Non-symptomatic Infections Research Articles

MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice.MethodsWhole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8+ T cells.ResultsOur results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2Kd showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2Kb in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2Kb inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8+ T cells caused by SARS-CoV-2/BMA8 infection.ConclusionsTaken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.

Analysis of the effects of the mutation of selected genes of pedilanthus leaf curl virus on infectivity, symptoms and the maintenance of tobacco leaf curl betasatellite

Pedilanthus leaf curl virus (PeLCV) is a widely encountered monopartite begomovirus with a wide host range that usually associates with a betasatellite. The cloned PeLCV used was highly infectious to Nicotiana benthamiana plants by agroinoculation and symptoms were enhanced by co-inoculation with tobacco leaf curl betasatellite (TbLCB). The study investigated the effects of the mutation of the coat protein (CP), V2, C2 and C4 genes of PeLCV on infectivity, symptoms and maintenance of TbLCB in N. benthamiana. Mutation of the CP abolished infectivity of PeLCV, which was not rescued by co-inoculation with TbLCB. Mutation of the V2 gene severely reduced infectivity that, in a small number of plants, was rescued by TbLCB, resulting in plants with very mild symptoms. Mutation of the C2 or V4 genes led to a significant reduction in virus infectivity, but also to non-symptomatic infections. Co-inoculation of either mutant with TbLCB led to a greater number of plants infected but fewer plants ultimately maintained the betasatellite, compared with inoculation of the betasatellite with the wild-type virus, indicating that the C2 and C4 proteins play a role in the maintenance of the betasatellite. For the C2 mutation, but not the C4 mutation, the presence of the betasatellite also resulted in mild symptoms. The results here, in conjunction with earlier studies, highlight commonalities as well as differences for the effects of gene mutations and interactions with betasatellites of different begomoviruses, indicating that begomovirus--betasatellite interaction is highly nuanced.

Screening for SARS-CoV-2 in non-symptomatic students and staff shows safe school openings under varying incidence with sufficient mandatory measures.

Screening for SARS-CoV-2 in non-symptomatic students and staff shows safe school openings under varying incidence with sufficient mandatory measures.

Asymptomatic individuals can increase the final epidemic size under adaptive human behavior

Infections produced by non-symptomatic (pre-symptomatic and asymptomatic) individuals have been identified as major drivers of COVID-19 transmission. Non-symptomatic individuals, unaware of the infection risk they pose to others, may perceive themselves—and be perceived by others—as not presenting a risk of infection. Yet, many epidemiological models currently in use do not include a behavioral component, and do not address the potential consequences of risk misperception. To study the impact of behavioral adaptations to the perceived infection risk, we use a mathematical model that incorporates the behavioral decisions of individuals, based on a projection of the system’s future state over a finite planning horizon. We found that individuals’ risk misperception in the presence of non-symptomatic individuals may increase or reduce the final epidemic size. Moreover, under behavioral response the impact of non-symptomatic infections is modulated by symptomatic individuals’ behavior. Finally, we found that there is an optimal planning horizon that minimizes the final epidemic size.

Assessment of Natural Immunity after Infection with SARS-CoV-2: An Analysis of Repeat Infections Among All 4 Million PCR Tested Individuals in Denmark in 2020

Background: The degree to which infection with SARS-CoV-2 confers immunity towards subsequent infection is not yet known. In 2020, as part of Denmark’s extensive, free-of-charge PCR-testing strategy, 4 million individuals (69% of the population) underwent 10.6 million tests. Using these national PCR-test data from 2020, we estimated the natural immunity towards SARS-CoV-2 after infection and investigated differences by age, sex and time since infection. Methods: Analysing the second surge of the epidemic (September–December, 2020) we compared infection rates between those with and without a previous positive test from the first surge (March–May). In an alternative time-to-event analysis, we compared infection rates throughout the year between those with and without a previous confirmed infection three or more months earlier. Rate ratios were adjusted for potential cofounders and natural immunity was estimated as one minus the rate ratio. Findings: Among PCR positive individuals from the first surge, 0·65% tested positive again during the second surge compared with 3·3% without a previous infection. The natural immunity was 80·5% (95% CI 75·4–84·5). The time-to-event analysis gave a similar estimate, as did the use of two and four months’ separation between repeat positive tests, and limiting the cohort to frequently tested health staff only. Among those aged 65+ years, observed immunity was 47% (95% CI 24·7–62·8). There was no difference in immunity by sex or evidence of waning immunity over time. Interpretation: Person-identifiable test results from large scale national PCR-testing in Denmark suggest that the within-season immunity following symptomatic or non-symptomatic infection is around 80%, although significantly lower in the elderly. These findings may inform decisions of which groups to vaccinate and advocate for vaccination of previously infected individuals as natural protection among elderly citizens cannot be relied upon. Funding: No designated funding was received for this study. DM was funded by the European Centers for Disease Control and Prevention programme EUPHEM. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The present study was based on existing administrative data and did not require ethical approval.

Epidemiology of European stone fruit yellows in Germany: the role of wild Prunus spinosa

A nationwide monitoring with regard to the presence and distribution of ‘Candidatus Phytoplasma prunorum’ and its vector, Cacopsylla pruni, has been carried out in Germany between 2013 and 2017. In total, 286 sites with cultivated and wild Prunus species were surveyed. 806 plant samples covering 94 administrative districts in all 13 federal area states and one city-state were analysed by PCR. Furthermore, 3108 C. pruni were caught in 63 districts and tested for ‘Ca. P. prunorum’. European stone fruit yellows was found mainly in symptomatic apricot, plum, almond and peach but also for the first time in Germany in sweet cherry. Non-symptomatic infections were detected in 437 randomly sampled P. spinosa at 104 sites without any stone fruit growing nearby representing a natural infection rate of 14%. The vector C. pruni was found on all P. spinosa plants at 62 sites spread across Germany. The infection rate of C. pruni was 1–2% regardless whether the insects were caught in stone fruit growing areas or at wild habitats. Our results strongly indicate that ‘Ca. P. prunorum’ is widespread in all natural habitats in Germany and that wild P. spinosa represent a major source of infection in stone fruit orchards. A representative sample of 1164 individuals of C. pruni captured at 100 sites was molecularly typed: all but one insect were of B-type, the one which is the proven vector of ‘Ca. P. prunorum’. C. pruni A-type was detected for the first time in Germany near the French border.

Understanding infection risk factors for integrated disease management of brown rot and grey mould in sweet cherry

Brown rot and grey mould cause significant losses in sweet cherry due to rot of fruit at harvest, particularly in wet years. Studies in a Tasmanian orchard found that Botrytis cinerea was associated with 95% of fruit which was symptomatic at harvest, while Monilinia spp. were not detected. Total rot at harvest varied significantly with cherry cultivar. To determine how disease develops during the season, samples of fruit from two cultivars ('Simone' and 'Regina') were obtained fortnightly over a 53 day period prior to commercial harvest and expression of latent non-symptomatic infections was induced. While incidence increased towards harvest, this study showed that a substantial amount of infection had already occurred prior to 53 days before harvest. To quantify how fruit susceptibility to infection changes over time, a controlled incubation experiment was conducted which showed that infection risk increases with time and the odds of infection was quantified for three different cultivars and three pathogens. This information will form a basis for development of grower tools to guide decision-making about infection risk.

Biological control of Botrytis cinerea on tomato plants using Streptomyces ahygroscopicus strain CK-15.

We developed a real-time PCR assay to specifically detect and quantify the efficacy of a biological fungicide from Streptomyces ahygroscopicus var. wuyiensis on tomato leaves. This fungicide, the natural secondary metabolite wuyiencin, is an antifungal agent against Botrytis cinerea. Specific primers were designed based on the β-actin gene sequences, which were used to detect a 303 bp fragment from B. cinerea isolates. Our assay is highly sensitive and can be used to reliably detect and quantify as little as 1·75 pg of B. cinerea DNA. We used this detection method to monitor the progression of B. cinerea infection in inoculated plant material under preventive (wuyiencin) and nonpreventive treatment. After 5 days, plants under preventive treatment exhibited a sharp decrease in fungal biomass and no symptoms, whereas plants under nonpreventive treatment displayed severe disease symptoms. The results demonstrate that wuyiencin has significant effects on B. cinerea in tomato plants and that real-time PCR is a reliable method for evaluating the effects of Streptomyces wuyiensis CK-15 on B. cinerea. Botrytis cinerea commonly produces latent or nonsymptomatic infection on and within plant tissues, which can develop into symptomatic infection when triggered by changes in environmental conditions or host plant physiology. In this study, we develop a specific, sensitive real-time PCR assay for detecting and quantifying B. cinerea on tomato leaves to determine the control efficacy of Streptomyces ahygroscopicus var. wuyiensis as a biological fungicide. Our findings demonstrate that wuyiencin has significant effects on B. cinerea in tomato plants and that real-time PCR is a reliable method for evaluating the effects of biological fungicides on plant pathogens.

Towards a West Nile Virus Vaccine

Towards a West Nile Virus Vaccine West Nile virus (WNV) is a significant mosquito-borne human pathogen belonging to the Flaviviridae family with dengue, yellow fever, and Japanese encephalitis viruses. Recently, WNV has emerged as an important public health concern in the Western hemisphere, where it has established an endemic zoonotic cycle. Outcomes of WNV infection range from benign, non-symptomatic infection to flu-like febrile illness to severe central nervous system (CNS) manifestations.

Fatal ulcerative colitis in a western lowland gorilla (gorilla gorilla gorilla)

A captive western lowland gorilla (Gorilla gorilla gorilla) presented with watery diarrhoea that progressed to become profuse and haemorrhagic. Faecal analyses revealed Balantidium (B.) coli trophozoites and salmonella-like bacteria. Despite treatment the gorilla died on the 5th day after onset of symptoms. Post-mortem examination revealed a severe erosive-ulcerative superficial and deep colitis. Histological examination of post-mortem samples of the colon showed plentiful B. coli invading into the mucosa and submucosa, whilst PCR screening of bacterial DNA could not confirm any bacteria species which could be connected to the clinical picture. As B. coli is usually a non-pathogenic gut commensal, and as this animal previously showed evidence of non-symptomatic infection of B. coli, it is possible that the switch in pathogenicity was triggered by an acute bacterial infection. Despite successful treatment of the bacterial infection the secondary deep invasion of B. coli was not reversed, possibly because of the failure of the treatment regimen, and led to the death of the gorilla.

Surgery of infrarenal inflammatory aneurysm of abdominal aorta infected with methicillin resistant Staphylococcus aureus in a patient undergoing haemodialysis

Inflammatory abdominal aortic aneurysm accounts for 5% to 10% of all cases of abdominal aortic aneurysm and differs from typical atherosclerotic abdominal aortic aneurysm in many important ways. Although both inflammatory and atherosclerotic abdominal aortic aneurysms most commonly affect the infrarenal portion of the abdominal aorta, patients with the inflammatory variant are younger and usually symptomatic, chiefly from back or abdominal pain. Unlike patients with atherosclerotic abdominal aortic aneurysm, most with the inflammatoryvariant have an elevated erythrocyte sedimentation rate or abnormalities of other serum inflammatory markers. Computed tomography and magnetic resonance imaging are both sensitive for demonstrating the cuff of soft tissue inflammation surrounding the aneurysm that is characteristic of inflammatory abdominal aortic aneurysm. Inflammatory abdominal aortic aneurysm can be primarily infected by degenaration of an infected artery (in less than 1% of cases), or can become secondary infected in the already existing aneurysm. Seconadary infection of the pre-existing aneurysm has big inffluence on treatment choice, but is also rare. Clinically non-symptomatic infection, also known as bacterial collonisation, can be very frequent, regarding a greatly increased number of positive intraoperative findings (10-15%). Prolonged intravascular catheterization, vascular grafting, repeated punctures with large bore needles, and decreased immune defence mechanism make uraemic patients undergoing haemodialysis more likely to develop Staphylococcus aureus bacteraemia and its complications. The case shows a gigantic inflammatory aneurysm of the abdominal aorta, localized infrarenally, which was solved successfully by resection of the aneurysm of the abdominal aorta, and interposition of Dacron tubular graft 22 mm. Bacterial examination of the aneurysmal sac was positive: methicillin-resistent Staphylococcus aureus was detected. There were no postoperative complications, and the final outcome was fully satisfactory. Control CT scans after 3, 6 and 12 months were regular, with signs of regression fibrosis of the retroperitoneum.,

Microsatellite characterization of Plasmodium falciparum from symptomatic and non-symptomatic infections from the Western Amazon reveals the existence of non-symptomatic infection-associated genotypes

In Western Amazon areas with perennial malaria transmission, long term residents frequently develop partial immunity to malarial infection caused either by Plasmodium falciparum or P. vivax, resulting in a considerable number of non-symptomatically infected individuals. For yet unknown reasons, these individuals sporadically develop symptomatic malaria. In order to identify if determined parasite genotypes, defined by a combination of eleven microsatellite markers, were associated to different outcomes--symptomatic or asymptomatic malaria--we analyzed infecting P. falciparum parasites in a suburban riverine population. Despite of detecting a high degree of diversity in the analyzed samples, several microsatellite marker alleles appeared accumulated in parasites from non-symptomatic infections. This result may be interpreted that a number of microsatellites, which are not directly related to antigenic features, could be associated to the outcome of malarial infection. The result may also point to a low frequency of recombinatorial events which otherwise would dissociate genes under strong immune pressure from the relatively neutral microsatellite loci.

Rapid turnover of Plasmodium falciparum var gene transcripts and genotypes during natural non-symptomatic infections

The var genes of Plasmodium falciparum code for the antigenically variant erythrocyte membrane proteins 1 (PfEMP1), a major factor for cytoadherence and immune escape of the parasite. Herein, we analyzed the var gene transcript turnover in two ongoing, non-symptomatic infections at sequential time points during two weeks. The number of different circulating genomes was estimated by microsatellite analyses. In both infections, we observed a rapid turnover of plasmodial genotypes and var transcripts. The rapidly changing repertoire of var transcripts could have been caused either by swift elimination of circulating var-transcribing parasites stemming from different or identical genetic backgrounds, or by accelerated switching of var gene transcription itself.

Interaction of secretory immunoglobulin A antibodies with Naegleria fowleri trophozoites and collagen type I.

In this work, we analyzed the in vitro interaction of human secretory immunoglobulin A (sIgA) antibodies with Naegleria fowleri trophozoites and the capacity of these antibodies to inhibit amoeba adherence to collagen type I. We also studied N. fowleri antigens that are recognized by sIgA, using immunoblot assays. Immunocytochemical analysis of the interaction showed a redistribution of antigens on the surface of trophozoites by sIgA antibodies. Ultrastructural analysis of antibody-amoeba interaction showed that besides the patching and cap formation, parasites were capable of eliminating the antigen-antibody complex produced on the surface. sIgA antibodies were capable of inhibiting the in vitro adhesion of trophozoites to collagen type I. We suggest that nonsymptomatic infections by N. fowleri may stimulate a local specific immunity that prevents trophozoite adhesion and invasion of nasal mucosa.

Entamoeba histolytica infections in captive primates.

A group based survey on the presence of Entamoeba histolytica and Entamoeba dispar using real-time PCR among 20 species of captive non-human primates was performed after diagnosis of E. histolytica dysentery in a spider monkey ( Ateles belzebuth hybridus). E. histolytica DNA was detected in three species of New World primates and in three species of Old World primates. In five of six E. histolytica isolates, it was possible to amplify the SREHP gene. They all revealed the same pattern after AluI digestion, indicating a common source of infection. E. dispar DNA was detected in two species of New World monkeys and three species of Old World monkeys. The results demonstrate that E. histolytica is capable of causing symptomatic and non-symptomatic infections in Old World and New World non-human primates. To our knowledge, this is the first report of E. histolytica sensu stricto in non-human primates after the redescription separating it from E. dispar in 1993.

Potential Interactions Between Rootstocks and Grapevine Latent Viruses

Among the virus or virus-like agents which cause disease in grapevines are several which produce latent or non-symptomatic infections in Vitis vinifera . Research suggests that the severity of disease may vary according to the genotype of the rootstock which is grafted with infected scion wood. This may explain the reports of virus-like diseases which have been observed in California in vineyards where certified rootstock has been grafted with non-certified scion wood selections which appeared disease free when grafted on AXR#1.

The male predominance in the incidence of infectious diseases in children: a postulated explanation for disparities in the literature.

In children, a male predominance in the incidence of symptomatic disease has been reported for some infectious agents and not for others. Not only are the factors underlying these sex differences poorly understood, but it is also not clear why the differences are described only for selected infectious diseases. In this study of sex- and age-specific incidence of infectious diseases in children, a possible explanation for the inconsistencies in the literature was explored. The sex ratio in reported disease incidence in Israel during a period of about 20 years was examined for various viral and bacterial infections. In addition, an hypothetical mathematical model was developed which assumes increased susceptibility to infectious disease (such as in relative immune deficiency) in a proportion of males. In children aged under 4 years, a higher incidence among males was consistently observed for all diseases, and the sex ratio varied between 1.16 (95% confidence interval (CI): 1.13-1.18) for shigellosis to 1.98 (95% CI: 1.79-2.17) for viral meningitis. The highest ratios were associated with the diseases which tend to present asymptomatically most often, which is consistent with the predictions of the model. The male excess in symptomatic disease appears to be present for most infectious diseases and this should be taken into account in studies comparing observed disease incidence between groups with different sex ratios. The inconsistencies in reports on the excess male morbidity for infectious diseases may be due to variations in symptomatic to asymptomatic infection ratios.

Science Ponders Whether HIV Acts Alone or Has Another Microbe's Aid

DEBATE has been rekindled over whether human immunodeficiency virus (HIV) itself grows virulent enough in body to cause acquired immunodeficiency syndrome (AIDS) and kill its host, or whether it has some help from another microbe. In San Francisco, at Sixth International Conference on AIDS, Jay A. Levy, MD, presented new data on increasing virulence. Levy is professor of medicine at University of California, San Francisco (UCSF), and discoverer—shortly after Pasteur Institute's Luc Montagnier, MD, and National Cancer Institute's Robert Gallo, MD—of similar organism he named AIDS-related virus. Levy and colleagues have found viral genetic changes that may help explain why HIV-positive people progress to AIDS. Their discoveries may also offer a new target for therapy. Recognizing diversity of HIV strains, Levy says, the surprising observation was made that an HIV strain obtained from an individual with nonsymptomatic infection was different from

Cystitis and Urethritis

CLASSIFICATION Although the terms cystitis, urethritis, and pyelonephritis are useful to the clinician for describing different clinically encountered varieties of urinary tract infection, one must not be limited only to site of localization when classifying urinary infections. Two other helpful schemes of classification (Table 1) have evolved based on pathogenesis1 and management.2 FREQUENCY OF OCCURRENCE Children and adolescents with cystitis or urethritis have urinary symptoms suggestive of urinary tract infection. In fact, not all symptomatic patients have true bacteriuria. Of all patients less than 15 years of age with urinary symptoms, only 9% were bacteriuric, and only 18% with dysuria had positive cultures for a pathogen.3 The incidence of true urinary tract infection from these data is 1.7 per 1,000 boys and 3.1 per 1,000 girls per year. The incidence of apparent first symptomatic urinary tract infection declines with increasing age, the decline being more rapid in boys (Figure). Patients with nonsymptomatic infections often feel more comfortable after treatment or more commonly may report loss of characteristic odor after appropriate therapy has been initiated for the positive culture results obtained for surveillance purposes. Data from large screening surveys of so-called healthy populations demonstrate a prevalence of unrecognized bacteriuria in 0.5% to 1.6% of school-aged girls.

Cystitis and urethritis.

CLASSIFICATION Although the terms cystitis, urethritis, and pyelonephritis are useful to the clinician for describing different clinically encountered varieties of urinary tract infection, one must not be limited only to site of localization when classifying urinary infections. Two other helpful schemes of classification (Table 1) have evolved based on pathogenesis1 and management.2 FREQUENCY OF OCCURRENCE Children and adolescents with cystitis or urethritis have urinary symptoms suggestive of urinary tract infection. In fact, not all symptomatic patients have true bacteriuria. Of all patients less than 15 years of age with urinary symptoms, only 9% were bacteriuric, and only 18% with dysuria had positive cultures for a pathogen.3 The incidence of true urinary tract infection from these data is 1.7 per 1,000 boys and 3.1 per 1,000 girls per year. The incidence of apparent first symptomatic urinary tract infection declines with increasing age, the decline being more rapid in boys (Figure). Patients with nonsymptomatic infections often feel more comfortable after treatment or more commonly may report loss of characteristic odor after appropriate therapy has been initiated for the positive culture results obtained for surveillance purposes. Data from large screening surveys of so-called healthy populations demonstrate a prevalence of unrecognized bacteriuria in 0.5% to 1.6% of school-aged girls.