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

<p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum </it>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.</p> <p>Methods</p> <p>A total of 353 <it>P. falciparum </it>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens

Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens

MBL-2 POLYMORPHISMS (CODON 54 AND Y-221X) AND LOW MBL LEVELS ARE ASSOCIATED WITH SUSCEPTIBILITY TO MULTI ORGAN DYSFUNCTION IN P. FALCIPARUM MALARIA IN ODISHA , INDIA

BackgroundMannose binding lectin, a plasma protein protects host from virus, bacteria and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria.MethodsA hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA.ResultsSevere malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore,on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P=0.006; B allele: P=0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P=0.009).ConclusionsThe observations of the present study reveal that MBL-2polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria

Nickel concentration dependent structural and optical properties of electrodeposited diamond like carbon thin films

Diamond like carbon (DLC) and composite nickel incorporated diamond-like carbon (Ni-DLC) films have been synthesized on ITO coated glass substrates using low voltage electrodeposition method. Modifications of structural and optical properties of thin films have been investigated with varying Ni concentration. Average grain size of Ni-DLC granules is found to decrease with increasing molarity of Ni in electrolytic solution. XRD pattern depicts multi-phase nature of Ni-DLC film. Incorporation of Ni nanoparticles in DLC matrix has been confirmed by TEM. Interestingly optical bandgap energy decreases from 2.31 to 1.58 eV with decrease in nickel content in the electrolytic bath. Simultaneously Urbach energy exhibits an increasing trend from 1.972 to 2.374 eV. Presence of sp2 and sp3 bonded carbons has been indicated by FTIR spectra. The number of sp2 bonding in carbon matrix is enhanced with dilution of electrolyte. The peaks in the range of ~600–750 cm−1 in Ni-DLC films have been attributed to metal incorporation into DLC matrix. Study reveals that the bandgap and the particle size of carbon nanocomposite films can be tailored by controlling the amount of nickel in the electrolyte

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

a b s t r a c t 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 &lt; 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.

Physicochemical Behaviors of Cationic Gemini Surfactant (14-4-14) Based Microheterogeneous Assemblies

A comprehensive study of micellization and microemulsion formation of a cationic gemini surfactant (tetramethylene-1,4-bis­(dimethyltetradecylammonium bromide; 14-4-14) in the absence or presence of hydrophobically modified polyelectrolyte, sodium carboxymethylcellulose (NaCMC), has been conducted by conductometry, tensiometry, microcalorimetry, and fluorimetry methods at different temperatures. Both critical micelle concentration and degree of ionization of the surfactant have been observed to increase with increasing temperature. The interfacial and thermodynamic parameters were evaluated. The standard Gibbs free energy of micellization (Δ<i>G</i>_m^°) is negative, which decreases with increase in temperature. Larger entropic contribution is observed compared to the enthalpy. The interaction of 14-4-14 with NaCMC produces coacervates which was determined from turbidimetry method. The pseudoternary phase behavior of the microemulsion systems comprising water (or NaCMC as additive), 14-4-14, isopropanol (IP) or <i>n</i>-butanol (Bu) as cosurfactant, and isopropyl myristate (IPM) were studied at 298 K. Phase diagrams reveal that IP derived microemulsions (in the absence of NaCMC) offer a large isotropic region compared to Bu-derived systems at comparable physicochemical conditions. Increasing the concentration of IP or Bu decreases the isotropic region in the phase diagram. NaCMC influences the microemulsion zone, depending upon its concentration, and type of cosurfactant and surfantant/cosurfactant ratio. Dynamic light scattering and conductometric measurements show the size of the droplet, threshold temperature of percolation, scaling parameters, and activation energy of the percolation process of 14-4-14/IP or Bu derived microemulsion systems without/with NaCMC at various physicochemical conditions. Bu exerts a greater effect to reduce θ_t than IP as a cosurfactant (in the absence of NaCMC) at comparable ω. On the other hand, IP showed better percolating effect than Bu in the presence of NaCMC. Bu and IP (as cosurfactant) and NaCMC (as additive) influenced the microemulsion droplet size (<i>D</i>_h) to different extents under comparable conditions. Temperature insensitive microemulsions have been reported at the studied temperature range (298–353 K). 14-4-14/IP (1:2)-derived microemulsion showed a fractured surface at fixed ω = 15, where ω is the water and surfactant molar ratio, and temperature (298 K); whereas, large scale mesospheres comprising multiple closely winded nanoslices and spheroid morphology were formed in 14-4-14/IP and 14-4-14/Bu microemulsions, respectively, in the presence of 0.01 g % NaCMC, at comparable conditions. These systems revealed good antimicrobial activity toward the strains of Gram-positive <i>Bacillus subtilis</i> and Gram-negative <i>Escherichia coli</i> bacteria at 298 K, and inhibitory effect was governed by ω, type of cosurfactant, and bacterial strains