Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults.

Objectives: Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.

The mRNA content of plasma extracellular vesicles provides a window into molecular processes in the brain during cerebral malaria.

The impact of cerebral malaria on the transcriptional profiles of cerebral tissues is difficult to study using noninvasive approaches. We isolated plasma extracellular vesicles (EVs) from patients with cerebral malaria and community controls and sequenced their mRNA content. Deconvolution analysis revealed that EVs from cerebral malaria are enriched in transcripts of brain origin.

Linking Cerebral Malaria Pathogenesis to APOE-Mediated Amyloidosis: Observations and Hypothesis.

Although most children with cerebral malaria fully recover, more than a fifth of the survivors develop post-discharge neurodevelopmental sequelae suggestive of advanced neuronal injury. However, the cerebral molecular processes initiating neurological dysfunction in cerebral malaria are still debatable. In this article, we explore available data and hypothesise that cerebral malaria might be linked to APOE-mediated amyloidosis, one of the pathological processes associated with Alzheimer's disease.

Distinct transcriptomic signatures define febrile malaria depending on initial infective states, asymptomatic or uninfected.

Background: Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate the maintenance of chronic symptomless infections that sustain malaria transmission.

Methods: Here, we determined the gene expression profiles of the parasite population and the corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (< 15 years).

From contigs towards chromosomes: automatic improvement of long read assemblies (ILRA).

Recent advances in long read technologies not only enable large consortia to aim to sequence all eukaryotes on Earth, but they also allow individual laboratories to sequence their species of interest with relatively low investment. Long read technologies embody the promise of overcoming scaffolding problems associated with repeats and low complexity sequences, but the number of contigs often far exceeds the number of chromosomes and they may contain many insertion and deletion errors around homopolymer tracts. To overcome these issues, we have implemented the ILRA pipeline to correct long read-based assemblies.

adapts its investment into replication transmission according to the host environment.

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor , is known to be influenced by host factors but a comprehensive model remains uncertain. Here, we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission.

Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes.

Investigating Outcomes of a Family Strengthening Intervention for Resettled Somali Bantu and Bhutanese Refugees: An Explanatory Sequential Mixed Methods Study.

Pre- and post-migration stressors can put resettled refugee children at risk of poor mental health outcomes. The Family Strengthening Intervention for Refugees (FSI-R) is a peer-delivered preventative home visiting program for resettled refugees that aims to draw upon families' strengths to foster improved family communication, positive parenting, and caregiver-child relationships, with the ultimate goal of reducing children's risk of mental health problems. Using an explanatory sequential mixed methods design, this study draws upon qualitative interviews with caregivers (n = 19) and children (n = 17) who participated in a pilot study of the FSI-R intervention in New England, as well as interventionists (n = 4), to unpack quantitative findings on mental health and family functioning from a randomized pilot study (n = 80 families).

Understanding mechanisms of change in a family-based preventive mental health intervention for refugees by refugees in New England.

Transnational migration of refugees is associated with poor mental health, particularly among children. We conducted a pilot trial of the Family Strengthening Intervention for Refugees (FSI-R), using a community-based participatory research (CBPR) approach to deliver a home-based intervention "for refugees by refugees" to improve family functioning and child mental health.  = 80 refugee families in the Greater Boston area participated in the study ( = 40 Somali Bantu families;  = 40 Bhutanese families) with  = 41 families randomized to care-as-usual.

Analysis of var Gene Transcription Pattern Using DBLα Tags.

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens, which are encoded by a multigene family called var genes, are exported and inserted onto the surface of the infected erythrocytes. PfEMP1 plays a key role in the pathogenesis of severe malaria and are major targets of naturally acquired immunity. Studying the expression pattern of var genes in P.

Maintenance of high temporal Plasmodium falciparum genetic diversity and complexity of infection in asymptomatic and symptomatic infections in Kilifi, Kenya from 2007 to 2018.

Background: High levels of genetic diversity are common characteristics of Plasmodium falciparum parasite populations in high malaria transmission regions. There has been a decline in malaria transmission intensity over 12 years of surveillance in the community in Kilifi, Kenya. This study sought to investigate whether there was a corresponding reduction in P.

Breadth of Antibodies to Variant Surface Antigens Is Associated With Immunity in a Controlled Human Malaria Infection Study.

Background: variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study.

Method: We used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous parasite isolates, and to two PfEMP1 DBLβ domains in blood samples collected a day before the challenge and 14 days after infection.

Extracellular vesicles isolated from milk can improve gut barrier dysfunction induced by malnutrition.

Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in children below the age of five. Severe acute malnutrition (SAM) is associated with intestinal barrier breakdown and epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30-150 nm) can travel to distant target cells through biofluids including milk.

Traditional Medicine and Help-Seeking Behaviors for Health Problems Among Somali Bantu Refugees Resettled in the United States.

Somali refugees have resettled in the United States in large numbers. The focus of this study was specifically on the Somali Bantu refugees, an ethnic minority group from Somalia. The goal of this study was to understand the following: (a) jinn (invisible beings or forces in Islamic theology) and related health problems resulting from jinn possession affecting Somali Bantu refugees, (b) types of traditional healing practices integrated into help-seeking behavior, and (c) pathways of care utilized to address health problems.

Family-Based Mental Health Promotion for Somali Bantu and Bhutanese Refugees: Feasibility and Acceptability Trial.

Purpose: There are disparities in mental health of refugee youth compared with the general U.S.

Population: We conducted a pilot feasibility and acceptability trial of the home-visiting Family Strengthening Intervention for refugees (FSI-R) using a community-based participatory research approach.

Exploring Gene Expression to Assess Host Selection Pressure on Parasites During Infancy.

In sub-Saharan Africa, children below 5 years bear the greatest burden of severe malaria because they lack naturally acquired immunity that develops following repeated exposure to infections by . Antibodies to the surface of infected erythrocytes (IE) play an important role in this immunity. In children under the age of 6 months, relative protection from severe malaria is observed and this is thought to be partly due to trans-placental acquired protective maternal antibodies.

No evidence of K13 artemisinin conferring mutations over a 24-year analysis in Coastal Kenya, but a near complete reversion to chloroquine wild type parasites.

Antimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over two decades of changing antimalarial drug policy in Kenya.

Antigenic cartography of immune responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).

Naturally acquired clinical immunity to Plasmodium falciparum is partly mediated by antibodies directed at parasite-derived antigens expressed on the surface of red blood cells which mediate disease and are extremely diverse. Unlike children, adults recognize a broad range of variant surface antigens (VSAs) and are protected from severe disease. Though crucial to the design and feasibility of an effective malaria vaccine, it is not yet known whether immunity arises through cumulative exposure to each of many antigenic types, cross-reactivity between antigenic types, or some other mechanism.

Stronger together: Community resilience and Somali Bantu refugees.

Objectives: Refugee populations are at risk of adverse mental health outcomes. It is important to identify refugee strengths at the community level that can be leveraged to overcome barriers to well-being. In pursuit of this goal, this study focuses on identifying what promotes community resilience among Somali Bantu refugees in the United States.

Long read assemblies of geographically dispersed isolates reveal highly structured subtelomeres.

: Although thousands of clinical isolates of are being sequenced and analysed by short read technology, the data do not resolve the highly variable subtelomeric regions of the genomes that contain polymorphic gene families involved in immune evasion and pathogenesis. There is also no current standard definition of the boundaries of these variable subtelomeric regions. : Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated the genomes of 15 isolates, ten of which are newly cultured clinical isolates.

Proteomic analysis of extracellular vesicles from a Kenyan clinical isolate defines a core parasite secretome.

Background: Many pathogens secrete effector molecules to subvert host immune responses, to acquire nutrients, and/or to prepare host cells for invasion. One of the ways that effector molecules are secreted is through extracellular vesicles (EVs) such as exosomes. Recently, the malaria parasite has been shown to produce EVs that can mediate transfer of genetic material between parasites and induce sexual commitment.

Public antibodies to malaria antigens generated by two LAIR1 insertion modalities.

In two previously described donors, the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 19 (ref. 1), was inserted between the V and DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes.

Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure.

Background: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have a growth advantage in immunologically naïve individuals. However, this idea has not been tested in longitudinal studies.

Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria.