Modelling the drivers of the spread of gene deletions in sub-Saharan Africa.

Elife

Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

Published: August 2017

Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent RDTs detect histidine-rich protein 2 (PfHRP2). However, gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of -deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed -deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% -deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of -deletion, and identify the geographic regions in which surveillance for -deletion should be prioritised.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602420PMC
http://dx.doi.org/10.7554/eLife.25008DOI Listing

Publication Analysis

Top Keywords

gene deletions
8
modelling drivers
4
drivers spread
4
spread gene
4
deletions sub-saharan
4
sub-saharan africa
4
africa rapid
4
rapid diagnostic
4
diagnostic tests
4
tests rdts
4

Similar Publications

Background: Citrin deficiency (CD) is an autosomal recessive metabolic disorder affecting the urea cycle and energy production. Diagnosis involves measuring ammonia, amino acid levels (eg: citrulline), with confirmation through solute carrier family 25 member 13 (SLC25A13) gene mutation analysis. Herein, we present a case report of a variant in the SLC25A13 gene that has not been previously reported in the literature.

View Article and Find Full Text PDF

Traumatic brain injury (TBI) can lead to chronic neuroinflammation, and neurodegeneration associated with long-term cognitive deficits. Following TBI, the acute neuroinflammatory response involves microglial activation and the release of proinflammatory cytokines and chemokines which induce the recruitment of peripheral immune cells such as monocytes and ultimately T cells. Persistent innate and adaptive immune cells response can lead to chronic neurodegeneration and functional deficits.

View Article and Find Full Text PDF

The viral serpin SPI-1 directly inhibits the host cell serine protease FAM111A.

J Biol Chem

January 2025

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, MN, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. Electronic address:

The host-range mutant of rabbitpox virus (RPXV) with a deletion in the gene encoding the serpin serine protease inhibitor 1 (SPI-1) fails to replicate efficiently in restrictive host cells. Depletion of the host cell serine protease FAM111A restores viral replication in these cells, suggesting that SPI-1 targets FAM111A to facilitate infection. However, direct evidence of SPI-1 inhibiting FAM111A has been lacking.

View Article and Find Full Text PDF

Unlabelled: Minimal residual disease (MRD) is the most important prognostic factor for B-cell acute lymphoblastic leukemia (B-ALL) however nearly 20-30% of patients relapsed even when they achieved negative MRD, how to identify these patients is less addressed. In this study, we aimed to reassess the prognostic significance of MRD and IKZF1 in adult B-ALL patients receiving pediatric chemotherapy regimens. In the PDT-ALL-2016 cohort (NCT03564470), adult B-ALL patients were treated with a pediatric-inspired regimen; patients were redefined as standard (MRD-negative and IKZF1wild-type), intermediate (MRD-positive or IKZF1 deletion), and high-risk (MRD-positive and IKZF1 deletion) groups by combining IKZF1 deletion status and MRD.

View Article and Find Full Text PDF

The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!