Toward Setting Minimum and Optimal Data to Report for Malaria Molecular Surveillance with Targeted Sequencing: The "What" and "Why".

The COVID-19 pandemic showcased the power of genomic surveillance in tracking infectious diseases, driving rapid public health responses and global collaboration. This same infrastructure is being leveraged for malaria molecular surveillance (MMS) in Africa to tackle challenges like artemisinin partial resistance and Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions. However, variability in sequencing methods and data reporting is currently limiting the validation, comparability, and reuse of data. To maximize the impact of MMS, we propose minimal and optimal data for reporting that maximize transparency and FAIR (Findable, Accessible, Interoperable, Reusable) principles. Rather than focusing on specific data formats, here, we propose what should be reported and why. Moving to reporting individual infection-level allele or microhaplotype data is central to maximizing impact of MMS. Reporting must adhere to local regulatory practices and ensure proper data oversight and management, preventing data colonialism and preserving opportunities for data generators. With malaria’s challenges transcending borders, reporting and adopting standardized practices is essential to advance research and strengthen global public health efforts.

Malaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.

Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs.

Malaria remains a major public health challenge worldwide. In order to ensure a prompt and accurate malaria diagnosis, the World Health Organization recommended the confirmatory parasitological diagnosis of malaria by microscopy and malaria rapid diagnostic test (RDT) prior to antimalarial administration and treatment. This study was designed to evaluate the performance of nested polymerase chain reaction (nested PCR), light microscopy, and Plasmodium falciparum histidine-rich protein 2 rapid diagnostic test (PfHRP2 RDT) in the detection of falciparum malaria in Akure, Nigeria. A cross-sectional and hospital-based study involving 601 febrile volunteer participants was conducted in Akure, Nigeria. Approximately 2–3 mL venous blood samples were obtained from each study participant for parasitological confirmation by microscopy and PfHRP2-based malaria RDT. Thick and thin films were prepared and viewed under the light microscope for parasite detection, parasite density quantification, and species identification, respectively. Dry blood spot samples were prepared on 3MM Whatman filter paper for nested PCR. The overall prevalence of microscopy, PfHRP2 RDT, and nested PCR were 64.89% (390/601), 65.7% (395/601), and 67.39% (405/601), respectively. The estimates of sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and Youden’s j index of microscopy and RDT were 96.30, 100.00, 100.00, 92.89, 97.50, 0.963, and 95.06, 94.90, 97.47, 90.29, 95.01, and 0.899, respectively. Malaria RDT recorded higher false negativity, compared microscopy (4.94% vs. 3.70%). A near perfect agreement was reported between microscopy and nested PCR, and between PfHRP2 RDT and nested PCR with Cohen’s kappa (k) values of 0.94 and 0.88, respectively. This study revealed that PfHRP2 RDT and microscopy continues to remain sensitive and specific for falciparum malaria diagnosis in the study area.

Parasitic infections remain a serious public health issue globally, requiring prompt and precise diagnosis. Traditional diagnostic techniques, such as microscopic examinations, immunological methods, such as enzyme-linked immunosorbent assay (ELISA), and molecular tests, such as polymerase chain reaction (PCR), are standard tools for parasite identification. However, traditional methods are time-consuming and have less sensitivity and specificity than nanobiosensors. Hence, the current review aims to analyze the nanobiosensors in detecting globally important human parasites, i.e.,Plasmodium, Leishmania, Echinococcus, Schistosoma, and Taenia, emphasizing their significance in the early detection and analyzing their future challenges. Nanobiosensors provide efficient, sensitive, and rapid diagnosis of parasites’ antigens or genetic material using nanomaterials, such as nanowires, quantum dots (QDs), metallic nanoparticles, and carbon nanotubes, as well as identification of biomarkers, including excretory–secretory products and microRNAs. Nanobiosensors can utilize diverse nanomaterials such as gold nanoparticles (AuNPs) for the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in Plasmodium, carbon nanotubes (CNTs) functionalized with anti-EgAgB antibodies for Echinococcus, and QDs labeled with DNA probes for the detection of Leishmania kDNA. Regarding Schistosoma, graphene oxide (GO)-based nanobiosensors with a soluble egg antigen (SEA) binding, and for Taenia, metallic nanobiosensors can detect parasites’ biomarkers even at low concentrations. Challenges for using nanobiosensors in parasitic infection diagnosis include limitations in mass production, biological matrix interference, and the need for standardization. Development of multiplex nanobiosensors using polymer nanofibers or hybrid nanoparticles for simultaneous detection of multiple pathogens, along with integration of lab-on-a-chip technology for point-of-care (PoC) platforms, is an important future prospect that needs to be worked on. In conclusion, considering the rapidly ongoing advancement of nanobiosensors, it is expected that they will aid the detection, treatment, and management of parasitic infections by providing new avenues for early detection, improved treatment, and improved disease management in the future.Graphical

The prevalence of malaria and coronavirus disease (COVID-19) is highly devastating and has led to a serious public health challenge worldwide. In order to ensure proper control and elimination, the State Ministry of Health (MoH) Ondo State, Nigeria conducted medical examinations in Iju/Itaogbolu, Igoba, and Ogbese Health centers to identify and confirm cases of COVID-19 and malaria infection. This study provides the outcome of the epidemiological investigation of the prevalence of COVID-19 and malaria in Akure North Local Government Area of Ondo State, Nigeria. The study was a hospital-based secondary data analysis comprising of 11,389 and 682 individuals who visited various health centers in Akure North Local Government Area (LGA) for medical examinations on malaria and COVID-19, respectively. The COVID-19 cases were investigated using the fluid sample collected with a nasal swab or a throat swab, or spit of saliva into a tube and confirmed by real-time polymerase chain reaction (RT-PCR). The Plasmodium falciparum histidine-rich protein 2 (PfHRP2) RDT was employed to detect the P.falciparum antigen among participants' blood samples. The total prevalence of malaria and COVID-19 were 67.6% and 12.4%, respectively. Meanwhile, the month of September recorded the highest malaria prevalence of 81.8% while the month of April recorded the least malaria prevalence of 56.4%. Similarly, the highest case of COVID-19 (18.8%) was recorded in the month of November while the least case (2.4%) was recorded in the month of April (p < 0.05). The age range of 12-59 months had the highest malaria prevalence of 74.9% while 0-24 days age range recorded the least prevalence of 15.2% (p > 0.05). Apparently, the children were more infected with malaria parasites while adults were more infected with COVID-19. Conclusively, malaria and COVID-19 infections were prevalent in the study area. Thus, the people should be enlightened on the deadly risk of malaria and COVID-19 through the health workers, social media, and the community leaders to ensure compliance with appropriate preventive measures.

Background & objectives:Despite major control efforts, malaria remains a major public health problem that still causes high mortality rate worldwide especially in Africa and Asia. Accurate and confirmatory diagnosis before treatment initiation is the only way to control the disease. The present study was undertaken to develop reagents using sandwich ELISA for simultaneous detection of PfHRP2 (Plasmodium falciparum histidine rich protein) and PfLDH (P. falciparum lactate dehydrogenase) antigens in the proven malaria cases.Methods:The antibodies were raised against two epitopes of PfHRP2 protein and three unique and unexplored epitopes of PfLDH protein. These antibodies were able to detect PfHRP2 and PfLDH antigens in culture supernatant and parasitized RBC lysate of P. falciparum, respectively up to 50 parasites/μl. The in-house reagents were tested in 200 P. falciparum positive patients residing in Baghpat district of Uttar Pradesh in northern India.Results:Microsphere (PLGA) with CpG ODN were used to generate high titre and high affinity antibodies against selected peptides of PfHRP-2 and pLDH antigen in mice and rabbit. The peptide specific peak titre varied from 12,800 - 102,400 with an affinity ranging 0.73 - 3.0 mM. The indigenously developed reagents are able to detect PfHRP2 and PfLDH antigens as low as 75 parasites/μl of blood with a very high sensitivity (96-100%) and specificity (100%).Interpretation & conclusions:The study highlight the identification of unique epitopes of PfHRP2 and PfLDH, and the generated antibodies against these antigens were used for quantitative estimation of these two antigens using sandwich ELISA. No corresreactivity with P. vivax infected patients was observed with the sera.

Background: Malaria remains a persistent public health challenge, particularly in sub-Saharan Africa, where asymptomatic falciparum malaria poses a significant threat. Asymptomatic cases serve as a crucial parasite reservoir, contributing to ongoing transmission.&#x0D; Aim: The study investigates the prevalence of asymptomatic falciparum malaria and assesses the occurrence of gene deletion in the Plasmodium falciparum Histidine Rich Protein 2 (Pf HRP2) gene in Makurdi, Benue State, Nigeria.&#x0D; Methodology: A cross-sectional study was conducted between September and October 2019, which involved 374 apparently healthy individuals from five communities. Malaria diagnosis utilized Rapid Diagnostic Test (RDT) kits, microscopy, and polymerase chain reaction (PCR) for Pf HRP2 gene assessment.&#x0D; Results: The study found a prevalence of 25.4% by RDT and 28.1% by microscopy. Asymptomatic falciparum malaria was significantly influenced by location, proximity to water bodies, bed net usage, and history of malaria treatment, while, age, and insecticide usage showed no significant impact. PCR results revealed amplified fragments with band sizes ranging from 600 to 900 base pairs in 40 positive isolates, eliminating Pf HRP2 gene deletion as a cause for false negatives observed between RDT and microscopy results.&#x0D; Discussion/Conclusion: The study highlights a high malaria transmission rate in Nigeria, emphasizing the role of location-specific factors and bed net usage in the proliferation of asymptomatic falciparum malaria. Importantly, no gene deletion was identified in the Pf HRP2 gene among the studied Plasmodium falciparum isolates.

Smart cities and digital public health are closely related. Managing digital transformation in urbanization and living spaces is challenging. It is critical to prioritize the emotional and physical health and well-being of humans and their animals in the dynamic and ever-changing environment they share. Human-animal bonds are continuous as they live together or share urban spaces and have a mutual impact on each other’s health as well as the surrounding environment. In addition, sensors embedded in the Internet of Things are everywhere in smart cities. They monitor events and provide appropriate responses. In this regard, accident and emergency informatics (A&EI) offers tools to identify and manage overtime hazards and disruptive events. Such manifold focuses fit with One Digital Health (ODH), which aims to transform health ecosystems with digital technology by proposing a comprehensive framework to manage data and support health-oriented policies. We showed and discussed how, by developing the concept of ODH intervention, the ODH framework can support the comprehensive monitoring and analysis of daily life events of humans and animals in technologically integrated environments such as smart homes and smart cities. We developed an ODH intervention use case in which A&EI mechanisms run in the background. The ODH framework structures the related data collection and analysis to enhance the understanding of human, animal, and environment interactions and associated outcomes. The use case looks at the daily journey of Tracy, a healthy woman aged 27 years, and her dog Mego. Using medical Internet of Things, their activities are continuously monitored and analyzed to prevent or manage any kind of health-related abnormality. We reported and commented on an ODH intervention as an example of a real-life ODH implementation. We gave the reader examples of a “how-to” analysis of Tracy and Mego’s daily life activities as part of a timely implementation of the ODH framework. For each activity, relationships to the ODH dimensions were scored, and relevant technical fields were evaluated in light of the Findable, Accessible, Interoperable, and Reusable principles. This “how-to” can be used as a template for further analyses. An ODH intervention is based on Findable, Accessible, Interoperable, and Reusable data and real-time processing for global health monitoring, emergency management, and research. The data should be collected and analyzed continuously in a spatial-temporal domain to detect changes in behavior, trends, and emergencies. The information periodically gathered should serve human, animal, and environmental health interventions by providing professionals and caregivers with inputs and “how-to's” to improve health, welfare, and risk prevention at the individual and population levels. Thus, ODH complementarily combined with A&EI is meant to enhance policies and systems and modernize emergency management.

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Malaria remains the biggest threat to public health, especially among pregnant women and young children in sub-Saharan Africa. Prompt and accurate diagnosis is critical for effective case management and detection of drug resistance. Conventionally, microscopy and rapid diagnostic tests (RDTs) are the tools of choice for malaria diagnosis. RDTs are simple to use and have been extensively used in the diagnosis of malaria among travelers to malaria-endemic regions, routine case management, and surveillance studies. Most RDTs target the histidine-rich protein (PfHRP) which is exclusively found in Plasmodium falciparum and a metabolic enzyme Plasmodium lactate dehydrogenase (pLDH) which is common among all Plasmodium species. Other RDTs incorporate the enzyme aldolase that is produced by all Plasmodium species. Recently, studies have reported false-negative RDTs primarily due to the deletion of the histidine-rich protein (pfhrp2 and pfhrp3) genes in field isolates of P. falciparum. Herein, we review published literature to establish pfhrp2/pfhrp3 deletions, the extent of these deletions in different geographical regions, and the implication in malaria control. We searched for publications on pfhrp2/pfhrp3 deletions and retrieved all publications that reported on this subject. Overall, 20 publications reported on pfhrp2/pfhrp3 deletions, and most of these studies were done in Central and South America, with very few in Asia and Africa. The few studies in Africa that reported on the occurrence of pfhrp2/pfhrp3 deletions rarely evaluated deletions on the flanking genes. More studies are required to evaluate the existence and extent of these gene deletions, whose presence may lead to delayed or missed treatment. This information will guide appropriate diagnostic approaches in the respective areas.

BackgroundMalaria presents a considerable threat to public health. Histidine-rich protein 2 (HRP 2) is the major protein released into human blood upon infection by Plasmodium falciparum. In this study, we aimed to evaluate the immunogenicity of HRP 2 exon II and the efficacy of novel monoclonal antibodies (mAbs) against HRP 2 for Point-of-Care Test (POCT).MethodsThe recombinant protein was expressed in soluble form in E. coli and used to immunize mice for mAb production. Two IgG1 mAbs (1A5 and 1C10) with high affinity, specificity and sensitivity for both native and recombinant HRP 2 were selected after fusion of mouse spleen with myeloma cells. The affinity constant of 1A5 and 1C10 were 7.15 and 4.91 × 10-7 L/mol, respectively. Subsequently, an immunochromatograhic assay was used for screening of clinical samples in endemic regions of China and Myanmar.ResultsThe immunochromatographic test retrospectively showed an overall sensitivity of 99.07%, and specificity of 100%. Sensitivity at parasite densities < 200, 200–2000, and > 2000 parasites/μL was 87.5, 98.7, and 100%, respectively.ConclusionsThese results suggest that HRP 2 exon II contains immunogenic sites similar to those of the native antigen and can be used for the development of mAbs suitable for malaria diagnosis in endemic communities.

Informatics has become an essential component of research in the past few decades, capitalizing on the efficiency and power of computation to improve the knowledge gained from increasing quantities and types of data. While other fields of research such as genomics are well represented in informatics resources, nutrition remains underrepresented. Nutrition is one of the most integral components of human life, and it impacts individuals far beyond just nutrient provisions. For example, nutrition plays a role in cultural practices, interpersonal relationships and body image. Despite this, integrated computational investigations have been limited due to challenges within nutrition informatics (nutri-informatics) and nutrition data. The purpose of this review is to describe the landscape of nutri-informatics resources available for use in computational nutrition research and clinical utilization. In particular, we will focus on the application of biomedical ontologies and their potential to improve the standardization and interoperability of nutrition terminologies and relationships between nutrition and other biomedical disciplines such as disease and phenomics. Additionally, we will highlight challenges currently faced by the nutri-informatics community including experimental design, data aggregation and the roles scientific journals and primary nutrition researchers play in facilitating data reuse and successful computational research. Finally, we will conclude with a call to action to create and follow community standards regarding standardization of language, documentation specifications and requirements for data reuse. With the continued movement toward community standards of this kind, the entire nutrition research community can transition toward greater usage of Findability, Accessibility, Interoperability and Reusability principles and in turn more transparent science.