T cell exhaustion is a state of T cell dysfunction that arises during many chronic infections and cancer. It is defined by poor effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. Exhaustion prevents optimal control of infection and tumors. Recently, a clearer picture of the functional and phenotypic profile of exhausted T cells has emerged and T cell exhaustion has been defined in many experimental and clinical settings. Although the pathways involved remain to be fully defined, advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.

T cell exhaustion

Sustainable Development Goals

The World Health Organization (WHO) World Malaria Report 2021 < https://www.who.int/publications/i/item/9789240040496 > estimates that there were 241 million malaria cases, including 627,000 deaths, worldwide in 2020, which represents around 14 million more cases, and 69,000 more deaths, than 2019. Approximately two-thirds of these additional deaths were linked to disruptions in the provision of malaria prevention, diagnosis and treatment during the COVID-19 pandemic. Sub-Saharan Africa continues to carry the heaviest malaria burden, accounting for about 95% of all cases and 96% of all deaths in 2020, with around 80% of deaths in the region among children under five years old. Since 2015, the baseline date for the WHO's global malaria strategy, registered increases in malaria deaths were reported in 24 countries. In the 11 countries that carry the highest burden of malaria worldwide, cases increased from 150 million in 2015 to 163 million cases in 2020, and malaria deaths increased from 390,000 to 444,600 over that same period. As in previous years, the report includes an up-to-date assessment on the burden of malaria at global, regional, and country levels, and tracks investment in malaria programmes and research, as well as detailing progress across the four intervention areas of prevention, diagnosis, treatment and surveillance. There are also dedicated chapters on malaria elimination and key threats, such as insecticide and drug resistance.

World malaria report 2011

https://www.who.int/malaria/mpac/mpac_mar2014_wmr2013.pdf

World Malaria Report 2013

Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, α + thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine.

https://sites.duke.edu/malaria/files/2012/10/Kwiatkowski-1.pdf

How malaria has affected the human genome and what human genetics can teach us about malaria.

/pdf/use-of-antenatal-care-services-and-presumptive-malaria-13e5e5md.pdf

Use of Antenatal Care Services and Presumptive Malaria During Pregnancy in San, Mali

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is an important malaria control strategy in sub-Saharan Africa. Indeed, it overcomes the risk of misdiagnosis due to low peripheral parasitemia during pregnancy by treating women with SP on predetermined schedules. However, over time, the spread of Plasmodium-resistant strains has threatened this strategy in many countries. As an alternative, the intermittent screening and treatment for pregnancy (ISTp) aims at a monthly screening of pregnant women, preferably by using very sensitive tests such as ultrasensitive rapid diagnostic tests (us-RDTs) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. Unlike IPTp-SP, ISTp prevents overuse of antimalarials limiting the drug pressure on parasites, an advantage which can be potentiated by using an ACT like pyronaridine-artesunate (Pyramax®) that is not yet used in pregnant women in the field.This study aims to compare the non-inferiority of ISTp using us-RDTs and Pyramax® versus IPTp-SP on malaria in pregnancy through a randomized clinical trial performed in Kisenso, Kinshasa, the Democratic Republic of the Congo, a malaria perennial transmission area.The results will be essential for the National Malaria Control Program to update the malaria prevention policy in pregnant women in the Democratic Republic of the Congo.ClinicalTrials.gov NCT04783051. 

Comparison of intermittent screening (using ultra-sensitive malaria rapid diagnostic test) and treatment (using a newly registered antimalarial pyronaridine-artesunate—PYRAMAX®) to standard intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria in pregnant wom

Kassoum Kayentao

Papers

Use of Antenatal Care Services and Presumptive Malaria During Pregnancy in San, Mali