Quantifying the effectiveness of betaherpesvirus-vectored transmissible vaccines.

Transmissible vaccines have the potential to revolutionize how zoonotic pathogens are controlled within wildlife reservoirs. A key challenge that must be overcome is identifying viral vectors that can rapidly spread immunity through a reservoir population. Because they are broadly distributed taxonomically, species specific, and stable to genetic manipulation, betaherpesviruses are leading candidates for use as transmissible vaccine vectors. Here we evaluate the likely effectiveness of betaherpesvirus-vectored transmissible vaccines by developing and parameterizing a mathematical model using data from captive and free-living mouse populations infected with murine cytomegalovirus (MCMV). Simulations of our parameterized model demonstrate rapid and effective control for a range of pathogens, with pathogen elimination frequently occurring within a year of vaccine introduction. Our results also suggest, however, that the effectiveness of transmissible vaccines may vary across reservoir populations and with respect to the specific vector strain used to construct the vaccine.

How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks.

Infectious disease outbreaks have become increasingly common and require global partnership for adequate preparedness and response. During outbreaks, medical countermeasures (MCMs)-vaccines, therapeutics, and diagnostics-need to reach patients quickly. Recent outbreaks exemplify that products with regulatory approval can expand access and reach patients quicker than investigational products. Unfortunately, insufficient funding globally and differences in funders' prioritization puts gains and future efforts at risk. Of primary concern is (1) lack of a feasible regulatory path and clinical capability to achieve regulatory approval for new MCMs for many diseases; and (2) the need for partners with the mandate, funding, and capabilities to support long-term sustainment of manufacturing capability and stockpiling of licensed products. Without collaboration, the global community runs the risk of losing the capabilities built through years of investment and being underprepared to combat future threats. Synergies between funders are critical to create long-term sustainment of products to ensure access.

Paranannizziopsis spp. Infection in Wild Vipers, Europe.

We describe the detection of Paranannizziopsis sp. fungus in a wild population of vipers in Europe. Fungal infections were severe, and 1 animal likely died from infection. Surveillance efforts are needed to better understand the threat of this pathogen to snake conservation.

Archival mitogenomes identify invasion by the Batrachochytrium dendrobatidis CAPE lineage caused an African amphibian extinction in the wild.

Outbreaks of emerging infectious diseases are influenced by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Deterioration in the population of the micro-endemic Tanzanian Kihansi spray toad (Nectophrynoides asperginis) occurred after the construction of a hydropower dam, implicating habitat modification in this species decline. Population recovery followed habitat augmentation; however, a subsequent outbreak of chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) led to the spray toad's extinction in the wild. We show using spatiotemporal surveillance and mitogenome assembly of Bd from archived toad mortalities that the outbreak was caused by invasion of the BdCAPE lineage and not the panzootic lineage BdGPL. Molecular dating reveals an emergence of BdCAPE across southern Africa overlapping with the timing of the spray toad's extinction. That our post-outbreak surveillance of co-occurring amphibian species in the Udzungwa Mountains shows widespread infection by BdCAPE yet no signs of ill-health or decline suggests these other species can tolerate Bd when environments are stable. We conclude that, despite transient success in mitigating the impact caused by dams' construction, invasion by BdCAPE caused the ultimate die-off that led to the extinction of the Kihansi spray toad.

Persistence of IgG and neutralizing antibodies in Crimean-Congo hemorrhagic fever survivors.

The World Health Organization classified Crimean-Congo hemorrhagic fever (CCHF) as a high-priority infectious disease and emphasized the performance of research studies and product development against it. Little information is available about the immune response due to natural CCHF virus (CCHFV) infection in humans. Here, we investigated the persistence of IgG and neutralizing antibodies in serum samples collected from 61 Iranian CCHF survivors with various time points after recovery (<12, 12-60, and >60 months after disease). The ELISA results showed IgG seropositivity in all samples while a pseudotyped based neutralization assay findings revealed the presence of neutralizing antibody in 29 samples (46.77%). For both IgG and neutralizing antibodies, a decreasing trend of titer was observed with the increase in the time after recovery. Not only the mean titer of IgG (772.80 U/mL) was higher than mean neutralizing antibody (25.64) but also the IgG persistence was longer. In conclusion, our findings provide valuable information about the long-term persistence of humoral immune response in CCHF survivors indicating that IgG antibody can be detected at least 8 years after recovery and low titers of neutralizing antibody can be detected in CCHF survivors.

Pathogen evolution following spillover from a resident to a migrant host population depends on interactions between host pace of life and tolerance to infection.

Changes to migration routes and phenology create novel contact patterns among hosts and pathogens. These novel contact patterns can lead to pathogens spilling over between resident and migrant populations. Predicting the consequences of such pathogen spillover events requires understanding how pathogen evolution depends on host movement behaviour. Following spillover, pathogens may evolve changes in their transmission rate and virulence phenotypes because different strategies are favoured by resident and migrant host populations. There is conflict in current theoretical predictions about what those differences might be. Some theory predicts lower pathogen virulence and transmission rates in migrant populations because migrants have lower tolerance to infection. Other theoretical work predicts higher pathogen virulence and transmission rates in migrants because migrants have more contacts with susceptible hosts. We aim to understand how differences in tolerance to infection and host pace of life act together to determine the direction of pathogen evolution following pathogen spillover from a resident to a migrant population. We constructed a spatially implicit model in which we investigate how pathogen strategy changes following the addition of a migrant population. We investigate how differences in tolerance to infection and pace of life between residents and migrants determine the effect of spillover on pathogen evolution and host population size. When the paces of life of the migrant and resident hosts are equal, larger costs of infection in the migrants lead to lower pathogen transmission rate and virulence following spillover. When the tolerance to infection in migrant and resident populations is equal, faster migrant paces of life lead to increased transmission rate and virulence following spillover. However, the opposite can also occur: when the migrant population has lower tolerance to infection, faster migrant paces of life can lead to decreases in transmission rate and virulence. Predicting the outcomes of pathogen spillover requires accounting for both differences in tolerance to infection and pace of life between populations. It is also important to consider how movement patterns of populations affect host contact opportunities for pathogens. These results have implications for wildlife conservation, agriculture and human health.

Human mpox presenting with penile edema and ulcer: A case report.

Human mpox, which has spread worldwide since May 2022, is characterized by symptoms involving the genital area; however, its treatment methods and clinical course are not completely understood. Furthermore, penile swelling in human mpox can be difficult to differentiate from cellulitis and antibiotic use has been reported in such cases. Herein, we report a case of human mpox in Japan with prominent penile swelling and persistent penile ulcers that improved without specific treatment. The patient was a Japanese man in his 20s with a history of having sexual intercourse with men frequently. He visited Tokyo Metropolitan Toshima Hospital because of a fever and rash in the genital area. Physical examination revealed vesicles on the limbs, penile pigmentation, and significant penile swelling and redness. There were no signs of cellulitis and symptomatic treatment was initiated with outpatient follow-up. After 7 days, an improving trend in penile swelling, redness, and pain was observed. However, a partially black skin ulcer with exudate was observed at the left coronal sulcus of the penis. Therefore, the symptomatic treatment was continued. On illness day 28, the penile swelling completely improved; however, the penile ulcer and pain persisted, and the exudate was observed again. By illness day 63, the pain in his anogenital area had disappeared, and the penile skin ulcer had healed. The following observations were noted in this case: (i) human mpox can improve without specific treatment such as tecovirimat administration and (ii) skin lesions in the genital area may change over time.

Ranking the risk of animal-to-human spillover for newly discovered viruses.

The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we are vulnerable to zoonotic viral threats. Strategies are needed to identify and characterize animal viruses that pose the greatest risk of spillover and spread in humans and inform public health interventions. Using expert opinion and scientific evidence, we identified host, viral, and environmental risk factors contributing to zoonotic virus spillover and spread in humans. We then developed a risk ranking framework and interactive web tool, SpillOver, that estimates a risk score for wildlife-origin viruses, creating a comparative risk assessment of viruses with uncharacterized zoonotic spillover potential alongside those already known to be zoonotic. Using data from testing 509,721 samples from 74,635 animals as part of a virus discovery project and public records of virus detections around the world, we ranked the spillover potential of 887 wildlife viruses. Validating the risk assessment, the top 12 were known zoonotic viruses, including SARS-CoV-2. Several newly detected wildlife viruses ranked higher than known zoonotic viruses. Using a scientifically informed process, we capitalized on the recent wealth of virus discovery data to systematically identify and prioritize targets for investigation. The publicly accessible SpillOver platform can be used by policy makers and health scientists to inform research and public health interventions for prevention and rapid control of disease outbreaks. SpillOver is a living, interactive database that can be refined over time to continue to improve the quality and public availability of information on viral threats to human health.

Ineffective responses to unlikely outbreaks: Hypothesis building in newly-emerging infectious disease outbreaks.

Over the last 30 years, there has been significant investment in research and infrastructure aimed at mitigating the threat of newly emerging infectious diseases (NEID). Core epidemiological processes, such as outbreak investigations, however, have received little attention and have proceeded largely unchecked and unimproved. Using ethnographic material from an investigation into a cryptic encephalitis outbreak in the Brong-Ahafo Region of Ghana in 2010-2013, in this paper we trace processes of hypothesis building and their relationship to the organizational structures of the response. We demonstrate how commonly recurring features of NEID investigations produce selective pressures in hypothesis building that favor iterations of pre-existing "exciting" hypotheses and inhibit the pursuit of alternative hypotheses, regardless of relative likelihood. These findings contribute to the growing anthropological and science and technology studies (STS) literature on the epistemic communities that coalesce around suspected NEID outbreaks and highlight an urgent need for greater scrutiny of core epidemiological processes.

Optimizing the detection of emerging infections using mobility-based spatial sampling.

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals' movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

[Characteristics and courses of COVID-19 in patients from the first through fifth waves of the disease: Focused on a single public health center in Tokyo, Japan].

Objective　Coronavirus disease 2019 (COVID-19) became a global public health threat, and local public health centers in Japan implemented an infectious disease response to support patients. The response was subsequently modified to meet the needs for each of the five waves of infection. The study aim was to analyze the characteristics and courses of the disease in patients with COVID-19 at a single public health center. The study period included the first through fifth waves of the disease.Methods　We utilized a descriptive epidemiological design in this study and data of patients with COVID-19 from one administrative district in Tokyo, Japan. We analyzed age, gender, nationality, symptoms at diagnosis, the route of infection, the recovery environment, and associated morbidity intervals, including case fatality rate, days from symptom onset to diagnosis, days from diagnosis to hospitalization, and recovery time for each of the first through fifth waves.Results　From February 2020 to November 2021, 11,252 patients were diagnosed with COVID-19. Specifically, in the first wave, 151 patients were diagnosed, followed by 803 in the second wave, 2,406 in the third wave, 1,480 in the fourth wave, and 6,412 in the fifth wave. Hospitalization was the primary recovery environment during the first wave, while home recovery became the primary approach from the third wave onward. The case fatality rate was highest during the first wave, likely because of limited testing and treatment options for severe cases. The median time from onset to diagnosis was seven days in the first wave, significantly longer than for the other waves. The median time from diagnosis to hospitalization was one day in the first through fourth waves but three days in the fifth wave. The extension of this interval suggests that hospitalization was delayed in this wave as the number of severe patients increased rapidly, likely because of the novel COVID-19 variant.Conclusion　This study of patients testing positive for COVID-19 provides valuable insights into the characteristics and courses of the pandemic within this district. These findings can inform regarding the development of effective strategies to manage the ongoing COVID-19 pandemic and other future emerging infectious diseases.

Development of an Accessible and Scalable Quantitative Polymerase Chain Reaction Assay for Monkeypox Virus Detection.

During the 2022 monkeypox (MPX) outbreak, testing has been limited and results delayed, allowing ongoing transmission. Gold-standard quantitative polymerase chain reaction (qPCR) diagnostics are difficult to obtain. This research adapted the June 2022 CDC MPX qPCR assay for broad implementation. Validated using MPX stocks in a matrix with multiple sample types, MPX was detected with cycle threshold (Ct) values 17.46-35.59 and titer equivalents 8.01 × 106 to 2.45 × 100 plaque-forming unit (PFU)/mL. The detection limit was 3.59 PFU/mL. Sensitivity and specificity were both 100%. This qPCR assay can be quickly and broadly implemented in research and public health laboratories to increase diagnostic capacity amid the growing MPX outbreak.

Predicting the fine-scale spatial distribution of zoonotic reservoirs using computer vision.

Zoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is critical for effective disease intervention but difficult to achieve at fine spatial scales. Here, we develop a method that learns the spatial distribution of a reservoir species from aerial imagery. Our approach uses neural networks to extract features of known or hypothesized importance from images. The spatial distribution of these features is then summarized and linked to spatially explicit reservoir presence/absence data using boosted regression trees. We demonstrate the utility of our method by applying it to the reservoir of Lassa virus, Mastomys natalensis, within the West African nations of Sierra Leone and Guinea. We show that, when trained using reservoir trapping data and publicly available aerial imagery, our framework learns relationships between environmental features and reservoir occurrence and accurately ranks areas according to the likelihood of reservoir presence.

Sex-biased infections scale to population impacts for an emerging wildlife disease.

Demographic factors are fundamental in shaping infectious disease dynamics. Aspects of populations that create structure, like age and sex, can affect patterns of transmission, infection intensity and population outcomes. However, studies rarely link these processes from individual to population-scale effects. Moreover, the mechanisms underlying demographic differences in disease are frequently unclear. Here, we explore sex-biased infections for a multi-host fungal disease of bats, white-nose syndrome, and link disease-associated mortality between sexes, the distortion of sex ratios and the potential mechanisms underlying sex differences in infection. We collected data on host traits, infection intensity and survival of five bat species at 42 sites across seven years. We found females were more infected than males for all five species. Females also had lower apparent survival over winter and accounted for a smaller proportion of populations over time. Notably, female-biased infections were evident by early hibernation and likely driven by sex-based differences in autumn mating behaviour. Male bats were more active during autumn which likely reduced replication of the cool-growing fungus. Higher disease impacts in female bats may have cascading effects on bat populations beyond the hibernation season by limiting recruitment and increasing the risk of Allee effects.

A Cross-Inoculation Experiment Reveals that Ophidiomyces ophiodiicola and Nannizziopsis guarroi Can Each Infect Both Snakes and Lizards.

Host range and specificity are key concepts in the study of infectious diseases. However, both concepts remain largely undefined for many influential pathogens, including many fungi within the Onygenales order. This order encompasses reptile-infecting genera (Nannizziopsis, Ophidiomyces, and Paranannizziopsis) formerly classified as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). The reported hosts of many of these fungi represent a narrow range of phylogenetically related animals, suggesting that many of these disease-causing fungi are host specific, but the true number of species affected by these pathogens is unknown. For example, to date, Nannizziopsis guarroi (the causative agent of yellow fungus disease) and Ophidiomyces ophiodiicola (the causative agent of snake fungal disease) have been documented only in lizards and snakes, respectively. In a 52-day reciprocal-infection experiment, we tested the ability of these two pathogens to infect currently unreported hosts, inoculating central bearded dragons (Pogona vitticeps) with O. ophiodiicola and corn snakes (Pantherophis guttatus) with N. guarroi. We confirmed infection by documenting both clinical signs and histopathological evidence of fungal infection. Our reciprocity experiment resulted in 100% of corn snakes and 60% of bearded dragons developing infections with N. guarroi and O. ophiodiicola, respectively, demonstrating that these fungal pathogens have a broader host range than previously thought and that hosts with cryptic infections may play a role in pathogen translocation and transmission. IMPORTANCE Our experiment using Ophidiomyces ophiodiicola and Nannizziopsis guarroi is the first to look more critically at these pathogens' host range. We are the first to identify that both fungal pathogens can infect both corn snakes and bearded dragons. Our findings illustrate that both fungal pathogens have a more general host range than previously known. Additionally, there are significant implications concerning the spread of snake fungal disease and yellow fungus disease in popular companion animals and the increased chance of disease spillover into other wild and naive populations.

Clustered cases of human adenovirus types 4, 7, and 14 infections in US Department of Defense Beneficiaries during the 2018-2019 season.

Human adenoviruses (HAdV) are genetically diverse and can infect a number of tissues with severities varied from mild to fatal. HAdV types 3, 4, 7, 11, 14, 21, and 55 were associated with acute respiratory illnesses outbreaks in the United States and in other countries. The risk of outbreaks can be effectively controlled by HAdV vaccination or mitigated by screening and preventive measures. During the influenza season 2018-2019, the DoD Global Respiratory Pathogen Surveillance Program (DoDGRS) received 24 300 respiratory specimens. HAdV samples that produced positive cytopathic effects in viral cultivation were subjected to next-generation sequencing for genome sequence assembly, genome typing, whole genome phylogeny, and sequence comparative analyses. A variety of HAdV types were identified in this study, including HAdV types 1-7, 14, 55, and 56. HAdV types 4, 7, and 14 were found in clustered cases in Colorado, Florida, New York, and South Carolina. Comparative sequence analyses of these isolates revealed the emergence of novel genetic mutations despite the stability of adenovirus genomes. Genomic surveillance of HAdV suggested possible undetected outbreaks and shed light on prevalence, genetic divergence, and viral evolution of HAdV. Continued surveillance will inform risk assessment and countermeasures.

Increased genetic diversity and immigration after West Nile virus emergence in American crows: No evidence for a genetic bottleneck.

Infectious diseases can cause steep declines in wildlife populations, leading to changes in genetic diversity that may affect the susceptibility of individuals to infection and the overall resilience of populations to pathogen outbreaks. Here, we examine evidence for a genetic bottleneck in a population of American crows (Corvus brachyrhynchos) before and after the emergence of West Nile virus (WNV). More than 50% of marked birds in this population were lost over the 2-year period of the epizootic, representing a 10-fold increase in adult mortality. Using analyses of single-nucleotide polymorphisms (SNPs) and microsatellite markers, we tested for evidence of a genetic bottleneck and compared levels of inbreeding and immigration in the pre- and post-WNV populations. Counter to expectations, genetic diversity (allelic diversity and the number of new alleles) increased after WNV emergence. This was likely due to increases in immigration, as the estimated membership coefficients were lower in the post-WNV population. Simultaneously, however, the frequency of inbreeding appeared to increase: Mean inbreeding coefficients were higher among SNP markers, and heterozygosity-heterozygosity correlations were stronger among microsatellite markers, in the post-WNV population. These results indicate that loss of genetic diversity at the population level is not an inevitable consequence of a population decline, particularly in the presence of gene flow. The changes observed in post-WNV crows could have very different implications for their response to future pathogen risks, potentially making the population as a whole more resilient to a changing pathogen community, while increasing the frequency of inbred individuals with elevated susceptibility to disease.

Inactivation of SARS-CoV-2 infectivity in platelet concentrates or plasma following treatment with ultraviolet C light or with methylene blue combined with visible light.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen; however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections can be minimized by implementing Pathogen Inactivation (PI), such as THERAFLEX MB-plasma and THERAFLEX UV-Platelets systems. Here we examined the capability of these PI systems to inactivate SARS-CoV-2. STUDY DESIGN AND METHODS: SARS-CoV-2 spiked plasma units were treated using the THERAFLEX MB-Plasma system in the presence of methylene blue (~0.8 µmol/L; visible light doses: 20, 40, 60, and 120 [standard] J/cm2 ). SARS-CoV-2 spiked platelet concentrates (PCs) were treated using the THERAFLEX UV-platelets system (UVC doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2 ). Samples were taken prior to the first and after each illumination dose, and viral infectivity was assessed using an immunoplaque assay. RESULTS: Treatment of spiked plasma with the THERAFLEX MB-Plasma system resulted in an average ≥5.03 log10 reduction in SARS-CoV-2 infectivity at one third (40 J/cm2 ) of the standard visible light dose. For the platelet concentrates (PCs), treatment with the THERAFLEX UV-Platelets system resulted in an average ≥5.18 log10 reduction in SARS-CoV-2 infectivity at the standard UVC dose (0.2 J/cm2 ). CONCLUSIONS: SARS-CoV-2 infectivity was reduced in plasma and platelets following treatment with the THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems, to the limit of detection, respectively. These PI technologies could therefore be an effective option to reduce the risk of transfusion-transmitted emerging pathogens.

Genomic characterization of emerging invasive Streptococcus agalactiae serotype VIII in Alberta, Canada.

Invasive Group B Streptococcus (GBS) can infect pregnant women, neonates, and older adults. Invasive GBS serotype VIII is infrequent in Alberta; however, cases have increased in recent years. Here, genomic analysis was used to characterize fourteen adult invasive serotype VIII isolates from 2009 to 2021. Trends in descriptive clinical data and antimicrobial susceptibility results were evaluated for invasive serotype VIII isolates from Alberta. Isolate genomes were sequenced and subjected to molecular sequence typing, virulence and antimicrobial resistance gene identification, phylogenetic analysis, and pangenome determination. Multilocus sequencing typing identified eight ST42 (Clonal Complex; CC19), four ST1 (CC1), and two ST2 (CC1) profiles. Isolates were susceptible to penicillin, erythromycin, chloramphenicol, and clindamycin, apart from one isolate that displayed erythromycin and inducible clindamycin resistance. All isolates carried genes for peptide antibiotic resistance, three isolates for tetracycline resistance, and one for macrolide, lincosamide, and streptogramin resistance. All genomes carried targets currently being considered for protein-based vaccines (e.g., pili and/or Alpha family proteins). Overall, invasive GBS serotype VIII is emerging in Alberta, primarily due to ST42. Characterization and continued surveillance of serotype VIII will be important for outbreak prevention, informing vaccine development, and contributing to our understanding of the global epidemiology of this rare serotype.

Shifting effects of host physiological condition following pathogen establishment.

Understanding host persistence with emerging pathogens is essential for conserving populations. Hosts may initially survive pathogen invasions through pre-adaptive mechanisms. However, whether pre-adaptive traits are directionally selected to increase in frequency depends on the heritability and environmental dependence of the trait and the costs of trait maintenance. Body condition is likely an important pre-adaptive mechanism aiding in host survival, although can be seasonally variable in wildlife hosts. We used data collected over 7 years on bat body mass, infection and survival to determine the role of host body condition during the invasion and establishment of the emerging disease, white-nose syndrome. We found that when the pathogen first invaded, bats with higher body mass were more likely to survive, but this effect dissipated following the initial epizootic. We also found that heavier bats lost more weight overwinter, but fat loss depended on infection severity. Lastly, we found mixed support that bat mass increased in the population after pathogen arrival; high annual plasticity in individual bat masses may have reduced the potential for directional selection. Overall, our results suggest that some factors that contribute to host survival during pathogen invasion may diminish over time and are potentially replaced by other host adaptations.