Infectious Disease Research Research Articles

Call for Papers: Infectious Diseases Research in the Global South: Treatments and Treatment Failures

Call for Papers: Infectious Diseases Research in the Global South: Treatments and Treatment Failures

Pharmacists leading the way in infectious diseases education, research, and patient care.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Past, Present, and Future of RNA Modifications in Infectious Disease Research.

In early 2024, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a roadmap for the future of research into mapping ribonucleic acid (RNA) modifications, which underscored the importance of better defining these diverse chemical changes to the RNA macromolecule. As nearly all mature RNA molecules harbor some form of modification, we must understand RNA modifications to fully appreciate the functionality of RNA. The NASEM report calls for massive mobilization of resources and investment akin to the transformative Human Genome Project of the early 1990s. Like the Human Genome Project, a concerted effort in improving our ability to assess every single modification on every single RNA molecule in an organism will change the way we approach biological questions, accelerate technological advance, and improve our understanding of the molecular world. Consequently, we are also at the start of a revolution in defining the impact of RNA modifications in the context of host-microbe and even microbe-microbe interactions. In this perspective, we briefly introduce RNA modifications to the infection biologist, highlight key aspects of the NASEM report and exciting examples of RNA modifications contributing to host and pathogen biology, and finally postulate where infectious disease research may benefit from this exciting new endeavor in globally mapping RNA modifications.

Federated learning as a smart tool for research on infectious diseases

BackgroundThe use of real-world data has become increasingly popular, also in the field of infectious disease (ID), particularly since the COVID-19 pandemic emerged. While much useful data for research is being collected, these data are generally stored across different sources. Privacy concerns limit the possibility to store the data centrally, thereby also limiting the possibility of fully leveraging the potential power of combined data. Federated learning (FL) has been suggested to overcome privacy issues by making it possible to perform research on data from various sources without those data leaving local servers. In this review, we discuss existing applications of FL in ID research, as well as the most relevant opportunities and challenges of this method.MethodsReferences for this review were identified through searches of MEDLINE/PubMed, Google Scholar, Embase and Scopus until July 2023. We searched for studies using FL in different applications related to ID.ResultsThirty references were included and divided into four sub-topics: disease screening, prediction of clinical outcomes, infection epidemiology, and vaccine research. Most research was related to COVID-19. In all studies, FL achieved good accuracy when predicting diseases and outcomes, also in comparison to non-federated methods. However, most studies did not make use of real-world federated data, but rather showed the potential of FL by using data that was manually partitioned.ConclusionsFL is a promising methodology which allows using data from several sources, potentially generating stronger and more generalisable results. However, further exploration of FL application possibilities in ID research is needed.

The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases.

Emerging infectious diseases are caused by unpredictable viruses with the dangerous potential to trigger global pandemics. These viruses typically initiate infection by utilizing the anionic structures of host cell surface receptors to gain entry. Lactoferrin (Lf) is a multifunctional glycoprotein with multiple properties such as antiviral, anti-inflammatory and antioxidant activities. Due to its cationic structure, Lf naturally interacts with certain host cell receptors, such as heparan sulfate proteoglycans, as well as viral particles and other receptors that are targeted by viruses. Therefore, Lf may interfere with virus-host cell interactions by acting as a receptor competitor for viruses. Herein we summarize studies in which this competition was investigated with SARS-CoV-2, Zika, Dengue, Hepatitis and Influenza viruses in vitro. These studies have demonstrated not only Lf's competitive properties, but also its potential intracellular impact on host cells, such as enhancing cell survival and reducing infection efficiency by inhibiting certain viral enzymes. In addition, the immunomodulatory effect of Lf is highlighted, as it can influence the activity of specific immune cells and regulate cytokine release, thereby enhancing the host's response to viral infections. Collectively, these properties promote the potential of Lf as a promising candidate for research in viral infectious diseases.

Viral hepatitis A in children: a false prosperity?

The article presents current data on the state of the issue of Hepatitis A (HA) in children in the Russian Federation and describes clinical and epidemiologic features of rare cases of severe course of the disease, as well as pathogenetic mechanisms of liver damage mediated by cell immune response. Objective. To identify clinical and epidemiologic features of the modern course of HA and its outcomes in children of Saint Petersburg within the period of 2018— 2023. Materials and methods. The study included 89 children diagnosed with HA, undergoing treatment at the Children's Research and Clinical Center for Infectious Diseases from 2018 to 2023. The analysis of disease progression in this group of patients was presented using clinical-anamnestic, epidemiologic, biochemical, virologic and instrumental data. Results. The analysis of infection sources showed a high frequency of HA infection within the family (44.9 ± 0.8%) and significantly less in childcare facilities and schools (7.9 ± 1.0%). The frequency of children with unidentified sources of infection remained high (47.2 ± 0.7%). One-third of all disease cases were imported from southern regions. Most hospitalized children had icteric HA (64.0 ± 0.6%) of moderate severity (79.8 ± 0.5%). Severe HA was observed in 6 patients (6.7 ± 1.0%). During the study, 17 patients (19.1 ± 0.9%) had a prolonged, complicated course of the disease, including ascites and aplastic anemia (12.6 ± 2.2%). Ascites was found in 4 patients with severe severity and in 5 patients with moderate severity of HA. Conclusions. Currently, there is an upward trend in the incidence of HA in the Russian Federation and Saint Petersburg, especially among schoolchildren (56.2%). A rather high frequency of severe (6.7%) and complicated forms (19.1%) of the disease is observed, and the growth of ascites and aplastic anemia cases in HA draws particular attention.

The ABCDs of nutritional assessment in infectious diseases research.

Malnutrition is the most common acquired cause of immunodeficiency worldwide. Nutritional deficiencies can blunt both the innate and adaptive immune response to pathogens. Furthermore, malnutrition is both a cause and consequence of infectious diseases. The bidirectional relationship between infectious diseases and undernutrition, as well as the inflammatory milieu of infectious diseases, can complicate nutritional assessment. This article aims to provide clinicians and researchers with an overview of commonly used tools to assess nutritional status, with a particular emphasis on their use in the context of infectious diseases. This includes anthropometric, biochemical, clinical/physical, and dietary assessments to screen and evaluate undernutrition, diet quality, and food insecurity effectively.

Novel Less Toxic, Lymphoid Tissue-Targeted Lipid Nanoparticles Containing a Vitamin B5-Derived Ionizable Lipid for mRNA Vaccine Delivery.

Following their approval by the Food and Drug Administration, lipid nanoparticles (LNPs) have emerged as promising tools for delivering mRNA vaccines and therapeutics. Ionizable lipids are among the essential components of LNPs, as they play crucial roles in encapsulating mRNA and facilitating its release into the cytosol. In this study, 17 innovative ionizable lipids using vitamin B5 are designed as the core structure, aiming to reduce toxicity, to maintain vaccine efficiency, and to ensure synthetic feasibility. The top-performing LNP in terms of mRNA vaccine delivery in the mouse model is LNP 5097, which is generated by incorporating ionizable lipid I97. mRNA⊂LNP 5097 demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long-term stability. Moreover, mRNA⊂LNP 5097 specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. The findings here suggest the high utility of LNP 5097, which includes novel vitamin B5-derived ionizable lipids with reduced toxicity, in mRNA vaccine research for both infectious diseases and cancer.

Evaluating the performance of a virtual platform ‘T-BOM’ for mentorship in tropical diseases research among early career scientists: Insights from a pilot in Nigeria and other resource-limited settings

BackgroundResearch mentorship plays a crucial role in advancing science. However, there are limited virtual platforms for cultivating mentorship among early career infectious diseases researchers in resource challenged settings. This study reports the findings from the utilization of a recently developed virtual mentorship platform, including its achievements, challenges and needs. MethodsWe developed a web-based application called Top-Bottom Open Mentorship (TBOM) freely accessible at www.tbommodel.com. The platform hosts mentors and allows mentees to send connection requests. In this paper, we present the utilization of this platform, including the opportunities and challenges encountered during the first year of implementation. Utilization data was generated monthly, while opportunities and challenges were captured using a users' perception survey. Data were analyzed in R software and summarized thematically as appropriate. ResultsBetween October 2022 and November 2023, the platform registered 81 users, comprising 63 mentees [54.3 % males, 75 % graduate students] from five countries [Nigeria, Cameroon, Brazil, Sudan, and Ghana], and 18 mentors [78 % males] from six countries [Nigeria, USA, Cameroon, Kenya, Brazil, and Tanzania]. Platform engagement increased from 19.4 % (7 users out of 36 who registered) to 51 % (41 users out of 81 who registered) over the year. Also, a total of 16 mentorship cycles were completed, with 9 currently running. Mentees reported having access to job opportunities, enhanced skills in writing, time management, and grant sourcing, and improved research prospects. However, challenges identified include time zone differences, limited number of mentors, mentee's readiness, and associated internet connection issues. InterpretationThe achievements of T-BOM over a period of one-year are challenged by intrinsic factors from both mentees and mentors, as well as erratic internet services in resource-limited settings. While the platform offers significant opportunities for improving research mentorship, these challenges need to be carefully addressed.

Recent Developments in Infectious Disease Research

The field of infectious disease research is rapidly evolving and advancing, driven by the demand to address both current and emerging threats to global health. The recent COVID-19 pandemic underscored the criticality of infectious disease outbreak preparedness and response, while factors such as climate change, migration, and globalization continue to influence disease transmission dynamics. Innovative approaches to infectious disease research are more essential than ever to prevent future pandemics and the spread of vectorborne diseases. This comprehensive review article investigates some recent pertinent developments in infectious disease research, including the development of a novel serosurveillance platform, modeled after the one designed during the COVID-19 pandemic, aimed at tackling the growing global threat of arboviruses. Also investigated in this article is the repurposing and application of mRNA vaccine technology, initially developed during the pandemic, to address the complex challenge of tick-borne Lyme disease. Finally, we outline several novel and cutting-edge strategies aimed at tackling the ever-mounting crisis of antimicrobial resistance (AMR). Each of these innovations marks a significant step forward in global health security and preparedness, offering promising solutions to the challenges of a rapidly evolving world, while drawing on the lessons learned from past outbreaks and epidemics.

Toscana Virus in Wild-Caught Sand Flies in Portugal, Findings from the National Vector Surveillance Network, 2023.

Phlebotomine sand flies play a crucial role in both human and veterinary medicine, acting as vectors for Leishmania parasites and most known phleboviruses. In Portugal, the REVIVE program, a comprehensive national surveillance network under the Ministry of Health, has included sand fly surveys since 2016. REVIVE aims to identify existing sand fly species in the country, determine which pathogens are circulating among them, and provide actionable insights for prevention and control measures when necessary. In this way, annually, from May to October, health technicians collect sand flies across mainland Portugal with CDC light traps. The collected sand flies are sent to the Centre for Vectors and Infectious Diseases Research for species identification and molecular screening of pathogens. On 21 September 2023, Toscana virus (TOSV), a well-known phlebovirus in the Mediterranean region due to its capacity to cause neurological disease, was detected in a pool of 30 sand flies collected in Algarve, the southernmost region of Portugal. A 668 bp partial sequence of the nucleoprotein gene shows similarity with TOSV strains from Spain. To our knowledge, this is the first detection of TOSV in its vector in this country, having previously only been reported in vertebrate hosts. These findings highlight the important role of ongoing surveillance efforts in monitoring and understanding the dynamics of sand fly-borne diseases in Portugal.

Infectious disease research grants

Infectious disease research grants

A protocol for a living mapping review of global research funding for infectious diseases with a pandemic potential - Pandemic PACT.

The COVID CIRCLE initiative Research Project Tracker by UKCDR and GloPID-R and associated living mapping review (LMR) showed the importance of sharing and analysing data on research at the point of funding to improve coordination during a pandemic. This approach can also help with research preparedness for outbreaks and hence our new programme the Pandemic Preparedness: Analytical Capacity and Funding Tracking Programme (Pandemic PACT) has been established. The LMR described in this protocol builds on the previous UKCDR and GloPID-R COVID-19 Research Project database with addition of the priority diseases from the WHO Blueprint list plus initial additions of pandemic influenza, mpox and plague. We capture data on new funding commitments directly from funders and map these against a core ontology (aligned to existing research roadmaps). We will analyse regularly collated new research funding commitments to provide an open, accessible, near-real-time overview of the funding landscape for a wide range of infectious disease and pandemic preparedness research and assess gaps. The periodicity of updates will be increased in the event of a major outbreak. We anticipate that this LMR and the associated online tool will be a useful resource for funders, policy makers and researchers. In the future, our work will inform a more coordinated approach to research funding by providing evidence and data, including identification of gaps in funding allocation with a particular focus on low- and middle-income countries.

Synthetic data: how could it be used in infectious disease research?

Synthetic data: how could it be used in infectious disease research?

Infectious Disease Research Laboratories in Africa Are Not Using AI Yet─Large Language Models May Facilitate Adoption.

Infectious Disease Research Laboratories in Africa Are Not Using AI Yet─Large Language Models May Facilitate Adoption.

In Commemoration of Dr. Farrokh Modabber: An Iranian Pioneer of Cellular Immunology, and Leishmaniases Vaccine Research in Iran and the World.

Born in 1940 in Rasht, Iran, Dr. Farrokh Modabber earned his B.A. in Bacteriology and Ph.D. in Microbiology from University of California, Los Angeles (UCLA). He joined the Harvard Medical School as a fellow before transitioning to a faculty role at Harvard School of Public Health (HSPH) and played a pivotal role in advancing Cellular Immunology. In the early 1970s, he returned to Iran as an Associate Professor at Pahlavi University in Shiraz. Subsequently, he rejoined HSPH before embarking on a tenure at Tehran University. As the head of the Pathobiology Department at Tehran University School of Public Health, he initiated the Tehran/Harvard joint M.Sc. program in Immunology, which played a crucial role in shaping the careers of numerous Iranian immunologists over the following decades. Dr. Modabber went on to hold esteemed positions such as Director General of the Pasteur Institute of Iran, visiting immunology lecturer at various universities, Coordinator of Research Capability Strengthening of WHO's Special Program for Research and Training in Tropical Diseases (TDR), Director of the Infectious Disease Research Institute (IDRI), and Senior Advisor of Drugs for Neglected Diseases initiative (DNDi), to name a few. This article highlights Dr. Modabber's impactful career, focusing on his efforts to combat global leishmaniasis.

Pneumococcal carriage and changes in serotype distribution post- PCV13 introduction in children in Matiari, Pakistan

BackgroundIn early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan. MethodsChildren <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September–October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates. ResultsOf the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively. ConclusionReplacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes.

Articulating the ultimate objectives of research capacity strengthening programmes: Why this is important and how we might achieve it.

'Research capacity strengthening' (RCS) is an umbrella term that can be used to describe a wide variety of activities conducted in support of diverse objectives premised upon distinct, potentially opposing, views. Despite this, the ultimate objective of RCS activities is rarely made explicit which can be problematic when diverse objectives are possible. By 'ultimate' objective we are referring to the overarching (often long-term) goal an RCS initiative is intended to contribute towards (e.g. better population health) as opposed to the more immediate 'proximate' (often short-term) objectives of any such activity (e.g. improved capacity to undertake infectious disease research). We argue a need for those funding, designing and implementing RCS initiatives to make clear statements as to the ultimate objective that they foresee their respective initiative contributing towards as well as the proposed pathway and associated assumptions that underlie their approach. Examples of distinct ultimate objectives for RCS initiatives are presented alongside fictitious examples of how they may be transparently reported from both a funder and implementor perspective. Such transparency should be routine within the scope of funding calls for RCS activities (even when such activities are only a minor component of the call), subsequent applications to those calls and any description of an applied RCS activity/ies and/or the associated outcomes thereof. The process of determining one's ultimate objective will further cause funders and actors to think through their respective initiatives more thoroughly and make informed choices and better designed RCS projects. Doing so would reduce any ambiguity associated with the use of the term 'research capacity strengthening' and would provide a stronger foundation for robust programme evaluation.

Determinants of possible inflammatory myocardial damage in acute intestinal infections in children

BACKGROUND: Non-coronary cardiomyopathies, including inflammatory cardiomyopathies, are one of the leading causes of disability and mortality in children and adults. Inflammatory cardiomyopathy in most cases is an outcome of myocarditis as a result of direct agent-dependent myocardial damage or autoimmune reactions in the absence of genetic predisposition. AIM: On the basis of clinical assessment of cardiovascular system changes, to develop a discriminant model to predict the possibility of myocardial damage of inflammatory genesis in acute intestinal infections (AII) in children. MATERIALS AND METHODS: In the Intestinal Infections Department of the Children’s Research and Clinical Center for Infectious Diseases of FMBA of Russia in the period 2020-2022, 33 children aged from 1 month to 13 years with AII of different etiology were consecutively observed, in whom, according to clinical, laboratory and instrumental examination data, for the first time in their lives, changes in cardiovascular system were detected. The sample was formed using an algorithm for diagnosing inflammatory myocardial lesions in points, the sum of which concluded that there were no or presence of such, which allowed us to identify group 1 (n = 24) and group 2 (n = 9), respectively. Etiological diagnosis of acute intestinal infections was performed in all children, clinical and laboratory data, results of a 12-channel electrocardiogram (ECG), transthoracic echocardiography (EchoCG) were evaluated. The differences in the groups were revealed using the Pearson chi-squared test and the Mann–Whitney test, which were considered reliable at p 0.05. The method of discriminant analysis was used. RESULTS: Functional systolic noise and increased cardiospecific enzymes were observed less frequently in group 1 than in group 2 (4.2%; 22.2% and 67%; 100%). Of the pathological ECG changes, violations of the repolarization process were observed (16.7%; 33.3%). No significant changes in the Echo-KG were detected. The viral etiology of acute intestinal infections dominated (79.2%; 88.9%). Changes in the hemogram were characterized by a high frequency of leukocytosis in group 1 (29.2%; 0%) and leukopenia in group 2 (4.2%; 22.2%). In group 1, there was a higher frequency of neutrophilosis (79.2%; 44.4%), rod-shaped shift (62.5%; 22.2%), thrombocytosis (29.2%; 0%), lymphocytopenia (95.8%; 55.6%; p 0.05), monocytosis (8.3%; 0%); increased C-reactive protein (41.7%; 33.3%), ALT (29.2%; 11.1%), urea (29.2%; 11.1%), leukocyturia (16.7%; 0%). CONCLUSIONS: Clinical evaluation of cardiovascular system changes in children with acute intestinal infections using a discriminant model allows to exclude myocardial damage of inflammatory genesis with high probability (95.7%), which is of practical importance.

Infectious disease research in the Association of Southeast Asian Nations region: a scientometric analysis.

This study compared the research output of Association of Southeast Asian Nations (ASEAN) countries to understand research trends and clarify past, present, and future patterns using scientometric techniques. This scientometric study systematically mined health and social science publications from the Web of Science and Scopus databases using keywords associated with infectious disease. The analysis included only English-language articles and review articles by authors from any ASEAN country. Publication, citation, and text co-occurrence network analyses were performed. R Studio and VOSviewer enabled data management, analysis, and visualization. Searches identified 12,511 articles published between 1925 and 2022, with a notable increase in research publications since 2003. The leading journals on infectious disease were associated with established publishing houses, including BMC, BMJ, and The Lancet. The most-cited articles were primarily global burden of disease studies, with 7,367 citations. Among ASEAN countries, Thailand, Malaysia, and Singapore had the most publications and collaborative efforts on the topic. Analysis of keyword co-occurrence revealed clusters related to global health, dengue, bacterial studies, non-dengue viral topics, and diagnostics. Most early studies examined diagnostics, gene and sequencing methodologies, and virology; later, the focus shifted toward herbal and alternative medicine. Recently, the research capacity of Southeast Asia has expanded dramatically, with substantial contributions from high-income countries. Intense cooperation between member states is essential, emphasizing the role of HICs in supporting their neighbors. Increased research efforts and collaboration must be dedicated to innovative approaches to combat persistent health conditions, along with emerging issues like climate change.