The effects of stress on gut virome: Implications on infectious disease and systemic disorders.

The role of gut microbiota in health and disease is being thoroughly examined in various contexts, with a specific focus on the bacterial fraction due to its significant abundance. However, despite their lower abundance, viruses within the gut microbiota are gaining recognition for their crucial role in shaping the structure and function of the intestinal microbiota, with significant effects on the host as a whole, particularly the immune system. Similarly, environmental factors such as stress are key in modulating the host immune system, which in turn influences the composition of the gut virome and neurological functions through the bidirectional communication of the gut-brain axis. In this context, alterations in the host immune system due to stress and/or dysbiosis of the gut virome are critical factors in the development of both infectious and noninfectious diseases. The molecular mechanisms and correlation patterns between microbial species are not yet fully understood. This literature review seeks to explore the interconnected relationship between stress and the gut virome, with a focus on how this interaction is influenced by the host's immune system. We also discuss how disturbances in this finely balanced system can lead to the onset and/or progression of diseases.

Detection strategies of infectious diseases via peptide-based electrochemical biosensors.

Infectious diseases have threatened human life for as long as humankind has existed. One of the most crucial aspects of fighting against these infections is diagnosis to prevent disease spread. However, traditional diagnostic methods prove insufficient and time-consuming in the face of a pandemic. Therefore, studies focusing on detecting viruses causing these diseases have increased, with a particular emphasis on developing rapid, accurate, specific, user-friendly, and portable electrochemical biosensor systems. Peptides are used integral components in biosensor fabrication for several reasons, including various and adaptable synthesis protocols, long-term stability, and specificity. Here, we discuss peptide-based electrochemical biosensor systems that have been developed over the last decade for the detection of infectious diseases. In contrast to other reports on peptide-based biosensors, we have emphasized the following points i) the synthesis methods of peptides for biosensor applications, ii) biosensor fabrication approaches of peptide-based electrochemical biosensor systems, iii) the comparison of electrochemical biosensors with other peptide-based biosensor systems and the advantages and limitations of electrochemical biosensors, iv) the pros and cons of peptides compared to other biorecognition molecules in the detection of infectious diseases, v) different perspectives for future studies with the shortcomings of the systems developed in the past decade.

Modeling the transmission mitigation impact of testing for infectious diseases.

A fundamental question of any program focused on the testing and timely diagnosis of a communicable disease is its effectiveness in reducing transmission. Here, we introduce testing effectiveness (TE)-the fraction by which testing and post-diagnosis isolation reduce transmission at the population scale-and a model that incorporates test specifications and usage, within-host pathogen dynamics, and human behaviors to estimate TE. Using TE to guide recommendations, we show that today's rapid diagnostics should be used immediately upon symptom onset to control influenza A and respiratory syncytial virus but delayed by up to two days to control omicron-era severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, while rapid tests are superior to reverse transcription quantitative polymerase chain reaction (RT-qPCR) to control founder-strain SARS-CoV-2, omicron-era changes in viral kinetics and rapid test sensitivity cause a reversal, with higher TE for RT-qPCR despite longer turnaround times. Last, we illustrate the model's flexibility by quantifying trade-offs in the use of post-diagnosis testing to shorten isolation times.

Metagenomic next-generation sequencing as a diagnostic tool in the clinical routine of an infectious diseases department: a retrospective cohort study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of circulating cell-free DNA from plasma is a hypothesis-independent broadband diagnostic method for identification of potential pathogens. So far, it has only been investigated in special risk populations (e.g. patients with neutropenic fever). PURPOSE: To investigate the extent to which mNGS (DISQVER® platform) can be used in routine clinical practice. METHODS: We collected whole blood specimens for mNGS testing, blood cultures (BC), and pathogen-specific PCR diagnostics. Clinical data and pathogen diagnostics were retrospectively reviewed by an infectious disease expert panel regarding the adjustment of anti-infective therapy. RESULTS: In 55 selected patients (median age 53 years, 67% male) with heterogeneous diagnoses, a total of 66 different microorganisms and viruses were detected using mNGS (51% viruses, 38% bacteria, 8% fungi, 3% parasites). The overall positivity rate of mNGS was 53% (29/55). Fifty-two out of 66 (79%) potential pathogens detected by mNGS were found in patients with primary or secondary immunodeficiency. The concordance rates of BC and pathogen-specific PCR diagnostics with mNGS testing were 14% (4/28) and 36% (10/28), respectively (p < 0.001). An additional bacterial pathogen (Streptococcus agalactiae) could only be detected by BC. Therapeutic consequences regarding anti-infective therapy were drawn from 23 pathogens (35% of detections), with 18 of these detections occurring in patients with immunodeficiency. CONCLUSIONS: We conclude that mNGS is a useful diagnostic tool, but should only be performed selectively in addition to routine diagnostics of infectious diseases. The limited number of patients and the retrospective study design do not allow any further conclusions.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases.

Eukaryotic cells can initiate several distinct self-destruction mechanisms to display essential roles for the homeostasis maintenance, development, and survival of an organism. Pyroptosis, a key response mode in innate immunity, also referred to as caspase-1-dependent proinflammatory programmed necrotic cell death activated by human caspase-1/4/5, or mouse caspase-1/11, plays indispensable roles in response to cytoplasmic insults and immune defense against infectious diseases. These inflammatory caspases are employed by the host to eliminate pathogen infections such as bacteria, viruses, protozoans, and fungi. Gasdermin D requires to be cleaved and activated by these inflammatory caspases to trigger the pyroptosis process. Physiological rupture of cells results in the release of proinflammatory cytokines, the alarmins IL-1ß and IL-18, symbolizing the inflammatory potential of pyroptosis. Moreover, long noncoding RNAs play direct or indirect roles in the upstream of the pyroptosis trigger pathway. Here, we review in detail recently acquired insights into the central roles of inflammatory caspases, inflammasomes, and pyroptosis, as well as the crosstalk between pyroptosis and long noncoding RNAs in mediating infection immunity and pathogen clearance.

mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases.

In the prevention and treatment of infectious diseases, mRNA vaccines hold great promise because of their low risk of insertional mutagenesis, high potency, accelerated development cycles, and potential for low-cost manufacture. In past years, several mRNA vaccines have entered clinical trials and have shown promise for offering solutions to combat emerging and re-emerging infectious diseases such as rabies, Zika, and influenza. Recently, the successful application of mRNA vaccines against COVID-19 has further validated the platform and opened the floodgates to mRNA vaccine's potential in infectious disease prevention, especially in the veterinary field. In this review, we describe our current understanding of the mRNA vaccines and the technologies used for mRNA vaccine development. We also provide an overview of mRNA vaccines developed for animal infectious diseases and discuss directions and challenges for the future applications of this promising vaccine platform in the veterinary field.

The Eukaryotic Linear Motif resource: 2022 release.

Almost twenty years after its initial release, the Eukaryotic Linear Motif (ELM) resource remains an invaluable source of information for the study of motif-mediated protein-protein interactions. ELM provides a comprehensive, regularly updated and well-organised repository of manually curated, experimentally validated short linear motifs (SLiMs). An increasing number of SLiM-mediated interactions are discovered each year and keeping the resource up-to-date continues to be a great challenge. In the current update, 30 novel motif classes have been added and five existing classes have undergone major revisions. The update includes 411 new motif instances mostly focused on cell-cycle regulation, control of the actin cytoskeleton, membrane remodelling and vesicle trafficking pathways, liquid-liquid phase separation and integrin signalling. Many of the newly annotated motif-mediated interactions are targets of pathogenic motif mimicry by viral, bacterial or eukaryotic pathogens, providing invaluable insights into the molecular mechanisms underlying infectious diseases. The current ELM release includes 317 motif classes incorporating 3934 individual motif instances manually curated from 3867 scientific publications. ELM is available at: http://elm.eu.org.

A Multicenter Study of Real-world Practice for Management of Abnormal Liver Function Tests in Children with Acute Infectious Diseases.

BACKGROUND: Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases. Few studies and no definite clinical guidelines for these conditions are available. The present study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea. METHODS: A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L without other specific conditions that could cause ALT elevation. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation. RESULTS: A total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2 ± 274.1 and 194.9 ± 316.1 IU/L (range 23-2,881, 60-2,949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month = 1.003; 95% confidence interval [CI], 1.001-1.004; P = 0.004), while the number of infection episodes (OR = 0.626; 95% CI, 0.505-0.777; P < 0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions. CONCLUSION: Abnormal liver function test after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice.

Nanomedicine as a promising strategy for the theranostics of infectious diseases.

Infectious diseases caused by bacteria, viruses, and fungi and their global spread pose a great threat to human health. The 2019 World Health Organization report predicted that infection-related mortality will be similar to cancer mortality by 2050. Particularly, the global cumulative numbers of the recent outbreak of coronavirus disease (COVID-19) have reached 110.7 million cases and over 2.4 million deaths as of February 23, 2021. Moreover, the crisis of these infectious diseases exposes the many problems of traditional diagnosis, treatment, and prevention, such as time-consuming and unselective detection methods, the emergence of drug-resistant bacteria, serious side effects, and poor drug delivery. There is an urgent need for rapid and sensitive diagnosis as well as high efficacy and low toxicity treatments. The emergence of nanomedicine has provided a promising strategy to greatly enhance detection methods and drug treatment efficacy. Owing to their unique optical, magnetic, and electrical properties, nanoparticles (NPs) have great potential for the fast and selective detection of bacteria, viruses, and fungi. NPs exhibit remarkable antibacterial activity by releasing reactive oxygen species and metal ions, exerting photothermal effects, and causing destruction of the cell membrane. Nano-based delivery systems can further improve drug permeability, reduce the side effects of drugs, and prolong systemic circulation time and drug half-life. Moreover, effective drugs against COVID-19 are still lacking. Recently, nanomedicine has shown great potential to accelerate the development of safe and novel anti-COVID-19 drugs. This article reviews the fundamental mechanisms and the latest developments in the treatment and diagnosis of bacteria, viruses, and fungi and discusses the challenges and perspectives in the application of nanomedicine.

Common communicable diseases in the general population in France during the COVID-19 pandemic.

In France, social distancing measures have been adopted to contain the spread of COVID-19, culminating in national Lockdowns. The use of hand washing, hydro-alcoholic rubs and mask-wearing also increased over time. As these measures are likely to impact the transmission of many communicable diseases, we studied the changes in common infectious diseases incidence in France during the first year of COVID-19 circulation. We examined the weekly incidence of acute gastroenteritis, chickenpox, acute respiratory infections and bronchiolitis reported in general practitioner networks since January 2016. We obtained search engine query volume for French terms related to these diseases and sales data for relevant drugs over the same period. A periodic regression model was fit to disease incidence, drug sales and search query volume before the COVID-19 period and extrapolated afterwards. We compared the expected values with observations made in 2020. During the first lockdown period, incidence dropped by 67% for gastroenteritis, by 79% for bronchiolitis, by 49% for acute respiratory infection and 90% for chickenpox compared to the past years. Reductions with respect to the expected incidence reflected the strength of implemented measures. Incidence in children was impacted the most. Reduction in primary care consultations dropped during a short period at the beginning of the first lockdown period but remained more than 95% of the expected value afterwards. In primary care, the large decrease in reported gastroenteritis, chickenpox or bronchiolitis observed during the period where many barrier measures were implemented imply that the circulation of common viruses was reduced and informs on the overall effect of these measures.

SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.

The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.

Oligonucleotide aptamers for pathogen detection and infectious disease control.

During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.

Nested pool testing strategy for the diagnosis of infectious diseases.

The progress of the SARS-CoV-2 pandemic requires the design of large-scale, cost-effective testing programs. Pooling samples provides a solution if the tests are sensitive enough. In this regard, the use of the gold standard, RT-qPCR, raises some concerns. Recently, droplet digital PCR (ddPCR) was shown to be 10-100 times more sensitive than RT-qPCR, making it more suitable for pooling. Furthermore, ddPCR quantifies the RNA content directly, a feature that, as we show, can be used to identify nonviable samples in pools. Cost-effective strategies require the definition of efficient deconvolution and re-testing procedures. In this paper we analyze the practical implementation of an efficient hierarchical pooling strategy for which we have recently derived the optimal, determining the best ways to proceed when there are impediments for the use of the absolute optimum or when multiple pools are tested simultaneously and there are restrictions on the throughput time. We also show how the ddPCR RNA quantification and the nested nature of the strategy can be combined to perform self-consistency tests for a better identification of infected individuals and nonviable samples. The studies are useful to those considering pool testing for the identification of infected individuals.

Paleogenomics of the prehistory of Europe: human migrations, domestication and disease.

A substantial portion of ancient DNA research has been centred on understanding European populations' origin and evolution. A rchaeological evidence has already shown that the peopling of Europe involved an intricate pattern of demic and/or cultural diffusion since the Upper Palaeolithic, which became more evident during the Neolithic and Bronze Age periods. However, ancient DNA data has been crucial in determining if cultural changes occurred due to the movement of ideas or people. With the advent of next-generation sequencing and population-based paleogenomic research, ancient DNA studies have been directed not only at the study of continental human migrations, but also to the detailed analysis of particular archaeological sites, the processes of domestication, or the spread of disease during prehistoric times. With this vast paleogenomic effort added to a proper archaeological contextualisation of results, a deeper understanding of Europe's peopling is starting to emanate.

Potential of CRISPR/Cas system in the diagnosis of COVID-19 infection.

INTRODUCTION: Emerging novel infectious diseases and persistent pandemics with potential to destabilize normal life remain a public health concern for the whole world. The recent outbreak of pneumonia caused by Coronavirus infectious disease-2019 (COVID-19) resulted in high mortality due to a lack of effective drugs or vaccines. With a constantly increasing number of infections with mutated strains and deaths across the globe, rapid, affordable and specific detections with more accurate diagnosis and improved health treatments are needed to combat the spread of this novel pathogen COVID-19. AREAS COVERED: Researchers have started to utilize the recently invented clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR/Cas)-based tools for the rapid detection of novel COVID-19. In this review, we summarize the potential of CRISPR/Cas system for the diagnosis and enablement of efficient control of COVID-19. EXPERT OPINION: Multiple groups have demonstrated the potential of utilizing CRISPR-based diagnosis tools for the detection of SARS-CoV-2. In coming months, we expect more novel and rapid CRISPR-based kits for mass detection of COVID-19-infected persons within a fraction of a second. Therefore, we believe science will conquer COVID-19 in the near future.

CRISPR-based diagnostics.

The accurate and timely diagnosis of disease is a prerequisite for efficient therapeutic intervention and epidemiological surveillance. Diagnostics based on the detection of nucleic acids are among the most sensitive and specific, yet most such assays require costly equipment and trained personnel. Recent developments in diagnostic technologies, in particular those leveraging clustered regularly interspaced short palindromic repeats (CRISPR), aim to enable accurate testing at home, at the point of care and in the field. In this Review, we provide a rundown of the rapidly expanding toolbox for CRISPR-based diagnostics, in particular the various assays, preamplification strategies and readouts, and highlight their main applications in the sensing of a wide range of molecular targets relevant to human health.

Cell Analysis from Dried Blood Spots: New Opportunities in Immunology, Hematology, and Infectious Diseases.

Blood cell analysis is a major pillar of biomedical research and healthcare. These analyses are performed in central laboratories. Rapid shipment from collection site to the central laboratories is currently needed because cells and biomarkers degrade rapidly. The dried blood spot from a fingerstick allows the preservation of cellular molecules for months but entire cells are never recovered. Here leucocyte elution is optimized from dried blood spots. Flow cytometry and mRNA expression profiling are used to analyze the recovered cells. 50-70% of the leucocytes that are dried on a polyester solid support via elution after shaking the support with buffer are recovered. While red blood cells lyse upon drying, it is found that the majority of leucocytes are preserved. Leucocytes have an altered structure that is improved by adding fixative in the elution buffer. Leucocytes are permeabilized, allowing an easy staining of all cellular compartments. Common immunophenotyping and mRNAs are preserved. The ability of a new biomarker (CD169) to discriminate between patients with and without Severe Acute Respiratory Syndrome induced by Coronavirus 2 (SARS-CoV-2) infections is also preserved. Leucocytes from blood can be dried, shipped, and/or stored for at least 1 month, then recovered for a wide variety of analyses, potentially facilitating biomedical applications worldwide.

A novel geo-hierarchical population mobility model for spatial spreading of resurgent epidemics.

Computational models for large, resurgent epidemics are recognized as a crucial tool for predicting the spread of infectious diseases. It is widely agreed, that such models can be augmented with realistic multiscale population models and by incorporating human mobility patterns. Nevertheless, a large proportion of recent studies, aimed at better understanding global epidemics, like influenza, measles, H1N1, SARS, and COVID-19, underestimate the role of heterogeneous mixing in populations, characterized by strong social structures and geography. Motivated by the reduced tractability of studies employing homogeneous mixing, which make conclusions hard to deduce, we propose a new, very fine-grained model incorporating the spatial distribution of population into geographical settlements, with a hierarchical organization down to the level of households (inside which we assume homogeneous mixing). In addition, population is organized heterogeneously outside households, and we model the movement of individuals using travel distance and frequency parameters for inter- and intra-settlement movement. Discrete event simulation, employing an adapted SIR model with relapse, reproduces important qualitative characteristics of real epidemics, like high variation in size and temporal heterogeneity (e.g., waves), that are challenging to reproduce and to quantify with existing measures. Our results pinpoint an important aspect, that epidemic size is more sensitive to the increase in distance of travel, rather that the frequency of travel. Finally, we discuss implications for the control of epidemics by integrating human mobility restrictions, as well as progressive vaccination of individuals.