Major Outbreaks Research Articles

Analytical and clinical evaluation of a duplex RT-qPCR assay for the detection and identification of o’nyong-nyong and chikungunya virus

The mosquito-borne alphavirus o’nyong-nyong virus (ONNV) has proven its potential to cause major human outbreaks. On the African continent, ONNV causes unspecific febrile illness and co-circulates with the close relative chikungunya virus (CHIKV). The true scale of ONNV burden is poorly understood in Africa, because of the scarce availability of molecular in-house and commercial assays, strong cross-reactivity between ONNV and CHIKV in serological assays and a lack of surveillance. We designed a new RT-qPCR assay targeting the E1 gene for the detection of ONNV that can be used in monoplex or in duplex format, combined with a previously published CHIKV monoplex assay targeting the nsp1. The lower limit of detection with 95% positivity rate was determined to be <10 RNA copies/µL in monoplex and duplex format for both ONNV and CHIKV. Both monoplex assays and the duplex assay proved to be linear within the tested range of approximately 108 to 102 RNA copies/µl, and showed 100% specificity against a wide panel of arbovirus supernatants as well as several other pathogens in clinical samples. Testing of CHIKV positive serum and ONNV spiked plasma samples confirmed the suitability of the assays in a clinical setting. The new assays provide a robust tool for molecular ONNV as well as ONNV/CHIKV simultaneous detection and may contribute to clarify the true burden of the two viruses, to improve arbovirus surveillance and to strengthen epidemics preparedness in Africa.

Australian Culex annulirostris mosquitoes are competent vectors for Japanese encephalitis virus genotype IV

Japanese encephalitis virus (JEV) is transmitted by Culex species of mosquitoes. In 2022, JEV belonging to a previously unrecognised lineage of genotype IV (GIV) caused a major outbreak of JE in South-eastern Australia, resulting in human cases and affecting piggeries. Cx. annulirostris has previously been implicated as the major vector of JEV in northern Australia where the virus has circulated since its first detection in 1995. Here, we showed that experimental infection of a laboratory colony of Australian Cx. annulirostris with the isolate JEV NSW/22 resulted in a 100% mosquito infection rate, with 87% of mosquito saliva samples testing positive by RT-qPCR at 14 days post-infection. Immunohistochemistry confirmed the presence of a replicating virus in the mosquito midgut and dissemination throughout the body, including the salivary glands. Our results also showed evidence of transovarial transmission of this virus; however, transstadial transmission from the eggs to the adult stage was not found. Comparison with an Indonesian isolate of GIV JEV and previous Australian isolates belonging to genotypes I and II showed that infection with JEV NSW/22 resulted in higher viral titres in the early stage of infection and higher proportions of mosquitoes with JEV-positive saliva, indicating a greater transmission potential compared to other isolates. This study provides compelling experimental evidence that Australian Cx. annulirostris is a highly efficient vector for the 2022 Australian JEV GIV outbreak strain.

An Immunoinformatic Approach for Identifying and Designing Conserved Multi-Epitope Vaccines for Coronaviruses

Background/Objectives: The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. Methods: This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. Results: A total of 132 epitopes were identified, with the majority of them found to be conserved across the bat CoVs, pangolin CoVs, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. Conclusions: In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses.

A Descriptive Comparison of the Epidemiological Characteristics of Delta and Omicron Variant-Driven Outbreaks in Bhutan

SARS-CoV-2 rapidly mutated, causing different waves of outbreaks worldwide. Bhutan experienced three major outbreaks of COVID-19 before experiencing the outbreak driven by the Omicron variant in January 2022. The data collected by the National Outbreak Investigation and Surveillance Team during the Delta variant-driven outbreak and Omicron outbreak were accessed and analyzed. The data were analyzed using R statistical software. Descriptive analysis was carried out for the entire dataset and the statistical comparison between the two outbreaks was carried out using student’s t-test and Pearson’s chi-square test. During the Delta variant-driven outbreak, a total of 1648 cases were reported, with a daily average of 13 cases. The highest one-day case number reported was 99. On the contrary, within 33 days, a total of 3788 cases were reported with a daily average of 115 cases during the Omicron outbreak. The highest one-day case number reported was 312. The median incubation period was 3 days (range = 0–18 days) and 1 day (range = 0–14 days) during the Delta and Omicron-driven outbreaks, respectively. The number of symptomatic cases was significantly higher during the Delta outbreak (p-value &lt; 0.0001). Of the total cases reported during the Delta outbreak, 1175 (71.3%) had received a single dose of the vaccine, 79 (5%) received two doses, while 394 (24%) were unvaccinated. During the Omicron outbreak, 1957 (52%) cases had received their booster (third dose), 904 (23.8%) received two doses and only 40 (1%) received a single dose of the vaccine. The number of unvaccinated cases was 887 (23.4%), of which 375 (10%) were children below 12 years. Our findings corroborate the enhanced transmissibility of the Omicron variant as reported elsewhere. We report significantly less symptomatic cases during the Omicron outbreak. Further, our data show that the incubation period for the Omicron variant is shorter compared to the Delta variant (p-value &lt; 0.0001).

A novel spatio-temporal prediction model of epidemic spread integrating cellular automata with agent-based modeling

Since 2019, major infectious disease outbreaks have placed tremendous pressure on global public health systems, triggering extensive research on the predictive modeling of infectious diseases. Cellular Automaton (CA) is primarily used in the spatial prediction of infectious diseases to establish a model to for simulating the interaction between different regions and the infection risk to simulate the transmission process of the disease and predict its development trend. However, CA models are governed by initial fixed rules and local interactions, and often fail to capture the complex dynamics of epidemic transmission, which are influenced by factors such as public behavior and government intervention. In view of these limitations, we propose a factorial simulation model for the spatial spread of epidemics, the CA-ABM, which divides agents into three categories–public, government, and hospital agents–to comprehensively express the macro factors that affect the development of epidemics. Agent-Based Modeling (ABM) influences the transition rules of the CA through agent choices, constraints and supporting behaviors. Focusing on the COVID-19 pandemic in mainland China from February 6 to March 20, 2020, we simulate its spread. The results showed an average improvement of 8.4 % in prediction accuracy, with few errors, RMSE under 200, and R2 values over 0.9 in most provinces, demonstrating strong macro-scale stability. This approach helps regions to understand influencing factors and enables targeted infection risk assessment and prevention. In addition, scenario analysis based on CA-ABM model changes epidemic decision-making from “prediction-response” to “scenario-response” and provides theoretical reference for future epidemic management.

Emerging mosquito-borne flaviviruses.

Flaviviruses comprise a genus of enveloped, positive-sense, single-stranded RNA viruses typically transmitted between susceptible and permissive hosts by arthropod vectors. Established flavivirus threats include dengue viruses (DENV), yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), which continue to cause over 400 million infections annually and are significant global health and economic burdens. Additionally, numerous closely related but largely understudied viruses circulate in animals and can conceivably emerge in human populations. Previous flaviviruses that were recognized to have this potential include ZIKV and WNV, which only became extensively studied after causing major outbreaks in humans. More than 50 species exist within the flavivirus genus, which can be further classified as mosquito-borne, tick-borne, insect-specific, or with no known vector. Historically, many of these flaviviruses originated in Africa and have mainly affected tropical and subtropical regions due to the ecological niche of mosquitoes. However, climate change, as well as vector and host migration, has contributed to geographical expansion, thereby posing a potential risk to global populations. For the purposes of this minireview, we focus on the mosquito-borne subgroup and highlight viruses that cause significant pathology or lethality in at least one animal species and/or have demonstrated an ability to infect humans. We discuss current knowledge of these viruses, existing animal models to study their pathogenesis, and potential future directions. Emerging viruses discussed include Usutu virus (USUV), Wesselsbron virus (WSLV), Spondweni virus (SPOV), Ilheus virus (ILHV), Rocio virus (ROCV), Murray Valley encephalitis virus (MVEV), and Alfuy virus (ALFV).

Analysis of Memory Antibody Responses in Individuals with Zika-Associated Guillain–Barré Syndrome

The Zika virus (ZIKV) was responsible for a major outbreak in 2015 in the Americas. Infections were associated with increased cases of microcephaly in infants and Guillain–Barré Syndrome (GBS) in adults. Our group previously demonstrated that Zika-associated GBS correlated with the increased neutralization of ZIKV and DENV2, but the antibody specificity was not analyzed. Here, we generated reporter virus particles (RVPs) of ZIKV with specific-point mutations that allowed us to investigate the specificity of circulating plasma antibodies at two different timepoints from individuals with Zika-associated GBS. We found that neutralizing antibody titers to ZIKV waned between one and two years post-ZIKV infection in GBS-negative but not GBS-positive individuals. Interestingly, plasma neutralization by GBS-negative individuals was more sensitive to a mutation at position N154A than plasma from GBS-positive individuals. To determine if waning was associated with different levels of B-cell activation at the time of infection, pro-inflammatory cytokines were measured, but no differences were observed in people with or without GBS. These data suggest subtle differences between GBS-positive and-negative individuals’ circulating antibodies, where antibodies from GBS-positive individuals may target different epitopes and remain in circulation longer as compared to GBS-negative individuals.

Iatrogenic botulism after intragastric botulinum neurotoxin injections – a major outbreak

BackgroundIntragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI.MethodsWe retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany.ResultsSeven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits.ConclusionOur study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

Burnout in Infection Control Practitioners During Public Health Crisis Events: A Mixed Methods Systematic Review Protocol

Background Infection prevention and control work environments are highly complex in nature and have long been associated with crisis events including serious infectious disease outbreaks. The role of infection control practitioners shifted exponentially during the COVID-19 pandemic and with this rapid and nebulous change came anxiety, emotional exhaustion and ultimately burnout. Burnout at work generally occurs as a response to chronic and prolonged exposure to emotionally challenging events, causing emotional exhaustion, feelings of cynicism, and lack of accomplishment at work. This systematic review aims to investigate burnout in infection control practitioners during public health crisis events (major outbreaks, epidemics, and pandemics) in upper-middle and high-income countries on a global scale. Methods A mixed-methods systematic review will be carried out and will include qualitative, quantitative and primary mixed-methods studies that investigate the different elements of burnout, during public health crisis events. After an initial scoping literature search, up to six databases will be searched for studies on burnout in relation to infection prevention practitioners. Study quality will be checked using standardised JBI critical appraisal tools. The proposed review will follow the JBI convergent integrated approach for mixed methods systematic reviews. Following data extraction, quantitative data will then be converted into ‘qualitized data’ in the form of textual descriptions. Discussion It is well documented that adverse conditions during public health crisis events can lead to burnout. This systematic review will investigate of burnout in infection control practitioners in upper-middle and high-income countries during public health crisis events. The findings will inform healthcare professionals, senior policy makers and researchers and will help contribute to a richer understanding of burnout and associated factors in infection control practitioners. Protocol registration number PROSPERO 2024 CRD42024508996.

Analysis of the interrelationship between precipitation and confirmed dengue cases in the city of Recife (Brazil) covering climate and public health information.

Large-scale epidemics of arboviruses, such as dengue, have heightened societal awareness regarding the necessity of combating the primary transmission vectors. Equally critical is the identification of environmental conditions and variables that influence vector population dynamics. Aedes aegypti, the primary vector of arboviruses such as dengue and Zika in Brazil, is closely associated with the climatic and geographical conditions of urban environments. This study examines the relationship between precipitation and confirmed dengue cases in Recife (Brazil), employing regression and quantile analyses to evaluate the influence of meteorological conditions on the disease's spread. The findings reveal a direct correlation between monthly averages of precipitation and confirmed cases, although this is apparent only when excluding years of epidemic peaks. The highest number of cases generally aligns with the rainy season, and the lowest with the dry season, with weak, moderate and strong precipitation events being closely linked to increased dengue incidence. However, notable discrepancies were identified: four out of six major outbreaks occurred in drier months, challenging the assumption of a straightforward relationship between rainfall and dengue incidence. These findings underscore the multifaceted nature of dengue dynamics, suggesting that while precipitation plays a significant role, other factors, including serotype circulation and broader climatic phenomena, are equally critical in driving outbreaks. This complexity highlights the need for a more comprehensive understanding of the mechanisms influencing dengue epidemics.

Optimalisasi Kandungan Al-Qur’an Dalam Menghadapi Wabah Penyakit

This article is the result of research based on the current reality regarding the handling of disease outbreaks, and linking it to the verses of the Qur'an. In the Qur'an, disease outbreaks are mentioned several times, which shows the potential for science that can be explored to be applied in the present era. Since early 2019, the world has been hit by a major outbreak caused by a small creature called a virus. Coronavirus Disease (COVID-19) has become a major threat that has an impact on life without discrimination; anyone is at risk of contracting this infectious disease. The COVID-19 outbreak was first detected in Wuhan City, China, at the end of 2019 and has spread to almost 200 countries around the world, including Indonesia. The Qur'an is a source of knowledge that contains various aspects of life, such as history, health, and exemplary behavior. Methods for dealing with various problems can also be taken from the information contained in the Qur'an. Therefore, as Muslims, we have an obligation to explore and understand how the knowledge contained in the Qur'an can be implemented in the current context.

Determining the New Norm Elements in Emergency Departments in Malaysia During a Pandemic: A Fuzzy Delphi Method.

Emergency departments (EDs) have had to cope with various pandemics, such as HIN1, Ebola and the currently ongoing COVID-19. This study aimed to determine the elements of the new norm that has introduced changes into healthcare systems, particularly EDs, during the COVID-19 pandemic and to obtain consensus from the experts, the Emergency physicians in EDs across Malaysia. No previous study has been conducted on this topic. This study used the fuzzy Delphi method (FDM) to acquire expert consensus. There were two phases in this study. The first involved extracting the elements to be assessed by the selected experts from a literature review. Three major domains were considered: infrastructure, governance and human resources. A total of 35 items were identified and divided into the three domains. In the second phase, the selected items were sent to a group of 15 ED physicians, who were asked to rate the items on a Likert-type scale. The data were then analysed using FDM. A total of 35 items were identified as possible new norms from a literature search for the three domains (governance, infrastructure and human resources). The first step of the FDM analysis showed that 9 out of the 35 items did not fulfil the initial requirement of the FDM, since the threshold value (d) must be lower than 0.2 (d </ 0.2). In meeting the second condition for the FDM, 25 out of the 35 items had an expert consensus of > 75%. Regarding the third requirement for FDM, only 1 out of the 35 items did not meet the criteria of an average fuzzy number (A value) of > 0.5. Finally, 25 items fulfilled all three requirements of FDM, so these were retained and the remaining 10 items were discarded. The FDM used in this study had identified 25 items achieved the required level of agreement by the chosen experts. The results of this study can be used to guide EDs in Malaysia to utilise the new norms items in mitigating major outbreak affecting the ED services.

A protocol for a living mapping review of global research funding for infectious diseases with a pandemic potential - Pandemic PACT.

The COVID CIRCLE initiative Research Project Tracker by UKCDR and GloPID-R and associated living mapping review (LMR) showed the importance of sharing and analysing data on research at the point of funding to improve coordination during a pandemic. This approach can also help with research preparedness for outbreaks and hence our new programme the Pandemic Preparedness: Analytical Capacity and Funding Tracking Programme (Pandemic PACT) has been established. The LMR described in this protocol builds on the previous UKCDR and GloPID-R COVID-19 Research Project database with addition of the priority diseases from the WHO Blueprint list plus initial additions of pandemic influenza, mpox and plague. We capture data on new funding commitments directly from funders and map these against a core ontology (aligned to existing research roadmaps). We will analyse regularly collated new research funding commitments to provide an open, accessible, near-real-time overview of the funding landscape for a wide range of infectious disease and pandemic preparedness research and assess gaps. The periodicity of updates will be increased in the event of a major outbreak. We anticipate that this LMR and the associated online tool will be a useful resource for funders, policy makers and researchers. In the future, our work will inform a more coordinated approach to research funding by providing evidence and data, including identification of gaps in funding allocation with a particular focus on low- and middle-income countries.

Global Health Security in Vision Care: Health Systems Strengthening During Ebola Virus Disease Outbreak Responses.

During the last decade, global health security has been threatened by major Ebola virus disease outbreaks in Western Africa (2014 to 2016) and in eastern Democratic Republic of the Congo (2018 to 2020). Particularly in Western Africa, the outbreak initially overwhelmed health care capacity in already fragile health systems. Thousands of survivors were at risk of newly recognized postacute ocular complications, and their need for urgent ophthalmic care challenged national vision health systems with scarce eye care services. In these unprecedently large outbreaks with implications for global health security, agile eye care responses were challenging, including in regard to decision coordination and requisite logistical needs. In this report, we detail vision care initiatives implemented in response to these outbreaks and highlight the need to include vision care as a critical component of the response to infectious disease outbreaks with eye health implications.

Unexpected Delayed Incursion of Highly Pathogenic Avian Influenza H5N1 (Clade 2.3.4.4b) Into the Antarctic Region.

The current highly pathogenic avian influenza H5N1 panzootic is having substantial impacts on wild birds and marine mammals. Following major and widespread outbreaks in South America, an incursion to Antarctica occurred late in the austral summer of 2023/2024 and was confined to the region of the Antarctic Peninsula. To infer potential underlying processes, we compiled H5N1 surveillance data from Antarctica and sub-Antarctic Islands prior to the first confirmed cases.

A scoping review of cultural issues concerning institutional quarantine and isolation during major multi‐country outbreaks in Africa: 2000–2023

AbstractBackground and AimsInfectious disease outbreaks pose significant challenges in Africa due to its ecology, socioeconomic conditions, and weak health systems. Implementing institutional quarantine and isolation (Q&amp;I) measures is crucial for managing major outbreaks. However, the cultural context often determines the success of these measures. This scoping review aims to examine existing evidence on the cultural aspects of institutional Q&amp;I in Africa over the past two decades, focusing on the COVID‐19 pandemic and other major multi‐country disease outbreaks.MethodsThis scoping review's protocol was registered with the Open Science Framework registry. Nine research databases were systematically searched to retrieve all relevant literature, followed by deduplication and a two‐stage screening process using the Rayyan web application. The inclusion of any literature into this review was based on a set of eligibility criteria. Also, manual searching of the reference lists of included literature was done to retrieve any other eligible literature. From the included literature, data were charted, collected, and summarized.FindingsOut of the 787 articles retrieved from the database searches, this review found only one to be eligible for inclusion. Also, no other eligible article was obtained after manual searching of the reference list for this article. The reviewed article presented empirical findings on the impact of COVID‐19 Q&amp;I protocols on traditional burial rites in Ghana. Many Ghanaian families were against their country's protocol because they felt it was insensitive to their traditional values and burial practices. Also, the way the protocol was implemented made some Ghanaian families feel that foreign burial practices were imposed on them, which bred feelings of cultural exclusion and neglect (by the government) among Ghanaians.ConclusionResearch evidence on the cultural implications of Q&amp;I in Africa is very scanty. More research is needed on this topic of public health interest.

Wide circulation of type 1 vaccine-derived poliovirus strains in clinical specimens from suspected cases of poliomyelitis, their contacts and in wastewater in Madagascar since late 2020

Madagascar has faced three major outbreaks of vaccine-derived polioviruses (VDPVs) in recent decades, with VDPV type 1 reemerging in late 2020. Here, we report the molecular characterization of these cVDPV1 strains. WHO protocols were used for poliovirus detection in stool and wastewater samples. Molecular genotyping was based on the 5′ non-coding (5′NC), VP1, and 3Dpol regions. From 2020 to 2022, 92 of 5690 stool samples and 129 of 1046 wastewater samples tested positive for cVDPV1. Genetic analysis of the VP1 gene revealed 1.3%–6.1% variability compared to the Sabin strain. Most sequences showed mutations at neurovirulence attenuation sites. Phylogenetic analysis distributed strains into four genogroups originating from Southern Madagascar. All analyzed cVDPV1 strains were recombinant, containing mutated oral polio vaccine sequences in VP1 and type C enterovirus sequences in other regions. This study demonstrated that all strains were closely related during this epidemic.

Effects of public concerns on favorable attitudes to pandemic containment policies: a two-wave panel survey study in Hong Kong.

Regions worldwide experienced uncontrolled COVID-19 outbreaks at different times, leading to increased health concerns yet decreased support for stringent containment measures. We aimed to understand this contradiction by examining the factors influencing attitudes toward COVID-19 containment policies in Hong Kong. Using two waves of panel data collected before and after the 2022 major outbreak N = 1148), we determined that concerns over politicization and economic implications, rather than health concerns, led to a decline in favorable attitudes. The study also revealed that political stance moderated the effect of politicization but not economic concern. Based on these findings, we offer several suggestions for public health institutions to improve public favorability: Institutions should undertake sustained efforts to reduce the politicization of containment policies. Providing economic support measures and detailed explanations to the public can help mitigate concerns. Additionally, institutions should respond more promptly to the public's economic concerns during health crises.

Evaluation of Etest and MICRONAUT-AM Assay for Antifungal Susceptibility Testing of Candida auris: Underestimation of Fluconazole Resistance by MICRONAUT-AM and Overestimation of Amphotericin B Resistance by Etest.

Multidrug-resistant Candida auris has recently caused major outbreaks in healthcare facilities. Rapid and accurate antifungal susceptibility testing (AST) of C. auris is crucial for proper management of invasive infections. The Commercial Sensititre Yeast One and Vitek 2 methods underestimate or overestimate the resistance of C. auris to fluconazole and amphotericin B (AMB). This study evaluated the AST results of C. auris against fluconazole and AMB by gradient-MIC-strip (Etest) and broth microdilution-based MICRONAUT-AM-EUCAST (MCN-AM) assays. Clinical C. auris isolates (n = 121) identified by phenotypic and molecular methods were tested. Essential agreement (EA, ±1 two-fold dilution) between the two methods and categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints were determined. Fluconazole resistance-associated mutations were detected by PCR-sequencing of ERG11. All isolates identified as C. auris belonged to South Asian clade I and contained the ERG11 Y132F or K143R mutation. The Etest-MCN-AM EA was poor (33%) for fluconazole and moderate (76%) for AMB. The CA for fluconazole was higher (94.2%, 7 discrepancies) than for AMB (91.7%, 10 discrepancies). Discrepancies were reduced when an MCN-AM upper-limit value of 4 µg/mL for fluconazole-susceptible C. auris and an Etest upper-limit value of 8 µg/mL for the wild type for AMB were used. Our data show that resistance to fluconazole was underestimated by MCN-AM, while resistance to AMB was overestimated by Etest when using the CDC's tentative resistance breakpoints of ≥32 µg/mL for fluconazole and ≥2 µg/mL for AMB. Method-specific resistance breakpoints should be devised for accurate AST of clinical C. auris isolates for proper patient management.

Epidemiology and molecular evolution of GI.1 sapovirus in the recent era.

Sapovirus (SaV) infection is increasing worldwide. Herein, we provided evidence of a significant increase in SaV infection in Japan during 2010-2022, primarily due to the considerable (p = 0.0003) rise of the GI.1 genotype. Furthermore, we found that all major and minor SaV outbreaks in Japan, including the largest SaV outbreak in 2021-2022, were caused by the GI.1 genotype. Therefore, to get insight into the underlying molecular mechanism behind this rising trend of the SaV GI.1 type, we selected 15 SaV GI.1 outbreak strains for complete genome analysis through next-generation sequencing. Phylogenetically, our strains remained clustered in different branches in lineages I and II among the GI.1 genotype. We showed all amino acid (aa) substitutions in different open reading frames (ORFs) in these strains. Importantly, we have demonstrated that the strains involved in the largest SaV outbreak in Japan in 2021-2022 belonged to lineage II and possessed the third ORF. We have identified some unique aa mutations in these major outbreak strains in the NS1 and NS6-NS7 regions that are thought to be associated with viral pathogenicity, cell tropism, and epidemiological competence. Thus, in addition to enriching the database of SaV's complete sequences, this study provides insights into its important mutations.