Procalcitonin is elevated in severe malaria and is a promising biomarker of severe malaria and multi-organ dysfunction: A cross-sectional study and meta-analysis.

BACKGROUND: Elevated procalcitonin (PCT) has been reported in bacterial infection and is positively associated with the severity of the disease. Patients with severe Plasmodium falciparum malaria also display higher procalcitonin levels compared to those with non-severe disease, indicating a possible role for bacterial infection in severe disease, however this observation remained variable in different study population. Furthermore, the significance of PCT in different clinical categories of severe malaria has not been evaluated so far. METHODS: A total of 74 P. falciparum-infected subjects were enrolled in the study comprising of 55 cases complicated malaria [cerebral malaria- 14; non-cerebral severe malaria- 21; multi-organ dysfunction- 20] and 19 uncomplicated cases. Serum levels of PCT were quantified by fluorescence immunoassay. For meta-analysis, the literature search was performed in different databases, and all relevant articles were screened, and eligible reports were identified based on predefined inclusion and exclusion criteria. The meta-analysis was performed by comprehensive meta-analysis software V3 and MedCalc 20.218. RESULTS: Patients with severe P. falciparum malaria had significantly higher PCT levels compared to uncomplicated cases (p = 0.01). Analysis of PCT in different categories of patients with severe malaria revealed significantly elevated PCT in multi-organ dysfunctions compared to those with uncomplicated malaria (p = 0.004) and cerebral malaria (p = 0.05). Interestingly the receiver operating characteristics curve analysis showed procalcitonin as a promising biomarker for differentiating severe malaria (AUC: 0.697, p = 0.01) and multi-organ dysfunction (AUC: 0.704, p = 0.007) from uncomplicated malaria and other clinical categories of falciparum malaria, respectively. Furthermore, meta-analysis also revealed an elevated procalcitonin in severe malaria and it could be an important biomarker in the management of severe disease. CONCLUSIONS: PCT is elevated in P. falciparum-infected patients and could be a good biomarker for diagnosis of severe malaria and multi-organ dysfunction. It can help in the management of severe disease with additional treatment options.

The role of MBL, PCT, CRP, neutrophil-lymphocyte ratio, and platelet lymphocyte ratio in differentiating infections from flares in lupus.

BACKGROUND: The distinction between infection and flare in systemic lupus erythematosus (SLE) has always been a dilemma for clinicians as the clinical and biochemical profiles overlap. The present study evaluated affordable biomarkers to distinguish infection from flare in an SLE cohort in a tertiary care center in eastern India. METHODS: One hundred and fifty-two SLE patients were clinically evaluated and enrolled in the present study. Hematological, immunological, and biochemical profiles and various biomarkers such as C reactive protein (CRP), procalcitonin (PCT), and Mannose-binding lectin (MBL) were quantified. RESULTS: One hundred and fifty-two patients (152) were enrolled in the present study and all had SLEDAI scores of more than 4. From which 70 had infection, and the common infections were urinary tract infection (34.28%) followed by pneumonia (27.14%). Neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) were significantly elevated in SLE with infections (NLR: 5.84 ± 2.47; CRP: 30.56 ± 41.63) than those with flare (NLR: 3.87 ± 2.62; CRP: 8.73 ± 9.53). The receiver operating characteristic curve (ROC) analysis revealed CRP, PLR, and NLR as important markers for predicting infections (CRP: AUC = 0.682, p = 0.0001; PLR: AUC = 0.668, p = 0.0008; NLR: AUC = 0.742, p < 0.0001). The MBL and PCT levels were comparable among SLE flare and those with infections. CONCLUSIONS: NLR and CRP levels are affordable biomarkers to distinguish infections from flares in SLE. MBL and PCT could not differentiate flare from an infection. Key Points • Biomarkers for the differentiation of infection and flare in SLE are limited. • NLR, PLR, and CRP are promising biomarkers to enable differentiation. • PCT and MBL are not ideal biomarkers to differentiate infection from flare.

Role of interleukin-6 and interferon-α in systemic lupus erythematosus: A case-control study and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting various organ systems with unknown etiology. Interleukin-6 (IL-6) and interferon-alpha (IFN-α) have been shown to have a major role in disease pathogenesis, and they correlate with SLE disease activity, but reports in the literature are conflicting. The present study aims to investigate the significance of IL-6 and IFN-α levels in SLE pathogenesis in an eastern Indian cohort. MATERIAL AND METHODS: 70 SLE patients fulfilled SLICC 2012 criteria, and 40 age- and gender-matched healthy controls (HC) were enrolled. Baseline characteristics along with disease activity were recorded for all patients. Levels of IL-6 and IFN-α were measured by using ELISA. For the meta-analysis, published articles were searched through different databases. Two independent researchers extracted data, and the meta-analysis was performed with CMA v3.1. RESULTS: The plasma levels of IL-6 and IFN-α in SLE patients were significantly elevated compared to HC (IL-6: p < .0001, IFN-α: p = 0.01). SLEDAI score correlated positively with plasma IL-6 (p < .0001, r = 0.46) and IFN-α levels (p < .0001; r = 0.47). Meta-analysis of previous reports, including our case-control data, revealed higher IL-6 (p < .0001) and IFN-α (p = .005) in SLE patients compared to HC. Furthermore, IL-6 (p < .0001, r = 0.526) and IFN-α (p < .0001; r = 0.371) levels positively correlated with the disease activity. CONCLUSION: IL-6 and IFN-α levels are elevated in SLE and they correlate with disease activity. Further studies with a larger sample size in different populations are required to validate our findings.

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study.

BACKGROUND: Cluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (-159 C > T) with susceptibility to SLE or disease severity needs to be defined. METHODS: Two hundred female SLE patients diagnosed on systemic lupus international collaborating clinics (SLICC) classification criteria and age, sex, matched healthy controls were enrolled in the present study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: Prevalence of mutant genotypes (CT and TT) and minor allele (T) of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT: P < 0.0001; OR = 3.26, TT:P < 0.0001; OR = 3.39; T:P = 0.0009, OR = 1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P = 0.0002, OR = 8.07; T: P = 0.001, OR = 1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLE disease activity index-2K (SLEDAI-2K) scores and 24 hours proteinuria. CONCLUSION: CD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.

TNF-α promoter polymorphisms (G-238A and G-308A) are associated with susceptibility to Systemic Lupus Erythematosus (SLE) and P. falciparum malaria: a study in malaria endemic area.

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine associated with autoimmune and infectious diseases. Importance of TNF-α in P. falciparum malaria and systemic lupus erythematosus (SLE) have been demonstrated. However, association of functional promoter variants with SLE and malaria is lacking in malaria endemic population. A total of 204 female SLE patients and 224 age and sex matched healthy controls were enrolled in the study. Three hundred fourteen P. falciparum infected patients with different clinical phenotypes were included. TNF-α polymorphisms (G-238A & G-308A) were genotyped by PCR-RFLP. Plasma levels of TNF-α was quantified by ELISA. Heterozygous mutants and minor alleles of TNF-α (G-238A and G-308A) polymorphisms were significantly higher in SLE patients compared to healthy controls and associated with development of lupus nephritis. In addition, both promoter variants were associated with severe P. falciparum malaria. SLE patients demonstrated higher levels of plasma TNF-α compared to healthy controls. TNF-α (G-238A and G-308A) variants were associated with higher plasma TNF-α. In conclusion, TNF-α (G-238A & G-308A) variants are associated with higher plasma TNF-α levels in SLE patients residing in malaria endemic areas and could be a contributing factor in the development of SLE and susceptibility to severe P. falciparum malaria.

Cytokine Signature Associated with Disease Severity in Dengue.

Dengue is the most rapidly spreading viral disease transmitted by the bite of infected Aedes mosquitos. The pathogenesis of dengue is still unclear; although host immune responses and virus serotypes have been proposed to contribute to disease severity. In this study, we examined the circulating dengue virus (DENV) and measured plasma levels of inflammatory mediators. Ninety-eight patients during a dengue outbreak in eastern India in 2016 were included in the study. The presence of DENV was demonstrated by detecting NS1 antigen; IgM capture ELISA and serotypes were discriminated by type-specific RT-PCR and/or sequencing. Plasma samples were assayed for 41-plex cytokine/chemokines using multiplex Luminex assay. Eighty-five (87%) samples were positive by NS1/IgM capture ELISA/RT-PCR. All four serotypes of DENV were detected in this outbreak, with DENV-2 as the predominant type, seen in 55% of cases. Mixed infections were seen in 39% of subjects. Among the host inflammatory biomarkers, GM-CSF, IFN-γ, IL-10, IL-15, IL-8, MCP-1, IL-6, MIP-1ß, and TNF-α levels were significantly increased in dengue with and without warning signs, in severe dengue patients in comparison to healthy controls. Four cytokines IFN-γ, GM-CSF, IL-10, and MIP-1ß correlated significantly with disease severity and could serve as potential predictor for disease severity. Information on the host biomarkers and the dengue serotype may help guide in optimizing effective intervention strategies.

Association between vitamin D receptor polymorphisms and systemic lupus erythematosus in an Indian cohort.

AIM: Systemic lupus erythematosus (SLE) is an autoimmune disorder with various clinical manifestations. Susceptibility to development of SLE has been linked to several factors, such as genetic, environmental and hormonal. Vitamin D appears to have a regulatory role on disease manifestation and activity. Vitamin D exerts its effect through vitamin D receptors (VDR). Several studies have demonstrated an association between VDR polymorphisms and susceptibility to SLE in different populations, although the results are still inconclusive. In the present study, we investigated the association of VDR polymorphisms with SLE in a cohort of patients from Odisha, India. METHODS: Female SLE patients (n = 331) who fulfilled the revised American College of Rheumatology classification criteria were enrolled along with 282 healthy controls from similar geographical areas. VDR polymorphisms (BsmI, ApaI, TaqI and FokI) were typed by polymerase chain reaction followed by restriction fragment length polymorphism. Plasma level of 25-OH vitamin D was quantified by enzyme-linked immunosorbent assay. RESULTS: Prevalence of FokI (Ff) and TaqI (Tt) heterozygotes were significantly higher in SLE patients compared to healthy controls (Ff: P < 0.0001, odds ratio [OR] = 2.80, 95%CI = 1.99-3.95; Tt: P < 0.0001, OR = 2.07, 95%CI = 1.49-2.89). Furthermore, the minor alleles of FokI (f) and TaqI (t) polymorphisms were also more frequent in SLE patients than healthy controls (f: P < 0.0001, OR = 1.96, 95%CI = 1.52-2.52; t: P = 0.0002, OR = 1.60, 95%CI = 1.25-2.09). CONCLUSIONS: FokI and TaqI variants are significantly associated with SLE in an eastern Indian cohort. The cause-effect relationship can be assessed from the combined analyses of VDR polymorphism, plasma vitamin D levels and clinical manifestations.

Host metabolic responses to Plasmodium falciparum infections evaluated by 1H NMR metabolomics.

The human malarial parasite Plasmodium falciparum causes the most severe forms of malarial infections, which include cerebral malaria and various organ dysfunctions amongst adults in India. So far no dependable clinical descriptor is available that can distinguish cerebral malaria from other symptomatically similar diseases such as sepsis and encephalitis. This study aims at evaluating the differential metabolic features of plasma samples from P. falciparum patients with varying severities, and patients suffering from symptomatically similar diseases. 1H Nuclear Magnetic Resonance (NMR) based metabolic profiling of the plasma of the infected individuals and the control population was performed. The differences in the plasma profiles were evaluated through multivariate statistical analyses. The results suggest malaria-specific elevation of plasma lipoproteins. Such an increase was absent in control populations. In addition, cerebral malaria patients exhibited a decrease in plasma glycoproteins; such a reduction was not observed in malarial patients without cerebral symptoms. The data presented here indicates that the metabolism and/or transport of the plasma lipids is specifically perturbed by malarial infections. The differential perturbation of the plasma glycoprotein levels in cerebral malaria patients may have important implications in the diagnosis of cerebral malaria.

Heterozygous mutants of TIRAP (S180L) polymorphism protect adult patients with Plasmodium falciparum infection against severe disease and mortality.

Toll-interleukin-1 receptor domain containing adapter protein (TIRAP) plays a crucial role in TLR2 and TLR4 signaling pathways. Glycosylphospatidylinositol (GPI), considered a toxin molecule of Plasmodium falciparum, interacts with TLR2 and 4 to induce an immune inflammatory response. A single nucleotide polymorphism at coding region of TIRAP (S180L) has been reported to influence TLRs signaling. In the present study, we investigated the association of TIRAP (S180L) polymorphism with susceptibility/resistance to severe P. falciparum malaria in a cohort of adult patients from India. TIRAP S180L polymorphism was typed in 347 cases of severe malaria (SM), 232 uncomplicated malaria and 150 healthy controls. Plasma levels of TNF-α was quantified by ELISA. Heterozygous mutation (S/L) conferred significant protection against MOD (multi organ dysfunction), NCSM (non-cerebral severe malaria) as well as mortality. Interestingly, homozygous mutants (L/L) had 16 fold higher susceptibility to death. TIRAP mutants (S/L and L/L) were associated with significantly higher plasma TNF-α levels compared to wild type (S/S). The results of the present study demonstrate that TIRAP S180L heterozygous mutation may protect patients against severe malaria and mortality.

Non-Classical monocytes display inflammatory features: Validation in Sepsis and Systemic Lupus Erythematous.

Given the importance of monocytes in pathogenesis of infectious and other inflammatory disorders, delineating functional and phenotypic characterization of monocyte subsets has emerged as a critical requirement. Although human monocytes have been subdivided into three different populations based on surface expression of CD14 and CD16, published reports suffer from contradictions with respect to subset phenotypes and function. This has been attributed to discrepancies in reliable gating strategies for flow cytometric characterization and purification protocols contributing to significant changes in receptor expression. By using a combination of multicolour flow cytometry and a high-dimensional automated clustering algorithm to confirm robustness of gating strategy and analysis of ex-vivo activation of whole blood with LPS we demonstrate the following: a. 'Classical' monocytes are phagocytic with no inflammatory attributes, b. 'Non-classical' subtype display 'inflammatory' characteristics on activation and display properties for antigen presentation and c. 'Intermediate' subtype that constitutes a very small percentage in circulation (under physiological conditions) appear to be transitional monocytes that display both phagocytic and inflammatory function. Analysis of blood from patients with Sepsis, a pathogen driven acute inflammatory disease and Systemic Lupus Erythmatosus (SLE), a chronic inflammatory disorder validated the broad conclusions drawn in the study.

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India.

Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.

Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha.

INTRODUCTION: Low levels of vitamin D have been associated with several autoimmune disorders including multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus (SLE). The major source of vitamin D is sunlight but exposure of SLE patients to UV rays has been shown to exacerbate disease pathology. Studies in various populations have shown an association between low vitamin D levels and higher SLE disease activity. METHODS: We enrolled 129 patients who fulfilled American College of Rheumatology criteria in the study. There were 79 treatment-naïve cases and 50 patients who were under treatment for underlying SLE. There were 100 healthy subjects from similar geographical areas included as controls. Plasma 25-OH vitamin D3 and interferon (IFN)-α levels were quantified by enzyme-linked immunosorbent assay (ELISA). The gene expression level of IFN-α was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Plasma 25-OH vitamin D3 significantly correlated in an inverse manner with systemic lupus erythematosus disease activity index (SLEDAI) scores (P <0.0001, r = -0.42), anti-dsDNA (P <0.0001, r = -0.39), plasma IFN-α (P <0.0001, r = -0.43) and levels of IFN-α gene expression (P = 0.0009, r = -0.45). Further, plasma levels of IFN-α positively correlated with gene expression of IFN-α (P <0.0001, r = 0.84). Treatment-naïve SLE patients displayed significantly higher plasma levels of IFN-α compared to patients under treatment (P <0.001) and controls (P <0.001). CONCLUSIONS: These results suggest an important role of vitamin D in regulating disease activity in SLE patients and the need to supplement vitamin D in their treatment.

TLR-9 promoter polymorphisms (T-1237C and T-1486C) are not associated with systemic lupus erythematosus: a case control study and meta-analysis.

Toll like receptors (TLRs) are essential molecules implicated in both innate and adaptive immune response. Polymorphisms in TLR gene have been associated with various infectious diseases and autoimmune disorders. Role of TLR9 has been elegantly demonstrated in both human systemic lupus erythematosus (SLE) and mice model of lupus. In the present study we investigated association of TLR-9 promoter polymorphisms (T-1237C and T-1486C) with susceptibility/resistance to SLE in an Eastern Indian state which is endemic to parasitic diseases. 210 Female SLE patients who fulfilled the American College of Rheumatology criteria were enrolled along with matched healthy controls from Odisha, India. TLR-9 polymorphisms (T-1237C and T-1486C) were typed by polymerase chain reaction followed by restriction fragment length polymorphism. For meta-analysis, relevant literatures were searched from PubMed database and comprehensive meta-analysis V2 software was employed for analysis. Allele and genotype frequency of TLR-9 promoter polymorphisms (T-1237C and T-1486C) were comparable among SLE patients and controls. Further, meta-analysis of earlier reports and present study did not reveal a significant association of TLR-9 (T-1237C and T-1486C) polymorphisms with SLE. Data from the present study suggest that TLR-9 promoter polymorphisms are not associated with susceptibility to SLE in an area endemic to parasitic diseases.

Decreased prevalence of sepsis but not mild or severe P. falciparum malaria is associated with pre-existing filarial infection.

BACKGROUND: Enhanced inflammatory host responses have been attributed as the cellular basis for development of severe malaria as well as sepsis. In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype. This suggests that successful control of filariasis by employing mass drug administration, could potentially contribute to an increase in incidence of sepsis and cerebral malaria in human communities. A case control study was undertaken to address this critical and urgent issue. METHODS: Eighty-nine patients with sepsis and one hundred and ninety-six patients with P. falciparum malaria all originating from Odisha, were tested for prevalence of circulating filarial antigens - a quantitative marker of active filarial infection. Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients. RESULTS: Prevalence of filarial antigenemia was significantly less in sepsis patients as compared to controls suggesting that pre-existing filariasis could influence development of sepsis. On the other hand, levels of circulating filarial antigen were comparable in severe malaria cases and healthy controls suggesting that development of severe malaria is independent of pre-existing W. bancrofti infections. Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections. CONCLUSIONS: These observations imply that successful control of filariasis could have adverse consequences on public health by increasing the incidence of sepsis, while the incidence of severe malaria may not adversely increase as a consequence of elimination of filariasis.

Low producer MBL genotypes are associated with susceptibility to systemic lupus erythematosus in Odisha, India.

Variants of MBL gene have been associated with autoimmune disorders. The aim of this study was to explore whether common polymorphisms in MBL gene are associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort from eastern India. A total of 108 female SLE patients and 105 age, sex, and ethnically matched healthy controls were enrolled in the study. MBL2 codon and promoter polymorphisms were genotyped by AS-PCR and dARMS PCR, respectively. Plasma level of MBL was quantified by ELISA. Higher frequency of BB genotype and minor allele (B) was observed in patients of SLE compared to healthy controls (BB genotype: P = 0.0002; OR = 5.75, 95% CI = 2.09-15.76, B allele: P < 0.0001; OR = 2.78, 95% CI = 1.66-4.64). MBL codon 54, H-550L, Y-221X polymorphisms and combined MBL genotypes contributed to plasma MBL levels. Prevalence of MBL low producer genotype (LXA/LYB, LYB/LYB and LXB/LXB) was significantly higher in SLE patients compared to healthy control. (P = 0.005; OR = 3.09, 95% CI = 1.38-6.91). On analysis of clinical manifestations, MBL low producer genotype was significantly associated with autoimmune haemolytic anaemia (P = 0.006; OR = 13.06). Results of the present study indicate MBL2 variants as possible risk factors for development of SLE and clinical manifestation in eastern India.

Complement receptor 1 variants confer protection from severe malaria in Odisha, India.

BACKGROUND: In Plasmodium falciparum infection, complement receptor-1 (CR1) on erythrocyte's surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue. METHODS: Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database. RESULTS: The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria. CONCLUSIONS: The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.

Mannose binding lectin: a biomarker of systemic lupus erythematosus disease activity.

INTRODUCTION: A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE. METHODS: In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures. RESULTS: Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29). CONCLUSIONS: Plasma MBL is a promising marker in the assessment of SLE disease activity.

Bacteraemia in adult patients presenting with malaria in India.

Severe falciparum malaria is a major health problem in Odisha, India, contributing to high mortality. Multi organ dysfunction is a predominant manifestation of severe disease in Odisha, unlike in Africa, where cerebral malaria and anaemia are common. There are several studies implicating bacteraemia with severe malaria in African children while there are no reports in adults in India. This study has addressed this issue by enrolling 67 P. falciparum infected adult patients categorized into severe and uncomplicated malaria. Blood culture failed to confirm bacteraemia in any sample with the exception of one case of uncomplicated malaria. Study is inconclusive with regard to use of antibiotics in adult patients.

Association of ABO blood group with severe falciparum malaria in adults: case control study and meta-analysis.

BACKGROUND: Erythrocyte-associated antigenic polymorphisms or their absence have perhaps evolved in the human population to protect against malarial infection. Studies in various populations consistently demonstrate that blood group 'O' confers resistance against severe falciparum infection. In India, Odisha state has one of the highest incidences of Plasmodium falciparum infection and contributes to the highest number of deaths by falciparum malaria. This study aims to evaluate the relationship between ABO blood group and severe malaria in an adult population at the tertiary care centre in Odisha. METHODS: A total of 353 P. falciparum infected subjects and 174 healthy controls were screened for ABO blood group. Falciparum-infected individuals were categorized as severe malaria and uncomplicated malaria. Severe malaria was further clinically phenotyped into cerebral malaria, non-cerebral severe malaria and multi-organ dysfunction. A meta-analysis was performed to assess the role of ABO blood group in severe malaria. RESULTS: Frequency of blood group 'B' was significantly higher in patients with severe malaria compared to the uncomplicated cases (P < 0.0001; OR = 4.09) and healthy controls (P < 0.0001; OR = 2.79). Irrespective of the level of clinical severity, blood group 'B' was significantly associated with cerebral malaria (P < 0.0001; OR = 5.95), multi-organ dysfunction (P < 0.0001; OR = 4.81) and non-cerebral severe malaria patients (P = 0.001; OR = 3.02) compared to the uncomplicated category. Prevalence of 'O' group in uncomplicated malaria (P < 0.0001; OR = 2.81) and healthy controls (P = 0.0003; OR = 2.16) was significantly high compared to severe malaria. Meta-analysis of previous studies, including the current one, highlighted the protective nature of blood group 'O' to severe malaria (P = 0.01). On the other hand, carriers of blood group 'A' (P = 0.04) and 'AB' (P = 0.04) were susceptible to malaria severity. CONCLUSIONS: Results of the current study indicate that blood group 'O' is associated with reduced and 'B' blood group with increased risk of development of severe malaria in Odisha, India. Meta-analysis also supports the protective nature of blood group 'O' from severe falciparum infection.