The STING allele R71H-G230A-R293Q (HAQ) was positively selected in Anatomically Modern Humans (AMH) during the Out of Africa (OoA) migration. Here, we show that 51.61% of Native Americans (NAM) are HAQ/HAQ , while only 6.45% are WT/WT. HAQ individuals are defective in DNA-induced type I IFNs responses, such as smallpox-induced IFNα production. 82.3% of NAM carry the HAQ allele, which helps explain the post-Columbus NAM population collapse from the smallpox epidemic. Similarly, in 12 sub-groups of Sub-Saharan Africans, we found 0% HAQ/HAQ , indicating ongoing negative selection reflecting Sub-Saharan Africa as the world's heaviest infectious-disease regions. To understand the positive selection of HAQ in non-Africans, we dephased HAQ haplotypes in 74 sub-populations worldwide, over ~4,000 individuals. We found that the HAQ allele evolved faster than the neutral H232 STING allele and had more generations during the OoA migration, increasing its frequency in non-Africans. A mouse model of HAQ housed in a Specific Pathogen-Free mouse facility generates more surviving pups than the H232 mice. In summary, the HAQ allele was positively selected during OoA migration but is negatively selected in Sub-Saharan Africa, underscoring its essential role in AMH adaptation to diverse environments.

Half a century after smallpox eradication, this feat has not been repeated, although there is hope for the Guinea worm. This article examines whether two uncommon genital ulcerative diseases, donovanosis and chancroid, should be targeted for eradication. Many think that their decline has been such that they might be heading towards spontaneous eradication, following more effective treatments, integration of sexually transmitted infection management in primary healthcare, enhanced condom use by sex workers and promotion of male circumcision. However, examples of syphilis and mpox suggest spontaneous eradication may be a fallacy.Donovanosis occurs sporadically in several countries, especially India. In other formerly endemic nations (eg, Papua New Guinea and the Papua region of Indonesia), the current epidemiological situation is unclear. Worldwide incidence might be a few hundred cases annually, perhaps a thousand. The availability of effective interventions, relatively easy clinical diagnosis, adequate laboratory tests and the absence of animal reservoirs suggest that eradication could be achieved through enhanced surveillance and a stronger contact tracing system with presumptive treatment of all sexual contacts, including sex workers.Chancroid's current annual caseload is unknown but likely in the hundreds of thousands of cases globally. Prior to eradication activities, a first phase should document its status in all previously endemic countries using molecular tests on patients presenting with genital ulcers in sentinel clinics. Additional research should investigate whether Haemophilus ducreyi in skin ulcers can cause genital infections. Chancroid is strongly associated with sex work: this is the tap that must be turned off. Where it remains endemic, sex workers' services should be supported to treat symptomatic cases, enhance condom use and deliver periodic presumptive treatment with azithromycin.Given their overlapping geographic distribution and the preponderant role of sex workers in transmission dynamics, an eradication programme could address both diseases simultaneously, with the same personnel.

The poxviruses are large, epitheliotropic, double-stranded DNA viruses that are pathogens of invertebrates and the mammalian, avian and reptilian vertebrate taxa including the familiar poxviruses of humans and domestic animals such as the variola virus or smallpox virus and the related vaccinia virus used for the live smallpox vaccine, mpox virus (formerly monkeypox virus), cowpox virus of rodents, and orf virus of sheep and goats. Poxviruses have also previously been described from teleost fishes including the common carp Cyprinus carpio, ayu Plecoglossus altivelis, Atlantic salmon Salmo salar, Atlantic cod Gadus morhua, red or Japanese seabream Pagrus major, and black bullhead Ameiurus melas. This report documents a novel poxvirus infection in a captive population of the endangered Knysna seahorse Hippocampus capensis. Histopathological examination revealed an epidermal keratinocytic dermatopathy with hypertrophy and subsequent progressive degeneration and necrosis of the affected cells; karyomegaly with a prominent nucleolus was also a feature of the affected cells. Ultrastructural examination of the affected keratinocytes revealed large and complex, intracytoplasmic virions with elliptical to discoid profiles and an average size of 548.5 nm (SD = 100.58) by 205.65 nm (SD = 21.19) consistent with a typical poxvirus morphology. Furthermore, metagenomic analysis revealed distinct genomic features, whereas phylogenetic analysis of nine core poxvirus genes demonstrated that the seahorse poxvirus forms a unique branch within the teleost poxvirus clade supporting its classification as a novel poxvirus with a proposed species name of Syngnathid cutaneouspox virus. Finally, this study confirms the utility of next-generation sequencing as a methodology for obtaining phylogenetically useful genomic sequences from archival formalin-fixed paraffin-embedded tissues.

Knowledge sharing in medical education is a continuous exchange of skills and expertise between scientists. Paediatric virology is a rapidly developing, new scientific field of medicine, which enhances multidisciplinary, expertise knowledge sharing between paediatric health professionals and scientists of different subspecialties. The present review discusses the recent core topics in paediatric viral infectious diseases discussed during the 11th Workshop on Paediatric Virology organised by the Institute of Paediatric Virology and presents its key messages, including: i) The history of smallpox vaccination; ii) the role of viral co-infections triggering invasive bacterial diseases; iii) the surge of invasive group A streptococcal disease during the post-coronavirus disease 2019 (COVID-19) era; iv) foetal brain imaging findings in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; v) the diabetogenic role of Coxsackie viruses in childhood; vi) adenovirus-related central nervous system manifestations in the paediatric population; vii) new challenges and opportunities of hepatis D virus infection in children; viii) the Swedish up-to-date human papillomavirus vaccination experience in childhood.

As measles resurges globally, we face an important strategic choice. Large outbreaks reflect declining vaccination coverage, inequities in health services access, conflict, population displacement, vaccine hesitancy, and inadequate investment in immunization programs. However, measles is more than a vaccine-preventable disease. Because of its extraordinary transmissibility, it functions both as a tracer of weaknesses in immunization systems and public health infrastructure, and as a potential tugboat for strengthening them.The Immunization Agenda 2030 highlights strong immunization systems, equitable service delivery, and effective surveillance as foundations for controlling vaccine-preventable diseases. Bill Foege, a leader of smallpox eradication, argued that measles eradication could reduce health inequalities while acting as a "tugboat" that pulls stronger immunization systems into place. This perspective is increasingly relevant. The capacities required for measles eradication, including high routine immunization coverage, sensitive surveillance, quality laboratory networks, rapid outbreak response, community engagement, and political accountability, are also fundamental to resilient health systems and preparedness for future pandemics.Rather than competing with health-system strengthening, measles eradication can accelerate it. The current resurgence should be viewed not only as a warning signal of system fragility but also as an opportunity to strengthen immunization systems, advance health equity, and renew commitment to global eradication.

Monkeypox virus (MPXV) has garnered global attention in recent years. MPXV is a DNA virus that is categorized as belonging to the Orthopoxvirus, exhibiting close genetic and structural similarities to variola virus (VARV) and vaccinia virus (VACV). Despite the World Health Organization (WHO) announcing in 2023 that the global outbreak of monkeypox (mpox) is no longer a public health emergency, the new occurrence reported in most regions shows the urgency of the development of medicines for mpox. In this review, we reviewed a huge amount of literature on mpox, summarizing its development, scientific findings, and trustworthy data when it comes to viral structure, binding targets, treatments, and intervention strategies. Because no antiviral agents have been formally authorized by the US Food and Drug Administration (FDA) or the WHO for the targeted treatment of mpox, coupled with the limited effectiveness demonstrated by current antiviral medications in clinical evaluations, the progressive emergence of drug resistance, and the ongoing threat posed by novel viral variants, the advancement of new antiviral therapeutics for mpox has emerged as an urgent priority within the domain of global public health. The purpose is to explore measures, therapy techniques, and the medication development process for mpox, including vaccines, antibodies, chemicals, natural drug monomers, traditional Chinese medicines (TCM), and Chinese herbal formulations. Also, it clearly differentiates the progress of approved drugs, preclinical candidate compounds, and computer-predicted molecules in the development of therapeutics for mpox. It is beneficial to comprehend MPXV's research basis, improve the understanding of preventive measures and treatment methods, and promote medical and healthcare services.

Monkeypox virus (MPXV) is a zoonotic virus endemic to Africa that has recently re-emerged, becoming the first orthopoxvirus with sustained human-to-human transmission since smallpox eradication. The 2022 global epidemic of MPXV was caused by Clade IIb virus (lineage B.1) that derived from the lineage A endemic to West Africa through APOBEC3 microevolution[1-3]. Here, comparison of lineage B.1 virus with its closest earlier A.1 ancestor reveals that despite only 46 nucleotide differences, lineage B.1 has attenuating phenotypic changes. Both viruses replicated equivalently in cell culture, but B.1 had defects in long-range spread, which mapped to APOBEC3 mutation E353K in OPG057 (F13L). MPXV B.1 was also defective in innate immune control, inducing higher IFNβ and innate immune signalling gene expression, and showing reduced capacity to suppress interleukin-1β-mediated responses, which mapped to APOBEC3 mutation R48C in OPG047 (F3L). Finally, MPXV B.1 had reduced virulence in a mouse model of MPXV infection relative to the ancestral A.1 strain. Our work demonstrates that the 2022 global outbreak MPXV was intrinsically attenuated, with attenuating mutations that are absent in concurrent, more severe clade IIb outbreaks. Our data also reveal that APOBEC3 editing is a mechanism of MPXV phenotypic variation, potentially contributing to clade evolution and competition.

The recent spread of human monkeypox (mpox) beyond Africa has attracted global attention. Although mpox is a DNA virus with relatively lower pandemic potential, and smallpox vaccines and therapeutics may offer protection, the distinct clinical features observed in the current outbreak highlight the need for novel antiviral drugs. Here, we developed a drug repurposing workflow based on interspecies protein analysis and advanced virtual screening, integrating pre- and post-docking processes. After screening 6,074 approved or clinical-stage drugs against viral DNA topoisomerase, we expanded the analysis to viral DNA polymerase, increasing the compound library to 11,484 molecules, including approved or clinical-stage drugs and DNA polymerase inhibitors from ChEMBL. To assess dynamic stability, we performed molecular dynamics (MD) simulations and quantified protein-ligand contact occupancy, distinguishing stably bound candidates from transient docking poses. The MD and convolutional neural-network (GNINA) scoring analyses converged on vindesine for DNA topoisomerase and LY2090314 for DNA polymerase. Importantly, the workflow was applied to targets with distinct prior information, including a structurally characterized DNA polymerase supported by homologue inhibitor data and a less-characterized DNA topoisomerase requiring homology modelling. These results illustrate an adaptable repurposing pipeline for prioritizing therapeutic candidates against emerging infectious diseases, although experimental validation remains required.

In recent years, mpox has emerged as a significant global public health threat. The widespread distribution of the virus, coupled with the legacy of historical smallpox vaccination, has underscored the critical need to serologically distinguish between natural mpox infection and vaccine-induced humoral immune responses. However, the high antigenic similarity among Orthopoxvirus species leads to the production of cross-reactive antibodies, limiting the differentiation capacity of conventional serological assays. This mini-review evaluates current serological approaches aimed at discriminating between mpox infection and vaccine-induced immunity. Specifically, we analyze multiplexed immunoassays, comparative ratios based on orthologous antigens, machine learning-supported serological models, peptide-based platforms, and recombinant protein-based enzyme-linked immunosorbent assay (ELISA) methods. The findings of this review indicate that multiplex immunoassays, orthologous antigen ratio-based approaches, and machine learning algorithms exhibit the highest discriminatory potential for distinguishing natural mpox infection from vaccine-induced immune responses. In addition, MPXV A27L and ATI-N-CPXV antigens may be considered promising candidates for serological differentiation, although their performance requires further investigation.

Guinea worm disease is approaching eradication, with only 10 human cases reported worldwide in 2025, the lowest annual total recorded. Yet the final phase of eradication presents complex clinical and public health challenges that differ from earlier stages of control. Persistent animal infections, particularly in dogs, civil conflict, fragile health systems, financing disruptions, and the need for prolonged surveillance threaten progress at the point when global attention may wane. Unlike smallpox, Guinea worm has been driven to near-eradication without a vaccine, curative drug, or rapid diagnostic test, relying instead on safe water, filtration, vector control, case containment, community education, reporting incentives, and sustained field operations. This Perspective argues that eradication remains achievable but requires a specific policy agenda: protected financing for surveillance, animal-source transmission control, safe-water measures, operational access, and certification through 2030. Completing the final mile would represent a permanent preventive achievement and a durable victory for neglected populations too often overlooked.