The investigation of factors associated with susceptibility to severe malaria is best achieved using case-control studies. The presence of a history of severe malaria in controls could affect the quality of their phenotype and study findings and hence should be rigorously determined. Here, we assessed the performance of a qualitative questionnaire to identify a history of cerebral malaria in controls in a case-control study of severe malaria in Mali.
View Article and Find Full Text PDFChildren with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear.
View Article and Find Full Text PDFUnlabelled: parasites, the causative organism of malaria, caused over 600,000 deaths in 2022. In Mali, causes the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to and some aspects of this immunity (e.
View Article and Find Full Text PDFIn Bandiagara, Mali, children experience on average two clinical malaria episodes per year. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, can vary dramatically among children. We simultaneously characterize host and parasite gene expression profiles from 136 Malian children with symptomatic falciparum malaria and examine differences in the relative proportion of immune cells and parasite stages, as well as in gene expression, associated with infection and or patient characteristics.
View Article and Find Full Text PDFBackground: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication.
Methods: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults.
In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484 genes.
View Article and Find Full Text PDFSARS-CoV-2 vaccines are useful tools to combat the Coronavirus Disease 2019 (COVID-19) pandemic, but vaccine reluctance threatens these vaccines' effectiveness. To address COVID-19 vaccine reluctance and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study in the US conducted December 2020-May 2021 of 36,711 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine.
View Article and Find Full Text PDFPlasmodium parasites caused 241 million cases of malaria and over 600,000 deaths in 2020. Both P. falciparum and P.
View Article and Find Full Text PDFA decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014-2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali.
View Article and Find Full Text PDFBackground: Before the coronavirus disease 2019 (COVID-19) pandemic, crowded and unsanitary living conditions lacking medical expertise made US detention centers hotbeds for infectious disease outbreaks. There have been 30 000 COVID-19 cases, positivity rates exceeding 50%, and 9 deaths in Immigration and Customs Enforcement custody, but the extent of disease among children under the care of the Office of Refugee Resettlement (ORR) has not been well-documented. We sought to evaluate the burden of COVID-19 among unaccompanied minors under the ORR's responsibility.
View Article and Find Full Text PDFWe used a protein microarray featuring Plasmodium falciparum field variants of a merozoite surface antigen to examine malaria exposure in Malian children with different severe malaria syndromes. Unlike children with cerebral malaria alone or severe malarial anemia alone, those with concurrent cerebral malaria and severe malarial anemia had serologic responses demonstrating a broader prior parasite exposure pattern than matched controls with uncomplicated disease. Comparison of levels of malaria-related cytokines revealed that children with the concurrent phenotype had elevated levels of interleukin (IL)-6, IL-8, and IL-10.
View Article and Find Full Text PDFEnzyme-linked immunosorbent assays (ELISAs) remain the gold standard for measuring antibodies, but are time-consuming and use significant amounts of precious sample and reagents. Protein microarrays represent an appealing alternative, particularly for studies focused on large gene families such as those encoding variant surface antigens in the malaria parasite Plasmodium falciparum. Such microarrays represent an ideal high-throughput platform to study antibody responses to hundreds of malaria parasite variant surface antigens at once, providing critical insights into the development of natural immunity to malaria.
View Article and Find Full Text PDFBackground: RIFINs and STEVORs are variant surface antigens expressed by P. falciparum that play roles in severe malaria pathogenesis and immune evasion. These two highly diverse multigene families feature multiple paralogs, making their classification challenging using traditional bioinformatic methods.
View Article and Find Full Text PDFgenes encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved segments.
View Article and Find Full Text PDFKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses.
View Article and Find Full Text PDFVector-borne pathogens cause many human infectious diseases and are responsible for high mortality and morbidity throughout the world. They can also cause livestock epidemics with dramatic social and economic consequences. Due to its high costs, vector-borne disease surveillance is often limited to current threats, and the investigation of emerging pathogens typically occurs after the reports of clinical cases.
View Article and Find Full Text PDFSARS-CoV-2 vaccines are powerful tools to combat the COVID-19 pandemic, but vaccine hesitancy threatens these vaccines’ effectiveness. To address COVID-19 vaccine hesitancy and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study conducted December 2020-May 2021 of 34,470 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine.
View Article and Find Full Text PDFPlasmodium falciparum circumsporozoite protein (CSP) is a major sporozoite surface protein and a key target of pre-erythrocytic malaria subunit vaccines. A full-length recombinant CSP (rCSP) based strategy could be advantageous, as this antigen includes a region critical to sporozoite cell attachment and hepatocyte invasion. The adjuvant Glucopyranosyl Lipid A-liposome Quillaja saponaria 21 (GLA-LSQ) functions as a TLR4 agonist, promotes antigen-specific T1 responses and stimulates cytotoxic T cell production.
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