Perturbations in the T cell receptor β repertoire during malaria infection in children: A preliminary study.

The changes occurring in the T cell repertoire during clinical malaria infection in children remain unknown. In this study, we undertook the first detailed comparative study of the T cell repertoire in African children with and without clinical malaria to test the hypothesis that clonotypic expansions that occur during infection will contribute to the generation of a T cell repertoire that is unique to each disease state. We profiled the complementarity-determining region 3 (CDR3) of the TCRβ chain sequences from children with infections (asymptomatic, uncomplicated and severe malaria) and compared these with sequences from healthy children.

Implementation of an efficient SARS-CoV-2 specimen pooling strategy for high throughput diagnostic testing.

The rapid identification and isolation of infected individuals remains a key strategy for controlling the spread of SARS-CoV-2. Frequent testing of populations to detect infection early in asymptomatic or presymptomatic individuals can be a powerful tool for intercepting transmission, especially when the viral prevalence is low. However, RT-PCR testing-the gold standard of SARS-CoV-2 diagnosis-is expensive, making regular testing of every individual unfeasible.

A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART.

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4.

A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries.

Meeting Report: WHO Workshop on modelling global mortality and aetiology estimates of enteric pathogens in children under five. Cape Town, 28-29th November 2018.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs.

Phenotypic Evidence of T Cell Exhaustion and Senescence During Symptomatic Malaria.

T cells play significant roles during infections. Their regulation of the immune response in symptomatic children with malaria has been deemed necessary to prevent immune associated pathology. In this study, we phenotypically characterized the expression of T cell inhibitory(PD-1, CTLA-4) and senescent markers (CD28(-), CD57) from children with symptomatic malaria, asymptomatic malaria and healthy controls using flow cytometry.

Predicting Antigenicity of Influenza A Viruses Using biophysical ideas.

Antigenic variations of influenza A viruses are induced by genomic mutation in their trans-membrane protein HA1, eliciting viral escape from neutralization by antibodies generated in prior infections or vaccinations. Prediction of antigenic relationships among influenza viruses is useful for designing (or updating the existing) influenza vaccines, provides important insights into the evolutionary mechanisms underpinning viral antigenic variations, and helps to understand viral epidemiology. In this study, we present a simple and physically interpretable model that can predict antigenic relationships among influenza A viruses, based on biophysical ideas, using both genomic amino acid sequences and experimental antigenic data.

Novel Strategies for Malaria Vaccine Design.

The quest for a licensed effective vaccine against malaria remains a global priority. Even though classical vaccine design strategies have been successful for some viral and bacterial pathogens, little success has been achieved for , which causes the deadliest form of malaria due to its diversity and ability to evade host immune responses. Nevertheless, recent advances in vaccinology through high throughput discovery of immune correlates of protection, lymphocyte repertoire sequencing and structural design of immunogens, provide a comprehensive approach to identifying and designing a highly efficacious vaccine for malaria.

Bayesian inference of antigenic and non-antigenic variables from haemagglutination inhibition assays for influenza surveillance.

Haemagglutination inhibition (HI) assays are typically used for comparing and characterizing influenza viruses. Data obtained from the assays (titres) are used quantitatively to determine antigenic differences between influenza strains. However, the use of these titres has been criticized as they sometimes fail to capture accurate antigenic differences between strains.

Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection.

Background: Asymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear.

Trans-Allelic Model for Prediction of Peptide:MHC-II Interactions.

Major histocompatibility complex class two (MHC-II) molecules are trans-membrane proteins and key components of the cellular immune system. Upon recognition of foreign peptides expressed on the MHC-II binding groove, CD4 T cells mount an immune response against invading pathogens. Therefore, mechanistic identification and knowledge of physicochemical features that govern interactions between peptides and MHC-II molecules is useful for the design of effective epitope-based vaccines, as well as for understanding of immune responses.

The Hayflick Limit and Age-Related Adaptive Immune Deficiency.

The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment.

Family planning practices of rural community dwellers in cross River State, Nigeria.

Background: Nigeria is the most populous nation in Africa and the seventh most populous in the world. Despite a high fertility rate of 5.5 per woman and a high population growth rate of 3.

The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells.

Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.

A simple mechanistic explanation for original antigenic sin and its alleviation by adjuvants.

A large number of published studies have shown that adaptive immunity to a particular antigen, including pathogen-derived, can be boosted by another, cross-reacting antigen while inducing suboptimal immunity to the latter. Although this phenomenon, called original antigenic sin (OAS), was first reported approximately 70 years ago (Francis et al. 1947 Am.

Factors associated with appropriate home management of uncomplicated malaria in children in Kassena-Nankana district of Ghana and implications for community case management of childhood illness: a cross-sectional study.

Background: Home management of uncomplicated malaria (HMM) is now integrated into the community case management of childhood illness (CCM), an approach that requires parasitological diagnosis before treatment. The success of CCM in resource-constrained settings without access to parasitological testing significantly depends on the caregiver's ability to recognise malaria in children under five years (U5), assess its severity, and initiate early treatment with the use of effective antimalarial drugs in the appropriate regimen at home. Little is known about factors that influence effective presumptive treatment of malaria in U5 by caregivers in resource-constrained malaria endemic areas.

T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity.

The T-cell receptor (TCR) repertoire is formed by random recombinations of genomic precursor elements; the resulting combinatorial diversity renders unlikely extensive TCR sharing between individuals. Here, we studied CDR3β amino acid sequence sharing in a repertoire-wide manner, using high-throughput TCR-seq in 28 healthy mice. We uncovered hundreds of public sequences shared by most mice.

Trauma death in a resource constrained setting: mechanisms and contributory factors, the result of analysing 147 cases.

Aims And Objectives: The objective of the following study is to analyze the trauma type (causes), injury pattern and factors that may have contributed to death within 72 h of admission into our emergency department (E.D).

Materials And Methods: An 18 month prospective observational study, done from April 2009 to September 2010.

CD4(+) T Cell-Receptor Repertoire Diversity is Compromised in the Spleen but Not in the Bone Marrow of Aged Mice Due to Private and Sporadic Clonal Expansions.

Reduction in T cell receptor (TCR) diversity in old age is considered as a major cause for immune complications in the elderly population. Here, we explored the consequences of aging on the TCR repertoire in mice using high-throughput sequencing (TCR-seq). We mapped the TCRβ repertoire of CD4+ T cells isolated from bone marrow (BM) and spleen of young and old mice.

Epidemiology of death in the emergency department of a tertiary health centre south-south of Nigeria.

Background: The emergency department (E.D) of any hospital is an important entry point of critically ill patients. The initial management of these patients is often challenging, and for valuable lives to be saved, the in fracture and manpower should be up to date.

CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging.

The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the epithelial layers of the choroid plexus (CP) are constitutively populated with CD4(+) effector memory cells with a T-cell receptor repertoire specific to CNS antigens.

Decombinator: a tool for fast, efficient gene assignment in T-cell receptor sequences using a finite state machine.

Summary: High-throughput sequencing provides an opportunity to analyse the repertoire of antigen-specific receptors with an unprecedented breadth and depth. However, the quantity of raw data produced by this technology requires efficient ways to categorize and store the output for subsequent analysis. To this end, we have defined a simple five-item identifier that uniquely and unambiguously defines each TcR sequence.