Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023.

Background: Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.

Objective: To assess the proportion of P.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P.

Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates.

Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P.

Improved species assignments across the entire genus using targeted sequencing.

Accurate species identification of the mosquitoes in the genus is of crucial importance to implement malaria control measures and monitor their effectiveness. We use a previously developed amplicon panel (ANOSPP) that retrieves sequence data from multiple short nuclear loci for any species in the genus. Species assignment is based on comparison of samples to a reference index using -mer distance.

A kalihinol analog disrupts apicoplast function and vesicular trafficking in malaria.

We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity or toxicity. Complementary chemical, molecular, and genomics analyses revealed that MED6-189 targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking.

Understanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory.

Plasmodium falciparum undergoes sequestration within deep tissues of the human body, spanning multiple organ systems with differing oxygen (O2) concentrations. The parasite is exposed to an even greater range of O2 concentrations as it transitions from the human to the mosquito host, suggesting a high level of plasticity as it navigates these different environments. In this review, we explore factors that may contribute to the parasite's response to different environmental O2 concentrations, recognizing that there are likely multiple pieces to this puzzle.

A low-cost culture- and DNA extraction-free method for the molecular detection of pneumococcal carriage in saliva.

Molecular methods have improved the sensitivity of the detection of pneumococcal carriage in saliva. However, they typically require sample culture enrichment and nucleic acid extraction prior to performing the detection assay and may limit scalability for extensive surveillance of pneumococcus, particularly in low-resource settings. We evaluated the performance of a DNA-extraction-free method for the detection of pneumococcus in saliva.

Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

Background: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance.

Methods: Data from two decades (2000-2020) of continuous molecular surveillance of P.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to infected mosquito bites.

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with : mosGILT, SAMSP1, AgSAP, and AgTRIO.

A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in Malaria.

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against and .

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

Background: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.

Methods: Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA).

Identification of an artemisinin-resistant kelch13 R515K mutant parasite in Senegal.

The emergence of artemisinin partial resistance (ART-r) in malaria parasites has substantially compromised the efficacy of antimalarial treatments across southeast Asia (SE Asia). The spread of ART-r within the African continent could jeopardize past progress made in reducing worldwide malaria burden. A clinical index malaria case was identified in Kaolack, Senegal with persistent fever after complete artesunate-amodiaquine (ASAQ) treatment.

Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study.

Background: Strong surveillance systems with wide geographic coverage are needed to detect and respond to reports of antimalarial drug resistance on the African continent. We aimed to assess the utility and feasibility of using blood-fed mosquitos (xenomonitoring) to conduct rapid surveillance of molecular markers associated with resistance in human populations.

Methods: We conducted three cross-sectional surveys in two rainy seasons and the interim dry season in southwest Burkina Faso between Oct 10, 2018, and Sept 17, 2019.

Routine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers.

While considerable attention was placed on SARS-CoV-2 testing and surveillance programs in the K-12 setting, younger age groups in childcare centers were largely overlooked. Childcare facilities are vital to communities, allowing parents/guardians to remain at work and providing safe environments for both children and staff. Therefore, early in the COVID-19 pandemic (October 2020), we established a PCR-based COVID-19 surveillance program in childcare facilities, testing children and staff with the goal of collecting actionable public health data and aiding communities in the progressive resumption of standard operations and ways of life.

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type, has often an aggressive course and is poorly responsive to current therapeutic approaches, so that 5-year survival rates for patients diagnosed with advanced disease is lower than 50%. The Epidermal Growth Factor Receptor (EGFR) has emerged as an established oncogene in HNSCC. Indeed, although HNSCCs are a heterogeneous group of cancers which differ for histological, molecular and clinical features, EGFR is overexpressed or mutated in a percentage of cases up to about 90%.

Ex vivo RSA and Pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

Introduction: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapies (ACTs), the current frontline malaria curative treatments. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in Sub-Saharan Africa where most malaria deaths occur.

Methods: Here, we evaluated susceptibility to dihydroartemisinin (DHA) from 38 isolates collected in 2017 in Thiès (Senegal) expressed with the Ring-stage Survival Assay (RSA).

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries.

Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5.

The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates.

Optimizing Plasmodium vivax serological surveillance within a coendemic epidemiological landscape.

Serological surveillance is a useful tool for revealing hotspots of transmission intensity or cryptic asymptomatic reservoirs, especially as malaria transmission declines. Such approaches can help us to understand malaria epidemiology, but also to guide interventions. Recently, Longley et al.

Leveraging genome editing to functionally evaluate Plasmodium diversity.

The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and ultimately eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria-causing pathogen and strain-specific immune neutralization.

Verapamil: prevention and treatment of cardio-renal syndromes in diabetic hypertensive patients?

Patients with diabetes mellitus (DM) often present other chronic comorbidities including arterial hypertension (AH), chronic kidney disease (CKD), ischemic heart disease (IHD) and heart failure with preserved ejection fraction (HFpEF). The frequent association of the latter conditions is considered part of the spectrum of cardio-renal syndromes (CRS), a group of disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. Verapamil is a non-dihydropyridine calcium channel blocker (CCB) widely used in the treatment of hypertension, chronic stable angina, secondary prevention of reinfarction, paroxysmal supra-ventricular tachycardia and for rate control in atrial fibrillation/flutter.

Repeatability and reproducibility of a handheld quantitative G6PD diagnostic.

Background: The introduction of novel short course treatment regimens for the radical cure of Plasmodium vivax requires reliable point-of-care diagnosis that can identify glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. While deficient males can be identified using a qualitative diagnostic test, the genetic make-up of females requires a quantitative measurement. SD Biosensor (Republic of Korea) has developed a handheld quantitative G6PD diagnostic (STANDARD G6PD test), that has approximately 90% accuracy in field studies for identifying individuals with intermediate or severe deficiency.

Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering.

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal-a region of exceptionally low malaria transmission (entomological inoculation rate less than 1).