Building a High-Level Isolation Unit in Rwanda and Establishing a Training Program for the Medical Management of Patients With High-Consequence Infectious Diseases.

Rwanda is a country in East Africa, a region characterized by highly mobile populations and outbreaks of high-consequence infectious diseases occurring on a regular basis. To increase the level of outbreak preparedness in the region, the Rwandan government and the German Ministry of Health signed a joint agreement to construct a new high-level isolation unit in Rwanda, the first in East Africa, and implement a training program for Rwandan healthcare workers to equip them with the necessary skills and knowledge for medical management of patients under high-level isolation conditions, including intensive care treatment. To better understand the scope and format of the planned training program, a needs assessment was performed based on findings from a standardized survey of 4 intensive care units in Rwanda as well as observations from 2 members of a German high-level isolation unit who completed clinical internships at Rwandan hospitals. In this case study, we describe the necessary steps to promote the sustainability and capabilities of the new high-level isolation unit in Kigali and ensure the successful implementation of the training program.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward.

Healthcare-seeking behavior and out-of-pocket payments in Erbil, Kurdistan Region of Iraq.

BACKGROUND: Understanding healthcare-seeking behavior and examining health expenditures can help determine possible barriers to accessing healthcare and direct more effective and inclusive healthcare systems. This study aimed to evaluate healthcare-seeking behavior and out-of-pocket healthcare expenditure in a sample of the population in Erbil, Iraq. METHODS: We conducted this cross-sectional study in Erbil, Kurdistan Region of Iraq, from October to December 2023. A convenience sample of 414 adults completed a self-administered online survey. The following data were collected: recent illness, sociodemographic characteristics, type of healthcare received, and cost of healthcare. RESULTS: The most common health conditions reported were communicable diseases (16.3%), musculoskeletal problems (13.1%), and noncommunicable diseases (12.7%). Approximately 85% of patients with health conditions requiring care sought healthcare; most visited private clinics (46.3%) and private hospitals (18.6%). The median total out-of-pocket healthcare expenditure in US dollars was 117.3 (interquartile range (IQR) = 45.6-410.0). The median total cost was much greater for participants who first visited a private health facility (USD 135.5, IQR = 57.3-405.6) than those who first visited a public facility (USD 76.8, IQR = 16.1-459.7). Participants ≥ 60 years spent significantly more than those < 14 years (USD 332, 95% CI = 211-453, p < 0.001). Evermarried participants spent significantly more than unmarried (USD 97, 95% CI = 1 to 192, p = 0.047). Health expenditures were significantly greater for noncommunicable diseases than infectious diseases (USD 232, 95% CI = 96-368, p = 0.001). After adjusting for covariates, age ≥ 60 years was independently associated with higher spending (USD 305, 95% CI = 153-457, p < 0.001). CONCLUSIONS: Most participants sought care from formal health services, preferring the private sector. Seeking care from private facilities incurred significantly higher costs than seeking care from public ones, which suggests potential barriers to accessing healthcare, particularly affordability. The findings underscore the importance of evaluating existing healthcare policies to enhance effectiveness and identify areas for improvement. This study can help policymakers and healthcare providers design effective interventions, allocate resources efficiently, and improve healthcare delivery.

An unclosed loop: Perspectives of community engagement in infectious disease clinical trials in sub-Saharan Africa.

BACKGROUND: Community engagement (CE) is pertinent to ethically and scientifically rigorous infectious disease clinical trials in sub-Saharan Africa (SSA). However, there are critiques that CE is not properly embedded in research processes and that there is uncertainty about what CE entails. The aim of this study was to gain an understanding of CE in infectious disease clinical trials in SSA, specifically factors affecting CE and existing strategies for engaging with communities. METHODS: Semi-structured telephone interviews were conducted with 20 community and clinical trial (CT) stakeholders who worked in SSA. The audio-recorded interviews were transcribed verbatim and analysed inductively using thematic analysis. RESULTS: Themes are as follows: 1) Communities are abandoned research-entities-a disconnect between scientific teams and communities was observed and knowledge translation was not prioritised at the community-level. 2) Us and them: community engagement teams vs investigators-CE teams expressed that researchers did not account for CE processes and often did not involve CE staff in their planning, and felt that their roles were not valued. 3) Ethical considerations: concerns and gaps-there were concerns that procedures were not standardised and that ethics processes were not adhered to. 4) Opportunities for improved CE practices-training needs were expressed, including for standardised practices, ethics, and for developing a holistic understanding of collaborating with communities. CONCLUSION: CE role players require intensive training to ensure ethical CE and that communities are treated with dignity. This includes 1) using collaborative strategies involving research and CE staff, 2) protocol-adherence that recognises CE as pertinent, 3) viewing communities as complex and building relationships that are sustainable, and 4) ensuring that knowledge translation is considered at a community-level. Further research is necessary to investigate potential training programmes that integrate these elements.

Clinic of Hope: bridging infectious disease and orthopaedic surgery in prosthetic joint infection management.

Prosthetic joint infections (PJIs) following total joint arthroplasty are a significant and costly complication. To address fragmented care typically seen with separate management, we established a combined infectious disease and orthopaedic surgery clinic at Duke Health in July 2020. This clinic focuses on patients experiencing acute deterioration or multiple PJI episodes, often at the stage where amputation is the only option offered. From July 2021 to March 2024, the clinic completed 974 visits with 319 unique patients. The clinic maintained a low no-show rate of 5.0%. Treatment plans included procedures such as debridement, antibiotics and implant retention (38%), as well as implant explantation and one-stage exchange (32% each), with amputation required in only 4% of cases. The integrated clinic model facilitated real-time, multidisciplinary care, improving patient outcomes and operational efficiency. This approach offers a promising model for managing complex infections.

Advances in Bacterial Lysate Immunotherapy for Infectious Diseases and Cancer.

Antigenic cell fragments, pathogen-associated molecular patterns, and other immunostimulants in bacterial lysates or extracts may induce local and systemic immune responses in specific and nonspecific paradigms. Based on current knowledge, this review aimed to determine whether bacterial lysate has comparable functions in infectious diseases and cancer treatment. In infectious diseases, including respiratory and urinary tract infections, immune system activation by bacterial lysate can identify and combat pathogens. Commercially available bacterial lysates, including OM-85, Ismigen, Lantigen B, and LW 50020, were effective in children and adults in treating respiratory tract infections, chronic obstructive pulmonary disease, rhinitis, and rhinosinusitis with varying degrees of success. Moreover, OM-89, Uromune, Urovac, Urivac, and ExPEC4V showed therapeutic benefits in controlling urinary tract infections in adults, especially women. Bacterial lysate-based therapeutics are safe, well-tolerated, and have few side effects, making them a good alternative for infectious disease management. Furthermore, a nonspecific immunomodulation by bacterial lysates may stimulate innate immunity, benefiting cancer treatment. "Coley's vaccine" has been used to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas with varying outcomes. Later, several similar bacterial lysate-based therapeutics have been developed to treat cancers, including bladder cancer, non-small cell lung cancer, and myeloma; among them, BCG for in situ bladder cancer is well-known. Proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, may activate bacterial antigen-specific adaptive responses that could restore tumor antigen recognition and response by tumor-specific type 1 helper cells and cytotoxic T cells; therefore, bacterial lysates are worth investigating as a vaccination adjuvants or add-on therapies for several cancers.

Occurrence of major infectious diseases and healthcare seeking among young children with disabilities in Sierra Leone using cross-sectional population-based survey data.

BACKGROUND: Children with disabilities are at risk of worse health outcomes compared to children without functional difficulties. Sierra Leone has one of the world's highest prevalences of functional difficulties among children, but little is known about the co-occurrence of major infectious diseases and healthcare-seeking behaviours among children with disabilities. METHODS: We used household survey cross-sectional data on children 2-4 years old and logistic regression models estimating ORs between functional difficulties and symptoms of infectious diseases including diarrhoea, fever and acute respiratory infection (ARI), adjusted for sex, age and stunting. We also examined whether caregivers sought advice or treatment for the illness from any source and if the child was given any treatment for the illness. RESULTS: There was an increased risk of fever among children with functional difficulty (adjusted OR (AOR)=1.3, 95% CI 1.1 to 1.8) and children with severe functional difficulty (AOR=1.6, 95% CI 1.0 to 2.7). Children with severe functional difficulty were also at increased risk of diarrhoea (AOR=1.8, 95% CI=1.1 to 3.3). There were no significant differences in seeking advice or treatment for diarrhoea, fever or ARI symptoms between the groups. CONCLUSIONS: In Sierra Leone, children with functional difficulties, especially severe functional difficulties, more often have symptoms of major childhood diseases that are known to increase under-5 mortality.

Single domain antibodies from camelids in the treatment of microbial infections.

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavy-chain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts.

Mapping the evidence on integrated service delivery for non-communicable and infectious disease comorbidity in sub-Saharan Africa: protocol for a scoping review.

INTRODUCTION: The concurrent occurrence of infectious diseases (IDs) and non-communicable diseases (NCDs) presents complex healthcare challenges in sub-Saharan Africa (SSA), where healthcare systems often grapple with limited resources. While an integrated care approach has been advocated to address these complex challenges, there is a recognised gap in comprehensive evidence regarding the various models of integrated care, their components and the feasibility of their implementation. This scoping review aims to bridge this gap by examining the breadth and nature of evidence on integrated care models for NCDs and IDs within SSA, thereby updating the current evidence base in the domain. METHODS AND ANALYSIS: Based on the Joanna Briggs Institute (JBI) framework for scoping reviews, this study will include peer-reviewed and grey literature reporting on integrated care models for NCD-ID comorbidities in SSA. A comprehensive search of published sources in electronic databases (PubMed, Scopus, Embase, the Cochrane Library, Health System Evidence and Research4Life) and grey literature (Google Scholar, EBSCO Open Dissertations and relevant organisational websites) will be conducted to identify sources of information reported in English from 2018 onwards. The review will consider sources of evidence reporting on integrated care model for NCDs such as diabetes; chronic cardiovascular, respiratory and kidney diseases; cancers; epilepsy; and mental illness, and comorbid IDs such as HIV, tuberculosis and malaria. All sources of evidence will be considered irrespective of the study designs or methods used. The review will exclude sources that solely focus on the differentiated or patient-centred care delivery approach, and that focus on other conditions, populations or settings. The reviewers will independently screen the sources for eligibility and extract data using a JBI-adapted data tool on the Parsifal review platform. Data will be analysed using descriptive and thematic analyses and results will be presented in tables, figures, diagrams and a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it will synthesise published data and does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to inform future research. STUDY REGISTRATION: OSF: https://doi.org/10.17605/OSF.IO/KFVEY.

Unmasking the NLRP3 inflammasome in dendritic cells as a potential therapeutic target for autoimmunity, cancer, and infectious conditions.

Proper and functional immune response requires a complex interaction between innate and adaptive immune cells, which dendritic cells (DCs) are the primary actors in this coordination as professional antigen-presenting cells. DCs are armed with numerous pattern recognition receptors (PRRs) such as nucleotide-binding and oligomerization domain-like receptors (NLRs) like NLRP3, which influence the development of their activation state upon sensation of ligands. NLRP3 is a crucial component of the immune system for protection against tumors and infectious agents, because its activation leads to the assembly of inflammasomes that cause the formation of active caspase-1 and stimulate the maturation and release of proinflammatory cytokines. But, when NLRP3 becomes overactivated, it plays a pathogenic role in the progression of several autoimmune disorders. So, NLRP3 activation is strictly regulated by diverse signaling pathways that are mentioned in detail in this review. Furthermore, the role of NLRP3 in all of the diverse immune cells' subsets is briefly mentioned in this study because NLRP3 plays a pivotal role in modulating other immune cells which are accompanied by DCs' responses and subsequently influence differentiation of T cells to diverse T helper subsets and even impact on cytotoxic CD8+ T cells' responses. This review sheds light on the functional and therapeutic role of NLRP3 in DCs and its contribution to the occurrence and progression of autoimmune disorders, prevention of diverse tumors' development, and recognition and annihilation of various infectious agents. Furthermore, we highlight NLRP3 targeting potential for improving DC-based immunotherapeutic approaches, to be used for the benefit of patients suffering from these disorders.

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.

By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.

Hybrid Cell Membrane-Based Nanoplatforms for Enhanced Immunotherapy against Cancer and Infectious Diseases.

Immunotherapy based on nanoplatforms is a promising approach to treat cancer and infectious diseases, and it has achieved considerable progress in clinical practices. Cell membrane-based nanoplatforms endow nanoparticles with versatile characteristics, such as half-life extension, targeting ability, and immune-system regulation. However, monotypic cell membrane usually fails to provoke strong immune response for immunotherapy while maintaining good biosafety. The integration of different cell-membrane types provides a promising approach to construct multifunctional nanoplatforms for improved immunotherapeutic efficacy by enhancing immunogenicity or targeting function, evading immune clearance, or combining with other therapeutic modalities. In this review, the design principles, preparation strategies, and applications of hybrid cell membrane-based nanoplatforms for cancer and infection immunotherapy are first discussed. Furthermore, the challenges and prospects for the potential clinical translation of hybrid cell membrane-based nanoplatforms are discussed.

Ten Clinical Pearls in Microbiology: How Effective Collaboration Optimizes Patient Care.

Medical microbiology laboratories play an essential role in patient care-appertaining to infectious diseases diagnostics and treatment, infection prevention, and antimicrobial stewardship. Collaboration between clinicians and the microbiology laboratory can promote and enhance the safety, quality, and efficiency of patient care. We review practical, evidence-informed core concepts to explicate how effective partnership between clinicians and the microbiology laboratory improves patient outcomes.

New technologies in therapeutic antibody development: The next frontier for treating infectious diseases.

Adaptive immunity to viral infections requires time to neutralize and clear viruses to resolve infection. Fast growing and pathogenic viruses are quickly established, are highly transmissible and cause significant disease burden making it difficult to mount effective responses, thereby prolonging infection. Antibody-based passive immunotherapies can provide initial protection during acute infection, assist in mounting an adaptive immune response, or provide protection for those who are immune suppressed or immune deficient. Historically, plasma-derived antibodies have demonstrated some success in treating diseases caused by viral pathogens; nonetheless, limitations in access to product and antibody titer reduce success of this treatment modality. Monoclonal antibodies (mAbs) have proven an effective alternative, as it is possible to manufacture highly potent and specific mAbs against viral targets on an industrial scale. As a result, innovative technologies to discover, engineer and manufacture specific and potent antibodies have become an essential part of the first line of treatment in pathogenic viral infections. However, a mAb targeting a specific epitope will allow escape variants to outgrow, causing new variant strains to become dominant and resistant to treatment with that mAb. Methods to mitigate escape have included combining mAbs into cocktails, creating bi-specific or antibody drug conjugates but these strategies have also been challenged by the potential development of escape mutations. New technologies in developing antibodies made as recombinant polyclonal drugs can integrate the strength of poly-specific antibody responses to prevent mutational escape, while also incorporating antibody engineering to prevent antibody dependent enhancement and direct adaptive immune responses.

Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.

Nanobodies are the smallest known antigen-binding molecules to date. Their small size, good tissue penetration, high stability and solubility, ease of expression, refolding ability, and negligible immunogenicity in the human body have granted them excellence over conventional antibodies. Those exceptional attributes of nanobodies make them promising candidates for various applications in biotechnology, medicine, protein engineering, structural biology, food, and agriculture. This review presents an overview of their structure, development methods, advantages, possible challenges, and applications with special emphasis on infectious diseases-related ones. A showcase of how nanobodies can be harnessed for applications including neutralization of viruses and combating antibiotic-resistant bacteria is detailed. Overall, the impact of nanobodies in vaccine design, rapid diagnostics, and targeted therapies, besides exploring their role in deciphering microbial structures and virulence mechanisms are highlighted. Indeed, nanobodies are reshaping the future of infectious disease prevention and treatment.

Innovative strategies for the surveillance, prevention, and management of pediatric infections applied to low-income settings.

INTRODUCTION: Infectious diseases still cause a significant burden of morbidity and mortality among children in low- and middle-income countries (LMICs). There are ample opportunities for innovation in surveillance, prevention, and management, with the ultimate goal of improving survival. AREAS COVERED: This review discusses the current status in the use and development of innovative strategies for pediatric infectious diseases in LMICs by focusing on surveillance, diagnosis, prevention, and management. Topics covered are: Minimally Invasive Tissue Sampling as a technique to accurately ascertain the cause of death; Genetic Surveillance to trace the pathogen genomic diversity and emergence of resistance; Artificial Intelligence as a multidisciplinary tool; Portable noninvasive imaging methods; and Prognostic Biomarkers to triage and risk stratify pediatric patients. EXPERT OPINION: To overcome the specific hurdles in child health for LMICs, some innovative strategies appear at the forefront of research. If the development of these next-generation tools remains focused on accessibility, sustainability and capacity building, reshaping epidemiological surveillance, diagnosis, and treatment in LMICs, can become a reality and result in a significant public health impact. Their integration with existing healthcare infrastructures may revolutionize disease detection and surveillance, and improve child health and survival.