Interchromosomal segmental duplication drives translocation and loss of histidine-rich protein 3.

Most malaria rapid diagnostic tests (RDTs) detect histidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions of and genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced field samples to understand these deletions better. deletion only occurred by chromosomal breakage with subsequent telomere healing.

A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies.

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P.

Adjunctive treatment of clinically severe babesiosis with red blood cell exchange: a case series of nineteen patients.

Background: Infection with the protozoan parasite Babesia, the causative agent of babesiosis, can result in asymptomatic to life-threatening illness. Severe cases of babesiosis are characterized by high levels of parasitemia (>4%-10%) and commonly treated with adjunctive red blood cell exchange (RCE) in addition to antimicrobial therapy. The efficacy of RCE in this context is unknown.

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

Background: In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.

Methods: We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania.

Accurate light microscopic diagnosis of South-East Asian ovalocytosis.

Introduction: South-East Asian ovalocytosis (SAO) is a common inherited red blood cell polymorphism in South-East Asian and Melanesian populations, coinciding with areas of malaria endemicity. Validation of light microscopy as a diagnostic alternative to molecular genotyping may allow for its cost-effective use either prospectively or retrospectively by analysis of archived blood smears.

Methods: We assessed light microscopic diagnosis of SAO compared to standard PCR genotyping.

Antibodies to PfsEGXP, an Early Gametocyte-Enriched Phosphoprotein, Predict Decreased Plasmodium falciparum Gametocyte Density in Humans.

Background: Antigametocyte-specific immune responses may regulate Plasmodium falciparum gametocyte density, providing the rationale for pursuing transmission-blocking vaccines (TBVs) that target gametocytes in the human host.

Methods: To identify novel antigametocyte TBV antigens, we interrogated the gametocyte proteome with our whole proteome differential screening method using plasma from a treatment-reinfection study conducted in western Kenya. At the start of the high-transmission season, 144 males (12-35 years) were enrolled and treated with quinine and doxycycline, peripheral venous blood samples were obtained, volunteers were observed, and weekly blood films were obtained for 18 weeks to quantify gametocytemia.

False-negative compatible antiglobulin crossmatches in samples with alloantibodies to cognate red blood cell antigens.

Background: Patient samples showing a positive indirect antiglobulin test are further tested to identify alloantibody specificity using a panel of phenotypically characterized group O reagent red blood cells (RBCs). Donor RBCs phenotypically negative for the antibody specificity are then serologically crossmatched using an antiglobulin reagent. This latter test is performed to identify any incompatibility due to the presence of undetected minor blood group antibodies and considered an important step in patient safety.

How do we reduce plasma transfusion in Rhode Island?

Background: Plasma transfusions are given to patients with coagulopathy, either prophylactically, before an invasive procedure; or therapeutically, in the presence of active bleeding; and as an exchange fluid in therapeutic plasma exchange for disorders such as thrombotic thrombocytopenic purpura. There is consensus that many prophylactic plasma transfusions are non-efficacious, and the misdiagnosis of thrombotic thrombocytopenic purpura results in unnecessary therapeutic plasma exchange.

Study Design And Methods: Beginning in 2001, programs to reduce plasma transfusion in the three major teaching hospitals in Rhode Island were initiated.

Acquired Factor XIII inhibitor associated with mantle cell lymphoma.

Background: Acquired Factor (F)XIII deficiency is a very rare bleeding diathesis with a potentially fatal outcome, previously described in the context of autoimmune disorders and leukemias. There is minimal information on autoantibody characterization and the role of antifibrinolytic therapy in patient management.

Case Report: A 79-year-old woman with a 3-month history of bruising and heavy menorrhagia presented with ongoing vaginal bleeding, symptomatic anemia, and a right thigh hematoma.

Autoimmune Cytopenias: Diagnosis & Management.

The autoimmune cytopenias are a related group of disorders in which differentiated hematopoietic cells are destroyed by the immune system. Single lineage disease is characterized by the production of autoantibodies against red cells (autoimmune hemolytic anemia [AIHA]), platelets (autoimmune thrombocytopenia [ITP]) and neutrophils (autoimmune neutropenia [AIN]) whereas multilineage disease may include various combinations of these conditions. Central to the genesis of this disease is the breakdown of central and/or peripheral tolerance, and the subsequent production of autoantibodies by both tissue and circulating self-reactive B lymphocytes with support from T helper lymphocytes.

Plasmodium falciparum gametocyte transit through the cutaneous microvasculature: A new target for malaria transmission blocking vaccines?

Malaria remains one of the most significant infectious diseases worldwide. Concordant with scaled intervention efforts and the emphasis of elimination and eradication on the agenda of many malaria control programs, the development of a malaria vaccine that reduces transmission of the parasite from human host to mosquito vector has been incorporated as an important new strategic goal. Transmission of malaria from man to mosquito relies on gametocytes, highly specialized sexual-stage parasites, that once mature, circulate in the peripheral vasculature of the human host.

Transfusion-transmitted anaplasmosis from a leukoreduced platelet pool.

Background: Human granulocytic anaplasmosis is an emerging tick-borne illness. Anaplasma phagocytophilum resides intracellularly, can cause asymptomatic infection, and can survive blood component refrigeration conditions for at least 18 days. To date, eight cases of transfusion-transmitted anaplasmosis (TTA) have been reported: seven attributed to red blood cell (RBC) units, five of which were prestorage leukoreduced using RBC leukoreduction filters, and one involving a process leukoreduced apheresis platelet (PLT) unit.

Sulfamethoxazole-induced thrombocytopenia masquerading as posttransfusion purpura: a case report.

Background: Drug-induced immune thrombocytopenia (DITP) is a rare clinical disorder characterized by accelerated platelet (PLT) clearance in the presence of drug-dependent antibodies. Distinguishing DITP from other immune-mediated disorders such as posttransfusion purpura (PTP) and autoimmune thrombocytopenia can represent a clinical challenge.

Case Report: A 68-year-old male with no prior transfusion history presented to the emergency department (ED) with dyspnea, epistaxis, and severe thrombocytopenia (<10 × 10(9)/L) 12 days after discharge from a hospital admission for a coronary artery bypass graft.

PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.

Programmed death 1 ligand 1 (PD-L1) is an immune regulatory molecule that limits antitumor immune activity. Targeting of PD-L1 and other immune checkpoint proteins has shown therapeutic activity in various tumor types. The expression of PD-L1 and its correlation with response to neoadjuvant chemotherapy in breast cancer has not been studied extensively.

Distance to Anopheles sundaicus larval habitats dominant among risk factors for parasitemia in meso-endemic Southwest Sumba, Indonesia.

Background: The decline in intensity of malaria transmission in many areas now emphasizes greater importance of understanding the epidemiology of low to moderate transmission settings. Marked heterogeneity in infection risk within these populations creates opportunities to understand transmission and guide resource allocation to greater impact.

Methods: In this study, we examined spatial patterns of malaria transmission in a hypo- to meso-endemic area of eastern Indonesia using malaria prevalence data collected from a cross-sectional socio-demographic and parasitological survey conducted from August to November 2010.

Impact of a spatial repellent on malaria incidence in two villages in Sumba, Indonesia.

A randomized, double-blinded, placebo-controlled study was conducted to examine the effect of spatial repellent (SR) in households at risk of malaria in Indonesia. Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages, all households were given either metofluthrin or placebo mosquito coils. Weekly blood smear screening and human-landing mosquito catches were done throughout the 6 months intervention.

Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer.

Purpose: Although tumor-infiltrating lymphocytes (TIL) have been associated with response to neoadjuvant therapy, measurement typically is subjective, semiquantitative, and unable to differentiate among subpopulations. Here, we describe a quantitative objective method for analyzing lymphocyte subpopulations and assessing their predictive value.

Experimental Design: We developed a quantitative immunofluorescence assay to measure stromal expression of CD3, CD8, and CD20 on one slide.

Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection.

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect.

Antibodies to rhoptry-associated membrane antigen predict resistance to Plasmodium falciparum.

Previously, we collected plasma from 143 male volunteers residing in an area of western Kenya where Plasmodium falciparum is holoendemic. Volunteers were cured of current malaria infection by use of drugs, blood was collected 2 weeks after treatment, and blood films were collected weekly for 18 weeks. We identified and pooled plasma from the 10 most resistant individuals (RP) and the 7 most susceptible individuals (SP) and used these pools in a differential screen of a P.