human malaria challenge

Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity...

Human-induced inputs of nitrogen (N) and phosphorus (P) into the biosphere have reached unprecedented levels, particularly N, leading to an escalating global anthropogenic N:P ratio. This ratio has emerged as a significant driver of environmental change, impacting organisms, ecosystems, and global food security. However, the implications of this ratio for human health have been largely overlooked and remain uncertain. This article aims to fill this knowledge gap by exploring the potential effects of N:P ratios on both non-infectious and infectious diseases...

Malaria is a deadly disease caused by protozoan pathogens of the Plasmodium parasite. Transmission to humans occurs through the bite of an infected female Anopheles mosquito. According to the World Health Organization (WHO), an estimated 247 million cases of malaria were recorded worldwide in 2021, with approximately 619 000 malaria deaths. The initial signs of malaria can be mild and challenging to diagnose due to the signs and symptoms being similar to those of other illnesses. The malaria burden remains largely concentrated in the WHO sub-Saharan African region and has been recognised as a significant contributor to morbidity and mortality...

Plasmodium vivax is the most prevalent cause of malaria in Thailand and is predominant in malarial endemic areas worldwide. P. vivax infection is characterized by low parasitemia, latent liver-stage parasites, or asymptomatic infections leading to underreported P. vivax cases. These are significant challenges for controlling and eliminating P. vivax from endemic countries. This study developed and evaluated a dot-blot enzyme-linked immunosorbent assay (ELISA) using PvMSP1-42 recombinant antigen for serological diagnosis based on the detection of antibodies against P...

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole-genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modeled as a mixture of sources from ancient Anatolia, Levant, and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam...

BACKGROUND: By 2022, the Government of Indonesia had successfully eliminated malaria in 389 out of 514 districts but continues to face a challenge in Eastern Indonesia where 95% of the total 2021 malaria cases were reported from Papua, West Papua and Nusa Tenggara Timur provinces. There is an increased recognition that malaria elimination will require a better understanding of the human behavioural factors hindering malaria prevention and treatment, informed by local context and local practice...

Genetic editing is a powerful tool for functional characterization of genes in various organisms. With its simplicity and specificity, the CRISPR-Cas9 technology has become a popular editing tool, which introduces site-specific DNA double-strand breaks (DSBs), and then leverages the endogenous repair pathway for DSB repair via homology-directed repair (HDR) or the more error-prone non-homologous end joining (NHEJ) pathways. However, in the Plasmodium parasites, the lack of a typical NHEJ pathway selects for DSB repair through the HDR pathway when a homologous DNA template is available...

The invasion of human erythrocytes by Plasmodium falciparum merozoites requires interaction between parasite ligands and host receptors. Interaction of Pf Rh5-CyRPA-Ripr protein complex with basigin, an erythrocyte surface receptor, via PfRh5 is essential for erythrocyte invasion. Antibodies raised against each antigen component of the complex have demonstrated erythrocyte invasion inhibition, making these proteins potential blood-stage vaccine candidates. Genetic polymorphisms present a significant challenge in developing efficacious vaccines, leading to variant-specific immune responses...

Human malaria, caused by five Plasmodium species ( P. falciparum, P. vivax, P. malariae, P. ovale , and P. knowlesi ), remains a significant global health burden. While most interventions target P. falciparum , the species associated with high mortality rates and severe clinical symptoms, non-falciparum species exhibit different transmission dynamics, remain hugely neglected, and pose a significant challenge to malaria elimination efforts. Recent studies have reported the presence of antigens associated with cross-protective immunity, which can potentially disrupt the transmission of various Plasmodium species...

BACKGROUND: Plasmodium vivax Duffy binding protein (PvDBP) is a merozoite surface protein located in the micronemes of P. vivax. The invasion of human reticulocytes by P. vivax merozoites depends on the parasite DBP binding domain engaging Duffy Antigen Receptor for Chemokine (DARC) on these red blood cells (RBCs). PvDBPII shows high genetic diversity which is a major challenge to its use in the development of a vaccine against vivax malaria. METHODS: A cross-sectional study was conducted from February 2021 to September 2022 in five study sites across Ethiopia...

BACKGROUND: The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy...

Microorganisms, encompassing both uni- and multicellular entities, exhibit remarkable diversity as omnipresent life forms in nature. They play a pivotal role by supplying essential components for sustaining biological processes across diverse ecosystems, including higher host organisms. The complex interactions within the human gut microbiota are crucial for metabolic functions, immune responses, and biochemical signalling, particularly through the gut-brain axis. Viruses also play important roles in biological processes, for example by increasing genetic diversity through horizontal gene transfer when replicating inside living cells...

BACKGROUND: Malaria remains an enduring public health concern in Indonesia, exacerbated by its equatorial climate that fosters the proliferation of Anopheles mosquitoes. This study seeks to assess the performance of the malaria elimination programme comprehensively. METHODS: Between May and August 2022, a qualitative study was conducted in Muara Enim Regency, South Sumatra Province, involving 22 healthcare professionals from diverse backgrounds. These informants were strategically chosen for their pivotal roles in providing profound insights into various facets of the malaria elimination programme...

New strategies are needed to reduce the incidence of malaria, and promising approaches include vaccines targeting the circumsporozoite protein (CSP). To improve upon the malaria vaccine, RTS,S/AS01, it is essential to standardize preclinical assays to measure the potency of next-generation vaccines against this benchmark. We focus on RTS,S/AS01-induced antibody responses and functional activity in conjunction with robust statistical analyses. Transgenic Plasmodium berghei sporozoites containing full-length P...

INTRODUCTION: 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 recombinant, full-length circumsporozoite protein vaccine (rCSP) administered with adjuvant GLA-LSQ on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naïve adults. Primary endpoints were safety and reactogenicity...

A single 300 mg dose of tafenoquine, in combination with chloroquine, is currently approved in several countries for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ≥16 years. Recently, however, Watson et al. suggested that the approved dose of tafenoquine is insufficient for radical cure, and that a higher 450 mg dose could reduce P. vivax recurrences substantially (Watson et al., 2022). In this response, we challenge Watson et al.'s assertion based on empirical evidence from dose-ranging and pivotal studies (published) as well as real-world evidence from post-approval studies (ongoing, therefore currently unpublished)...

Malaria is a vector-borne disease caused by Plasmodium parasites of which Plasmodium falciparum contributed to an estimated 247 million cases worldwide in 2021 (WHO malaria report 2022). The P. falciparum Circumsporozoite protein (PfCSP) covers the surface of the sporozoite which is critical to cell invasion in the human host. PfCSP is the leading pre-erythrocytic vaccine candidate and forms the basis of the RTS'S (Mosquirix® ) malaria vaccine. However, high-yield production of full-length PfCSP with proper folding has been challenging...

Obesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise...

BACKGROUND: Zoonotic malaria is a growing public health threat in the WHO Southeast Asia (SEA) and Western Pacific (WP) regions. Despite vector-control measures, the distribution of Macaque fascicularis and M. nemestrina, and Anopheles mosquitoes carrying non-human simian malaria parasites poses challenges to malaria elimination. The systematic review assesses the literature on knowledge and malaria-preventive practices in zoonotic malaria-affected areas across the WHO SEA and WP, aiming to identify challenges for malaria control...

[This corrects the article DOI: 10.3389/fimmu.2023.1242306.].