identified clinical and laboratory predictors of mortality and neurological sequelae in CM included Blantyre coma score of 0-2(p = 0.018) prolonged coma recovery time > 26 hours (p = 0.026), abnormal breathing pattern (p = 0.0124), absent corneal reflex (p = 0.012), absent pupillary reflex (p = 0.012), depressed tendon reflex (p = 0.028), hyperreflexia (p =0.014), retinal haemorrhage (p =0.001), duration of admission (p=0.000), hyper parasitaemia (p=0.001), hypoglycemia (p= 0.014) and leucocytosis (p = 0.008). Independent determinants of immediate post-recovery neurological deficits and death were hyper-parasitaemia (OR = 8.657, p = 0.017.) and leucocytosis (OR = 1.090; p = 0.035 Conclusion: CM is a potentially reversible encephalopathy associated with high mortality and sequelae. Affected children with the above listed clinical / haematological parameters especially hyperparasitemia and leucocytosis should be given proactive management to improve the outcome.

Effect Analysis of Artemisiae Annuae Herba and Chuanxiong Rhizoma in Treatment of Cerebral Malaria Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio^® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.

A Case of Severe Falciparum Malaria in a Returned Traveler

@#Primary care providers should be alert to travel-related infections. Around 10-40% of returning travelers from all destinations and 15-70% of travelers from tropical settings experience ill health, either overseas or upon returning home.1 A systematic approach concentrating on possible infections should be undertaken based on the patient’s travel location, immunization history, presence of malaria chemoprophylaxis at the destination, other potential exposures, incubation period, and clinical presentation.2-3 The World Health Organization (WHO) website is constantly being updated on specific travel-related infections and recent geographical outbreaks. In this paper, we report a case of severe falciparum malaria in a returned traveler.

Current advances in research on adjuvant therapy for cerebral malaria / 药学学报

Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.

Study of Hematological Parameters in Plasmodium Falciparum Malaria in Tertiary Care Hospital

Background: Malaria still continue to be a major killer ofmankind especially in developing countries. Almost all deathsand severe disease are due to plasmodium falciparum. It isobserved that the patients of falciparum malaria with liver, renaland hematological abnormalities are more vulnerable todevelopment of complications like cerebral malaria, anaemia,acute respiratory distress syndrome etc.Methods: 50 cases of plasmodium falciparum malariadiagnosed by peripheral smear examination or byimmunochromatographic tests were included in the study. Allthese patients are subjected to blood investigations.Results: 68% patients were males with sex ratio M:F was2.12: 1. Majority of patients (26%) belong to age group of 21-30 years. Most common presentation was fever in 100% ofpatients, followed by headache in 48% of patients, vomiting in46% of patients. 18% and 14% patients having haemoglobinbetween <7 and 7-9 mg% respectively with mean haemoglobinwas 09.69+-2.95mg% with range of 2.5-15 mg%.58% patientshaving WBC count between 4000 – 11000/mm3 with mean was7074 +/-4049.48/mm3 with range of 1200-17800/mm3. 28%patients were seen having platelet count between 50001 –75000/dl and 75001-150000/dl and only 8% patients werehaving platelet count <25000/dl. Mean RBSL level was 98.3+/-23.47 mg % with range of 54 – 190 mg%. 08% patients werehaving RBSL less than 60mg%. Only 4%patients were showingderranged bleeding, clotting time and PT-INR .But none ofpatients showing bleeding diathesis. P Falciparum malaria withrenal and liver dysfunction mostly associated with coagulationabnormality with or without bleeding diathesis having badprognosis.

Combination Artesunate and Tinospora crispa Decreases Ubiquitin, HIF-1α, VEGF and iNOS Expression in Brain of Cerebral Malaria Mice Model

Introduction: Cerebral malaria is the most severe complication of Plasmodium falciparum infection. The pathophysiology of cerebral malaria is still unclear, but it is expected caused by cytoadherence, rosetting, autoagglutinations and abundant pro-inflammatory response that will induce the release of secondary molecules like ubiquitin, HIF-1, VEGF, and iNOS. Aim: To determine the effect of Artesunate and brotowali extract (Tinospora crispa) against the expression of ubiquitin, HIF-1α, VEGF and iNOS in the brain of cerebral malaria mice model. Methods: An experimental study of post-test only control group using CB57BL/6J mice model malaria had been done. Samples were divided into 7 groups: negative control (K-), positive control (K+), Artesunate 32 mg/BWkg/ day (P1), Tinospora crispa 70 mg/BWkg/day (P2), combination Artesunate and Tinospora crispa dose 50 mg/ kgBW (P3), combination Artesunate and Tinospora crispa dose 60 mg/kgBW (P4) and combination Artesunate and Tinospora crispa dose 70 mg/kgBW (P5). Mice model were decapitated at 7th day after infection. Expression of ubiquitin, HIF-1α, VEGF, and iNOS was measured by immunohistochemistry. Result: One Way ANOVA showed different expression of ubiquitin, HIF-1α, VEGF and iNOS among groups. Tukey test showed, there was no significant difference in expression of ubiquitin, VEGF and iNOS among single therapy (Artesunate or Tinospora crispa) with combination therapy (p>0.05). Expression of HIF-1α were significantly different between single therapy (Artesunate or Tinospora crispa) with combination therapy of Artesunate and Tinospora crispa 60 mg/kgBW (p=0.019, p=0.013) and combination therapy of Artesunate and Tinospora crispa 70 mg/kgBW (p=0.034; p=0.023). Pearson correlation showed negative correlation between Tinospora crispa dose and expression of HIF-1α (p=0.001; r=-0.832) and iNOS (p=0.001, r=-0.874). Conclusion: The combination of Artesunate and brotowali (Tinospora crispa) extract generally decreases Ubiquitin, HIF-1 α, VEGF dan iNOS expression of cerebral malaria model although only brain HIF-1α expression gives significant decreasing.

Analysis of clinical profile and prescription pattern of malaria in a tertiary care hospital in Karnataka, India

Background: Malaria is one of the leading causes of morbidity and mortality in developing countries like India. Plasmodium falciparum and Plasmodium vivax are the commonest species implicated for an increased incidence of malaria in India. The pattern of disease, signs, and symptoms vary from place to place, region to region due to demographic variations. The current study was undertaken to study the differences in the clinical profile of malaria, particularly signs and symptoms, complications and response to treatment in malaria.Methods: A retrospective, single center, surveillance study was carried out at a tertiary health care center in Mangalore. All patients aged above 18 years diagnosed as malaria by peripheral smear method and rapid diagnostic tests were included in the study. The clinical features, complications, and response to treatment were noted.Results: Fifty eight patients diagnosed as malaria were included in the study. Compared to other studies and nationwide incidences, here P. vivax emerged as the leading cause of malaria. All patients presented with fever varying from 3-20 days. About 30 patients complained of headache and 21 patients presented with malaise. In about 6 patient’s complications were seen. Majority of patients received artemisinin derivatives followed by chloroquine for treatment of malariaConclusions: Previous thinking that complications are only seen with P. falciparum has to be changed. Now many complications, mild as well as severe type are seen in P. vivax malaria. Drug resistance is another global problem which needs to be tackled wisely by systematic usage of antimalarials.

Clinical profile and renal complications among cases of malaria in children attending a tertiary care hospital of South India

Background: Malaria is one of the major vectors borne disease globally responsible for 1 million deaths a year. Changing trends in the causative species and epidemiological distribution have identified icterus and renal involvement as an emerging complication associated with severe mortality in children. The objectives of this study were aimed to study the clinical profile of malaria cases admitted in a pediatric ward. The study also highlights the involvement of renal manifestations in the cases with regard to species distribution and associated complications in the study group.Methods: A prospective study for 14 months was conducted, and all positive cases of malaria admitted in paediatric unit were enrolled and socio demographic data, clinical history were collected, and biochemical investigations were performed and analyzed. SPSS software version 12 was used for analysis. Statistical significance was set at p ?0.05.Results: About 278 subjects with 55.4% males, 44.6% females and with 5-10 years was most common age group. 102 cases of vivax malaria, 152 cases were falciparum and 24 were mixed cases. Cerebral malaria, hyperparasitemia was identified in 28 cases, DIC in 5.04% of cases. Renal involvement was observed in 38.16% of falciparum infections and 27.45% of vivax infections. 68 cases developed acute renal failure as a severe complication.Conclusions: 'Renal involvement is more in falciparum and mixed infections than vivax malaria. Early diagnosis and prompt treatment help in early recovery of cases and halts to progression to renal failure. An urgent need for a biomarker for early identification of renal involvement in malaria before biochemical involvement is detected.

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

A study of clinical profile of patients with malaria in tertiary care hospital

Background: Malaria a tropical disease has a wide clinical spectrum ranging from uncomplicated disease to a fatal one. The objectives were to study clinical profile of Malaria with special reference to its complications and outcome. Materials and methods: A study was carried out in a tertiary care hospital including total of 50 patients diagnosed with P. Vivax or P. Falciparum Malaria. Data on patients’ clinical details with investigations, complications, and outcome was studied. Results: Out of 50 patients (37 male and 13 female), 41 had P. Vivax and 9 had P. Falciparum Malaria. Total 3 patients were complicated; two had cerebral malaria due to P.falciparum and one had multi organ failure due to P. vivax which eventually succumbed. Conclusions: Clinical profile of Malaria was studied which suggest, P.falciparum malaria was more complicated; which comprises cerebral complications, renal complication, hepato-biliary and respiratory complications leading to increased morbidity and mortality. It was observed that P. vivax had better outcome but it can also present with serious and life-threatening complication.

Evaluation of complications and factors associated with multi-organ dysfunction in malaria: a cross sectional study

Background: Prevalence of complications in malaria continues to grow even with reducing number of malaria cases. Complications associated with malaria can involve multiple organs. There is paucity of literature on factors associated with multi organ dysfunction in different types of malaria.Methods: Our aim was to study the clinical profile of complications in different types of malaria with specific focus on multi-organ dysfunction (MODS). In this cross-sectional study confirmed cases of malaria were enrolled.Results: Plasmodium vivax malaria was the predominant type seen in 74.1% cases. The overall prevalence of thrombocytopenia was 61.5%, hepatic dysfunction 58%, cerebral malaria 16.1%, Hypoglycemia 7.5%, bleeding 34.5%, acute respiratory distress syndrome (ARDS) 5.7% and acute kidney injury (AKI) 49.4%. Hypoglycemia was significantly higher in mixed malaria (0.025, p = 0.025). Hepatic dysfunction and hyperbilirubinemia were significantly higher in mixed malaria (p=0.001). Mortality was seen in mixed malaria (p = 0.007). Only those with mixed malaria died (13%). Patients with MODS had higher prevalence of rashes (p <0.0001) and cerebral malaria (p = 0.000). Serum levels of urea, creatinine, Bilirubin, Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) were significantly higher in patients with MODS (p<0.0001 for all variables). On evaluating factors associated with multi-organ dysfunction presence of cerebral malaria [OR: 6.4 (95% CI): 2.4 to 17.4; p<0.0001], type of malaria (Vivax or Falciparum or both) [1.77 (1.03 to 3.03); p=0.0038], and hypoglycemia [4.4 (1.08 to 17.8); p=0.038] were statistically significant on multivariate analysis.Conclusions: The present study demonstrates the factors associated with multi organ dysfunction and its impact on clinical outcome in different types of 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.

Protective effects of artesunate combination on experimental cerebral malaria and nerve injury / 中国中药杂志

Cerebral malaria (CM) is the leading cause of death in children under 5 years in Africa, severe neurological sequelae may occur in surviving children. Although artesunate has made breakthrough progress in the clinical treatment of CM, the clinical problems of high mortality and high morbidity have not yet been completely resolved. In this study, an experimental cerebral malaria (ECM) model was established by infecting C57BL/6 mice with Pb ANKA (Plasmodium berghei ANKA) to compare parasitemia level, survival rates, and rapid murine coma behavior scale scores, cerebral microvascular obstruction, haemozoin deposition in the liver, body temperature and weight to investigate the anti-cerebral malaria effect of the artesunate compound combination. The results showed that the artesunate compound combination could improve the survival rate of Pb ANKA-infected mice, reduce the level of parasitemia, effectively improve the symptoms of ECM neurological injury, reduce cerebrovascular obstruction and haemozoin deposition in the liver, and also significantly improve body temperature, weight and other basic indicators. The results showed that the artesunate compound combination improved the pathological changes and neurological damage caused by CM. It is expected to provide a theoretical basis for human cerebral malaria patients in clinical adjuvant therapy.

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. http://www.apjtm.org/article.asp?issn=1995-7645;year=2018;volume=11;issue=6;spage=376;epage=380;aulast=Wah;type=2.