Human Infection Research Articles

Multiple spacer sequence typing of Coxiella burnetii carried by ticks in Gansu, China.

Coxiella burnetii is a zoonotic pathogen that causes Q fever and is found worldwide. Ticks serve as the primary reservoir, playing an important role in maintaining the natural cycle of C. burnetii. C. burnetii is transmitted to animals when ticks feed on their blood. However, information on C. burnetii infection in ticks remains limited, despite the widespread prevalence of the infection in humans and animals across China. In this study, 192 engorged ticks were collected from Baiyin City of Gansu Province, China. The presence of Coxiella burnetii in ticks was specifically identified by detecting the IS1111 gene using nested polymerase chain reaction (nPCR). In addition, the 16S rRNA gene of C. burnetii was molecularly characterized using nPCR. A total of 10 spacer sequences (Cox 2, 5, 18, 20, 22, 37, 51, 56, 57, and 61) were amplified using PCR against positive specimens for MST analysis. All collected ticks were identified as Hyalomma marginatum, and 90 of them tested positive for C. burnetii, with a positive rate of 46.9% (90/192). The 16S rRNA gene analysis showed that the novel C. burnetii variants detected in this study were closely related to other C. burnetii strains in the world. The allele codes found in the present study for loci Cox2-Cox5-Cox18-Cox20-Cox22-Cox37-Cox51-Cox56-Cox57-Cox61 were 8-4-9-5-7-5-2-3-11-6. This represents a novel combination of allele values, similar to MST28, currently designated as MST85 in the Multi Spacers Typing (MST) database. Our results revealed the circulation of a novel MST genotype of C. burnetii in Baiyin City, Gansu Province, China. The detection of C. burnetii in ticks suggests a potential public health risk to the local human population.

An amphipathic peptide combats multidrug-resistant Staphylococcus aureus and biofilms

The emergence of drug-resistant Staphylococcus aureus (S. aureus) has resulted in infections in humans and animals that may lead to a crisis in the absence of highly effective drugs. Consequently, the development of alternative or complementary antimicrobial agents is urgently needed. Here, a series of peptides derived from AP138 were designed with high expression, antimicrobial activity, and antibiofilm properties via bioinformatics. Among them, the best derived peptide, A24 (S9A), demonstrated the greatest stability and bactericidal efficiency against multidrug-resistant S. aureus in a physiological environment, with a high hydrophobicity of 35%. This peptide exhibited superior performance compared to the preclinical or clinical antimicrobial peptides (AMPs). A24 displayed increased biocompatibility in vitro and in vivo, exhibiting a low hemolysis rate (less than 3%), minimal cytotoxicity (survival rate exceeding 85%), and no histotoxicity. A24 had the capacity to destroy cell walls, increase cell membrane permeability, and induce increases in intracellular ATP and ROS levels, which resulted in the rapid death of S. aureus. A24 inhibited the formation of early biofilms and eliminated both mature biofilms (40–50%) and persisters (99.9%). Therapeutic doses of A24 were shown to exhibit favorable safety profiles and bactericidal efficacy in vivo and could reduce bacterial loads of multidrug-resistant S. aureus by 4–5 log10 CFU/0.1g levels in mouse peritonitis and endometritis models. Furthermore, A24 increased the survival rate to 100% and exhibited anti-inflammatory properties in a mouse model. The aforementioned data illustrate the potential of A24 as a pharmaceutical agent for the treatment of bacterial infections, including peritonitis and endometritis, in animal husbandry with multidrug-resistant S. aureus infections.

Triage performance of DNA methylation for women with high-risk human papillomavirus infection.

DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3). The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

Clinical management of chronic wound infections: The battle against biofilm.

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection. Biofilm also enables greater tolerance to antimicrobial agents in chronic wound infections compared with acute wound infections. Given the difficulty in eliminating wound biofilm, a multi-targeted strategy (namely biofilm-based wound care) involving debridement and antimicrobial therapies were introduced and have been practiced since the early 2000s. More recently, acknowledgement of the speed at which biofilm can develop and hence quickly interfere with wound healing has highlighted the need for an early anti-biofilm strategy to combat biofilm before it takes control and prevents wound healing. This strategy, referred to as wound hygiene, involves multiple tools in combination (debridement, cleansing, and antimicrobial dressings) to maximise success in biofilm removal and encourage wound healing. This review is intended to highlight the issues and challenges associated with biofilm-induced chronic infections, and specifically address the challenges in chronic wound management, and tools required to combat biofilm and encourage wound healing.

Toxoplasma gondii Prevalence and Risk Factors among Female Students at Al-Yemenia University, Sana'a City, Yemen

Abstract Background: Toxoplasmosis is one of the most common human infections worldwide. It is caused by the intracellular protozoan Toxoplasma gondii. Therefore, this study aimed to determine the prevalence of Toxoplasma gondii infection among female students at Al-Yemenia University in Yemen. Methods: Two hundred female students were selected for this study and screened for Toxoplasma gondii antibodies using an immunochromatographic technique (ICT). Demographic, socioeconomic, risk factors, and behavioral data were collected using a pre-tested questionnaire via face-to-face interviews. Results: The seropositivity rate for T. gondii was (6.0%). The majority were from age groups of 18–20 and 21–24 years (41.7%), who lived in the urban area (83.3%), unmarried individuals (83.8%), and middle-income participants (66.7%), with a non-significant difference (P &lt; 0.05). Female students who washed vegetables before eating had a high risk of T. gondii infection (OR = 4.810), followed by raising cats in the house (OR = 3.812), and had a history of blood transfusion (OR = 1.618). Conclusion: This study reported low seroprevalence among female students at Al-Yemenia University, Yemen. Environmental sanitation, personal hygiene, and health education are all required for promotion to prevent Toxoplasma gondii infection among female students.

Cost-Effectiveness of Extending Human Papillomavirus Vaccination to Population Subgroups Older Than 26 Years Who Are at Higher Risk for Human Papillomavirus Infection in the United States.

In June 2019, the U.S. Advisory Committee on Immunization Practices recommended shared clinical decision making regarding potential human papillomavirus (HPV) vaccination of men and women aged 27 to 45 years ("mid-adults"). To examine the incremental cost-effectiveness ratios (ICERs) and number needed to vaccinate (NNV) to prevent 1 HPV-related cancer case of expanding HPV vaccination to subgroups of mid-adults at increased risk for HPV-related diseases in the United States. Individual-based transmission dynamic modeling of HPV transmission and associated diseases using HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation). Published data. All U.S. mid-adults and higher-risk subgroups within this population. 100 years. Health care sector. Expanding 9-valent HPV vaccination to mid-adults and higher-risk subgroups. ICERs and NNVs. Expanding 9-valent HPV vaccination to all mid-adults, those with more lifetime partners, and those who have just separated was projected to cost an additional $2 005 000, $763 000, and $1 164 000 per quality-adjusted life-year (QALY) gained, respectively. The NNVs to prevent 1 additional HPV-related cancer case were 7670, 3190, and 5150, respectively, compared with 223 for vaccination of persons aged 9 to 26 years (vs. no vaccination). The mid-adult strategy with the lowest ICER and NNV was vaccinating infrequently screened mid-adult women who have just separated and have a higher number of lifetime sex partners (ICER, $86 000 per QALY gained; NNV, 470). Uncertainty about rate of new sex partners and natural history of HPV among mid-adults. Vaccination of mid-adults against HPV is substantially less cost-effective and produces higher NNVs than vaccination of persons younger than 26 years under all scenarios investigated. However, cost-effectiveness and NNV are projected to improve when higher-risk mid-adult subgroups are vaccinated, such as mid-adults with more sex partners and who have recently separated, and women who are underscreened. Centers for Disease Control and Prevention.

Influenza virus infection and aerosol shedding kinetics in a controlled human infection model.

We use a controlled human infection model to assess respiratory and aerosol shedding kinetics to expand our knowledge of influenza infection dynamics and help inform future studies aimed at understanding human-to-human transmission.

Plotting the major proteins of borealpox virus

In an era marked by rapid environmental transformations, the viability of numerous species hinges crucially on their ability to navigate and adjust to shifting climatic conditions through migration. Yet, amidst this natural quest for survival, a consequential and often overlooked consequence emerges: the inadvertent transportation of a diverse array of parasites and pathogens across landscapes. This phenomenon poses a substantial and tangible threat to global health, particularly in the wake of recent outbreaks and pandemics fueled by zoonotic viruses, which leap from animals to humans. These viruses, originating in animals but capable of infecting humans, serve as poignant reminders of the intricate relationship between human and wildlife health, and the potential dangers of disregarding this delicate balance. In 2015, the borealpox virus (BRPV) [formerly Alaskapox virus (AKPV)], classified as an Orthopoxvirus, was first identified in a woman living near Fairbanks, Alaska. The BRPV causes borealpox disease. The first recorded fatality attributed to BRPV infection occurred in January 2024. Current evidence suggests that BRPV primarily targets small mammals, particularly red-backed voles and shrews, as evidenced by sampling efforts in the Fairbanks North Star Borough. However, it is likely that the virus is more widespread among Alaska’s small mammal populations, potentially leading to undiagnosed human infections. Additionally, domestic pets, such as cats and dogs, may also contribute to the transmission of the virus. To date, no instances of human-to-human transmission have been documented, but the lack of diagnostics and vaccines for BRPV remains a concerning gap. This paper aims to address this issue by reporting the structure and epitopes of the major proteins of BRPV. This data could serve as a foundation for the development of novel diagnostics and vaccines to combat BRPV, thereby mitigating its impact on both human and animal populations.

In vitro and in vivo characterization of a novel West Nile virus lineage 2 strain

Over recent decades, West Nile virus (WNV) has continued to expand its geographical range, emerging in previously non-endemic areas, including northern Europe. In Europe, WNV lineage 2 strains are most prevalent and cause sporadic outbreaks of WNV disease in humans each transmission season. Here, we assessed the virulence of a newly emerged WNV lineage 2 strain that was isolated in the Netherlands in 2020 (WNV-NL20) and caused several cases of West Nile disease in humans and used a WNV lineage 2 strain related to major outbreaks of neuroinvasive disease in humans in central and south-eastern Europe in 2010 (WNV-578/10) as a reference. Infection of primary human cells of the blood-brain barrier in vitro did not show major differences in replication kinetics between WNV-578/10 and WNV-NL20. Experimental infection of mice showed that both WNV strains induced significant weight loss, neurological signs, and lethal disease. Neurological involvement was confirmed for both WNV strains by the presence of infectious virus and viral antigen in the brain. In conclusion, we show that the recent WNV-NL20 strain that emerged in the Netherlands is neurovirulent in mice. The use of in vitro and in vivo models to characterize the pathogenesis of emerging WNV strains may aid in predicting the neurovirulence of WNV infections in humans during potential future outbreaks.

Seoul orthohantavirus evades innate immune activation by reservoir endothelial cells

Seoul orthohantavirus evades innate immune activation by reservoir endothelial cells

Occurrence of Salmonella enterica in faecal sludge from Nigeria and genetic relatedness with strains associated with human infections in Africa.

This study investigated occurrence of Salmonella in faecal sludge from public toilets in Nigeria, and genetic relatedness of strains which have been reported to cause human infection across Africa. The study collected 150 human sludge from public toilets, and identified Salmonella through culture and PCR. Isolates were tested for antimicrobial susceptibility and sequenced using Illumina MiSeq. Draft sequences were compared with sequence data from Enterobase and Genbank. Twenty-four (16.0%) of sewage samples were positive for Salmonella [CI95 (10.2- 21.8)]. S. Give (sequence type (ST) 516), S. Seftenberg (ST-14), and S. Chester (ST-411) were the most prevalent serovars found in 45.8%, 16.7%, and 16.7% of samples, respectively. Most of the isolates were sensitive to the antimicrobials tested, only one isolate of S. Derby showed resistance to ampicillin and cefazolin. Notably, 91.7% of the strains had the aac (6)-Iaa gene, and point mutations in parC, gyrA and acrB. S. Chester showed genetic relatedness with strains from Benin Republic and South Africa. There is genetic relatedness of present strains and those associated with human infections in Africa.

Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI.

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown. Using HSV-1 with intact and ablated gE-mediated IgG Fc binding, and Fc-engineered antibodies with modified ability to interact with gE/gI, we investigated the role of the vFcR in viral pathogenesis and mAb-mediated protection from nHSV. The gD-specific human mAb HSV8 modified to lack binding to gE exhibited enhanced neutralization and in vivo protection compared to its native IgG1 form. This improved protection by the engineered mAbs was dependent on the presence of the vFcR. Human IgG3 allotypes lacking vFcR binding also exhibited enhanced antiviral activity in vivo, suggesting that vaccines that robustly induce IgG3 responses could show enhanced protection. suggesting the value of vaccination strategies that robustly induce this subclass. Lastly, analysis of longitudinal responses to acute primary genital infection in humans raised the possibility that unlike most viruses, HSV may exhibited slow induction of IgG3. In summary, this study demonstrates that mAbs lacking the ability to interact with the vFcR can exhibit improved protection from HSV-offering new prospects for antibody-based interventions.

A pan-genotypic hepatitis E virus replication inhibitor with high potency in a rat infection model

BACKGROUND & AIMSHepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs. METHODSHEV subgenomic replicon systems were used to screen a small library of pre-selected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems; the efficacy of the compound was assessed in the athymic nude rat HEV infection model. RESULTSCompound JNJ-9117 exerts pan-genotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between three crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5’-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was in infected rats highly effective in lowering viral RNA load in liver and feces to (almost) undetectable levels. CONCLUSIONSJNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase 1 studies with JNJ-9117 have been initiated in healthy human volunteers.

Safety and Efficacy of Immunization with a Late-Liver-Stage Attenuated Malaria Parasite

BackgroundCurrently licensed and approved malaria subunit vaccines provide modest, short-lived protection against malaria. Immunization with live-attenuated Plasmodium falciparum malaria parasites is an alternative vaccination strategy that has potential to improve protection.MethodsWe conducted a double-blind, controlled clinical trial to evaluate the safety, side-effect profile, and efficacy of immunization, by means of mosquito bites, with a second-generation genetically attenuated parasite (GA2) — a mei2 single knockout P. falciparum NF54 parasite (sporozoite form) with extended development into the liver stage. After an open-label dose-escalation safety phase in which participants were exposed to the bites of 15 or 50 infected mosquitoes (stage A), healthy adults who had not had malaria were randomly assigned to be exposed to 50 mosquito bites per immunization of GA2, an early-arresting parasite (GA1), or placebo (bites from uninfected mosquitoes) (stage B). After the completion of three immunization sessions with 50 mosquito bites per session, we compared the protective efficacy of GA2 against homologous P. falciparum controlled human malaria infection with that of GA1 and placebo. The primary end points were the number and severity of adverse events (in stages A and B) and blood-stage parasitemia greater than 100 P. falciparum parasites per milliliter after bites from GA2-infected mosquitoes (in stage A) and after controlled human malaria infection (in stage B).ResultsAdverse events were similar across the trial groups. Protective efficacy against subsequent controlled human malaria infection was observed in 8 of 9 participants (89%) in the GA2 group, in 1 of 8 participants (13%) in the GA1 group, and in 0 of 3 participants in the placebo group. A significantly higher frequency of P. falciparum–specific polyfunctional CD4+ and Vδ2+ γδ T cells were observed among participants who received GA2 than among those who received GA1, whereas GA2 and GA1 induced similar antibody titers targeting the P. falciparum circumsporozoite protein.ConclusionsIn this small trial, GA2 was associated with a favorable immune induction profile and protective efficacy, findings that warrant further evaluation. (Funded by the Bontius Foundation; ClinicalTrials.gov number, NCT04577066.)

Relationship between knowledge and attitude about human papillomavirus infection and vaccination in female nursing students

Introduction: Human papillomavirus (HPV) infection is the primary cause of cervical cancer, which is the second-leading cause of women’s death in Indonesia, and that is why a national HPV vaccination program is required to address this issue. A preliminary survey of 20 female nursing students revealed that 70% were unaware of the HPV virus, 80% were unaware of cervical cancer, and 80% were unaware that HPV could lead to cervical cancer. This study aimed to determine the relationship between knowledge and attitude about human papillomavirus infection and vaccination in female nursing students. Methods: This descriptive-quantitative study used a cross-sectional design and univariate and bivariate analysis.

Modulation of Monocyte Effector Functions and Gene Expression by Human Cytomegalovirus Infection

Modulation of Monocyte Effector Functions and Gene Expression by Human Cytomegalovirus Infection

An orally available Mpro/TMPRSS2 bispecific inhibitor with potent anti-coronavirus efficacy in vivo.

Coronaviruses have caused three major endemics in the past two decades. Alarmingly, recent identification of novel zoonotic coronaviruses that caused human infections suggests the risk of future coronavirus outbreak caused by spillover infection from animal reservoirs remains high 1,2 . Therefore, development of novel therapeutic options with broad-spectrum anti-coronavirus activities are urgently needed. Here, we develop an orally-available bispecific inhibitor, TMP1, which simultaneously targets key coronavirus replication protease M pro and the essential airway protease TMPRSS2 3,4 . TMP1 shows broad-spectrum protection not only against different SARS-CoV-2 variants but also against multiple human-pathogenic coronaviruses in vitro. By using the K18-hACE2 transgenic mouse, hDPP4 knock-in mouse and golden Syrian hamster models, we demonstrate TMP1 cross-protects against highly-pathogenic coronaviruses (SARS-CoV-1, SARS-CoV-2 and MERS-CoV) in vivo and efficiently abrogates SARS-CoV-2 transmission. Through structural and mutagenesis studies, we confirmed the direct interaction of TMP1 with M pro and TMPRSS2, and pinpoint the key sites of interactions. Importantly, TMP1 inhibits the infection of nirmatrelvir-resistant SARS-CoV-2 escape mutants. Together, our findings demonstrate the antiviral potential of the novel bispecific M pro /TMPRSS2 antiviral design against human-pathogenic coronaviruses and other emerging coronaviruses.

Evaluation of Serological Tests for Different Disease Stages of Leptospirosis Infection in Humans.

Leptospirosis is a zoonotic disease that is widely distributed around the world and presents symptoms similar to other febrile illnesses in tropical regions, which complicates clinical diagnosis. This study aimed to evaluate the performance and agreement between serological diagnostic tests for detecting both acute and convalescent human leptospirosis, using the micro agglutination test (MAT) as a reference in an endemic region of the Colombian Caribbean. A prospective descriptive study was conducted on 275 participants with suspected leptospirosis. Paired serum samples were obtained, and an epidemiological survey was conducted. Using the MAT as the gold standard, we calculated positive and negative predictive values, sensitivity, specificity, and kappa index. A Bayesian latent class model was also used to compare the diagnostic tests. In 223 paired serum samples, the sensitivity values for various stages of the disease ranged between 10.8% to 54.1% in the acute and 6.1% to 66.7% during the convalescent phase compared to the MAT. According to the Bayesian model, sensitivity was 9.5% to 75.3% in the acute phase and 5.7% to 85.3% in the convalescent phase. The Kappa value, an indicator of agreement, was moderate for the IgM ELISA in the acute phase (0.553) and substantial in the convalescent phase (0.692). The MAT was the best confirmatory test in both acute and convalescent phases of leptospirosis. Despite the high specificity of ELISA, 21.62% of participants identified as negative by IgM-ELISA in both phases were subsequently confirmed as positive by the MAT. It is necessary to re-evaluate diagnostic guidelines that do not employ the MAT for confirmation and to enhance the diagnostic and clinical identification of leptospirosis within healthcare institutions and public health laboratories while providing a rapid and reliable test for its implementation.

Neutrophil prime unique transcriptional responses in intestinal organoids during infection with nontyphoidal Salmonella enterica serovars.

Nontyphoidal strains of Salmonella enterica are a major cause of foodborne illnesses, and infection with these bacteria results in inflammatory gastroenteritis. Polymorphonuclear leukocytes (PMNs), also known as neutrophils, are a dominant immune cell type found at the site of infection in Salmonella-infected individuals, but how they regulate infection outcome is not well understood. Here, we used a co-culture model of primary human PMNs and human intestinal organoids to probe the role of PMNs during infection with two of the most prevalent Salmonella serovars: Salmonella enterica serovar Enteritidis and Typhimurium. Using a transcriptomics approach, we identified a dominant role for PMNs in mounting differential immune responses including production of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. We also identified specific gene sets that were induced by PMNs in response to Enteritidis or Typhimurium infection. By comparing host responses to these serovars, we uncovered differential regulation of host metabolic pathways particularly induction of cholesterol biosynthetic pathways during Typhimurium infection and suppression of RNA metabolism during Enteritidis infection. Together, these findings provide insight into the role of human PMNs in modulating different host responses to pathogens that cause similar disease in humans.IMPORTANCENontyphoidal serovars of Salmonella enterica are known to induce robust recruitment of polymorphonuclear leukocytes (PMNs) in the gut during early stages of infection, but the specific role of PMNs in regulating infection outcome of different serovars is poorly understood. Due to differences in human infection progression compared to small animal models, characterizing the role of PMNs during infection has been challenging. Here, we used a co-culture model of human intestinal organoids with human primary PMNs to study the role of PMNs during infection of human intestinal epithelium. Using a transcriptomics approach, we define PMN-dependent reprogramming of the host response to Salmonella, establishing a clear role in amplifying pro-inflammatory gene expression. Additionally, the host response driven by PMNs differed between two similar nontyphoidal Salmonella serovars. These findings highlight the importance of building more physiological infection models to replicate human infection conditions to study host responses specific to individual pathogens.

Association between human herpesviruses infections and childhood neurodevelopmental disorders: insights from two-sample mendelian randomization analyses and systematic review with meta-analysis

BackgroundThe potential roles of viral infections in neurodevelopmental disorders (NDDs) have been suggested based on previous studies. Given the high prevalence of human herpesviruses (HHVs), the associations between HHVs infection and the risk of NDDs warrant explored.MethodsOur study employs a two-sample Mendelian randomization (MR) analysis and systematic review with meta-analysis to investigate whether genetically predicted HHVs infection are linked to three main childhood NDDs—autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS). We utilized genetic variants associated with HHV infections in genome-wide association study (GWAS) summary datasets of European populations to establish instrumental variables and statistics for three NDDs obtained from Psychiatric Genomics Consortium. MR analysis was performed using inverse-variance weighted, MR Egger, weighted median, simple median, weighted mode, and MR-PRESSO. In addition, publications associating HHVs infection with three NDDs were systematically searched using PubMed, Web of Science, and three Chinese databases for meta-analyses.ResultsThe MR results found no evidence to support a link between genetically predicted HHVs infection and the risk of NDDs based on existing datasets. Twenty-seven observational studies on children with HHVs infection and NDDs were considered eligible. Meta-analysis showed that cytomegalovirus and HHV-6 infection were related with ASD, while Epstein-Barr virus and cytomegalovirus infection were associated with TD in Chinese population. Conclusions: These results contribute to a comprehensive understanding of the possibilities underlying HHV infections in affecting childhood NDDs. Further research is necessary to include larger and more robust statistics of HHV infections and NDDs.Trial registrationThis systematic review was registered at PROSPERO as CRD42024554169. Retrospectively registered 26 July 2024.