Complicated Plasmodium Falciparum Malaria Research Articles

Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.

ObjectiveCerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels).MethodsWe used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co‐localisation in the retinal microvasculature.ResultsIn ‘true‐CM’ subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74–91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8–24%) in ‘faux‐CM’ (P‐value = 0.001). 41% (IQR = 28–49%) of capillaries in ‘true‐CM’ subjects showed co‐localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in ‘faux‐CM’ (IQR = 0–3.9%, P‐value = 0.01). Vascular leak was rare in the absence of MMP8 staining.ConclusionMatrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.

Optimizing the Intensive Care Treatment of Severe and Complicated Plasmodium falciparum Malaria in Nonimmune Patients.

This study analyses the intensive care treatment of 48 patients admitted to the Intensive Care Unit (ICU) at the Infectious Diseases Clinical Hospital No. 2, Moscow, Russia, between 2007 and 2019, with a severe and complicated form of P. falciparum malaria (B50.8 ICD 10). Objective. The aim of this study was to improve the intensive care treatment for severe and complicated P. falciparum malaria. The treatment strategy implemented was aimed at preventing ischaemia-reperfusion injury to organs, as well as haemorrhagic complications. The ICU Case Management Protocol set up indications for transferring patients to the ICU which provide preventive (prior to the development of renal failure) application of extracorporeal hemocorrection methods (continuous venous-venous hemodiafiltration and plasmapheresis in a plasma exchange mode) and mechanical ventilation under a medically induced coma, given impaired consciousness as the initial symptom of patients. Results. Successful treatment outcome in a majority of the patients (93.8%), shorter ICU length of stay (6.67 ± 1.9 days as compared to 94 ± 1.6 before introduction of the protocol), a median parasite clearance time of 37.50 hours (95% CI 36.21–38.18), and a reduced mortality rate from 29.1% to 6.25% support the efficacy of the ICU protocol in managing severe and complicated P. falciparum malaria.

M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema

BackgroundPulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE.MethodsLung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes.ResultsLung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups.ConclusionsThe study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.

Inhibition of EIF-5A prevents apoptosis in human cardiomyocytes after malaria infection.

In this study, a determination of Troponin I and creatine kinase activity in whole-blood samples in a cohort of 100 small infants in the age of 2-5years from Uganda with complicated Plasmodium falciparum malaria suggests the prevalence of cardiac symptoms in comparison to non-infected, healthy patients. Troponin I and creatine kinase activity increased during infection. Different reports showed that complicated malaria coincides with hypoxia in children. The obtained clinical data prompted us to further elucidate the underlying regulatory mechanisms of cardiac involvement in human cardiac ventricular myocytes. Complicated malaria is the most common clinical presentation and might induce cardiac impairment by hypoxia. Eukaryotic initiation factor 5A (eIF-5A) is involved in hypoxia induced factor (HIF-1α) expression. EIF-5A is a protein posttranslationally modified by hypusination involving catalysis of the two enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase. Treatment of human cardiomyocytes with GC7, an inhibitor of DHS, catalyzing the first step in hypusine biosynthesis led to a decrease in proinflammatory and proapoptotic myocardial caspase-1 activity in comparison to untreated cardiomyocytes. This effect was even more pronounced after co-administration of GC7 and GPI from P. falciparum simulating the pathology of severe malaria. Moreover, in comparison to untreated and GC7-treated cardiomyocytes, co-administration of GC7 and GPI significantly decreased the release of cytochrome C and lactate from damaged mitochondria. In sum, coadministration of GC7 prevented cardiac damage driven by hypoxia in vitro. Our approach demonstrates the potential of the pharmacological inhibitor GC7 to ameliorate apoptosis in cardiomyocytes in an in vitro model simulating severe malaria. This regulatory mechanism is based on blocking EIF-5A hypusination.

A potential for crosstalk between inflammation, coagulation and oxidative stress host responses in malaria induced mid-gestational pregnancy loss in a rodent model

Abstract Despite an overall reduction in the global malaria burden, placental malaria (PM) is a major complication of Plasmodium falciparum malaria that impacts hundreds of thousands of pregnancies annually. Primigravid women living in Sub-Saharan Africa are especially prone to PM and often experience poor maternal-fetal health outcomes though pregnancy loss, preterm delivery and infant low birth weight. Mouse models for malaria infection during pregnancy have been instrumental in our current understanding of PM, however our understanding remains incomplete. In the laboratory of Dr. Julie Moore, we have developed a mouse model of infection during pregnancy using the murine-infective species P. chaubaudi chaubaudi AS (PccAS). Infection initiated at gestation day 0 (GD 0) in mice deficient in tumor necrosis factor (TNF) function or signaling and intact C57BL/6J control mice treated with antioxidant and anticoagulant drugs reveals distinct differences in pregnancy outcome at mid-gestation (GD 10). While control mice lose their pregnancies, TNF deficient and drug-treated mice experience rescue of mid-gestational pregnancy and display improved offspring viability at sacrifice. These preliminary findings suggest that by disrupting the function of key host mediators of severe malaria, it may be possible to mitigate negative pregnancy outcomes associated with malaria. Through strategic use of TNF modified mice, combined with studies of gene expression and tissue localization, this work aims to investigate crosstalk between three major host responses to infection - inflammation, coagulation and oxidative stress – and characterize how their interplay may contribute to PM pathogenesis and associated negative pregnancy outcomes.

Long-Term Neurological Deficits in Child Survivors of Plasmodium falciparum Cerebral Malaria in Sub-Saharan Africa

Cerebral malaria, characterized by multiple seizures, coma, and other neurological abnormalities, is a particularly devastating complication of Plasmodium falciparum malaria. Children in sub-Saharan Africa comprise the most susceptible group to cerebral malaria worldwide, with more than 575,000 cases each year. Long-term neurological deficits—including motor impairments, language regression, cognitive deficits, behavioural abnormalities, and epilepsy—occur in approximately 25% of child survivors of cerebral malaria, which is now recognized as the leading cause of childhood neurodisability in sub-Saharan Africa. These neurological sequelae generate a significant economic and social burden as child survivors’ impaired intellectual function impacts their prospects for education and future employment. While current understanding of risk factors, disease mechanisms, and treatments for these neurological deficits is lacking, recent studies have shown great promise in revolutionizing the way that cerebral malaria is diagnosed and treated. It is speculated that during an acute attack of cerebral malaria, an inflammatory response to malarial antigens in neural blood vessels triggers a cascade of events that ultimately results in cerebral tissue damage and hemorrhaging into the brain, causing long-term brain damage. Potential risk factors for neurological deficits include the duration of coma, the occurrence of multiple seizures, and high fever. Malaria retinopathy and angiopoietin are being investigated as potential biomarkers to improve the definitive diagnosis of cerebral malaria. New drug therapies to prevent long-term neurological deficits after cerebral malaria include erythropoietin and statins, and cognitive rehabilitation and speech therapy have been shown to be successful in rehabilitating survivors.

Acute severe pancreatitis in falciparum malaria

Though different organs have been involved in falciparum malaria, pancreas has not been a common organ involved so far. Pancreatitis is a rare complication of Plasmodium falciparum malaria. The patient was admitted with low Glasgow Coma Scale and was febrile and in hypotension, and with oral bleeding. Preliminary investigations revealed leukocytosis, severe anemia, low platelet count, abnormal renal function test, deranged liver enzymes with conjugated hyperbilirubinemia, raised international normalized ratio, and hypoalbuminemia. Arterial blood gas showed metabolic acidosis. The raised pancreatic enzymes with radiological evidence of pancreatitis helped establish the diagnosis. Patient's condition improved with antimalarial, blood transfusion, circulatory support, and hemodialysis. The most possible mechanism of pancreatitis in malaria is microvascular occlusion with resultant ischemia, activation of pancreatic enzymes, and injury to pancreas due to autodigestion. Prognosis was good in our case of malarial pancreatitis.

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

SummaryBackgroundThe global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya.MethodsWe did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category.Findings2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70–0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99–1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22–2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86–1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82–1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls.InterpretationHeterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments.FundingWellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative).

Vascular dysfunction as a target for adjuvant therapy in cerebral malaria.

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions.

Nuclear factor kappa B in urine sediment: a useful indicator to detect acute kidney injury in Plasmodium falciparum malaria

BackgroundAcute kidney injury (AKI) is one of the major complications of Plasmodium falciparum malaria, especially among non-immune adults. It has recently been revealed that activation of transcription factor nuclear factor kappa B (NF-κB) induces pro-inflammatory gene expression involved in the development of progressive renal inflammatory diseases. The aim of this study was to determine whether urinary sediment NF-κB p65 can act as a biomarker for AKI in patients with P. falciparum malaria.MethodsUrinary sediments from malaria patients, including Plasmodium vivax malaria, uncomplicated P. falciparum malaria, complicated P. falciparum malaria without AKI (serum creatinine-Cr <3 mg/dl) and complicated P. falciparum malaria with AKI (Cr ≥3 mg/dl) were used to determine NF-κB p65 level by sandwich enzyme-linked immunosorbent assay (ELISA). Urinary sediments obtained from healthy controls were used as a normal baseline. Correlations between levels of urinary sediment NF-κB p65 and pertinent clinical data were analysed.ResultsUrinary sediment NF-κB p65 levels were significantly increased on the day of admission (day 0) and on day 7 post-treatment in complicated P. falciparum malaria patients with AKI, compared with those without AKI (p = 0.001, p <0.001, respectively), P. vivax patients (all p <0.001) and healthy controls (all p <0.001). NF-κB p65 levels in urinary sediment cells showed a significant positive correlation with serum Cr (Day 0: rs = 0.792; p <0.001, Day 7: rs = 0.605; p <0.001) and blood urea nitrogen (BUN) (Day 0: rs = 0.839; p <0.001, Day 7: rs = 0.596; p <0.001).ConclusionsUrinary sediment NF-κB p65 level is a useful indicator for estimating renal tubular epithelial cell damage and subsequent development of AKI among patients with P. falciparum malaria.

Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review

BackgroundSevere malaria remains a major cause of pediatric hospital admission across Africa. Invasive bacterial infection (IBI) is a recognized complication of Plasmodium falciparum malaria, resulting in a substantially worse outcome. Whether a biological relationship exists between malaria infection and IBI susceptibility remains unclear. We, therefore, examined the extent, nature and evidence of this association.MethodsWe conducted a systematic search in August 2012 of three major scientific databases, PubMed, Embase and Africa Wide Information, for articles describing bacterial infection among children with P. falciparum malaria using the search string ‘(malaria OR plasmodium) AND (bacteria OR bacterial OR bacteremia OR bacteraemia OR sepsis OR septicaemia OR septicemia).’ Eligiblity criteria also included studies of children hospitalized with malaria or outpatient attendances in sub-Saharan Africa.ResultsA total of 25 studies across 11 African countries fulfilled our criteria. They comprised twenty cohort analyses, two randomized controlled trials and three prospective epidemiological studies. In the meta-analysis of 7,208 children with severe malaria the mean prevalence of IBI was 6.4% (95% confidence interval (CI) 5.81 to 6.98%). In a further meta-analysis of 20,889 children hospitalised with all-severity malaria and 27,641 children with non-malarial febrile illness the mean prevalence of IBI was 5.58 (95% CI 5.5 to 5.66%) in children with malaria and 7.77% (95% CI 7.72 to 7.83%) in non-malaria illness. Ten studies reported mortality stratified by IBI. Case fatality was higher at 81 of 336, 24.1% (95% CI 18.9 to 29.4) in children with malaria/IBI co-infection compared to 585 of 5,760, 10.2% (95% CI 9.3 to 10.98) with malaria alone. Enteric gram-negative organisms were over-represented in malaria cases, non-typhoidal Salmonellae being the most commonest isolate. There was weak evidence indicating IBI was more common in the severe anemia manifestation of severe malaria.ConclusionsThe accumulated evidence suggests that children with recent or acute malaria are at risk of bacterial infection, which results in an increased risk of mortality. Characterising the exact nature of this association is challenging due to the paucity of appropriate severity-matched controls and the heterogeneous data. Further research to define those at greatest risk is necessary to target antimicrobial treatment.

A case of acute respiratory distress syndrome with Plasmodium vivax malaria

Malaria is an important treatable cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the tropics and in the returning traveller in the nonendemic areas. ARDS is an important complication in severe, complicated Plasmodium falciparum malaria and has been described rarely in Plasmodium vivax and Plasmodium ovale malaria also. Malarial ALI/ARDS is more common in adults than in children. Pregnant women and nonimmune individuals are more prone to develop this condition. Increased alveolar capillary permeability resulting in intravascular fluid loss into the lungs appears to be the key pathophysiologic mechanism. The diagnosis of malaria is confirmed by slide microscopy supported by the use of rapid antigen tests. Patients with malarial ARDS should be managed in an ICU. Careful attention must be paid to haemodynamic stabilisation and optimising fluid balance. We hereby present a case of a 28-year-old man who presented with ARDS and P. vivax malaria demonstrated by slide microscopy.

Cross‐presentation of malaria antigen by brain microvessels: why CD8+ T cells are critical for the pathogenesis of experimental cerebral malaria

Cross‐presentation of malaria antigen by brain microvessels: why <scp>CD</scp>8⁺ T cells are critical for the pathogenesis of experimental cerebral malaria

Hematological Parameters in Severe Complicated Plasmodium falciparum Malaria among Adults in Aden

Objective: To study some hematological parameters in adult patients with complicated severe malaria and their relations to clinical outcome. Materials and Methods: This was a prospective study, including 77 patients from Aden Governorate with complicated severe malaria over the course of 2 years (2010-2011). Results: The common form of severe malaria in Aden was cerebral malaria (25.9%), followed by renal failure (18.2%), severe anemia (16.9%), and hepatitis (14.3%), with a case fatality rate of 7.8%. Hemoglobin concentration was significantly different among the various complications of severe malaria, while platelet and white blood cell counts did not show such differences. The mean age was older among patients that died. Hematological parameters did not significantly differ among dead or surviving patients. Thrombocytopenia was seen in 42.9% of patients and 18.2% of these had platelet counts of <50.0x109/L. However, none of them developed bleeding.Conclusion: This study concluded that hematological changes are common complications encountered in severe malaria, but they are not related to the clinical outcome. Conflict of interest:None declared.

Incidence of renal involvement in malaria in children of odisha.

About 500 million people suffer from malaria leading to death in 2-3 million cases every year, of which about 1 million are children. Horstman et al., 1985, and Weber et al., 1991, demonstrated an acute renal failure as a well-described complication of Plasmodium falciparum malaria in nonimmune adults and a major contributor to their mortality. In children, renal failure, though not very common, has become a rising issue leading to death. This study aims at determining the incidence of renal complication in malaria cases reported in children of Odisha. 108 cases of malaria who were admitted to Department of Paediatrics, SCB Medical College and Hospital and Sardar Vallab Bhai Patel Post Graduate Institute of Paediatrics, Cuttack, Odisha, India during the period from July 2006 to November 2008 were included in the prospective study. Extensive investigations were carried out to check for renal involvement in these cases. 50.9% of cases showed some form of renal involvement, most of which were recorded in age group of 5–10 years. Overall, males had a higher incidence than females. 62.7% of total cases infected with P. falciparum showed renal involvement though mixed infections with both P. falciparum and P. vivax had 100% renal involvement.

Association of ABO blood groups and complicated Plasmodium falciparum malaria in Accra, Ghana

Background: Balamuthia amoebic encephalitis (BAE) is a serius human disease (caused by Balamuthia mandrillaris) almost lways leading to death. An important step in BAE is amoebae nvasion of the bloodstream, followed by their haematogenous pread. Balamuthia mandrillaris entry into the central nervous sysem (CNS)most likely occurs at the blood–brain barrier (BBB) sites. acrophages are thought to be the first line of defense in many nfectious diseases and are present in high numbers during infecions. The objective of the present study was to determine the mpact of cytokines and macrophages on the virulence characterstics of B. mandrillaris in vitro. Methods: In vitro, B. mandrillaris were used to demonstrate he effects of cytokines and macrophages on the physiological nd morphological characteristics of amoeba. Using human brain icrovascular endothelial cells (HBMEC), which constitutes the lood–brain barrier, adhesion and cytotoxicity assays were perormed. To investigate the engulfing property of the amoeba, hagocytosis assays were performed using fluorescein isothioyanate (FITC) labeledE. coliK12.Moreover zymographyassaywere lso used to observe the proteolytic activity of amoeba. Results: It was observed B. mandrillaris exhibited >90% binding nd>70% cytotoxicity toHBMECwhichwas further enhanced in the resence of cytokines and macrophages. It has also been observed hat cytokines TNFand TGFsignificantly increased the B. manrillaris numbers in the presence ofmacrophages. It is important to ote that amoebic numbers were more than doubled in the presnce of cytokines and macrophages within 24h. We have shown in he past the bacteria uptake by B. mandrillaris is limited which is urther significantly inhibited in the presence of cytokines during hagocytosis assays. Zymography assays revealed that cytokines nd macrophages have no inhibitory effect on proteolytic activty of B. mandrillaris. In addition the activated macrophages also ould not show any vital inhibitory effects on amoebic virulence roperties. Conclusion: Overall we described for the first time that ytokines and macrophages has no inhibitory effects on the virlence properties of B. mandrillaris in vitro.

Significant Association of KIR2DL3-HLA-C1 Combination with Cerebral Malaria and Implications for Co-evolution of KIR and HLA

Cerebral malaria is a major, life-threatening complication of Plasmodium falciparum malaria, and has very high mortality rate. In murine malaria models, natural killer (NK) cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria. To investigate the role of NK cells in the developmental process of human cerebral malaria, we conducted a case-control study examining genotypes for killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was significantly associated with the development of cerebral malaria when compared with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52–6.48, P = 0.00079, corrected P = 0.02). In contrast, no other KIR-HLA pairs showed a significant association with cerebral malaria, suggesting that the NK cell repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional responses that facilitate development of cerebral malaria. Furthermore, the frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower in malaria high-endemic populations. These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic populations because of the propensity of interaction between KIR2DL3 and C1 to favor development of cerebral malaria. Our findings provide one possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its effect on the global distribution of malaria, KIR and HLA.

Plasmodium vivax presenting as acute glomerulonephritis in a 3-year-old child

Although acute glomerulonephritis is a rare complication of Plasmodium falciparum malaria, it has not been reported in connection with Plasmodium vivax. We report a case of complicated P. vivax malaria presenting as acute glomerulonephritis. A three-year-old boy presented with high grade fever, a seven-day history of the progressive swelling of his body and a one-day history of vomiting. An examination revealed hypertension (>95th percentile), pallor and hepatosplenomegaly. Investigations showed a platelet count 80,000/mm(3) with haematuria [20-30 red blood cells/high power field with more than 80% dysmorphic red blood cells]. A peripheral smear showed the presence of trophozoites of P. vivax. The patient was diagnosed as having P. vivax causing acute glomerulonephritis and was treated successfully with antimalarials and enalapril. With the changing epidemiological pattern of malaria, especially in endemic areas, unusual complications such as acute glomerulonephritis may sometimes present in cases of P. vivax malaria.

Blood group O protects against complicated Plasmodium falciparum malaria by the mechanism of inducing high levels of anti-malarial IgG antibodies

In a prospective clinical study in North Kordofan (Western Sudan), the possible association between blood groups and anti-malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 184 individuals were consecutively enrolled from an outpatient clinic. Sixty six (35.9%) patients were classified as complicated malaria (CM), 53 (28.8%) with uncomplicated malaria (UM) and 65 (35.3%) were malaria free controls (MFC). Phenotypes of ABO blood groups were typed using commercial anti-sera. The antibody responses to MSP2 malaria antigens were assessed by an enzyme-linked immunosorbent assay (ELISA). The frequency of O blood group was significantly lower in those with CM when compared with MFC and UM patients (P value < 0.001 and 0.002 respectively). The levels of IgG1, IgG2 and IgG3 antibodies were statistically significantly higher in UM and MFC compared with CM patients. Statistical analysis indicated that higher levels of total IgG, IgG1, IgG2, and IgG3 specific to the MSP2 (both antigen forms, 3D7 and FC27) were associated with a reduced risk of complicated CM in O blood type carriers than in non-O blood type carriers, P value <0.001. Taken together, the current study indicates that blood group O is associated with a reduction in the risk of developing complicated malaria in western Sudan. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite-neutralizing immune mechanisms.

Clinical Profile and Outcome of Complicated Plasmodium falciparum Malaria

Context: Complicated Plasmodium falciparum Malaria is a syndrome and a disease of protean, clinical manifestations including jaundice, ARF, ARDS and multi-organ failure. Aims: The objectives of the present study are to study clinical features, complications and factors affecting outcome of patients with complicated P. falciparum Malaria. Settings and Design: This retrospective descriptive study was conducted at tertiary care centre in western Maharashtra from January 2010 to December 2010. Methods and Material: Total 73 patients with complicated P. falciparum malaria who presented with fever having positive trophozoites of P. falciparum in blood smear were included. SPSS (version-10) software was used for all statistical calculations. Results: A total 73 patients had complicated P. falciparum malaria with 52 were males and 21 were female patients. Total 9 (12.32 %) patients were presented with shock as a presenting feature. Four (5.47 %) patients had hypoglycaemia at the time of admission. Total 43 (58.90 %) patients had jaundice, 37 (50.68 %) had anaemia, 28 (38.35 %) had cerebral malaria, 7 (9.58 %) had acute renal failure, 5 (6.84 %) had ARDS and 5 (6.84 %) had thrombocytopenia. Total 46 patients had single complication in the form of cerebral malaria 14 (19.17 %), jaundice 15 (20.54 %) and anaemia 16 (21.91 %). Total 14 patients had two complications in the form of jaundice with ARF 02 (2.73 %) with one (50 %) death and jaundice with anaemia 12 (16.43 %). Total 9 (12.32 %) patients had three complications in the form of cerebral malaria with jaundice with anaemia with 3 deaths (33.33 %). Total 5 (6.84 %) patients had multiple complications in the form of cerebral malaria with ARF with ARDS with thrombocytopenia with 4 (80 %) death. Case fatality rate was 10.95 %. The case fatality rate with ARDS was 80 % (4/5), with ARF was 57.14 % (4/7) and with cerebral malaria it was 25 % (7/28). Case fatality rate was highest in patients with pulmonary complication (ARDS) compared to ARF, cerebral malaria, jaundice and anaemia with 'p' < 0.001. Conclusions: Acute renal failure and ARDS were least common presentation with poor outcome. In present study most common presentation was with jaundice and anaemia next to that was cerebral malaria. The case fatality rate of P. falciparum malaria was 10.95 %. Overall case fatality rate was highest with multi-organ dysfunction (80 %). Unusual early renal and pulmonary complications were the presenting features of complicated P. falciparum malaria were observed in present study. Presenting feature as a shock was invariably associated with either ARDS or ARF with high mortality. This study highlights the burden of complicated malaria including multi-organ dysfunction in western Maharashtra.