Antiretroviral therapy transformed HIV from a nearly uniform death sentence into a manageable chronic condition by blocking new rounds of infection. Yet the therapy does nothing to the proviral DNA already stitched into the genomes of long-lived host cells. As soon as treatment lapses, the reservoir seeds rapid viral rebound. Understanding why particular infected clones persist for years, while others decay, has therefore become one of the most consequential questions in HIV research, and the new findings suggest the answer lies partly in the immune environment the reservoir cells inhabit rather than in the virus alone.

Natural killer cells are innate lymphocytes that patrol the body and kill stressed or infected cells without requiring the antigen-specific recognition that defines T and B lymphocytes. Their activity is governed by a delicate balance of activating and inhibitory receptors. KIR2DL1 is an inhibitory killer-cell immunoglobulin-like receptor that recognizes specific HLA class I molecules, the same surface proteins that HIV-exposed cells display. The education model of NK cell biology holds that a developing NK cell calibrates its functional competence through interactions between its inhibitory receptors and self-HLA; a KIR2DL1-positive NK cell in an individual carrying the corresponding HLA ligand becomes ‘educated,’ or licensed, to respond vigorously when that ligand is lost or altered, as frequently happens during viral infection.

The study demonstrates that these education states are not a fleeting influence but leave durable imprints on the reservoir. By examining cells from people who had spent years, in some cases many years, on suppressive antiretroviral regimens, the researchers found that proviruses surviving over the long term were not distributed randomly across the infected cell population. Instead, their persistence correlated with features of the innate immune landscape, indicating that some infected cells had been preferentially spared or eliminated depending on how the NK cell compartment of that individual had been trained.

This reframes the reservoir as an active participant in a prolonged evolutionary standoff with the immune system. Cells harboring intact, replication-competent proviruses that somehow avoid NK-mediated killing gain a survival advantage and expand, sometimes through clonal proliferation, over years of therapy. Cells that present vulnerabilities to educated NK cells are progressively culled. The result is a reservoir sculpted by immune pressure, analogous in some respects to how antigen escape shapes the evolution of the virus in untreated infection, but operating here through germline-encoded innate receptors rather than clonal adaptive recognition.

The technical achievement underlying these conclusions is considerable. Single-cell approaches now allow researchers to connect proviral sequence, integration site, transcriptional state, and surface phenotype in the same individual cell, converting what was once a population-level average into a high-resolution map of reservoir heterogeneity. Combined with deep characterization of NK cell receptor repertoires and their HLA ligands in each study participant, such methods make it possible to ask which immune configurations leave measurable signatures on which reservoir lineages, and the study deployed precisely this integrative strategy across cohorts on long-term therapy.

The clinical implications are potentially far-reaching. Current cure strategies aim to ‘shock and kill’ the reservoir, using latency-reversing agents to force latent proviruses into expression so that immune or pharmacological effectors can destroy the exposed cells. If KIR2DL1-educated NK cells already exert selection pressure on the reservoir, then the efficiency of such interventions may depend heavily on whether the killing arm of the strategy is matched to the individual’s NK cell education status and HLA type. A shock-and-kill regimen delivered to a person whose NK cells are poorly licensed against their own reservoir cells might flush virus into the open without achieving meaningful depletion.

This line of thinking points toward precision immunotherapies for HIV. Just as cancer immunotherapy increasingly considers the tumor microenvironment and the patient’s innate immune competence, curative interventions for HIV may need to account for innate immune imprints. Engaging NK cells deliberately, through bispecific killer-cell engagers, cytokine modulation, or engineered NK products, could in principle tip the standoff in favor of the host. Conversely, therapies that inadvertently impair NK education or function might relax selection pressure and allow reservoir clones to expand unchecked during what was assumed to be stable suppression.

The findings also resonate with a broader shift in virology: the recognition that innate immunity is not merely a rapid first response but a long-lived determinant of infection outcomes. Trained immunity, NK cell memory-like behavior, and receptor education all illustrate that innate cells carry histories. In chronic infections treated for years with suppressive drugs, those histories accumulate and leave fingerprints on the surviving pathogen population. HIV, the most intensively studied persistent human virus, now appears to bear such fingerprints in its reservoir.

Substantial questions remain. The relationship between KIR2DL1 education and reservoir persistence will need to be validated across larger and more diverse cohorts, since KIR and HLA genotype distributions vary substantially across populations, and HIV epidemiology is concentrated in regions where such genetic diversity is greatest. Whether innate selection can be therapeutically harnessed to shrink the reservoir, or only to shape it, is unresolved. But the conceptual contribution is clear: the latent HIV reservoir is not hidden from the immune system in any absolute sense. It has been living under innate immune surveillance all along, and the cells that persist during long-term antiretroviral therapy are, in part, the survivors of that surveillance. Any credible path to a cure will have to reckon with the imprints that this ancient arm of immunity has already left on the virus’s last refuge.

Subject of Research: The influence of KIR2DL1-educated natural killer cells on the persistence of latent HIV-1 reservoir cells during long-term antiretroviral therapy.

Article Title: Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy

Article References: Tan, T. S., Sun, W., Gao, C., Viard, M., Walters, L. C., Lancien, M., Yuki, Y., Van, T. N., Casquero, C., Guo, X., Hoh, R., Haas, D. W., Michael, N., Kirk, G. D., Yendewa, G., Gandhi, R. T., Kassaye, S. G., Tien, P. C., Walker, B. D., … Lichterfeld, M. (2026). Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy. Nature Immunology. https://doi.org/10.1038/s41590-026-02637-w

Image Credits: AI Generated

DOI: 10.1038/s41590-026-02637-w

Keywords: HIV-1, viral reservoir, natural killer cells, KIR2DL1, NK cell education, antiretroviral therapy, viral latency, innate immunity, HIV cure research, Nature Immunology, immunotherapy, proviral persistence

The study, published in Plant Cell Reports, reveals that Ralstonia solanacearum does not attack tomato roots at random. Instead, during early infection, the bacterium preferentially colonizes the sites where lateral roots emerge, and it actively promotes the development of new lateral roots, thereby generating additional entry points for itself. This finding reframes the root system not merely as a passive barrier but as a dynamic developmental structure that the pathogen can manipulate to its own advantage. The work builds on a growing body of evidence that soil-borne pathogens target root developmental programs, but it goes further by identifying a specific host gene that mediates this manipulation.

At the center of the discovery is auxin, the plant hormone that governs lateral root formation. The researchers found that during the early stage of infection, endogenous auxin accumulates significantly in tomato root tissues. This hormonal surge was accompanied by the transcriptional upregulation of a group of cell wall remodeling genes with potential auxin responsiveness, suggesting that the pathogen co-opts the plant’s own growth signaling machinery to loosen and restructure the cell walls that normally stand between the bacterium and the plant’s interior.

Among the genes induced during this early window, one stood out: SlXTH3, a member of the xyloglucan endotransglycosylase/hydrolase, or XTH, family. XTH enzymes are the cell wall’s remodeling specialists. They cut and rejoin xyloglucan, the hemicellulose polymer that tethers cellulose microfibrils together, allowing the wall to expand during growth without losing its structural integrity. SlXTH3 is predominantly expressed in roots, and the team showed that its expression rises sharply during the early phase of Ralstonia infection, precisely when the bacterium is seeking entry.

To test whether SlXTH3 is merely a bystander or an active player, the researchers generated tomato lines in which the gene was either overexpressed or silenced through RNA interference. The results were striking. Seedlings overexpressing SlXTH3 produced more lateral roots and allowed markedly greater early colonization by the bacterium, while SlXTH3-silenced lines showed the opposite tendency, with fewer lateral roots and reduced bacterial establishment. In other words, the amount of this single wall-remodeling enzyme directly influenced how easily the pathogen could gain a foothold in the root.

The mechanistic picture deepened when the team examined the biochemical and immune consequences of altering SlXTH3 activity. Roots of overexpressing lines displayed increased xyloglucan endotransglycosylase activity and elevated hemicellulose content, consistent with enhanced wall loosening and remodeling. Critically, these same lines showed suppressed reactive oxygen species bursts in response to flg22, a well-characterized bacterial flagellin peptide that normally triggers pattern-triggered immunity in plants. The silenced lines, by contrast, mounted stronger ROS bursts and stronger overall root immune outputs. This indicates that SlXTH3 does not simply open physical doors in the wall; it also dampens the plant’s chemical alarm system, blunting one of the first lines of defense against bacterial attack.

The consequences for disease were equally clear. Overexpression of SlXTH3 promoted disease progression and increased bacterial proliferation within the plants, whereas silencing the gene helped attenuate disease development. Taken together, these results establish SlXTH3 as a key susceptibility factor for Ralstonia solanacearum during tomato root infection. The pathogen, the authors conclude, exploits SlXTH3-mediated lateral root development and immune-response suppression to promote the establishment of infection and aggravate disease, turning a routine component of the plant’s growth program into a vulnerability.

The findings fit into a broader and increasingly influential framework in plant pathology: the idea that development and defense are deeply intertwined, and that pathogens frequently target the junction between them. Auxin has long been known to play multiple roles during plant-pathogen interactions, often acting in ways that favor the pathogen, and previous work in Arabidopsis has shown that antagonistic interactions between auxin and salicylic acid signaling regulate bacterial infection through lateral roots. The cell wall itself is now recognized as an active arena of immunity, where changes in wall composition can trigger or suppress disease resistance responses. What the new study adds is a concrete, crop-relevant example of how a pathogen harnesses an auxin-responsive wall-remodeling gene to simultaneously create infection sites and weaken immune signaling in the root.

The practical implications could be significant. Because SlXTH3 silencing reduced bacterial colonization and disease development, the gene represents an attractive target for breeding or gene-editing approaches aimed at producing tomato varieties with enhanced resistance to bacterial wilt. Reducing SlXTH3 activity might carry trade-offs for root development and plant vigor, and any such costs would need to be carefully evaluated in the field. Nevertheless, the identification of a single, well-defined susceptibility gene offers a much more tractable goal than the complex, multigenic resistance traits that have so far proved difficult to deploy against this pathogen.

More broadly, the study underscores how much remains to be learned about the opening moves of soil-borne infections. Much of plant pathology has focused on what happens after a pathogen enters the xylem and begins to spread through the vascular system, but the new work highlights the decisive importance of the earliest hours and days at the root surface, where colonization sites are chosen, walls are remodeled and immune alarms are raised or silenced. By revealing that Ralstonia solanacearum actively shapes the root architecture of its host to manufacture its own entry points, the Hainan University team has not only identified a promising resistance target but also opened a new window onto the covert developmental negotiations that unfold beneath the soil surface whenever a deadly pathogen meets a susceptible root.

Subject of Research: The role of the auxin-responsive cell wall remodeling gene SlXTH3 in promoting Ralstonia solanacearum root infection and bacterial wilt susceptibility in tomato

Article Title: Auxin-responsive SlXTH3 promotes Ralstonia solanacearum infection by modulating lateral root development and root immunity in tomato

Article References: Zheng, X., Du, X., Chen, J., Liang, H., Wu, W., & Wang, P. (2026). Auxin-responsive SlXTH3 promotes Ralstonia solanacearum infection by modulating lateral root development and root immunity in tomato. Plant Cell Reports, 45(10), Article 286. https://doi.org/10.1007/s00299-026-03968-6

Image Credits: AI Generated

DOI: 10.1007/s00299-026-03968-6

Keywords: tomato, Ralstonia solanacearum, bacterial wilt, SlXTH3, auxin, lateral root development, cell wall remodeling, xyloglucan endotransglycosylase, root immunity, reactive oxygen species, plant pathology, susceptibility gene

A new study from Korea University College of Medicine, published in Nature Immunology on June 15, 2026, offers a detailed molecular portrait of how an mRNA-based influenza vaccine may accomplish exactly that. Led by Associate Professor Jiwon Lee of the Department of Convergence Medicine and the Vaccine Innovation Center, and conducted in collaboration with Professor Ali Ellebedy and his group at Washington University in St. Louis, the investigation compared an investigational quadrivalent mRNA influenza vaccine, designated mRNA-1010, against the licensed conventional split-virion vaccine Fluarix in a head-to-head clinical evaluation. The central question was whether the mRNA platform could stimulate stronger and more persistent germinal-center responses than a conventional vaccine, and whether that persistence would translate into a measurably broader antibody repertoire in the blood.

The germinal center is the crucible where vaccine-induced immunity is forged. Within specialized microenvironments of draining lymph nodes, B cells that recognize vaccine antigen undergo rounds of proliferation, somatic hypermutation, and selection. Each cycle introduces random mutations into the genes encoding the B-cell receptor, and only those variants whose mutated receptors bind antigen with higher affinity are permitted to survive and expand. Over weeks, this Darwinian process generates plasma cells that secrete high-affinity antibodies and memory B cells that persist for years. The duration and intensity of germinal-center activity are therefore widely regarded as key determinants of both the breadth and the durability of antibody responses. A vaccine that keeps germinal centers active for longer gives B cells more opportunities to mutate, diversify, and explore antibody solutions that recognize conserved or varied features of the virus.

To test whether mRNA vaccination extends this critical phase, the researchers enrolled 75 healthy adults aged 20 to 50 years and followed them across two influenza seasons. Of these, 38 participants received mRNA-1010 and 37 received Fluarix. Blood samples were collected at multiple time points through 26 weeks after vaccination, allowing the team to track the evolution of circulating antibodies over nearly half a year. Crucially, a subset of participants also underwent ultrasound-guided fine-needle aspiration of draining axillary lymph nodes, an invasive but informative procedure that enabled direct sampling of germinal centers as they formed and matured. This combination of peripheral blood monitoring and lymph-node sampling is rare in human vaccine studies and gave the investigators an unusually complete view of the immune response as it unfolded in real time.

The laboratory analysis was correspondingly comprehensive. The team deployed flow cytometry to characterize immune cell populations, ELISpot assays to quantify antigen-specific antibody-secreting cells, single-cell RNA sequencing and B-cell receptor sequencing to resolve individual B-cell lineages, serum IgG proteomics to catalog circulating antibody clonotypes, and a battery of antibody binding and neutralization assays to test functional activity against antigenically diverse influenza strains. Together, these methods profiled the response at scales ranging from single cells to whole serum, providing a multidimensional dataset that conventional vaccine trials, which typically rely on bulk antibody titers alone, cannot match.

The findings were striking. The mRNA vaccine elicited a substantially more diverse and broader serum antibody repertoire than Fluarix, according to Dr. Lee. Most notably, influenza-specific germinal-center responses persisted for up to 26 weeks in 5 of 13 mRNA-1010 recipients whose draining lymph nodes were sampled, while persistent germinal centers were not detected among any of the Fluarix recipients sampled. Six months of sustained germinal-center activity after a single vaccination is an unusually long window of B-cell evolution, and it suggests that the mRNA platform provides antigen persistence and inflammatory signaling that keep the selection machinery running far longer than a conventional protein-based split-virion preparation.

That prolonged activity left a measurable imprint on the antibody repertoire. The mRNA vaccine increased the diversity of the serum IgG repertoire and promoted the diversification of pre-existing B-cell lineages through somatic hypermutation, meaning that antibodies the immune system had already learned to make against earlier influenza exposures were not merely recalled but actively refined and expanded. These molecular changes were associated with broader antibody binding across antigenically diverse influenza strains and with significantly greater increases in neutralization titers against 11 of 13 A/H1N1 viruses tested. In practical terms, the antibodies generated after mRNA vaccination recognized a wider range of viral variants and neutralized more of them, including strains that differed antigenically from those contained in the vaccine itself. Dr. Lee summarized the distinction succinctly: the mRNA platform does not simply produce more antibodies, it produces a more diversified antibody response, which leads to greater binding and neutralizing breadth.

A key methodological strength of the study was Ig-Seq, a mass-spectrometry-based technology that identifies individual antibody clonotypes circulating in the blood after vaccination. Conventional vaccine studies typically measure bulk binding or neutralization titers, aggregate numbers that reveal how much antibody activity is present but say little about its composition. Ig-Seq resolves the response down to individual antibody clonotypes, revealing which antibody lineages emerged, expanded, and diversified after vaccination. Combined with B-cell receptor sequencing, this molecular-level approach allowed the researchers to trace the genealogical trees of antibody families as they mutated and branched over the six-month observation period, directly linking sustained germinal-center activity in the lymph node to the diversification of antibodies measurable in the serum. The authors identify Ig-Seq as a defining strength of the work because it captures information that bulk serology fundamentally cannot.

The broader implications reach toward the long-sought goal of a more universal influenza vaccine. If mRNA vaccination can sustain germinal-center activity for months rather than weeks, it creates a temporal window in which B cells can accumulate mutations that broaden their recognition of the virus’s antigenic landscape. This mechanism could in principle support protection that carries over between seasons, reducing the need for annual reformulation and re-vaccination. However, the authors are careful to note that further studies are needed to determine whether these broadened responses translate into multi-season protection or permit longer vaccination intervals. The study population consisted of healthy adults aged 20 to 50, and future research must investigate whether the same benefits are maintained in older adults and immunocompromised populations, whose germinal-center function, B-cell repertoire diversity, and overall immune responsiveness differ substantially from those of healthy younger recipients.

What the study establishes, with unusual molecular resolution, is a mechanistic bridge between a vaccine platform and the quality of the immunity it generates. Persistent germinal centers, diversified B-cell lineages, and a broader serum antibody repertoire form a coherent causal chain, and tools such as Ig-Seq now make each link observable in humans. As mRNA technology matures beyond its first applications, findings like these suggest that its most consequential contribution to vaccinology may lie not in speed of development but in the depth and breadth of the immune memory it leaves behind, offering a rational template for influenza vaccines designed to stay ahead of a virus that never stops changing.

Subject of Research: A clinical study comparing mRNA-1010 and Fluarix influenza vaccines in healthy adults, examining germinal-center persistence and antibody repertoire breadth

Article Title: Korea University study uncovers how mRNA vaccination may broaden flu antibody responses

Article References: Korea University study uncovers how mRNA vaccination may broaden flu antibody responses. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: mRNA vaccine, influenza, germinal center, antibody breadth, B cells, somatic hypermutation, Ig-Seq, neutralization, vaccinology, Nature Immunology, Korea University, immune repertoire

The scientific case for immunisation has never been stronger. Modelling of fifty years of the Expanded Programme on Immunization shows that vaccines have made a major contribution to improved survival and health worldwide. Recent evaluations of meningococcal B vaccines demonstrate how careful development, rigorous surveillance and real-world data can produce highly effective and safe products that substantially reduce severe childhood disease. Human papillomavirus vaccination has been associated with a substantial reduction in invasive cervical cancer risk, and rotavirus vaccination is recognised as a highly effective tool against severe gastroenteritis and hospitalisation in young children. The economic returns are equally striking: a recent American Academy of Pediatrics policy statement estimates that from 1994 to 2003 vaccination averted 500 million cases of vaccine-preventable disease, 32 million hospitalisations and 1.1 million deaths in the United States, saving 540 billion dollars in direct costs and 2.7 trillion dollars in indirect costs. European studies confirm similar reductions in disease and economic burden, and the World Health Organization has recognised that vaccines also curb antimicrobial resistance by preventing infections that would otherwise require antibiotics.

Yet the academy argues that this evidence base is being undermined by two interacting sets of barriers: access and acceptance. Access barriers include missed opportunities for vaccination during routine health visits, long travel distances and transportation costs in rural or underserved settings, weak follow-up and reminder systems, and limited timeliness in completing vaccine series. Socioeconomic position, maternal education and health literacy shape both the ability to navigate services and the capacity to interpret vaccination information. Marginalised and mobile groups, including migrants, refugees and displaced persons, face additional structural and administrative obstacles, fragmented care and legal and language barriers. Systematic reviews show that migrant and refugee populations in Europe often experience lower vaccination coverage than host populations, and recent register-based evidence among Ukrainian refugee children in Norway illustrates how mobility and incomplete records leave significant gaps in documented immunisation.

Acceptance barriers compound the problem. Parental confidence in vaccines varies between countries and communities and can be weakened by institutional mistrust, pandemic fatigue, inconsistent policy messaging and misinformation. In Europe, false claims are commonly amplified through social media, messaging applications and politicised narratives, gaining traction when families encounter access barriers, receive contradictory advice or perceive vaccine-preventable diseases as remote threats. The academy stresses that effective responses require far more than fact sheets: they demand social listening, pre-bunking and rapid correction of false claims, multilingual community engagement, trusted clinicians and community messengers, and transparent policy decisions visibly aligned with scientific evidence. Vaccine confidence, the paper argues, must be treated as a dynamic challenge that shifts with events rather than a static attitude to be measured once.

The consequences of these immunity gaps are no longer hypothetical. A comprehensive review in The New England Journal of Medicine documented a dramatic resurgence of measles, with more than 395,000 confirmed cases worldwide in 2024 and a further sharp increase in early 2025. Measles is emphatically not a benign childhood illness: it can cause encephalitis, post-infectious immune amnesia and subacute sclerosing panencephalitis, a devastating late complication. In the WHO European Region, more than 127,000 measles cases were recorded in 2024, double the number in 2023 and the highest figure since 1997, with children under five accounting for more than 40 percent of cases and 38 deaths reported. Pertussis has surged in parallel, with nearly 300,000 cases reported in the European Region in 2024, more than a three-fold increase on the previous year. Earlier joint statements by the European Commission, WHO Europe and UNICEF had already linked missed measles vaccination during and after the COVID-19 period to an up to sixty-fold increase in reported cases in 2023 compared with 2022.

The position paper sets out the cost of inaction in stark terms. Epidemiologically, clusters of susceptible children drive recurrent outbreaks, cross-border transmission and avoidable deaths. Individually, children who contract vaccine-preventable diseases may suffer acute illness, hospitalisation, long-term disability or death, along with interrupted education and psychological and financial burdens for families. Economically, outbreaks divert resources from routine care into emergency response, contact tracing, post-exposure prophylaxis and catch-up campaigns. At the system level, failure to invest in surveillance, digital records, workforce training and tailored communication perpetuates a reactive cycle in which gaps are detected late, responses are mounted under pressure, and the same vulnerabilities recur. Beyond the return of disease itself, the academy warns that inaction erodes trust and resilience in preventive child-health systems.

A central technical recommendation concerns documentation. Across Europe, increasing cross-border mobility makes reliable vaccination records essential, yet documentation remains fragmented, often non-digital and non-interoperable, making immunity gaps difficult to detect when children move between health systems. The academy calls for a pan-European digital vaccination-record standard: not a single central database, but an agreed minimum interoperable dataset, mapped to national schedules, protected by data-governance safeguards, and usable in routine care and catch-up vaccination, especially for mobile children and displaced families. It likewise urges expansion of national Immunisation Information Systems capable of real-time or at least quarterly coverage monitoring, detection of missed doses, automated reminders and recalls, and rapid outbreak response. Higher-resource systems may expand such infrastructure directly, while more decentralised or resource-constrained systems may need a staged approach beginning with a core dataset, regional pilots and paper-to-digital transition plans.

Measurement of behavioural barriers is another priority. The academy recommends embedding the WHO Behavioural and Social Drivers of Vaccination tools, the European Centre for Disease Prevention and Control’s 2025 social and behavioural science toolkit, and the Vaccine Barriers Assessment Tool into routine programme assessments, so that interventions are tailored to measured confidence, social norms, practical obstacles and trust rather than generic campaigns. It proposes a minimum monitoring framework tracking coverage for MMR, DTP, polio, HPV and other recommended vaccines by age, geography and equity strata, alongside timeliness, zero-dose and under-immunised children, stock-outs, outbreak incidence, reasons for under-vaccination and the proportion of vaccinators trained in evidence-based communication. Similar proposals have suggested that countries be assessed on their capacity to use social and behavioural data as a fourth indicator in the Joint External Evaluation tool.

Because vaccination is delivered by different professionals across Europe, the recommendations extend beyond paediatricians to general practitioners, nurses, school-health services, public-health teams and community health workers. Preventive paediatric care remains highly heterogeneous across the continent, and not all professionals involved in vaccine delivery have received formal immunisation training. The academy calls for structured education in vaccinology, contraindications, safety communication, motivational interviewing, culturally competent care and outbreak communication, drawing on the WHO Regional Office communication training module and the WHO Pocket book of primary health care for children and adolescents. On the contested question of mandates, the paper holds that compulsory vaccination can be ethically defensible only under strict conditions: when voluntary approaches have failed, disease risk is substantial, access barriers have been addressed, the measure is proportionate, time-limited and legally authorised, and medical exemptions and transparent monitoring protect public trust. Empathetic, patient-centred communication remains the first-line response, supported by narratives of preventable complications that illustrate, but never replace, scientific evidence.

The position paper concludes with a call to shift from high-level advocacy to measurable implementation. It urges harmonised Europe-wide surveillance, interoperable digital records, routine measurement of behavioural and access barriers, equity-focused catch-up schedules that screen for missed doses at primary-care, emergency, school-entry and adolescent contacts, and outreach to migrants, refugees, underserved urban districts and remote rural areas. It also warns that recent legal, regulatory and political shifts, combined with the spread of misinformation, have weakened long-standing protections for immunisation programmes, and that policy choices diverging from scientific evidence can rapidly undermine public health gains. Grounding its appeal in the WHO/UNICEF strategy for child and adolescent health adopted by all 53 Member States of the European Region, the academy frames the issue as a matter of children’s fundamental rights: every child deserves scientifically proven, safe interventions that protect them from avoidable harm. Protecting children today, the paper argues, safeguards the health, trust and resilience of future generations.

Subject of Research: Barriers to paediatric immunisation coverage and strategies to restore childhood vaccination rates in Europe

Article Title: Improving paediatric immunisation coverage rates: a position paper of the European Academy of Paediatrics

Article References: Dornbusch, H. J., Pana, Z. D., Torso, S. D., Hadjipanayis, A., Brierley, J., Karara, N., De Guchtenaere, A., Buttigieg, M., Grossman, Z., Kantor, I., Titomanlio, L., Wyder, C., Jullien, S., Craig, B. J., Pastore, R., Benes, O., Heininger, U., & Koletzko, B. (2026). Improving paediatric immunisation coverage rates: a position paper of the European Academy of Paediatrics. The Lancet Regional Health – Europe, 70, Article 101851. https://doi.org/10.1016/j.lanepe.2026.101851

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101851

Keywords: childhood vaccination, vaccine hesitancy, measles, pertussis, European Academy of Paediatrics, immunisation coverage, digital vaccination records, misinformation, vaccine equity, public health, migrant health, Immunisation Information Systems

The study rests on a simple but powerful epidemiological premise: antibodies of the immunoglobulin G class persist for years after infection or vaccination, so their prevalence in a population acts as a cumulative record of exposure. Because hepatitis A and hepatitis E are both transmitted primarily through the faecal-oral route, their seroprevalence patterns are tightly coupled to sanitation, water quality, hygiene practices and socio-economic conditions. When a community improves its water and sanitation infrastructure, the age at which children first encounter these viruses tends to rise, shifting the burden of susceptibility toward older individuals in whom infection is more likely to cause symptomatic disease. This phenomenon, known as epidemiological transition, is one of the central concerns for vaccination policy in low- and middle-income countries undergoing rapid urban development.

To test whether such a transition was underway in Vellore, the team drew on biobanked serum samples from 600 participants in the 2013 survey and 558 participants in the 2022 survey, all aged between one and forty years. Each sample was tested for IgG antibodies specific to hepatitis A virus and hepatitis E virus. The investigators then stratified seroprevalence estimates by age, gender and residential cluster, allowing them to detect not only overall changes between the two survey years but also geographic heterogeneity within the city. Statistical comparisons of seropositivity between years were carried out using proportion tests or Fisher’s exact tests, depending on the structure of the data.

The hepatitis A results were striking in their consistency. Seroprevalence exceeded 80 percent among children aged one to five years in both surveys and climbed to 100 percent among individuals aged sixteen and above, in 2013 as well as 2022. No statistically significant differences in hepatitis A seroprevalence were observed between the two survey years in any age stratum. In practical terms, nearly every resident of urban Vellore had been infected with hepatitis A virus by early adulthood in both eras, and infection continued to occur early in childhood. The virus, in this setting, remains firmly endemic, and the population’s collective immunity remains high.

Hepatitis E told a different story. IgG seroprevalence against this virus was low among children and adolescents in both surveys and increased progressively with age, a pattern consistent with sporadic rather than sustained childhood transmission. Among adults aged twenty-six to forty years, seroprevalence rose from 18 percent in 2013, with a 95 percent confidence interval of 12 to 27 percent, to 24 percent in 2022, with a 95 percent confidence interval of 16 to 32 percent. Although this increase suggests a possible gradual accumulation of exposure in adulthood, the change did not reach statistical significance, and the authors are careful not to overinterpret it. Across both viruses, no significant gender-based differences in seropositivity were detected.

Cluster-wise analysis added a spatial dimension to these findings. Hepatitis A seroprevalence was uniformly high across all residential clusters sampled in Vellore, reflecting the pervasive nature of early-life exposure to the virus throughout the urban environment. Hepatitis E seroprevalence, by contrast, was both low and heterogeneous across clusters, indicating that exposure to this virus is patchy and likely driven by localised factors such as intermittent contamination of water supplies, sanitation gaps in specific neighbourhoods, or differences in food handling practices. This heterogeneity matters for surveillance design, because a citywide average can easily mask pockets of elevated risk where outbreaks of hepatitis E, which can be particularly dangerous for pregnant women, may originate.

Beyond simple prevalence counts, the study employed more sophisticated quantitative tools to probe hepatitis A transmission dynamics. The researchers applied contact matrix and mixture modelling to the serological data to estimate the effective reproduction number, Re, for hepatitis A in each survey year. Mixture modelling, which treats the antibody distribution in a population as a blend of distributions from susceptible and immune individuals, allows researchers to infer the force of infection even from cross-sectional snapshots. The analysis yielded an Re below 1 in both serosurveys, indicating that secondary transmission of hepatitis A was not sustaining epidemic growth in either era, despite the accumulation of susceptible individuals in older age groups over time. This finding suggests that while the age profile of susceptibility may be shifting slowly, the underlying transmission intensity has not yet crossed the threshold that would fuel outbreaks among older, more vulnerable populations.

The implications for vaccination policy are significant. In many middle-income countries that have improved sanitation, hepatitis A has transitioned from a disease of early childhood, where infection is usually asymptomatic, to one affecting older children and adults, in whom clinical illness and occasional severe outcomes are more common. This shift is the classic argument for universal childhood hepatitis A vaccination: immunising children early both protects them and reduces circulation, indirectly shielding older susceptible individuals. The Vellore data show that this transition, while anticipated, has not yet materialised in measurable form; immunity remains high and acquired early, and the effective reproduction number remains below one. The authors note that their findings should inform age-specific considerations for hepatitis A vaccination policy in urban India as it undergoes transition, implying that the window for deciding on vaccination strategy remains open but should be monitored with continued serosurveillance.

For hepatitis E, the picture is one of limited but persistent and age-dependent exposure. The low seroprevalence among the young means that a large fraction of the population reaches adulthood without prior immunity, and the gradual rise in seropositivity with age reflects cumulative adult exposure. The authors highlight the need for targeted hepatitis E surveillance, particularly because the virus causes substantial morbidity in pregnant women and can trigger large outbreaks when water supplies are compromised. The modest, non-significant rise in adult seroprevalence between 2013 and 2022 is consistent with continued low-level transmission that could accelerate under adverse conditions, making sustained monitoring essential.

Perhaps the clearest message of the study is a reaffirmation of the value of water, sanitation and hygiene interventions. The stability of hepatitis A immunity over the decade, and the continued containment of hepatitis E transmission below epidemic thresholds, support continued investment in WASH infrastructure as the backbone of enteric virus control in urban India. At the same time, the study demonstrates the power of repeated, geographically stratified serosurveys using biobanked samples to detect epidemiological change before it becomes clinically visible. As Indian cities continue to grow and modernise, the balance between endemic early-childhood infection and emerging adult susceptibility will determine whether hepatitis A vaccination becomes a public health priority, and whether hepatitis E remains a smouldering, localised threat or flares into wider outbreaks. The Vellore data provide a rigorous baseline against which that future can be measured.

Subject of Research: Decadal changes in IgG seroprevalence of hepatitis A and E virus in urban Vellore, India

Article Title: Decadal changes in IgG seroprevalence of hepatitis A and E virus in Urban Vellore, India: Persistent Endemicity or Epidemiological Shift?

Article References: Decadal changes in IgG seroprevalence of hepatitis A and E virus in Urban Vellore, India: Persistent Endemicity or Epidemiological Shift?. (n.d.). https://doi.org/10.1186/s12879-026-14413-0

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14413-0

Keywords: Hepatitis A, Hepatitis E, IgG seroprevalence, serosurvey, enteric infections, WASH, epidemiological transition, urban India, effective reproduction number, vaccination policy, Decadal, changes

The outbreak first came to the attention of the World Health Organization on May 2, 2026, when passengers aboard the MV Hondius, which carried 147 crew members and passengers from 23 countries, presented with fever and gastrointestinal symptoms that rapidly progressed to pneumonia, shock, and acute respiratory distress syndrome. Laboratory confirmation of Andes virus infection by polymerase chain reaction followed between May 4 and May 6. By July 2, 2026, 13 cases had been identified on the vessel, 12 confirmed and one probable, and three patients had died, yielding a case fatality ratio of 23 percent. Epidemiologists hypothesize that an initial case acquired the infection from a rodent before boarding, with subsequent human-to-human transmission occurring during the prolonged, close contact that confined shipboard conditions inevitably produce.

Andes virus, formally Orthohantavirus andesense, occupies a unique position among hantaviruses. While hantaviruses are typically transmitted from rodents to humans through contact with urine, feces, or saliva, and humans are generally considered dead-end hosts, Andes virus is the only hantavirus documented to spread efficiently between people. First identified in Argentina in 1995, the virus has an incubation period ranging from 7 to 42 days, with a median of 18 days, and viral RNA has been detected in blood, respiratory secretions, urine, and semen. Transmission can occur through mucosal or respiratory exposure to infectious respiratory particles, although the virus is not classified as highly airborne. Case fatality ratios have reached 50 percent in some settings, and the virus has a documented history of super-spreading events, most dramatically during Argentina’s 2018 to 2019 outbreak, when transmission at a large social gathering linked to three super-spreaders produced the largest Andes virus outbreak recorded to date, with a case fatality ratio of approximately 32 percent.

Genomic sequencing of viruses isolated from the MV Hondius passengers detected no new lineages, and the circulating strain closely resembled Andes virus lineages previously identified in Argentina and Chile. The outbreak’s reproductive number was estimated at 0.7, considerably lower than the median reproductive numbers of 2.12 and 0.96 observed before and after infection control measures during the Argentine outbreak. Because the incubation period can extend to six weeks, disembarked passengers were asked to quarantine for 42 days, a duration that health authorities calculate provides a 96 percent probability of safe release. The episode has nonetheless highlighted the vulnerability of international transportation systems, where restricted spaces, overcrowding, inadequate ventilation, and limited access to intensive care can amplify transmission. Experts now recommend screening passengers boarding from hantavirus-endemic regions, controlling rodents on ships and in harbors, and establishing approved protocols for managing infectious diseases in international waters.

The pathogenesis of Andes virus infection centers on endothelial dysfunction. Hantaviruses target endothelial cells, producing enhanced microvascular permeability in the principal target organs: the lungs in hantavirus cardiopulmonary syndrome, which predominates in the Americas, and the kidneys in hemorrhagic fever with renal syndrome, which prevails in Europe and Asia. Immune-mediated mechanisms play a pivotal role. CD8-positive T cell activation has been documented during acute phases of both syndromes, immunoblasts circulate in patients experiencing shock or pulmonary edema, and fatal cases show high densities of cytokine-releasing cells in lung tissue. Elevated levels of tumor necrosis factor alpha can drive capillary leakage, pulmonary edema, and shock, while high interleukin 2 levels increase vascular permeability. Hantavirus cardiopulmonary syndrome unfolds in three phases: a prodromal phase of non-specific flu-like symptoms, a cardiopulmonary phase marked by pulmonary capillary leak and hemodynamic compromise that can culminate in cardiogenic shock, and a convalescent recovery phase.

Early diagnosis is critical because no specific antiviral agent exists. Reverse transcription polymerase chain reaction can detect viral RNA in whole blood during the asymptomatic and prodromal phases, and serological confirmation relies on IgM and IgG assays performed with chemiluminescence immunoassay technology. IgM antibodies appear at symptom onset, rise within a week, and clear after one to three months, whereas IgG antibodies emerge three to seven days after symptoms begin and persist for years, making them unsuitable for early diagnosis. Notably, some polymerase chain reaction-positive cases have been entirely asymptomatic, and viremia can precede symptoms. Differential diagnoses during the prodromal phase include influenza, COVID-19, viral and atypical pneumonias, yellow fever, dengue, leptospirosis, endocarditis with pulmonary edema, sepsis with acute respiratory distress syndrome, and arenavirus infections, underscoring the diagnostic challenge clinicians face.

Clinically, initial symptoms of hantavirus cardiopulmonary syndrome typically emerge one to eight weeks after exposure and include chills, fever, gastrointestinal upset, nausea, vomiting, diarrhea, headache, dizziness, and myalgia, before sudden progression to respiratory distress, hypotension, and shock. A recent systematic review and meta-analysis identified prognostic factors for severe outcomes, including female sex, age over 18, rural residence, pulmonary infiltrates on chest radiographs, underlying disease with elevated serum creatinine and hematocrit, and signs of bleeding. For patients with severe disease, extracorporeal membrane oxygenation can be life-saving; in experienced centers in the United States, Argentina, and Chile, ECMO-supported survival has ranged from approximately 60 to 75 percent. Timely administration of antipyretics, vasopressors, fluid therapy, mechanical ventilation, and renal replacement therapy, tailored to infection severity and organ involvement, remains the foundation of care.

On the pharmacological front, favipiravir is the most studied antiviral under consideration for Andes virus, though most safety and efficacy data derive from its use against other viral infections. A recently published case report described a 69-year-old man, diagnosed through screening after repatriation from the cruise ship, who received a combination of oral favipiravir, subcutaneous icatibant, intravenous then oral ribavirin, and oral baricitinib over a proposed 10-day course. The patient developed hypoxemia, hyponatremia, thrombocytopenia, and bilateral interstitial infiltrates roughly 24 hours after diagnosis, but recovered clinically, radiologically, and laboratory-wise from day two without progressing to shock or requiring vasopressors or invasive ventilation. Ribavirin and favipiravir were discontinued on days five and nine, respectively, after recurrent diarrhea and hyponatremia. The authors caution that a single favorable outcome cannot establish efficacy, and larger studies are required. Icatibant, a selective bradykinin B2 receptor antagonist, is hypothesized to alleviate bradykinin-driven vascular leakage, while the interleukin 6 receptor antagonist tocilizumab showed striking signals in a MEURI case series: five of five untreated ICU patients with Andes virus cardiopulmonary syndrome died, compared with four of five survivors among those receiving a single 8 mg/kg intravenous dose within 24 hours of admission. By contrast, a double-blind randomized trial in Chile found that high-dose intravenous methylprednisolone provided no significant clinical benefit in hantavirus cardiopulmonary syndrome, and monoclonal antibodies, molnupiravir, and baloxavir remain at earlier stages of investigation.

Vaccine development remains an empty pipeline in Western nations, with no approved hantavirus vaccine in the United States or Europe, although the inactivated Hantavax vaccine is used in Korea and China. A DNA vaccine targeting the Andes virus glycoprotein has completed Phase I testing: in a randomized controlled trial of 48 healthy adults, needle-free administration of 2 mg or 4 mg doses in three- or four-dose schedules was generally well tolerated, induced neutralizing antibodies, and achieved seropositivity rates of 67 to 90 percent by day 337, with only mild to moderate adverse events. Viral vector vaccines based on vesicular stomatitis virus and mRNA vaccines using both uridine and N1-methylpseudouridine platforms are in preclinical development, and recombinant human monoclonal antibodies JL16 and MIB22 have provided high levels of post-exposure protection in animal models by neutralizing viral glycoproteins. The review’s authors conclude that while the public health risk from the current outbreak remains low, the MV Hondius episode demonstrates that Andes virus could become a broader global concern, and they urge accelerated development of specific antivirals and vaccines, particularly mRNA platforms, alongside sustained vigilance in isolation, physical distancing, rodent control, and global cooperation to manage unpredictable outbreaks in the years ahead.

Subject of Research: Epidemiology, pathogenesis, and pharmacological management of the 2026 Andes virus outbreak linked to a cruise ship

Article Title: Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak

Article References: Ghasemiyeh, P., & Mohammadi-Samani, S. (2026). Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak. Virology Journal, 23(1), Article 208. https://doi.org/10.1186/s12985-026-03298-9

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03298-9

Keywords: Andes virus, hantavirus, hantavirus cardiopulmonary syndrome, MV Hondius, cruise ship outbreak, human-to-human transmission, favipiravir, tocilizumab, ECMO, DNA vaccine, mRNA vaccine, public health

At the molecular level, the circulating strain belongs to the family Orthomyxoviridae and carries a negative-sense, single-stranded, segmented RNA genome that encodes the structural and non-structural proteins required for its replication cycle. The two primary surface glycoproteins, hemagglutinin and neuraminidase, govern the critical steps of host cell attachment, viral entry, and release of progeny virions. Hemagglutinin binds to alpha-2,6-linked sialic acid receptors, which are abundantly expressed on human upper respiratory epithelial cells, anchoring the virus to its preferred portal of entry. Once attached, the virion is taken up by receptor-mediated endocytosis, and the low pH of the endosome triggers a conformational change in hemagglutinin that fuses the viral envelope with the endosomal membrane. This allows uncoating of the viral ribonucleoprotein complexes and their import into the host cell nucleus, where the viral RNA-dependent RNA polymerase executes replication and transcription. Neuraminidase then cleaves terminal sialic acid residues from the host cell surface, preventing newly formed virions from aggregating and permitting efficient budding and dissemination throughout the respiratory tract.

Environmental conditions in the National Capital Region play a decisive role in shaping transmission dynamics, and they differ sharply from the patterns seen in temperate climates. Rather than producing a single crisp winter peak, northern India experiences seasonal viral persistence predisposed by high ambient humidity, monsoon precipitation, and subsequent winter thermal inversions that trap polluted air close to the ground. High humidity and poor air circulation in enclosed spaces facilitate the stability and transport of fine micro-aerosols alongside the larger respiratory droplets generated by coughing, sneezing, and even vocalization. Indoor crowding during spells of inclement weather increases close-contact exposure, while contaminated environmental surfaces serve as secondary vectors for indirect mucosal self-inoculation when people touch their faces after contact with contaminated fomites. Following exposure, the virus exhibits an incubation period of roughly one to four days, a window during which asymptomatic or presymptomatic viral shedding can seed community transmission chains well before the first overt clinical presentation, complicating efforts to contain spread through symptom-based screening alone.

The clinical spectrum of A(H1N1) infection ranges from mild, uncomplicated upper respiratory illness to fulminant, life-threatening systemic disease. Typical uncomplicated cases present with abrupt-onset fever, non-productive cough, pharyngeal erythema, nasal congestion, severe retro-orbital or generalized headache, diffuse myalgia, and profound constitutional fatigue. Pediatric cohorts frequently show prominent gastrointestinal involvement, including nausea, vomiting, and diarrhea, layered on top of systemic febrile illness. In a subset of patients, viral tropism for the lower respiratory tract precipitates rapid tissue damage, characterized by necrotizing tracheobronchitis, diffuse alveolar damage, impaired gas exchange, and eventual acute respiratory distress syndrome. Viral destruction of the respiratory epithelium also strips away a critical innate barrier, leaving the lower airways highly vulnerable to secondary bacterial superinfections, most notably those caused by Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes. These bacterial complications historically account for a substantial share of influenza-related morbidity and mortality, which is why clinicians are urged to watch for clinical deterioration beyond the expected viral course.

Identifying high-risk populations is central to early intervention and rational allocation of scarce clinical resources. Pregnant women represent an exceptionally vulnerable cohort because physiological alterations in cell-mediated immunity, decreased chest wall compliance, and elevated maternal oxygen consumption collectively heighten the risk of rapid pulmonary decompensation. The extreme age groups face elevated danger as well: infants under five years experience heightened morbidity because of immature immune responses, while adults aged sixty-five and older are compromised by immunosenescence, the gradual decline of immune function with age. Individuals with underlying chronic comorbidities, including diabetes mellitus, chronic obstructive pulmonary disease, bronchial asthma, congestive heart failure, chronic renal insufficiency, hepatic dysfunction, neurological disorders, morbid obesity, and active immunosuppression, face significantly higher rates of hospitalization, intensive care unit admission, and death. For these groups, clinicians emphasize that even seemingly mild respiratory symptoms early in an influenza wave warrant a low threshold for testing and antiviral treatment.

Clinical monitoring during the surge must emphasize rapid detection of red-flag indicators that signal acute physiological deterioration. In adults, key warning signs requiring immediate emergency evaluation include progressive dyspnea, tachypnea, persistent central chest pressure, low peripheral oxygen saturation, central cyanosis, acute alteration of mental status, persistent high fever unresponsive to antipyretics, or a clinical relapse following transient symptom resolution. That last pattern, a biphasic worsening after apparent improvement, is particularly concerning because it often heralds secondary bacterial pneumonia. In pediatric patients, critical warning indicators include intercostal retractions, grunting, nasal flaring, lethargy, poor oral fluid intake leading to dehydration, persistent irritability, and breakthrough febrile seizures. Prompt recognition of these signs facilitates timely admission to higher-level care facilities capable of providing advanced respiratory support, including oxygen therapy and mechanical ventilation, which can be decisive in severe lower respiratory tract disease.

Definitive clinical management, the analysis stresses, relies on rigorous diagnostic testing and targeted pharmacological therapy rather than empirical broad-spectrum interventions. Reverse transcription-polymerase chain reaction remains the gold standard diagnostic technique for hospitalized or severe cases, enabling accurate differentiation of H1N1 from co-circulating respiratory pathogens such as SARS-CoV-2, respiratory syncytial virus, adenovirus, and bacterial pneumonia. This differential matters because treatment pathways diverge sharply: antivirals benefit influenza, whereas antibacterial agents are clinically ineffective against a primary viral pathogen and contravene global antimicrobial stewardship principles when used empirically. The authors are emphatic that antibiotics should be strictly reserved for cases with confirmed or highly suspected secondary bacterial co-infections, a discipline that protects both individual patients from unnecessary drug exposure and the broader community from accelerating antimicrobial resistance, an already serious problem in South Asian healthcare settings.

On the therapeutic front, neuraminidase inhibitors, particularly oral oseltamivir, form the cornerstone of antiviral therapy for patients with severe, progressive, or complicated disease, as well as for all high-risk individuals presenting with respiratory illness during the surge. Timing is critical: antiviral treatment provides optimal benefit when initiated within 48 hours of symptom onset, significantly dampening viral replication, shortening the duration of illness, and lowering the incidence of severe complications. Meta-analytic evidence from hospitalized H1N1pdm09 cohorts has linked early neuraminidase inhibitor use with reduced mortality, reinforcing the case for prompt empirical treatment of high-risk patients even before laboratory confirmation returns. Because the drug targets the neuraminidase protein rather than the hemagglutinin antigen that drifts seasonally, it retains activity against the A/Missouri/11/2025-like variant now circulating in India, providing a reliable pharmacological backstop while vaccination programs catch up.

Prevention, ultimately, remains the most cost-effective strategy, and the authors outline a comprehensive, layered framework. Annual seasonal influenza vaccination sits at its core, with the current vaccine exhibiting strong antigenic concordance with the circulating A(H1N1)pdm09 clade, a consequence of the World Health Organization’s strain selection for the 2025-2026 Northern Hemisphere season. Around that pharmacological anchor, the framework integrates non-pharmaceutical interventions: home isolation of symptomatic individuals, frequent hand hygiene, respiratory etiquette, enhanced indoor ventilation, and the use of well-fitted N95 respirators in high-density environments such as public transport, markets, and healthcare facilities. For a densely populated tropical and subtropical megaregion where monsoon humidity and winter thermal inversions prolong viral viability, these measures collectively reduce the effective reproduction number of the virus. The 2026 surge, the analysis concludes, is a reminder that seasonal influenza remains a formidable and recurring public health threat, but one whose trajectory can be substantially blunted by surveillance, vaccination, judicious antiviral use, and disciplined antimicrobial stewardship.

Subject of Research: The 2026 seasonal resurgence of influenza A(H1N1)pdm09 in India and evidence-based strategies for its prevention and clinical management

Article Title: H1N1 seasonal surge in India, 2026: Emerging public health threat and evidence based preventive strategies

Article References: Choudhary, O. P., & Choudhary, P. (2026). H1N1 seasonal surge in India, 2026: Emerging public health threat and evidence based preventive strategies. New Microbes and New Infections, 73, Article 101836. https://doi.org/10.1016/j.nmni.2026.101836

Image Credits: AI Generated

DOI: 10.1016/j.nmni.2026.101836

Keywords: H1N1, influenza A(H1N1)pdm09, India, Delhi-NCR, seasonal influenza, oseltamivir, neuraminidase inhibitors, influenza vaccination, RT-PCR, respiratory transmission, public health surveillance, antimicrobial stewardship

The team, based in Hungary and collaborating internationally, engineered the K1F bacteriophage, a T7-family virus that specifically infects Escherichia coli strains shielded by a K1 polysaccharide capsule, a feature associated with invasive, clinically dangerous E. coli such as those causing neonatal meningitis. Rather than relying on the classical strategy of reporter phages, which carry a transgene that the infected bacterium must transcribe and translate before any signal appears, the researchers exploited the sequence of ejection proteins that T7-like phages deliver into the host cytoplasm at the very start of infection. These intracapsid proteins, known as ICPs, are packed inside the viral head and are propelled into the bacterium in a defined order, where several of them refold to build the ejectosome, a tubular channel through which the viral genome passes.

The reporters in this system exploit the peculiar biochemistry of nanoluciferase, a small and intensely bright enzyme derived from the deep-sea shrimp Oplophorus gracilirostris. Nanoluciferase can be split into two fragments, a larger C-terminal piece and a smaller N-terminal piece, neither of which glows on its own. Crucially, when the fragments meet in solution in the presence of the substrate Furimazine, they spontaneously reassemble into an active enzyme that emits blue light. The researchers fused the small N-terminal fragment, abbreviated NnLuc, to two of the phage’s ICPs, gp6.7 and gp14, ensuring that the reporter fragment would travel inside the capsid, inert and sequestered, until the virus encountered a host it could infect.

Constructing such phages required careful genetic engineering. The team built donor plasmids carrying extra copies of the g6.7 or g14 genes fused in-frame to the NnLuc sequence and inserted these constructs into the K1F genome at a position previously shown to tolerate foreign DNA without instability. Recombinant phages were then selected using a CRISPR-Cas9 counter-selection system that cleaves the genomes of wild-type phages, allowing only the engineered versions to propagate. Phenotypic testing confirmed that the modified viruses grew to titres similar to wild type, with only a slight reduction in plaque size for one construct, indicating that the fusion proteins imposed minimal fitness costs on the viruses.

Initial experiments verified that the fusion proteins were indeed packaged into the phage heads and remained functional. When the researchers heat-treated the engineered phages to crack open the capsids and released their contents into a solution containing the purified C-terminal nanoluciferase fragment, the mixtures glowed brightly, confirming that the packaged NnLuc fusions could reconstitute active luciferase once liberated. Controls using wild-type phage, plasmid-free bacterial extracts, or intact capsids produced little or no signal, with one exception: intact K1Fe6.7::NnLuc particles produced a modest background glow, apparently due to soluble fusion protein contaminating the phage lysate, a problem the team believes can be solved with ultrafiltration purification.

The decisive experiments followed in living cells. When E. coli EV36, a K1-capsulated strain carrying a plasmid that expressed the C-terminal fragment, was challenged with either engineered phage, luminescence rose significantly above controls within minutes. In contrast, E. coli Nissle 1917, which expresses the reporter fragment but wears a non-cognate K5 capsule that the K1F phage cannot dock onto, produced no signal at all, demonstrating that phage binding and injection are strict prerequisites for light emission. Kinetic measurements showed the signal became statistically significant roughly seven minutes and fifty seconds after phage addition, and a more sensitive protocol detected a robust difference as early as five minutes and forty-five seconds after infection.

Those early time points matter because, in the T7 phage family, transcription and translation of late viral genes, including the g6.7 and g14 genes whose products were tagged, do not begin until at least seven to eight minutes after infection. Any luminescence detected before that window therefore cannot originate from the host expressing the reporter gene; it must come from proteins physically injected from the viral capsid. To seal the argument, the researchers treated infected cells with rifampicin, a transcription inhibitor, or tetracycline, a translation inhibitor. At six and a half minutes post-infection, the luminescent signal from cells infected with K1Fe14::NnLuc was completely unaffected by either inhibitor, while K1Fe6.7::NnLuc retained the majority of its signal, providing the first direct evidence that protein injection alone can betray a successful phage infection.

Of course, a diagnostic that only detects bacteria pre-engineered to express half of a luciferase would be of little practical use. To address this, the team built a model diagnostic system in which wild-type, unmodified bacteria are infected by the reporter phages and then supplied externally with column-purified C-terminal nanoluciferase along with the NanoGlo reagent, which contains the Furimazine substrate and a lysis agent that opens the bacterial envelope and allows the two fragments to meet. In this configuration, the cognate K1-capsulated strain generated signals two orders of magnitude brighter than in earlier experiments, and positive versus negative samples were clearly distinguished just three minutes after phage addition, the strongest evidence yet that the emitted light arises purely from injected protein.

Sensitivity testing revealed an important trade-off between speed and detection limit. When cell lysis occurred after only eight minutes of infection, relying solely on the injected enzyme fragments, roughly 690,000 cells per well, corresponding to about 23 million cells per milliliter, were required for reliable detection. Extending the infection to fifteen minutes, which allowed some de novo reporter production, and lengthening the luminescence incubation lowered the limit to 12,000 cells per well, roughly 3.5 million cells per milliliter. The authors note that reported bacterial concentrations in cerebrospinal fluid of children with E. coli K1 meningitis range from about 20,000 to 40 million cells per milliliter, with a mean near 200,000, meaning that even this unoptimized prototype already operates within a clinically relevant range.

The researchers envision the technology as the foundation of cheap, lateral-flow-style tests in which all reactive components, the dried C-terminal fragment, the substrate, and the engineered phage, are pre-loaded in a device, and the user supplies only the sample and moisture. Background noise could be further reduced by purifying phage lysates more stringently, deleting the wild-type copies of the ICP genes to load more reporter per capsid, or deploying the chemistry in microfluidic lab-on-a-chip devices that concentrate reactions into tiny volumes. In the longer term, combinatorial multichannel chips could classify bacteria by genus, species, and strain in sequence. Because phage binding directly reports viral sensitivity, the same platform could help physicians assemble personalized phage-therapy cocktails on the spot, potentially shrinking the turnaround of precision antibacterial treatment from hours to the few minutes that can decide outcomes in severe infection.

Subject of Research: Expression-free bacteriophage-based detection of target bacteria via conditional release of encapsidated reporter proteins

Article Title: Rapid, expression‐free bacteriophage‐based specific detection of target bacteria by conditional release of encapsidated reporter molecules

Article References: Avramucz, Á., Wheatley, J. P., Liyanagedera, S. B. W., Fehér, T., & Amaee, R. (2026). Rapid, expression‐free bacteriophage‐based specific detection of target bacteria by conditional release of encapsidated reporter molecules. Bioengineering & Translational Medicine, Article e70171. https://doi.org/10.1002/btm2.70171

Image Credits: AI Generated

DOI: 10.1002/btm2.70171

Keywords: bacteriophage, bacterial detection, nanoluciferase, diagnostics, K1F phage, E. coli, ejectosome, intracapsid proteins, biosensor, phage therapy, antimicrobial resistance, rapid testing

Strongyloides stercoralis is a soil-transmitted helminth that infects an estimated 300 to 600 million people worldwide, yet it remains notoriously difficult to diagnose because the parasite persists at low levels in the intestine and sheds larvae intermittently. What makes the infection clinically dangerous is its unique ability to complete its life cycle entirely within the human host through autoinfection, allowing the worm to survive for decades. In individuals whose immunity becomes suppressed, for example by corticosteroid therapy or other conditions, the parasite can multiply uncontrollably and cause hyperinfection syndrome, a frequently fatal complication. Understanding the immune landscape of chronic infection is therefore not merely an academic exercise; it is central to identifying who is at risk and how the disease can be detected earlier.

The research team enrolled 82 individuals with confirmed S. stercoralis infection and 48 uninfected controls living in the same endemic region of Khuzestan province, a design that allowed them to distinguish infection-specific immune changes from background environmental exposures common to both groups. All infected participants presented with eosinophilia, an elevated count of eosinophils, the white blood cells classically associated with defense against parasitic worms. To probe the immune response, the investigators developed in-house enzyme-linked immunosorbent assays to measure antibodies directed against Strongyloides antigens, together with bead-based multiplex assays capable of quantifying a broad panel of cytokines and chemokines in serum.

The antibody results were striking in their subclass specificity. Infected individuals showed significantly elevated Strongyloides-specific immunoglobulin G responses compared with endemic healthy controls, but this elevation was not uniform across all IgG classes. Instead, IgG4 and IgG1 emerged as the dominant subclasses, while IgG2 responses were minimal. This pattern is immunologically meaningful: IgG4 is the subclass most consistently induced by chronic helminth exposure and is often interpreted as a marker of prolonged, repeated antigenic stimulation under a regulatory immune environment. The prominence of IgG1 alongside it suggests a robust, active antibody response to the parasite rather than a purely dampened one, painting a picture of coexisting activation and regulation that is characteristic of long-term worm carriage.

The cytokine data reinforced this type 2 orientation. Infected participants displayed significantly increased serum concentrations of interleukin-4, interleukin-5, interleukin-13, and interleukin-9, the canonical cytokines produced by type 2 helper T cells and, in the case of IL-9, by the increasingly recognized type 9 lineage. IL-4 drives class switching toward IgG4 and IgE, IL-5 recruits and activates eosinophils, and IL-13 promotes mucus production and tissue remodeling at mucosal barriers, all mechanisms directly relevant to expelling intestinal worms. The elevation of IL-9 adds an interesting dimension, as this cytokine has been implicated in mast cell responses and barrier immunity, processes thought to contribute to controlling helminth establishment in the gut.

Perhaps the most unexpected finding concerned the chemokine CXCL9, an interferon-inducible chemokine typically associated with type 1 inflammatory responses and the recruitment of T cells and natural killer cells. The researchers recorded a striking increase in CXCL9 among infected subjects, standing in apparent contrast to the dominant type 2 profile. Meanwhile, the majority of Th1- and Th17-associated cytokines, along with several pro-inflammatory chemokines, were either reduced during infection or increased after treatment and parasite clearance. This suggests that S. stercoralis actively suppresses inflammatory pathways while leaving, or even provoking, a specific interferon-driven chemokine signal, a combination that may reflect the parasite’s strategy of securing long-term survival while the host retains enough immune pressure to keep worm numbers in check.

A longitudinal component of the study strengthened the causal interpretation of these immune signatures. Eighteen patients were reassessed at least six months after receiving albendazole, one of the standard anthelmintic drugs used against strongyloidiasis. Following treatment and presumed parasite clearance, the researchers documented significant reductions in eosinophil counts, parasite-specific IgG1, IgG2, and IgG4 levels, and serum concentrations of both IL-9 and IL-10, the latter being an immunoregulatory cytokine often elevated during chronic helminth infection. In contrast, systemic IL-4 concentrations increased after therapy, an intriguing reversal that the authors note alongside the broader normalization of the infection-associated immune profile. The parallel decline of antibodies, type 2 cytokines, and regulatory signals after cure indicates that these markers track active infection rather than permanent immune reprogramming.

The clinical implications of this work are considerable. Serological diagnosis of strongyloidiasis already relies heavily on detecting parasite-specific antibodies, and the demonstration that IgG4 and IgG1 dominate the response supports the use of subclass-specific assays to improve sensitivity and specificity, particularly in endemic regions where cross-reactivity with other helminths complicates interpretation. Moreover, the finding that antibody levels and type 2 and type 9 cytokines fall measurably after successful treatment raises the possibility of using these immune markers as indicators of cure, something parasitological methods alone have struggled to provide given the intermittent shedding of larvae. In an era of increasing immunosuppressive therapy worldwide, reliable tools to verify parasite elimination before immunosuppression could save lives.

The study also contributes to a broader scientific conversation about how helminths modulate human immunity. Chronic worm infections are widely studied for their immunoregulatory effects, which some researchers hope to harness for treating autoimmune and inflammatory diseases. By documenting, in a well-characterized human cohort, the coordinated suppression of Th1 and Th17 pathways alongside a preserved interferon-inducible chemokine response, the Iranian-German team provides a nuanced dataset that moves beyond the simple dichotomy of type 1 versus type 2 immunity. It shows that natural infection produces a layered and partially contradictory immune landscape whose resolution after treatment can now be followed over time.

Limitations remain, as with any field study conducted in an endemic setting. The number of longitudinally followed patients was modest, and the six-month follow-up window, while sufficient to observe significant immune changes, leaves open questions about the long-term durability of antibody and cytokine normalization. The endemic controls, though carefully selected, cannot fully exclude prior exposure or unrecognized low-level infection. Nevertheless, the study stands as a substantial advance for a disease that has long been overshadowed by better-known tropical parasites. For the millions of people carrying S. stercoralis, many of them unaware of their infection, this work brings the prospect of sharper diagnostics, clearer markers of therapeutic success, and a deeper understanding of the delicate immune equilibrium that this remarkable parasite has evolved to maintain within its human host.

Subject of Research: Immune response profiling in Strongyloides stercoralis infection

Article Title: Systemic profiles of Strongyloides-specific IgG subclass, cytokine, and chemokine response in an eosinophilic Iranian population infected with Strongyloides stercoralis

Article References: Beiromvand, M., Ashiri, A., Rafiei, A., Heepmann, L., Hartmann, W., Linnemann, L., Tappe, D., Veit, A., & Breloer, M. (2026). Systemic profiles of Strongyloides-specific IgG subclass, cytokine, and chemokine response in an eosinophilic Iranian population infected with Strongyloides stercoralis. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07683-9

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07683-9

Keywords: Strongyloides stercoralis, strongyloidiasis, IgG subclasses, cytokines, chemokines, eosinophils, type 2 immunity, albendazole, immunomodulation, Iran, neglected tropical disease, parasitic infection

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that thrives in the damaged tissue of severe burns, where the loss of the skin barrier and prolonged hospitalization create ideal conditions for colonization. The organism is intrinsically resistant to many antimicrobial classes and readily acquires further resistance, and its capacity to form biofilms—structured bacterial communities encased in a self-produced extracellular matrix—makes eradication exceptionally difficult. Biofilms shield cells from antibiotics and immune defenses, driving therapeutic failure and recurrence in burn units and intensive care settings worldwide.

To gauge the scale of the problem in their region, the team collected 75 non-duplicate clinical P. aeruginosa isolates from patients at educational hospitals in Hamedan, Iran, between October 2024 and March 2025. Forty-nine isolates came from burn wounds and 26 from respiratory samples. Using Kirby-Bauer disk diffusion testing interpreted against Clinical and Laboratory Standards Institute breakpoints, the researchers found resistance was highest for ceftazidime at 78.67 percent, imipenem at 72 percent, and gentamicin at 69.33 percent. Overall, 57 isolates, or 76 percent, met the internationally accepted definition of multidrug resistance, meaning non-susceptibility to at least one agent in three or more antimicrobial categories.

Biofilm formation proved nearly universal. Seventy-four of the 75 isolates, or 98.7 percent, produced biofilms in the crystal violet microtiter assay, and every multidrug-resistant isolate did so, with 37 of the 57 classified as strong producers. From the burn-wound collection, the investigators selected nine isolates for detailed analysis—seven multidrug-resistant and two non-multidrug-resistant—all of which showed strong or intermediate biofilm formation, alongside the reference strain PAO1 as a standardized comparator.

The compound under investigation, (5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl)(pyridin-2-yl)methanol, is a heterocyclic scaffold bearing a 3-methoxyphenyl substituent and a pyridin-2-yl methanol moiety, synthesized and characterized previously with purity above 95 percent confirmed by NMR. Against the nine selected burn isolates, the derivative yielded geometric mean minimum inhibitory and bactericidal concentrations of 20.54 and 41.21 micrograms per milliliter for planktonic cells. For biofilm-associated cells, the minimum biofilm inhibitory and eradication concentrations were 52.56 and 105.11 micrograms per milliliter, respectively. The higher eradication value reflects the well-known tolerance of mature biofilms, whose extracellular matrix limits drug penetration and access to embedded cells.

Checkerboard microdilution assays then tested whether the oxadiazole could potentiate gentamicin, an aminoglycoside protein synthesis inhibitor, and imipenem, a broad-spectrum carbapenem. Against planktonic cells, the gentamicin combination produced geometric mean fractional inhibitory and bactericidal concentration indices of 0.54 and 0.50, while the imipenem combination yielded 0.72 and 0.62. Against biofilm cells, the corresponding fractional biofilm indices ranged from 0.55 to 0.62, indicating similar gains in antibiofilm activity. Full synergy, defined as an index below 0.5, was observed in three of the nine isolates, with most others showing partial synergy, and no antagonism was detected in any combination.

The most mechanistically revealing results came from gene expression analysis. When the researchers exposed PAO1 and two clinical isolates to sub-inhibitory concentrations of the oxadiazole, quantitative real-time PCR revealed significant, concentration-dependent downregulation of two biofilm-associated genes: lasR, the master transcriptional regulator of the quorum-sensing system that coordinates virulence factor production and biofilm maturation, and algD, which encodes GDP-mannose dehydrogenase, the key enzyme in alginate biosynthesis that determines biofilm matrix thickness and stability. Log2 fold changes reached as low as minus 4.12 for both genes, with regression analysis showing strong concentration-response relationships and coefficients of determination between 0.888 and 0.969.

Because these transcriptional changes occurred at concentrations below the biofilm-inhibitory endpoint, the authors interpret them as evidence that the compound interferes with the regulatory machinery of biofilm formation rather than simply killing cells. They caution, however, that reduced gene expression alone does not establish a definitive molecular mechanism, since changes in viability or broader transcriptional responses could contribute, and that exopolysaccharide production and quorum-sensing signal levels were not directly measured in this study. Plausible mechanisms proposed for oxadiazoles elsewhere include disruption of bacterial membrane integrity, inhibition of essential enzymatic pathways, interference with nucleic acid synthesis, and altered permeability that enhances antibiotic uptake.

The dose-reduction implications are clinically significant. In previous work by the same group, the compound showed no significant cytotoxicity at concentrations up to 15.62 micrograms per milliliter, with an estimated IC50 range of 15.62 to 31.25 micrograms per milliliter. Combining the oxadiazole with gentamicin or imipenem lowered the fractional concentrations needed for antibacterial and antibiofilm effects, potentially allowing the compound to operate within its non-cytotoxic range while restoring activity to antibiotics against which the isolates had substantial resistance. The authors emphasize that the findings support the derivative as a promising adjunctive or alternative strategy for biofilm-related multidrug-resistant P. aeruginosa infections in burn patients, but that translation requires pharmacokinetic profiling, stable formulations, direct cytotoxicity testing of the combinations, and rigorous in vivo efficacy and toxicity studies in animal burn-infection models before clinical use can be considered.

Subject of Research: Antibacterial and antibiofilm activity of a 1,3,4-oxadiazole derivative against multidrug-resistant Pseudomonas aeruginosa from burn wound infections

Article Title: Antibacterial and antibiofilm properties of 1,3,4-oxadiazoles against multidrug-resistant Pseudomonas aeruginosa isolated from burn infections – an in vitro study

Article References: Nazari, M., Majzoobi, M. M., Alikhani, M. Y., & Imani Fooladi, A. A. (2026). Antibacterial and antibiofilm properties of 1,3,4-oxadiazoles against multidrug-resistant Pseudomonas aeruginosa isolated from burn infections – an in vitro study. International Microbiology. https://doi.org/10.1007/s10123-026-00890-5

Image Credits: AI Generated

DOI: 10.1007/s10123-026-00890-5

Keywords: Pseudomonas aeruginosa, burn wound infection, multidrug resistance, biofilm, 1,3,4-oxadiazole, lasR, algD, quorum sensing, synergistic therapy, gentamicin, imipenem, antimicrobial resistance