Complications Of Severe Malaria Research Articles

Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria

Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15–25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin–proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort (n = 340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers.

Immunofluorescence study of cytoskeleton in endothelial cells induced with malaria sera

BackgroundEndothelial cells (ECs) play a major role in malaria pathogenesis, as a point of direct contact of parasitized red blood cells to the blood vessel wall. The study of cytoskeleton structures of ECs, whose main functions are to maintain shape and provide strength to the EC membrane is important in determining the severe sequelae of Plasmodium falciparum malaria. The work investigated the cytoskeletal changes (microfilaments-actin, microtubules-tubulin and intermediate filaments-vimentin) in ECs induced by malaria sera (Plasmodium vivax, uncomplicated P. falciparum and complicated P. falciparum), in relation to the levels of pro-inflammatory cytokines.MethodsMorphology and fluorescence intensity of EC cytoskeleton stimulated with malaria sera were evaluated using immunofluorescence technique. Levels of tumour necrosis factor (TNF) and interferon (IFN)-gamma (γ) were determined using enzyme-linked immunosorbent assay (ELISA). Control experimental groups included ECs incubated with media alone and non-malaria patient sera. Experimental groups consisted of ECs incubated with malaria sera from P. vivax, uncomplicated P. falciparum and complicated P. falciparum. Morphological scores of cytoskeletal alterations and fluorescence intensity were compared across each experiment group, and correlated with TNF and IFN-γ.ResultsThe four morphological changes of cytoskeleton included (1) shrinkage of cytoskeleton and ECs with cortical condensation, (2) appearance of eccentric nuclei, (3) presence of “spiking pattern” of cytoskeleton and EC membrane, and (4) fragmentation and discontinuity of cytoskeleton and ECs. Significant damages were noted in actin filaments compared to tubulin and vimentin filaments in ECs stimulated with sera from complicated P. falciparum malaria. Morphological damages to cytoskeleton was positively correlated with fluorescence intensity and the levels of TNF and IFN-γ.ConclusionsECs stimulated with sera from complicated P. falciparum malaria showed cytoskeletal alterations and increased in fluorescence intensity, which was associated with high levels of TNF and IFN-γ. Cytoskeletal changes of ECs incubated with complicated P. falciparum malaria sera can lead to EC junctional alteration and permeability changes, which is mediated through apoptotic pathway. The findings can serve as a basis to explore measures to strengthen EC cytoskeleton and alleviate severe malaria complications such as pulmonary oedema and cerebral malaria. In addition, immunofluorescence intensity of cytoskeleton could be investigated as potential prognostic indicator for malaria severity.

Pathogenetic mechanisms and treatment targets in cerebral malaria.

Malaria, the most prevalent mosquito-borne infectious disease worldwide, has accompanied humanity for millennia and remains an important public health issue despite advances in its prevention and treatment. Most infections are asymptomatic, but a small percentage of individuals with a heavy parasite burden develop severe malaria, a group of clinical syndromes attributable to organ dysfunction. Cerebral malaria is an infrequent but life-threatening complication of severe malaria that presents as an acute cerebrovascular encephalopathy characterized by unarousable coma. Despite effective antiparasite drug treatment, 20% of patients with cerebral malaria die from this disease, and many survivors of cerebral malaria have neurocognitive impairment. Thus, an important unmet clinical need is to rapidly identify people with malaria who are at risk of developing cerebral malaria and to develop preventive, adjunctive and neuroprotective treatments for cerebral malaria. This Review describes important advances in the understanding of cerebral malaria over the past two decades and discusses how these mechanistic insights could be translated into new therapies.

Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria

Severe anemia is an important contributor to mortality in children with severe malaria. Anemia in malaria is a multi-factorial complication, since dyserythropoiesis, hemolysis and phagocytic clearance of uninfected red blood cells (RBCs) can contribute to this syndrome. High levels of oxidative stress and immune dysregulation have been proposed to contribute to severe malarial anemia, facilitating the clearance of uninfected RBCs. In a cohort of 552 Ugandan children with severe malaria, we measured the levels of xanthine oxidase (XO), an oxidative enzyme that is elevated in the plasma of malaria patients. The levels of XO in children with severe anemia were significantly higher compared to children with severe malaria not suffering from severe anemia. Levels of XO were inversely associated with RBC hemoglobin (ρ = − 0.25, p < 0.0001), indicating a relation between this enzyme and severe anemia. When compared with the levels of immune complexes and of autoimmune antibodies to phosphatidylserine, factors previously associated with severe anemia in malaria patients, we observed that XO is not associated with them, suggesting that XO is associated with severe anemia through an independent mechanism. XO was associated with prostration, acidosis, jaundice, respiratory distress, and kidney injury, which may reflect a broader relation of this enzyme with severe malaria pathology. Since inhibitors of XO are inexpensive and well-tolerated drugs already approved for use in humans, the validation of XO as a contributor to severe malarial anemia and other malaria complications may open new possibilities for much needed adjunctive therapy in malaria.

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.

Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.

Dengue and Malaria Coinfection in An Overweight Child

Background: Dengue and malaria are infectious diseases transmitted by mosquitos mainly in tropical countries, including Indonesia, but there are only a few cases where both diseases are endemic in the same region. Malaria is difficult to diagnose in a dengue-endemic area due to the similar clinical symptoms. As a result, it can be misdiagnosed and affect treatment, resulting in a negative outcome. Case Presentation: This study presented a case of dengue and malaria coinfection in a 14-year-old overweight boy who was admitted to the hospital with fever, shivers, and a severe headache. Microscopic examination showed several form of Plasmodium falciparum’s trophozoite ring (Fig 1). Laboratories test showed a low thrombocyte level, 79.000/µL, hematocrit of 43.8%, serologic anti-dengue IgM was negative, and anti-dengue IgG was positive. Dengue therapy was administered in accordance with the World Health Organization's Dengue Diagnosis Guidelines, as well as the antimalarial drugs dihydroartemisinin-piperaquine and primaquine. There was no bleeding or shock during the five days of treatment, and no severe malaria complications were discovered. The patient was discharged with an improved general condition and normal hematological results. Conclusion: This paper aimed to emphasize the significance of early detection and appropriate management of dengue and malaria co-infection in dengue endemic areas in order to achieve a positive outcome and prevent complications.

Spontaneous Splenic Rupture: Case Report from Yekatit 12 Medical College Hospital, Addis Ababa, Ethiopia

Splenic rupture can be traumatic or non-traumatic (spontaneous). The spleen is the commonest solid organ injured in blunt abdominal injury. Spontaneous splenic rupture is rare and one cause of acute abdomen which can lead to morbidity and mortality. Among patients having spontaneous splenic rupture, majority of them have underlying splenic pathology of different causes such as hematologic, infectious, inflammatory, drugs or mechanical. In endemic area of malaria, spontaneous splenic rupture is one of fatal complication of severe malaria fortunately it is rare complication. In rare cases there may be no splenic pathology identified which is called idiopathic. The treatment of ruptured spleen is mainly splenectomy though there are cases reports of angioembolization as treatment option. Here we present a case report of 20 year old male patient who presented with diffuse abdominal pain of 3 days duration with signs of generalized peritonitis. During exploratory laparotomy, he was having ruptured spleen with blood in the peritoneum. He was managed with splenectomy and cross match transfusion after the bleeding was controlled. The patient was discharged improved after he took pentavalent vaccine. In conclusion, though spontaneous splenic rupture is rare over all there are different case reports of this condition and one has to consider it as differential diagnosis in patient who presented with acute abdomen of unclear causes and especially if the patient has underlying diseases or drugs that can affect the spleen.

Post Malaria Neurological Syndrome: Unknown, Underestimated, or Underdiagnosed? First Report Done in Gambia

Post-malaria neurological syndrome (PMNS) is a rare self-limiting neurological complication that can occur after recovery from malaria, usually severe falciparum malaria. It is characterized by a myriad of neuropsychiatric manifestations including mild neurological deficit to severe encephalopathy. PMNS is a debated entity, is a rare complication of severe malaria that might be underreported. It can develop up to 2 months after clearance of parasitemia. Clinical features can be variable. Most cases are self-limited, but more severe cases may benefit from steroid therapy. There are several neurological syndromes that can occur following complete recovery from malaria, in particular Plasmodium falciparum. These PMNS include, delayed cerebellar ataxia (DCA), acute inflammatory demyelinating polyneuropathy (AIDP) and acute disseminated encephalomyelitis (ADEM). In 2021 according to WHO report, the African region was home to 95% of all malaria cases and 96% of deaths. Paradoxically, reports of post malaria neurological syndrome in west Africa sub region are practically null, it is not clear if it is due to lack of knowledge regarding the disease, underdiagnosis or combination of factors, the first case of post malaria neurological syndrome in Gambia is described below. The objective is to show that cases exist, but due to lack of knowledge by health personnel they are overwhelmingly underdiagnosed.

Misidentification of Plasmodium Species by Cross-Reacting Primers and Cerebral Malaria Caused by Plasmodium vivax

Abstract Introduction The clinical presentation of a case as cerebral malaria with molecular identification confirming it as Plasmodium vivax underlines the importance of using molecular tools to identify the species and type of malaria. The possibility of the relationship between the complication observed during clinical diagnosis and the multifactorial molecular changes could likely be the reason for terming it cerebral malaria. Methods We report four cases analyzed using the quantitative buffy coat technique followed by classical Giemsa stained thick-film microscopy, and nested polymerase chain reaction for the genus-specific region of Plasmodium targeting 18S rDNA followed by species-specific identification with a different set of primers and products confirmation with sequencing. Results Primers targeting P. knowlesi generated the expected product size of 153 base pairs that, upon sequencing, matched with the P. vivax sequence reflecting the relatedness of the species. Likewise, primers targeting P. ovale generated a 456 product whose sequence matched the P. vivax sequence. Conclusion Infection with P. vivax can potentially cause cerebral malaria, and P. vivax can cause severe malaria complications alone or mixed with other species and can show cerebral malaria signs, which are typically associated with P. falciparum infections. The sequence relatedness reflects the genome similarity between P. knowlesi and P. ovale with P. vivax. The need to reconfirm with an additional set of newly reported primers is mandatory.

Genome-wide liver transcriptomic profiling of a malaria mouse model reveals disturbed immune and metabolic responses

BackgroundThe liver is responsible for a range of functions in vertebrates, such as metabolism and immunity. In malaria, the liver plays a crucial role in the interaction between the parasite and host. Although malarial hepatitis is a common clinical complication of severe malaria, other malaria-related liver changes have been overlooked during the blood stage of the parasite life-cycle, in contrast to the many studies that have focused on parasite invasion of and replication in the liver during the hepatic stage of the parasite.MethodsA rodent model of malaria was established using Plasmodium yoelii strain 17XL, a lethal strain of rodent malaria, for liver transcriptomic profiling.ResultsDifferentially expressed messenger RNAs were associated with innate and adaptive immune responses, while differentially expressed long noncoding RNAs were enriched in the regulation of metabolism-related pathways, such as lipid metabolism. The coexpression network showed that host genes were related to cellular transport and tissue remodeling. Hub gene analysis of P. yoelii indicated that ubiquitination genes that were coexpressed with the host were evolutionarily conserved.ConclusionsOur analysis yielded evidence of activated immune responses, aberrant metabolic processes and tissue remodeling changes in the livers of mice with malaria during the blood stage of the parasite, which provided a systematic outline of liver responses during Plasmodium infection.Graphical

Factors Associated with Acute Kidney Injury among Children with Severe Malaria at Kiryandongo General Hospital, Uganda.

Malaria remains one of the leading health problems of the developing world, and acute kidney injury (AKI) is a well-recognized complication of severe malaria in adults; but the clinical importance of AKI in paediatric severe malaria is not well documented. Knowledge of the prevalence and factors associated with AKI among children with severe malaria is among the key strategies, which can help to reduce the burden of AKI among this vulnerable group. Methodology. A hospital-based prospective cross-sectional descriptive and analytic study of children with severe malaria was carried out at Kiryandongo General Hospital. The study involved 350 children with severe malaria attending the study site from August to October 2021. Questionnaires were administered to caretakers to obtain sociodemographic characteristics. Medical data were obtained through physical examination followed by laboratory tests. Blood samples were tested for creatinine and blood smear for malaria. Data were analyzed using binary logistic regression (bivariate and multivariate) to assess for the factors associated with AKI. A p value < 0.05 was considered statistically significant. The mean age of children with severe malaria was 7.0 ± 3.8 years, and 54.3% of them were male. Of the 350 children enrolled, 167 had AKI, giving an overall AKI prevalence of 47.7% (95% CI: 42.5-53.0). The factors that were significantly associated with AKI among children with severe malaria included caretaker with no formal education (aOR = 21.0, 95% CI: 1.68-261.18, p = 0.018), caretaker with primary education level (aOR = 4.5, 95% CI: 1.41-14.12, p = 0.011), age of child < 5 years (aOR = 1.8, 95% CI: 1.07-2.88, p = 0.025), history of receiving NSAIDs (aOR = 5.6, 95% CI: 2.34-13.22, p < 0.001), moderate anemia (aOR = 3.1, 95% CI: 1.39-6.94, p = 0.006), and severe anemia (aOR = 3.8, 95% CI: 1.66-8.55, p = 0.002). The prevalence of AKI was high among children with severe malaria in Kiryandongo General Hospital. Acute kidney injury among children with severe malaria was associated with low level of education of caretakers, age of children less than 5 years, history of receiving NSAIDs, and anemia. The management of severe malaria should include screening for AKI especially in children under five years of age, anemic, and those who have received NSAIDs.

A severe case of Plasmodium falciparum malaria imported by a French traveler from Cameroon to French Guiana despite regular intake of Artemisia annua herbal tea

The use of herbal tea with Artemisia annua by travelers and traditional communities in Africa has increased in recent years as a supposed form of malaria prophylaxis, although its use is not recommended due to lack of efficacy. The risk of severe malaria complications that can lead to death is real regarding said behavior, and awareness needs to be raised. We report a case of severe Plasmodium falciparum malaria imported in the Amazon rainforest by a traveler returning from Cameroon who treated himself with Artemisia annua herbal tea.

The Association between CRP Levels with Comorbidities, Species, and Complications of Severe Malaria

Background: Malaria remains a leading cause of mortality in sub-Saharan Africa (including Sudan). C-reactive protein (CRP) is useful as a marker of severity in malaria. African studies have shown that serum CRP levels correlate with parasite burden and complications in malaria, especially falciparum. However, there are no data on CRP levels in Sudanese malaria patients. This study aims to evaluate the association between CRP levels with comorbidities, species, and complications of severe malaria Subjects and Methods: A cross-sectional study enrolled 65 severe malaria patients at Khartoum state hospitals during the period from April to June2021. Manifestations of severe malaria were defined according to WHO criteria. Data regarding demographics, presenting symptoms &amp; signs, laboratory investigations, complications, length of hospital stay and outcomes were collected. CRP was classified as elevated when the measured level was &gt;10 mg/l. Results: Among 65 patients, 33(50.8%) were females and 32(49.2%) were males, and mean age was 48±21 years. The main manifestation of severe malaria diagnosis criteria was anemia in 26(40%) patients. Most of the patients had density 1+ (n=53; 81.5%) and were infected by P. falciparum (n=61; 93.8%). The overall case fatality rate for malaria was 8% (n=15 patients). The mean of CRP was 72±57 mg/L and 84% (n=55) of patients had elevated levels above 10 mg/L (ranged from 10-100 mg/L in 52%, and above 100 mg/L in 32%). The elevated CRP levels were significantly DM (P= 0.048), high malaria parasite density in blood film (P= 0.001), P. falciparum (P= 0.33), presence of complications (P= 0.001) and death (P= 0.003) Conclusion: Elevated CRP levels were found in a considerable proportion of severe malaria patients. CRP is an effective biomarker in assessing malaria severity and poor prognosis in term of complications development and mortality.

Complications of Kidney in Severe Malaria

Malaria is an infectious protozoan parasitic disease transmitted by Anopheles spp mosquito. As a disease entity, malaria is still a major global health problem due to its morbidity and mortality that endangered millions of individuals inhabitants in tropical region. Kidney derangement is moderately frequent in severe malaria caused by the species P. falciparum and also P. malariae, but seldom this condition has also been reported in malaria due to P. vivax. Severe or complicated malaria can occur due to delay or failure of treatment. Making correct and early diagnosis is a prerequisite for successful treatment. Actually, a series of events that begins with the entry of blood protozoa into the host which then causes hemodynamic disturbances and loss of normal capillary capacity. Hemodynamic dysfunction, immune response and with addition from the consequences of severe malaria complications in other organs (e.g., liver) leading to worsening of kidney function in severe malaria. This paper cover the recent findings of kidney involvement in severe malaria and other important facts related to this issue.

Deficiency of migration inhibitory factor influences the gut microbiota of C57BL/6 mice infected with Plasmodium berghei ANKA.

Cerebral malaria (CM), as one of the most common complications in severe malaria, has threatened millions of individuals’ neurological health and even their lives. Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory factor in humans, seems to be a risk factor for death in patients with CM, but its functional mechanism remains unclear. To verify whether affecting the intestinal microbes of the host was one of the mechanisms by which MIF regulates CM, C57BL/6 mice, including WT + PbA, MIF-KO + PbA and their uninfected controls, were sent for 16S rRNA-based sequencing targeting the V4 region of the intestinal microbiota through the Illumina MiSeq platform. The results showed that OTU clustering, alpha and beta diversity in the four groups involved had evident variation. The relative abundance at different taxonomic levels, especially the dominant intestinal flora, was obviously changed. The LEfSe analysis screened out several biomarkers, including significantly reduced Ligilactobacillus (Lactobacillus murinus) in WPbA mice compared to the WT group and Akkermansia (Akkermansia_muciniphila) in KPbA mice compared to the WPbA group. For MIF KO groups, mice infected with PbA or uninfected showed significant enrichment of producers of short-chain fatty acids, including Dubosiella and Faecalibaculum (Faecalibaculum rodentium) in KPbA, and Lachnospiraceae_NK4A136_group and Firmicutes_bacterium_M10-2 in KO. This study not only further proved the gut microbiota changes in C57BL/6 mice caused by PbA infection, but also found that MIF deletion directly affected the changes in the gut microbiota of C57BL/6 mice before and after PbA infection. This finding reveals a potential mechanism by which MIF regulates CM. Combining MIF with potential microbial biomarkers will provide a promising idea to develop combined drugs for improving CM in the future.

Treatment Reducing Endothelial Activation Protects against Experimental Cerebral Malaria.

Cerebral malaria (CM) is the most severe neurological complication of malaria caused by Plasmodium falciparum infection. The available antimalarial drugs are effective at clearing the parasite, but the mortality rate remains as high as 20% of CM cases. At the vascular level, CM is characterized by endothelial activation and dysfunction. Several biomarkers of endothelial activation have been associated with CM severity and mortality, making the brain vascular endothelium a potential target for adjunctive therapies. Statins and Angiotensin II Receptor Blockers (ARBs) are drugs used to treat hypercholesterolemia and hypertension, respectively, that have shown endothelial protective activity in other diseases. Here, we used a combination of a statin (atorvastatin) and an ARB (irbesartan) as adjunctive therapy to conventional antimalarial drugs in a mouse experimental model of CM. We observed that administration of atorvastatin–irbesartan combination decreased the levels of biomarkers of endothelial activation, such as the von Willebrand factor and angiopoietin-1. After mice developed neurological signs of CM, treatment with the combination plus conventional antimalarial drugs increased survival rates of animals 3–4 times compared to treatment with antimalarial drugs alone, with animals presenting lower numbers and smaller hemorrhages in the brain. Taken together, our results support the hypothesis that inhibiting endothelial activation would greatly reduce the CM-associated pathology and mortality.

Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria.

Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.

Incidence and predictors of acute kidney injury in children with severe malaria

&#x0D; &#x0D; &#x0D; Background Acute kidney injury (AKI) is an underrecognized complication of severe malaria and an independent risk factor for mortality among children.&#x0D; Objective To determine the incidence and factors predictive of AKI as defined by the pediatric risk, injury, failure, loss, and end-stage (pRIFLE) criteria in children with severe malaria and to assess in-hospital mortality rates in malarial AKI (MAKI).&#x0D; Methods This was a prospective cohort study in 170 children aged 0.5 to 14 years with confirmed Plasmodium falciparum on peripheral blood smears and clinical and/or laboratory features of severe malaria. Serum creatinine was determined using the Jaffe method and glomerular filtration rate (eGFR) was estimated using the Schwartz equation. The primary outcome was the incidence of AKI as defined by the pRIFLE criteria. Secondary outcomes included in-hospital mortality comparison between AKI and non-AKI groups, as well as factors predictive of AKI.&#x0D; Results The incidence of MAKI was 61.2% (104/170) and was comparable between males (66.7%) and females (70.6%). Mean eGFR was lower among children with AKI than those without [42.00 (SD 22) vs. 98.7 (SD 3.9) mL/min/1.73m2, respectively; P=0.005]. Children with MAKI were categorized as having risk (47/104; 45.2%), injury (33/104; 31.7%), or failure (24/104; 23.1%). Mortality rates in AKI and non-AKI subjects were comparable (4.8% vs. 4.6%; P=0.888). Predictors of MAKI were hemoglobinuria [adjusted OR (aOR) 3.948; 95%CI 1.138 to 8.030], deep acidotic breathing (aOR 2.991; 95%CI 3.549 to 66.898), and longer hospital stay (aOR 2.042; 95%CI 3.617 to 12.156). Children with MAKI were more likely to have a longer hospital stay by a mean of 2.5 days.&#x0D; Conclusion AKI is a common complication in children with severe malaria. MAKI has a low mortality rate comparable to those with severe malaria but without AKI. Hemoglobinuria, deep acidotic breathing, and longer hospital stay were predictive of MAKI.

Plasmodium falciparum Parasite Lines Expressing DC8 and Group A PfEMP1 Bind to Brain, Intestinal, and Kidney Endothelial Cells.

Cytoadhesion of Plasmodium falciparum-infected red blood cells is a virulence determinant associated with microvascular obstruction and organ complications. The gastrointestinal tract is a major site of sequestration in fatal cerebral malaria cases and kidney complications are common in severe malaria, but parasite interactions with these microvascular sites are poorly characterized. To study parasite tropism for different microvascular sites, we investigated binding of parasite lines to primary human microvascular endothelial cells from intestine (HIMEC) and peritubular kidney (HKMEC) sites. Of the three major host receptors for P. falciparum, CD36 had low or negligible expression; endothelial protein C receptor (EPCR) had the broadest constitutive expression; and intercellular adhesion molecule 1 (ICAM-1) was weakly expressed on resting cells and was strongly upregulated by TNF-α on primary endothelial cells from the brain, intestine, and peritubular kidney sites. By studying parasite lines expressing var genes linked to severe malaria, we provide evidence that both the DC8 and Group A EPCR-binding subsets of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family encodes binding affinity for brain, intestinal, and peritubular kidney endothelial cells, and that DC8 parasite adhesion was partially dependent on EPCR. Collectively, these findings raise the possibility of a brain-gut-kidney binding axis contributing to multi-organ complications in severe malaria.

Effects of Leishmania Species on Immune Response against Malaria Parasite in Malaria Leishmania Coinfections

Both malaria and leishmania are most widespread protozoon parasitic diseases, certainly in tropical countries of the world. Malaria leishmania coinfection is common in leishmaniasis endemic areas which is mostly endemic to malaria too.&#x0D; Researchers notice that in cases of malaria leishmania coinfection , leishmania species find the some extent the outcome of malaria infection , but also behavior of malaria parasite species play a significant role to figure the consequences of it. While L. donovani protect from severe malaria complications by suppression of major histocompatibility class Ⅱ , so it diminish the clinical severity of malaria but not malaria parasite density due to dysfunction of major histocompatibility class I, which controlled by suppressed one, In another side L. mexicana tends to sequester in macrophages and lead to severe clinical outcomes when it coexisted with malaria parasite at same host. Experimental studies required to know more information about coinfection of different malaria and leishmania species to establish clinical research.&#x0D; Leishmania infection excluded when studies aim to assess the immune response to only malaria parasite, experimental studies required involving different species of malaria and leishmania.