exudates and Hemolysis

Acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation and improves renal function in severe falciparum malaria but has not been evaluated in other infections with prominent hemolysis, including Plasmodium knowlesi malaria.. PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.. During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).. Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.. NCT03056391.

Topics: Acetaminophen; Acute Kidney Injury; Creatinine; Hemoglobins; Hemolysis; Humans; Kidney; Malaria; Malaysia; Plasmodium knowlesi

Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe. Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.. Clinicaltrials.gov, NCT03056391 . Registered on 12 October 2016.

Topics: Acetaminophen; Acute Kidney Injury; Antioxidants; Biomarkers; Hemolysis; Humans; Malaria; Malaysia; Multicenter Studies as Topic; Oxidative Stress; Plasmodium knowlesi; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome

Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.

Topics: Acute Kidney Injury; Adult; Angiopoietin-2; Creatinine; E-Selectin; Endothelial Cells; Erythrocytes; Female; Hemoglobins; Hemolysis; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Malaria, Falciparum; Malaysia; Male; Microvessels; Nitric Oxide; Osteoprotegerin; Plasmodium knowlesi; Young Adult

Haemolytic disease of the foetus and newborn (HDFN) is caused by maternal red blood cells (RBC) alloimmunisation resulted from incompatibility of maternal and foetal RBCs. However, only a few HDFN attributed to anti-M were reported, varying from asymptomatic to severe anaemia with hydrops foetalis and even intrauterine death. A case of severe HDFN due to anti-M alloantibody from an alloimmunized grandmultiparous Malay woman with recurrent pregnancy loss is reported here. The newborn was delivered with severe and prolonged anaemia which required frequent RBC transfusions, intensive phototherapy and intravenous immunoglobulin administration. Although anti-M is rarely known to cause severe HDFN, a careful serological work-up and close assessment of foetal well-being is important, similar to the management of RhD HDFN. Alloimmunisation with anti-M type can lead to severe HDFN and even foetal loss.

Topics: Adult; Erythroblastosis, Fetal; Female; Fetal Development; Fetus; Hematologic Diseases; Hemolysis; Humans; Hydrops Fetalis; Isoantibodies; Malaysia; Pregnancy

A total of 58 Gram-positive bacteria strains were isolated from the marine environment and screened for potential probiotics for disease prevention and improving the productivity of tiger grouper Epinephelus fuscoguttatus larvae and juveniles. The bacteria were identified as Bacillus licheniformis, B. subtilis, B. circulans, B. sphaericus, B. cereus, Brevibacillus brevis, Corynebacterium propinquum, Leifsonia aquatica and Paenibacillus macerans. Only 24 strains showed antagonistic activities against four pathogenic strains; Vibrio alginolyticus, V. harveyi, V. parahaemolyticus and Aeromonas hydrophila, where two of the Bacillus strains, B12 and B45 demonstrated intermediate to highest level of inhibitory activity against these pathogenic strains, respectively. Further assessment by co-culture assay showed that Bacillus strain B12 exhibited a total inhibition of V. alginolyticus, while B45 strain displayed no inhibitory activity. Mixed culture of Bacillus B12 and B45 strains to outcompete V. alginolyticus was observed at a cell density of 10(7) CFU ml(-1). Molecular identification and phylogenetic tree analysis have categorized Bacillus strain B12 to the reference strains GQ340480 and JX290193 of? B. amyloliquafaciens, and Bacillus strain B45 with a reference strain JF496522 of B. subtilis. Safety tests of probionts by intraperitoneal administration of B12 and B45 strains at cell densities of 103, 105 and 10(7) CFU ml(-1) revealed no abnormalities and cent percent survival for healthy Epinephelus fuscoguttatus juveniles within 15 days of experimental period. Overall, the study revealed that Bacillus B12 strain possesses tremendous probiotic potential that could be used as a feed supplement in tiger grouper diets. ?

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Aquaculture; Bacillus; Coculture Techniques; Diet; Fishes; Hemolysin Proteins; Hemolysis; Malaysia; Phylogeny; Probiotics

Haemoglobinuria is an uncommon complication of severe malaria, reflecting acute intravascular haemolysis and potentially leading to acute kidney injury. It can occur early in the course of infection as a consequence of a high parasite burden, or may occur following commencement of anti-malarial treatment. Treatment with quinine has been described as a risk factor; however the syndrome may also occur following treatment with intravenous artesunate. In Malaysia, Plasmodium knowlesi is the most common cause of severe malaria, often associated with high parasitaemia. Asplenic patients may be at additional increased risk of intravascular haemolysis.. A 61 years old asplenic man was admitted to a tertiary referral hospital in Sabah, Malaysia, with severe knowlesi malaria characterized by hyperparasitaemia (7.9 %), jaundice, respiratory distress, metabolic acidosis, and acute kidney injury. He was commenced on intravenous artesunate, but1 day later developed haemoglobinuria, associated with a 22 % reduction in admission haemoglobin. Additional investigations, including a cell-free haemoglobin of 10.2 × 10(5) ng/mL and an undetectable haptoglobin, confirmed intravascular haemolysis. The patient continued on intravenous artesunate for a total of 48 h prior to substitution with artemether-lumefantrine, and made a good recovery with resolution of his haemoglobinuria and improvement of his kidney function by day 3.. An asplenic patient with hyperparasitaemic severe knowlesi malaria developed haemoglobinuria after treatment with intravenous artesunate. There are plausible mechanisms for increased haemolysis with hyperparasitaemia, and following both splenectomy and artesunate. Although in this case the patient made a rapid recovery, knowlesi malaria patients with this unusual complication should be closely monitored for potential deterioration.

Topics: Artemisinins; Artesunate; Hemoglobinuria; Hemolysis; Humans; Malaria; Malaysia; Male; Middle Aged; Plasmodium knowlesi; Splenectomy

Gamma-irradiation of blood components is regarded a safe procedure used for prevention of transfusion associated graft-versus-host disease. However, reports showed that irradiation can cause erythrocyte haemolysis and damage to the RBC membrane. In University Kebangsaan Malaysia Medical Centre (UKMMC), a number of suspected transfusion reactions (TR) featured unusual isolated episodes of red-coloured-urine or haemoglobinuria among paediatric patients without clinical features of acute haemolytic TR. Haemolysis of irradiated red cells was suspected as a cause. This study was conducted to evaluate haemolytic changes of RBC components following irradiation. A prospective, pre- and post- irradiation comparative study was conducted on 36 paired RBC-components in the blood-bank, UKMMC in the year 2013. Samples were tested for plasma-Hb, percent-haemolysis, plasma-potassium (K⁺) and lactate dehydrogenase (LDH) level. Post-irradiation mean plasma-Hb and percent-haemolysis were significantly higher than pre-irradiation values at 0.09 ±0.06g/dl VS 0.10 ± 0.06g/dl and 0.19 ± 0.13% VS 0.22 ± .13% respectively, while plasma-K⁺ and LDH values did not show significant difference. However, the mean percent-haemolysis level was still within recommended acceptable levels for clinical use, supporting that irradiated RBC units were safe and of acceptable quality for transfusion. There was no conclusive reason for isolated haemoglobinuria following transfusion of irradiated red-cell products. Further research is suggested to investigate the other possible causes.

Topics: Blood Component Transfusion; Cross-Sectional Studies; Erythrocytes; Graft vs Host Disease; Hemolysis; Humans; Malaysia; Prospective Studies

To evaluate the mosquito larvicidal potential of the native Bacillus thuringiensis isolate BtReXO2, which was isolated from a tropical rain forest ecosystem in Malaysia. This study also aimed at determining the phenotypic and biochemical characteristics of the isolate.. The phenotypic characterization was carried out by growing the isolate in nutrient broth to observe the colonial morphology, vegetative cells, sporulation, motility and haemolytic activity. The parasporal crystal morphology was determined by Coomassie Brilliant Blue (CBB) staining of the sporulated cells and then observed under light microscope. The mosquito larvicidal assay was conducted with the second instar larvae of Culex quinquefasciatus and Aedes albopictus to determine the entomocidal potency of the isolate. The total protein profile was determined by SDS-PAGE.. Preliminary phenotypic and biochemical characterization showed that the isolate is motile, an indirect indication of the virulence of the strain and exhibited hemolytic activity, an important feature of antidipteran Bacillus thuringiensis strains. Study on the crystal morphology showed the presence of cuboidal crystals, another characteristic feature of a mosquitocidal Bacillus thuringiensis strains. Bioassay with the second instar larvae of Culex quinquefasciatus, Aedes albopictus established the antidipteran activity of this native Bacillus thuringiensis isolate. Protein profile analysis revealed the unique pattern showing high molecular mass as well as low molecular mass proteins corresponding to the Cry and Cyt proteins respectively. The protein profile is strikingly different from other mosquitocidal strains such as Bacillus thuringiensis subsp.israelensis and Bacillus thuringiensis subsp. jegathesan Periodical introduction of such native strains of Bacillus thuringiensis will add a new weapon in the armoury to manage the vector borne diseases and also in the management of insect resistance.

Topics: Aedes; Animals; Bacillus thuringiensis; Bacillus thuringiensis Toxins; Bacterial Proteins; Culex; Endotoxins; Hemolysin Proteins; Hemolysis; Insecticides; Larva; Malaysia; Pest Control, Biological; Trees

Topics: Adult; Antimalarials; Artemether; Artemisinins; Blood Transfusion; Doxycycline; Ethanolamines; Fluorenes; Hemolysis; Humans; Lumefantrine; Malaria; Malaysia; Male; Mefloquine; Microscopy; Phylogeny; Plasmodium knowlesi; Polymerase Chain Reaction; Protozoan Proteins; Quinine; Recurrence

Vegetative proteins from Malaysian strains of Bacillus thuringiensis israelensis strains (Bt 11, Bt 12, Bt 15, Bt 16, Bt 17, Bt 21 and Bt 22) and Bacillus sphaericus H-25 strains (Bs 1 and Bs 2) were screened for haemolytic, cytotoxic and larvicidal activity. SDS-PAGE profiles of the Bacillus thuringiensis strains studied consistently showed major bands of 33-37 kDa and 47 kDa. Bt 16 also showed two bands of 66 kDa and 45 kDa similar to the previously reported binary vegetative protein, Vip1Ac (66 kDa) and Vip 2Ac (45 kDa). Both the Bacillus sphaericus strains showed a 35 kDa band that was similiar to a previously reported vegetative protein, the Mtx2 protein. Bs 2 also contains a 37 kDa band, similar to another vegetative protein, the Mtx 3 protein. With the exception of Bt 17 and Bt 21, vegetative proteins from all Bacillus thuringiensis and Bacillus sphaericus strains were highly haemolytic to human erythrocytes, causing more than 75% haemolysis at the highest concentration of 200 microg/ml. High haemolytic activity was associated with high cytotoxic activity with most of the haemolytic strains being indiscriminately cytotoxic to both CEM-SS (human T lymphoblastoid) and HeLa (human uterus cervical cancer) cell lines. Interestingly, the less haemolytic vegetative proteins from Bt 17 and Bt 21 demonstrated cytotoxic activity comparable to that of the highly haemolytic vegetative proteins. Bt 21 displayed toxicity towards both cell lines while Bt 17 was more toxic towards CEM-SS cells. Bioassay against Aedes aegypti and Culex quinquefasciatus larvae revealed that vegetative proteins from the Bacillus thuringiensis strains had activity against both species of larvae but vegetative proteins from Bacillus sphaericus were weakly larvicidal towards Cx. quinquefasciatus only.

Topics: Aedes; Animals; Bacillus thuringiensis; Bacterial Proteins; Biological Assay; Culex; Electrophoresis, Polyacrylamide Gel; Erythrocytes; HeLa Cells; Hemolysis; Humans; Larva; Malaysia; Pest Control, Biological; Rabbits

The objective of this study is to determine the role of carbohydrates on the toxic effect of parasporal inclusion proteins isolated from Malaysian mosquitocidal Bacillus thuringiensis (Bt) strains on erythrocytes (human and rat). Dose response analyses on the effect of these parasporal inclusions on human and rat erythrocytes suggest that toxin action is selective depending on bacterial strains and source of erythrocytes. Results from this study suggest Bt toxin is a lectin which recognizes specific plasma membrane glycoconjugate receptor(s) with a terminal residue of either D-mannose (Man), N-acetyl-D-galactosamine (GalNAc), N-acetyl-D-glucosamine (GlcNAc) or even a combination of these monosaccharides.

Topics: Animals; Bacillus thuringiensis; Bacterial Proteins; Dose-Response Relationship, Drug; Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Lectins; Malaysia; Monosaccharides; Pest Control, Biological; Rats; Soil Microbiology; Species Specificity; Spores, Bacterial

The role of hemolysis in the pathophysiology of neonatal jaundice (NNJ) in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency has been questioned recently. The aim of the present study was to determine the contribution of hemolysis to the pathophysiology of jaundice in Malay neonates with G6PD deficiency and NNJ.. Four groups of babies were included in the study: (i) G6PD deficient with NNJ; (ii) G6PD deficient without NNJ; (iii) G6PD normal with NNJ; and (iv) normal controls. Babies with other known causes of jaundice were excluded from the study. All subjects underwent the following investigations on day 3-5 after birth: hemoglobin level (Hb), serum bilirubin level, carboxyhemoglobin (CO-Hb) concentration, reticulocyte count and full blood picture. The results of the investigations were compared between the groups using SPSS version 11.. Babies with G6PD and jaundice had a similar percentage of CO-Hb to babies with G6PD without NNJ or babies with normal G6PD and NNJ (1.76 +/- 0.40% vs 1.66 +/- 0.31% and 1.67 +/- 0.28%, respectively; P: 0.23 and 0.41, respectively). Total Hb levels and reticulocyte counts were not significantly different between the groups. The blood film showed more (even though not reaching significance) hemolysis in the G6PD patients but results of the blood film were very similar for G6PD patients with and those without NNJ.. Hemolysis is not a main determinant of neonatal jaundice in G6PD-deficient babies.

Topics: Bilirubin; Carboxyhemoglobin; Case-Control Studies; Cross-Sectional Studies; Female; Glucosephosphate Dehydrogenase Deficiency; Hemoglobins; Hemolysis; Humans; Infant, Newborn; Jaundice, Neonatal; Malaysia; Male; Reticulocyte Count; Risk Factors

A total of 87 market fish samples representing five types of fish were evaluated for the presence of Aeromonas spp. Of the samples examined, 69%, 55%, 11.5% and 2.3% harbored Aeromonas spp., A. veronii biovar sobria, A. hydrophila and A. caviae, respectively. The 60 isolated Aeromonas spp. strains were further examined for hemolytic activity, resistance to antimicrobial agents and presence of plasmids. Hemolytic activity varied widely among the isolated strains. Though all the isolates demonstrated resistance to three or more of the antibiotics tested, all were susceptible to ceptazidime. Thirty-four (56.7%) of the sixty isolates harbored plasmids, with sizes ranging from 2.3 to 15.7 kb. These results indicate that hemolytic, multiple antibiotic resistant and genetically diverse aeromonads are easily recovered from fish in this region.

Topics: Aeromonas; Animals; Anti-Bacterial Agents; Consumer Product Safety; Drug Resistance, Multiple, Bacterial; Fishes; Food Microbiology; Hemolysis; Malaysia; Microbial Sensitivity Tests; Plasmids; Seafood

Topics: alpha-Thalassemia; Base Sequence; beta-Thalassemia; Ethnicity; Globins; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Incidence; Malaysia; Molecular Sequence Data; Mutation

Approximately 57% of clinical and 33% of poultry isolates examined produced a cytotoxin. Cytotoxic activity was detected in 25 (50%) isolates of Campylobacter of which 12 were isolated from bloody diarrhea and 9 from watery stools. The cytotoxin titers were low, ranging from 2 to 16. The crude filtrates from 50 Campylobacter isolates showed no cytotoxic effect in Vero cells, no fluid accumulation in suckling mice and no hemolytic activity.

Topics: Animals; Bacterial Toxins; Campylobacter; Cells, Cultured; Chlorocebus aethiops; Cytotoxins; Diarrhea; Hemolysis; Humans; Malaysia; Mice; Vero Cells

Topics: Amino Acids; Animals; Chemical Phenomena; Chemistry; Cobra Cardiotoxin Proteins; Elapid Venoms; Electrophoresis, Polyacrylamide Gel; Guinea Pigs; Hemolysis; Humans; In Vitro Techniques; Lethal Dose 50; Malaysia; Rats

Topics: Blood Protein Electrophoresis; Erythrocyte Count; Female; Fetal Hemoglobin; Hematocrit; Hemoglobinopathies; Hemoglobins; Hemoglobins, Abnormal; Hemolysis; Homozygote; Humans; Malaysia; Pregnancy; Pregnancy Complications, Hematologic; Reticulocytes; Thalassemia

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Birth Weight; Blood; Diet; Female; Fetal Death; Hemoglobins; Hemolysis; Hemorrhage; Humans; Malaysia; Nutrition Disorders; Parasite Egg Count; Pregnancy; Pregnancy Complications, Hematologic; Socioeconomic Factors