Asymptomatic Infection Research Articles

Detection of subclinical EEHV infection in captive Asian elephants (Elephas maximus) in Peninsular Malaysia through a molecular approach

Detection of subclinical EEHV infection in captive Asian elephants (Elephas maximus) in Peninsular Malaysia through a molecular approach

Trends in CRKP Prevalence and Risk Factors for CRKP Hospital-Acquired Infections in Pediatric Patients Pre-, During-, and Post-COVID-19 Pandemic.

This study aims to delineate the epidemiological trends of carbapenem-resistant Klebsiella pneumoniae (CRKP) in pediatric patients before, during, and after coronavirus disease 2019 (COVID-19) pandemic and to assess the risk factors of CRKP hospital-acquired infections (CRKP-HAIs) across these three periods. We retrospectively collected the clinical data of pediatric patients diagnosed with K. pneumoniae infection at the Children's Hospital of Nanjing Medical University from January 2018 to March 2024. Carbapenemase-related genes were detected by PCR, and statistical analysis was conducted using SPSS 25.0. The current study found that modifications in the COVID-19 pandemic prevention and control measures and antibiotic therapies impact the epidemiological trends and antimicrobial resistance of CRKP. Binary logistic regression analyses revealed various independent risk factors for CRKP-HAIs before, during, and after the COVID-19 pandemic. Healthcare institutions must intensify surveillance for HAIs, continuously monitor and avoid risk factors for CRKP-HAIs, and formulate targeted preventive and control measures to effectively reduce the incidence and spread of these infections. Further, consistent surveillance of CRKP strains coproducing carbapenemase genes is crucial for mitigating the potential health risks in pediatric patients.

Severe Panton–Valentine-Leukocidin-Positive Staphylococcus aureus Infections in Pediatric Age: A Case Report and a Literature Review

Background: Infections caused by S. aureus strains encoding Panton–Valentine leukocidin (PVL-SA) have become increasingly relevant in community settings and can cause severe conditions in pediatric populations. We present the pediatric case of an invasive disease caused by PVL-SA and provide a literature review of severe manifestations caused by these strains in children. Methods: A PubMed search (February 2024) found studies that included relevant clinical outcomes, diagnostics, and treatments, excluding cases of asymptomatic infection or in adult populations. A logistical multivariate analysis was used to find predictors of the need for intensive care. Results: A 10-year-old boy came to the attention of our Pediatric Infectious Diseases Unit with fever, chest pain, and tachypnea. A rapid worsening of his clinical conditions was observed, with the development of necrotizing pneumonia, osteomyelitis, deep vein thrombosis (DVT), and multiple abscesses. Blood cultures confirmed the presence of PVL-producing methicillin-resistant S. aureus (MRSA). The initial treatment included linezolid and ceftaroline and was later adjusted to clindamycin, daptomycin, and fosfomycin, with clinical improvement. Discussion: Our review collected 36 articles, including 156 pediatric cases of severe PVL-SA infection. Bacteremia was present in 49% of cases, lung infection in 47%, and osteomyelitis in 37%. The presence of pulmonary localization was predictive of the need for intensive care, O.R. 25.35 (7.46–86.09; p < 0.001). Anti-toxin molecules were used in about half the cases where information on treatment was reported. Our report highlights the capacity of PVL-SA to cause life-threatening complications in children, while also discussing the full range of its clinical spectrum and the most effective therapeutic approaches.

Morphological classification of anaemia and neutrophil patterns in pregnant women with asymptomatic malaria parasite infection

Morphological classification of anaemia and neutrophil patterns in pregnant women with asymptomatic malaria parasite infection

Transmission dynamics of dengue with asymptomatic infection and a case study in Bangladesh

Transmission dynamics of dengue with asymptomatic infection and a case study in Bangladesh

SARS-CoV-2 RNA Presence in Outdoor Air of Public Spaces in Valladolid During Winter, 2021

As SARS-CoV-2 continues to evolve and herd immunity establishes, an increasing number of asymptomatic infections have been reported, increasing the risk of airborne spread of the virus. Most of the studies regarding SARS-CoV-2 RNA presence in air refer to indoor environments, with few studies having reported SARS-CoV-2 RNA in outdoor air. The aim of this study was to assess the presence of SARS-CoV-2 RNA at two different settings, crowded outdoor versus empty outdoor environments in Valladolid, Spain, during winter 2021. Using a Coriolis® air sampler, samples were taken from nine different locations within the city center. RNA extraction and a one-step RT-qPCR were carried out. Six out of the 20 air samples were found to be positive, and they were all obtained from crowded outdoor environments. These results highlight that although in less quantity, SARS-CoV-2 RNA is still present in outdoor air, especially at moments of relaxed mitigation efforts and depending on the number of people present.

Differential TLR2 and TLR4 mediated inflammatory and apoptotic responses in asymptomatic and symptomatic Leptospira interrogans infections in canine uterine tissue

Leptospirosis is major zoonotic disease with global implications, affecting both domestic animals and humans. It is caused by Leptospira interrogans (L. interrogans), which can damage multiple organs, including the kidneys, liver, testes, and uterus. Despite this, L. interrogans can also persist asymptomatically in tissues, akin to nonpathogenic strains. The mechanisms driving asymptomatic infections remain poorly understood. This study investigated the role of L. interrogans in asymptomatic infection within the uterine tissue of canines, focusing on the differential expression of Toll-like receptors (TLRs)2 and 4 and their roles in inflammatory and apoptotic pathways. We hypothesized that TLR2 and TLR4 coexpression is crucial for eliciting inflammation and apoptosis, whereas TLR4 alone might be insufficient. Our findings revealed that in symptomatic infections, both TLR2 and TLR4 are coexpressed, leading to markedly elevated levels of the proinflammatory cytokines IL-10, IL-1β, TNF-α, and IL-6. This enhanced inflammatory response is further evidenced by increased CD4 expression, indicating robust T helper cell activation. In contrast, asymptomatic infections are characterized by exclusive TLR4 expression, with inflammatory markers remaining at baseline levels. Additionally, we observed that L. interrogans induces apoptosis in symptomatic animals through TLR2 and TLR4 mediated activation of Caspase 8 and Caspase 3. These findings illustrate that L. interrogans drives both inflammation and apoptosis via the combination of TLR2 and TLR4 actions. When only TLR4 is activated, the immune response is insufficient, resulting in an asymptomatic disease course. This study provides novel insights into the differential roles of TLR receptors in leptospirosis, offering potential directions for targeted therapeutic strategies.

Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma.

Corticosteroid-responsive type 2 (T2) inflammation underlies the T2-high asthma endotype. However, we hypothesized that type 1 (T1) inflammation, possibly related to viral infection, may also influence corticosteroid response. To determine the frequency and within-patient variability of T1-high, T2-high, and T1/T2-high asthma endotypes and whether virally influenced T1-high disease influences corticosteroid response in asthma. Patients in the Severe Asthma Research Program (SARP)-3 had sputum collected at baseline, after intramuscular (triamcinolone acetonide) corticosteroid treatment, and at 1 and 3-year follow-ups. Sputum cell RNA was used for whole transcriptome gene network and viral metagenomic analyses. We then profiled patients as highly expressing T1 and/or T2 gene networks and established the influence of these endotypes on corticosteroid responsiveness and likelihood of viral transcript detection in the airways. We found that 22% and 35% of asthma patients highly expressed T1 and T2 network genes, respectively, and that 8.5% highly expressed both networks. Asthma severity outcomes were worse in T2-high compared to T1-high asthma and most severe in the T1-high/T2-high subgroup. Corticosteroid treatment strongly suppressed T2 but poorly suppressed T1 gene expression, and corticosteroid-associated improvements in FEV1 occurred only in patients with T1-low/T2-high disease and not in T1-high/T2-high patients. Viral metagenomic analyses uncovered that 24% of asthma sputum samples tested positive for a respiratory virus and high viral carriage was associated with 14-fold increased risk of T1-high disease. Airway type 1 immune responses are relatively common in asthma, are largely corticosteroid-resistant, and are associated with sub-clinical viral infection.

High-throughput screening for respiratory pathogens within pigs in Denmark; analysis of circulating porcine respiratory coronaviruses and their association with other pathogens

Porcine respiratory coronavirus (PRCV) typically causes subclinical or mild respiratory infections in pigs, but may lead to more severe disease with other factors. PRCV infection in Denmark was initially detected in 1984, but data are lacking about its current prevalence and diversity. Antibodies against PRCV were detected in about 75 % of recent pig sera from Denmark. In addition, pig nasal swab samples were screened for PRCV and 12 other respiratory pathogens using a high-throughput RT-qPCR system. All targeted pathogens were detected but at different prevalences. Significant associations were found between the presence of PRCV and certain other pathogens. From PRCV positive samples, partial spike gene sequences and complete nucleocapsid coding sequences were determined. In phylogenetic analyses, these PRCVs clustered with earlier European PRCVs and were distinct from transmissible gastroenteritis virus. We conclude that PRCV is widespread within the pig population in Denmark. Further studies on the significance of PRCV are warranted.

P18 encoded by FgGMTV1 is responsible for asymptomatic infection in Fusarium graminearum.

Mycovirus-fungus interplay often leads to asymptomatic infections. Our study identifies p18, a novel protein from the genomovirus FgGMTV1, as a key determinant of asymptomatic infection in Fusarium graminearum. A p18-null mutant exhibits a pronounced hypovirulent phenotype. By modulating viral accumulation, p18 promotes asymptomatic infection and facilitates vertical transmission via conidia. This insight deepens our understanding of mycovirus-fungus interactions and introduces a novel strategy for biocontrol using engineered mycoviruses.

Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection

Di(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections but can sometimes cause severe diseases such as pancreatitis, myocarditis, and meningoencephalitis. Though CVB infections are common, severe illness is relatively rare, and it is unclear what factors mediate disease severity. In this study, we sought to determine the effects that DEHP has on CVB infection in a variety of human cell types to evaluate whether this plastic-derived pollutant could represent a proviral environmental factor. Methods: HeLa cervical cancer cells, human induced pluripotent stem cell-derived brain-like endothelial cells (iBECs), and Caco-2 colon carcinoma cells were exposed to 40 µg/mL DEHP for 24 h prior to infecting with enhanced green fluorescent protein (EGFP)-expressing CVB. The severity of the infection was evaluated via fluorescence microscopy and flow cytometry-based viral EGFP detection, viral plaque assay on tissue culture media, and Western blotting to detect VP1 viral capsid protein. Interferon-associated proteins such as interferon regulatory factor (IRF) 3, IRF7, interferon-induced transmembrane (IFITM) 2, and IFITM3 were measured by Western blotting. The roles of IFITM2 and IFITM3 in the context of CVB infection were evaluated via siRNA silencing. Results: We found that DEHP drastically increased CVB infection in each of the cell types we tested, and, while the cellular processes underlying DEHP’s proviral properties were not entirely clear, we observed that DEHP may subvert CVB-induced interferon signaling and elevate levels of IFITMs, which appeared to bolster CVB infection. Conclusions: DEHP may represent a major environmental factor associated with the severity of CVB infection. Further understanding of how DEHP exacerbates infection may better elucidate its potential role as a proviral environmental factor.

Translocation of the Alphanucleorhabdovirus X proteins from the cytoplasm into the nucleus through interaction with nucleocapsid protein is essential for viral pathogenesis

The diverse rhabdoviruses infecting plants and animals have conserved genome organizations, and the functions of viral structural proteins have been extensively studied. However, increasing number of rhabdoviruses have been found to encode various accessory proteins, whose specific roles during viral infection remain poorly understood. In this study, we investigated the function of the X proteins encoded by several members of the genus Alphanucleorhabdovirus. Using the recently established eggplant mottled dwarf virus (EMDV) reverse genetics system, we found that recombinant EMDV lacking the X gene was able to systemically infect Nicotiana benthamiana plants, albeit with reduced efficiency. However, this deletion mutant was largely restricted to the veinal tissues and caused asymptomatic infections. The EMDV X protein, which localized to the cytoplasm when expressed alone, was translocated to the nucleus via a specific interaction with the nucleocapsid (N) protein. Through analyzing the interactions of the X deletion mutants and the infection phenotypes of the derived EMDV deletion mutants, we demonstrated that the carboxyl-terminal region of the X protein (amino acids 71–83) is crucial for its interaction with the N protein and for viral pathogenesis. Moreover, the X proteins encoded by related alphanucleorhabdoviruses could fully or partially complement the functions of EMDV X in viral infection. These findings provide new insights into the roles of accessory proteins in plant rhabdovirus infection.

Implementation of reactive case detection strategy recommendations towards malaria elimination in the Shai Osudoku district of Ghana

Ghana has refocused its national malaria programme to align with an agenda of malaria elimination. The key interventions in the strategic plan include enhancing epidemiological surveillance for reactive case detection (RACD). Identifying asymptomatic infections using index cases can help understand the epidemiology of malaria and guide its elimination. The study determined asymptomatic carriage in index cases household members and neighbours living near index cases and the suitability of diagnostic accuracy to inform RACD. A cross-sectional health centre and community-based studies were conducted in the Shai Osudoku district. Passive surveillance involved 19 index cases that triggered RACD in 67 index cases household members and 414 neighbours. Malaria was diagnosed using rapid diagnostic test (RDT) kits, microscopy and quantitative polymerase chain reaction (qPCR). Overall malaria prevalence was 8.00% [CI95: 5.78–10.73] by RDT, 10.00% [CI95: 7.51–12.97] by microscopy and 12.60% [CI95: 9.82–15.83] by qPCR. Index cases household members were 2 times more likely of having malaria compared to their neighbours. Across cohorts, significant difference [p = 0.012] was observed between index cases household members and neighbours by qPCR. The mean distribution of Plasmodium spp. parasite densities among positive outcomes of the RDT test in study participants was 162 [IQR: 77.75–3919] parasite/µL of blood, and 96.00 [IQR: 48.00–181.30] parasite/µL of blood in RDT negative outcomes. The mean parasite densities associated with RDT positive results differed significantly from that of the RDT negative results [p = 0.026]. Index cases household members were more likely of having malaria compared to their neighbours. RACD is needed to identify asymptomatic malaria infections and complement efforts that target individuals in low transmission and elimination areas.

Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

To report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD). Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks). During TP1, 190 patients were randomized (placebo=49, 5 mg=47, 50 mg=47, 300 mg=47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81/90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA change from week 24: -1.45, -0.46, -4.69, -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (CTCAE v4.03 grade 3 according to laboratory listings) were observed in 3 patients during the post-treatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM+). In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.

Serum protein electrophoretic profile changes in West Nile virus-naturally infected horses

Serum protein electrophoresis (SPE) is widely used to evaluate protein changes associated with several pathologies, aiming to assist clinical diagnosis. This study determines, for the first time, SPE profile changes in West Nile virus-naturally infected horses. Sixty horses with different clinical and infection status (encephalitis, asymptomatic infection, and immunologically naïve) were included. Total protein concentrations were determined via an automated biuret method and SPE was performed using a cellulose acetate membrane-based automated system. Statistical analysis revealed significantly higher total protein between both infected horse groups (encephalitis, asymptomatic) and naïve controls. Horses with encephalitis had higher globulin and α2-globulin levels than the other two groups (asymptomatic, naïve), along with lower albumin percentage and albumin-to-globulin ratio. Furthermore, γ-globulin levels were significantly higher in asymptomatically infected compared to control horses. These findings highlight the diagnostic value of SPE profile determination, assisting the clinicians, and providing the grounds for further research.

Three modes of viral adaption by the heart.

Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly 1000 human hearts profiled by RNA sequencing. Among virus-positive cases (~20%), we identified three robust adaptions in the host transcriptome related to inflammatory nuclear factor κB (NF-κB) signaling and posttranscriptional regulation by the p38-MK2 pathway. The adaptions are not determined by the infecting virus, and they recur in infections of human or animal hearts and cultured cardiomyocytes. Adaptions switch states when NF-κB or p38-MK2 is perturbed in cells engineered for chronic infection by the cardio-pathogenic virus, coxsackievirus B3. Stratifying viral responses into reversible adaptions adds a targetable systems-level simplification for infections of the heart and perhaps other organs.

Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

BackgroundPlasmodium falciparum (P. falciparum) remains a significant public health challenge globally, especially in sub-Saharan Africa (SSA), where it accounts for 99% of all malaria infections. The outcomes of P. falciparum infection vary, ranging from asymptomatic to severe, and are associated with factors such as host immunity, parasite genetic diversity, and multiplicity of infection (MOI). Using seven neutral microsatellite markers, the current study investigated P. falciparum genetic diversity and MOI in both asymptomatic and symptomatic malaria individuals in Uganda.MethodsThis cross-sectional study analyzed 225 P. falciparum isolates from both asymptomatic and symptomatic malaria patients, ranging in age from 6 months to ≥ 18 years. P. falciparum genetic diversity, MOI, and multi-locus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34–313, and C3M69–383. Genetic data analysis was performed using appropriate genetic analysis software.ResultsP. falciparum infections exhibited high genetic diversity in both asymptomatic and symptomatic individuals. The mean expected heterozygosity (He) ranged from 0.79 in symptomatic uncomplicated malaria cases to 0.81 in asymptomatic individuals. There was no significant difference (p = 0.33) in MOI between individuals with asymptomatic and symptomatic infections, with the mean MOI ranging from 1.92 in symptomatic complicated cases to 2.10 in asymptomatic individuals. Polyclonal infections were prevalent, varying from 58.5% in symptomatic complicated malaria to 63% in symptomatic uncomplicated malaria cases. A significant linkage disequilibrium (LD) was observed between asymptomatic and symptomatic uncomplicated/complicated infections (p < 0.01). Genetic differentiation was low, with FST values ranging from 0.0034 to 0.0105 among P. falciparum parasite populations in asymptomatic and symptomatic uncomplicated/complicated infections.ConclusionThere is a high level of P. falciparum genetic diversity and MOI among both symptomatic and asymptomatic individuals in Uganda. Asymptomatic carriers harbor a diverse range of parasites, which poses challenges for malaria control and necessitates targeted interventions to develop effective strategies.

A potential platform for future vaccine trials identifies high incidence of symptomatic and asymptomatic influenza infection among children aged 6-23 months in South Africa.

Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both, are important for developing improved vaccines. We estimated influenza infection incidence, and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design. We conducted a prospective cohort study among children aged 6-23 months from May-October 2022. Study nurses collected symptom and temperature data and mid-turbinate nasal swabs twice-weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza using PCR. Of 230 healthy, screened children, 93 were enrolled of whom 87 (94%) completed 6-months follow-up. 95% (4245/4476) of scheduled nurse, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections and 67% (9245/13768) of scheduled symptom diaries were completed. PCR-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 and 1 (2%) had 3 episodes. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (interquartile range 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregiver's diaries of reported and measured fever were 19%(25/73,34%) and 11%(15/73,21%) higher than nurse-reported (11/73,15%) and -measured fevers (7/73,10%), respectively. The incidence of influenza infection was high and mainly symptomatic suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design.

Gonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria meningitidis induce modest cross-protection against gonococcal infection. However, the presence of proteins in OMVs derived from N. gonorrhoeae that manipulate immune responses could hamper their success as a vaccine. Here we modified two key immunomodulatory proteins of the gonococcus; RmpM, which can elicit 'blocking antibodies', and PorB, an outer membrane porin which contributes to immunosuppression. As meningococcal PorB has adjuvant properties, we replaced gonococcal PorB with a meningococcal PorB. Immunisation with OMVs from N. gonorrhoeae lacking rmpM and expressing meningococcal porB elicited higher antibody titres against model antigens in mice compared to OMVs with native PorB. Further, a gonococcal protein microarray revealed stronger IgG antibody responses to a more diverse range of antigens in the Nm PorB OMV immunised group. Finally, meningococcal PorB OMVs resulted in a Th1-skewed response, exemplified by increased serum IgG2a antibody responses and increased IFNɣ production by splenocytes from immunised mice. In summary, we demonstrate that the replacement of PorB in gonococcal OMVs enhances immune responses and offers a strategy for gonococcal vaccine development.

Inhibition of protein kinase D and its substrate phosphatidylinositol-4 kinase III beta blocks common human coronavirus replication.

Human coronaviruses can lead to a range of clinical symptoms, from asymptomatic infection to severe illness and death, with a limited array of antiviral drugs available. Protein kinase D (PKD) is involved in various cellular processes, such as cell proliferation, apoptosis, and membrane fission of the Golgi apparatus. However, the specific role of PKD in the human coronavirus life cycle remains unclear. In this study, we found that PKD inhibitors effectively attenuated human coronavirus replication at the trans-Golgi network (TGN) stage in the viral life cycle. Furthermore, inhibiting PKD reduced PI4KIIIβ activation, thereby blocking viral replication in the host cells. Importantly, PI4KIIIβ inhibitors also blocked human coronavirus replication. Thus, PKD may represent a promising therapeutic target against both current circulating and future emerging coronaviruses.