Antibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria.

BACKGROUND: Antibodies to variant surface antigens (VSAs) such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) may vary with malaria severity. The influence of ABO blood group on antibody development is not understood. METHODS: Immunoglobulin G antibodies to VSAs in Papua New Guinean children with severe (n = 41) or uncomplicated (n = 30) malaria were measured by flow cytometry using homologous P falciparum isolates. Isolates were incubated with ABO-matched homologous and heterologous acute and convalescent plasma. RNA was used to assess var gene transcription. RESULTS: Antibodies to homologous, but not heterologous, isolates were boosted in convalescence. The relationship between antibody and severity varied by blood group. Antibodies to VSAs were similar in severe and uncomplicated malaria at presentation, higher in severe than uncomplicated malaria in convalescence, and higher in children with blood group O than other children. Six var gene transcripts best distinguished severe from uncomplicated malaria, including UpsA and 2 CIDRα1 domains. CONCLUSIONS: ABO blood group may influence antibody acquisition to VSAs and susceptibility to severe malaria. Children in Papua New Guinea showed little evidence of acquisition of cross-reactive antibodies following malaria. Var gene transcripts in Papua New Guinean children with severe malaria were similar to those reported from Africa.

The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children.

BACKGROUND: Antibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure. METHODS: Six-hundred and one young Malawian children from a randomized trial of prenatal nutrient supplementation with iron and folic acid or pre- and postnatal multiple micronutrients or lipid-based nutrient supplements were followed up weekly at home and febrile episodes were investigated for malaria from birth to 18 months of age. Antibodies were measured for 601 children against merozoite surface proteins (MSP1 19kD, MSP2), erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2 (Rh2A9), schizont extract and variant surface antigens expressed by Plasmodium falciparum-infected erythrocytes (IE) at 18 months of age. The antibody measurement data was related to concurrent malaria infection and to documented episodes of clinical malaria. RESULTS: At 18 months of age, antibodies were significantly higher among parasitaemic than aparasitaemic children. Antibody levels against MSP1 19kD, MSP2, schizont extract, and IE variant surface antigens were significantly higher in children who had documented episodes of malaria than in children who did not. Antibody levels did not differ between children with single or multiple malaria episodes before 18 months, nor between children who had malaria before 6 months of age or between 6 and 18 months. CONCLUSIONS: Antibodies to merozoite and IE surface antigens increased following infection in early childhood, but neither age at first infection nor number of malaria episodes substantially affected antibody acquisition. These findings have implications for malaria surveillance during early childhood in the context of elimination. Trials registration Clinical Trials Registration: NCT01239693 (Date of registration: 11-10-2010). URL: http://www.ilins.org.

Effect of nutrient supplementation on the acquisition of humoral immunity to Plasmodium falciparum in young Malawian children.

BACKGROUND: There is evidence that suggests that undernutrition has a detrimental effect on malarial immunity in children. The aim of the study was to discover whether nutrient supplementation improved development of malarial antibody immunity in children up to 18 months of age. METHODS: The study was conducted with a subset of 432 Malawian children from a randomized controlled trial of nutritional supplements. The arms included pre- and postnatal small-quantity lipid-based nutrient supplements for both mother and child; prenatal supplementation with iron and folic acid; and pre- and postnatal supplementation with multiple micronutrients. Paired plasma samples were collected at 6 and 18 months of age. The levels of antibodies against merozoite surface protein 1 (MSP1 19kD) and MSP2, erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2A (Rh2A9), schizont extract and variant antigens expressed on the surface of infected erythrocytes were measured. RESULTS: At 18 months of age, 5.4% of children were parasitaemic by microscopy and 49.1% were anaemic. Antibodies to the tested merozoite antigens and schizont extract increased between 6 and 18 months and this increase was statistically significant for MSP1, MSP2 and EBA175 (p < 0.0001) whereas IgG to variant surface antigens decreased with increasing age (p < 0.0001). However, the supplementation type did not have any impact on the prevalence or levels of antibodies at either 6 or 18 months of age to any of the tested malaria antigens in either univariate analysis or multivariate analysis after adjusting for covariates. CONCLUSIONS: Pre- and postnatal lipid-based nutrient supplementation did not alter malaria antibody acquisition during infancy, compared to prenatal supplementation with iron and folic acid or pre- and postnatal supplementation with multiple micronutrients. Trail registeration Clinicaltrials.gov registration number NCT01239693.

A Rare Coexistence of Multiple Myeloma and Polycythemia Vera.

Multiple myeloma (MM) is classically associated with organ dysfunction leading to hypercalcemia, renal insufficiency, anemia and bone disease, known as the CRAB criteria. More than 70% of patients with MM present with anemia. Few rare case reports, however, have demonstrated the presentation of MM associated with polycythemia. We present an interesting case of a 65-year-old female who was initially diagnosed with monoclonal gammopathy of undetermined significance (MGUS) which progressed to smoldering myeloma and later developed into MM. The patient also had coexisting polycythemia vera (PCV). We discuss the typical patient presentations as well as the expanded diagnostic criteria for MM. The pathophysiology explaining the coexistence of polycythemia and MM will be explored as well.

Anti-malarial investigation of Acorus calamus, Dichapetalum gelonioides, and Leucas aspera on Plasmodium falciparum strains.

INTRODUCTION: Malaria is a significant global health concern and adversely affects people in developing countries including Bangladesh. The causative agent Plasmodium falciparum is resistant to several currently available anti-malarial drugs, such as mefloquine, chloroquine, and artemisinin-based combination therapy (ACT), and this has been a major global challenge towards the control of the disease. There is urgent need for novel anti-malarial chemotherapeutic agents. METHODOLOGY: The present study aimed to evaluate antimalarial activity of methanolic extracts of three Bangladeshi medicinal plants- Acorus calamus, Dichapetalum gelonioides and Leucas aspera - against both chloroquine sensitive (3D7) and resistant (Dd2) strains of P. falciparum. Histidine-rich protein 2 (HRP2) based ELISA was used to evaluate the in vitro inhibitory activity of the extracts. RESULTS: D. gelonioides extract showed moderate (IC50 = 19.15 µg/mL) and promising activity (IC50 = 10.43 µg/mL) against 3D7 and Dd2 strains respectively. A. calamus remained inactive against both 3D7 (IC50 = 72.29 µg/mL) and Dd2 strain (IC50 = 67.81 µg/mL). L. aspera initially remained inactive against 3D7 strain (IC50 = 60.51 µg/mL), but displayed promising activity (IC50 = 7.693) against Dd2 strain. CONCLUSIONS: This is the first time these plant materials have been assessed for their in vitro antimalarial properties. It is pivotal to conduct further phytochemical analysis of D. gelonioides and L. aspera to evaluate the presence of potential novel antimalarial drug compounds.

Seed oils from non-conventional sources in north-east India: potential feedstock for production of biodiesel.

A total of nine oilseeds with more than 15 wt% oil have been investigated for evaluating them as feedstock for biodiesel industries. Fatty acid profiles of all the nine oil samples have been determined by GC-MS analysis. The saponification numbers, gross heats of combustion of the oils and those of corresponding fatty acid methyl esters (FAMEs) as well as cetane indices of the FAMEs have been calculated empirically. Iodine values have been determined experimentally. These values have been used for predicting the quality of the corresponding biodiesels. If prepared from these oils, biodiesels are likely to meet the major specification of biodiesel standards of the USA, Germany and European Standard Organisation. Seed oil from Cucumis sativus is found rich in linoleic acid which is considered an essential fatty acid of biological significance.