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We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread. The SARS-CoV-2 Delta variant has spread rapidly worldwide. Here, the authors characterise a single chain of transmission of Delta in China, and find evidence that it is more infectious and replicates faster during early infection compared to early pandemic lineages.

Defining the immune dynamics of Japanese encephalitis (JE) in healthy individuals is crucial for assessing population susceptibility and evaluating the effectiveness of vaccinations. We conducted a cross-sectional serological survey of anti-JEV IgG antibodies and anti-JEV neutralizing antibodies (nAbs) in Guangzhou City, Zhanjiang City and Heyuan City of Guangdong Province, China. A total of 691 participants were included from 2018-2022, among whom 50 were dengue IgG antibody positive and 641 were dengue IgG antibody negative. In the total population, the anti-JEV IgG antibody positivity rate detected by enzyme-linked immunosorbent assay (ELISA) was 51.37% (95% CI: 47.64-55.11%), and the neutralizing antibody positivity rate detected using the microneutralization test (MNT) was 73.22% (95% CI: 69.92-76.54%). Among the 641 dengue IgG antibody-negative subjects, the anti-JEV IgG antibody positivity rate by ELISA and the neutralizing antibody positivity rate by MNT were 48.05% (95% CI: 44.17-51.93%) and 72.07% (95% CI: 68.59-74.56%), respectively. Comparable geographical seroprevalences of either anti-JEV IgG or neutralizing antibody were observed in Guangzhou City, Heyuan City and Zhanjiang City, respectively (49.52% vs. 48.04% vs. 47.45%, 65.71% vs. 70.46% vs. 76.47%, respectively). Antibody positivity rates in all age groups exhibited a U-shaped curve, with the lowest rate occurring in the 7-18-year-old age group. With respect to the vaccine dose, the anti-JEV nAb positivity rate and geometric mean titer (GMT) detected by MNT were higher in those who received two doses of live attenuated vaccine than in those who received one dose or 0 doses (80.57% vs. 55.81% vs. 55.09% and 25.92 vs. 12.19 vs. 16.47, respectively). In the 641 dengue IgG antibody-negative subjects, moderate consistency between the MNT and ELISA results was observed (Kappa = 0.47, rs = 0.76). The high seroprevalence in participants indicated a neglected transmission of JE, which highlights the importance of strengthening the surveillance of JEV in this area. The vaccination program against JEV is highly needed because of immune gaps in adults, e.g., boosters for adults aged 7-39 years.

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.

Hirschsprung-associated enterocolitis (HAEC) is one of the most severe complications in patients with Hirschsprung's disease (HSCR). Previous research has indicated that acetylcholine (ACH) plays an anti-inflammatory role during inflammation by acting on the α7 nicotinic acetylcholine receptor(α7nAchR) to promote the secretion of anti-inflammatory factors. However, the specific role of ACH in HAEC remains unclear. This experiment aims to explore the sources of ACH in HSCR and its anti-inflammatory mechanisms, thereby identifying new directions for the prevention and treatment of HAEC. We analyzed single-cell transcriptome data from HSCR to identify cells that secrete ACH and observed their distribution using immunofluorescence. In mice, F4/80, iNOS, ARG-1 and CD206 were used to identify and locate M1 and M2 macrophages in different intestinal segments. Western blot, reverse transcription-quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay were used to test the levels of IκBα, tumor necrosis factor-α, interleukin-10, and the macrophage activation pathway proteins JAK2 and STAT3 in different intestinal segments of mice. Organoid and cell culture techniques were used to verify the anti-inflammatory mechanism of ACH models. scRNA-seq analysis revealed that tuft cells expressed the CHAT protein. In HSCR, aganglionic segments exhibited heightened cholinergic activity compared with dilated ganglionic segments. In HAEC, inflammation was mainly concentrated in the dilated ganglionic segment and was associated with an increase in M1 macrophages, whereas the aganglionic segment showed less inflammation and was associated with an increase in M2 macrophages. Furthermore, experiments showed that intestinal organoids containing tuft cells promoted an increase in M2 macrophage markers, and ACH promoted M2 macrophage polarization. Differences in inflammation among various intestinal segments in HAEC may be linked to ACH secreted by tuft cells. Drugs targeting tuft cells have the potential to become important components of HAEC treatment in the future.

Background From 2022 to 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by Omicron variants spread rapidly in Guangdong Province, resulting in over 80% of the population being infected. Results To investigate the levels of neutralizing antibodies (NAbs) in individuals following the rapid pandemic and to evaluate the cross-protection against currently circulating variants of SARS-CoV-2 in China, neutralization assay and magnetic particle chemiluminescence method were used to test the 117 serum samples from individuals who had recovered 4 weeks post-infection. The results indicated that the levels of NAbs against prototype and Omicron variants BA.5 were significantly higher than those against Omicron variants BQ.1, XBB.1.1, XBB.1.9, XBB.1.16 and EG.5, regardless of whether the infection was primary or secondary. Conclusions The cross-protection provided by NAbs induced by prototype and Omicron BA.5 variants was limited when challenged by BQ.1, XBB.1.1, XBB.1.9, XBB.1.16 and EG.5 variants. This indicates that we should pay more attention to the risk of multiple infection from any novel Omicron variants that may emerge in the near future.

Purpose This study aims to identify independent risk factors for mixed urinary incontinence (MUI) in parous women using a multicenter epidemiological study and to establish and validate a predictive nomogram. Methods A large-scale survey was conducted from June 2022 to September 2023, including parous women aged over 20 selected through stratified random sampling. Data encompassed sociodemographic and obstetric histories, comorbidities, and standardized questionnaires. The primary goal was to identify high-risk factors for MUI, while the secondary was to develop a nomogram. Risk factors were determined using univariable and multivariable analyses. The nomogram's performance was assessed via concordance index (C-index) and calibration plots through internal and external validation. Results A total of 7709 women participated, with an MUI prevalence of 6.8%. Independent risk factors included higher body mass index, urban residence, postmenopausal status, multiple vaginal deliveries, history of pelvic surgery and macrosomia, family history of pelvic floor dysfunction, hypertension, and constipation. The area under the curve for the nomogram model was 0.717 in the training set, 0.714 for internal validation, and 0.725 for external validation. The calibration plots showed a good agreement between the predicted and observed outcomes. Conclusion This study identifies key risk factors for MUI in parous women and introduces a validated nomogram with high but not perfect predictive accuracy. The model enables early identification and management of MUI, though further refinement could enhance accuracy.

Background: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in Guangdong Province, measuring Anti-Nm IgG with serogroups A, C, Y, and W, and analyzed the trends using a generalized additive model (GAM). Results: During 2019–2022, 7752 participants were included. The overall antibody positivity rate for serogroups A, C, Y, and W were 60.75%, 15.51%, 32.83%, and 14.56%, respectively. High Anti-Nm IgG was in children aged 0–5 and 5–10 years old. Geometric mean concentrations (GMCs) of Anti-Nm IgG were higher and correlated positively with vaccine doses compared with unvaccinated individuals. The GMC showed a consistent decrease trend in the vaccinated and a U-shaped curve in populations. The declined rates of GMC were 1.59 (95% CI: 1.03, 2.14) µg/mL, 1.65 (95% CI: 1.28, 2.03), 0.62 (95% CI: 0.22, 1.03), and 0.31 (95% CI: 0.08, 0.53) µg/mL per year for serogroups A, C, Y, and W, respectively. Conclusions: There were differences in antibody positivity rate and GMC for the four serogroups of ECM in the healthy individuals of Guangdong Province, with serogroup A showing the highest, and the demographic differences highlighted the high seroprevalence of Neisseria meningitidis in younger people. The variable prevalence rates among serogroups A, C, Y, and W and the observed decline in antibody titers underscore the need for adjustments in the immunization program targeting the meningococcal vaccine.

Guangdong is a hyperepidemic area of dengue, which has over 0.72 million cumulative cases within the last four decades, accounting for more than 90% of cases in China. The local epidemic of dengue in Guangdong is suspected to be triggered by imported cases and results in consequent seasonal transmission. However, the comprehensive epidemiological characteristics of dengue in Guangdong are still unclear. The epidemiology, seroprevalence, molecular evolution of dengue virus, and the development of policies and strategies on the prevention and control of dengue were analyzed in Guangdong, China from 1978 to 2017. Seasonal transmission of dengue virus in Guangdong, China was mainly sustained from July to October of each year. August to September was the highest risk period of local dengue outbreaks. Most of the dengue cases in Guangdong were young and middle-aged adults. Five hundred and three fatal cases were recorded, which declined within the last two decades ( = 10). The serological test of healthy donors' serum samples showed a positive rate of 5.77%. Dengue virus 1-4 (DENV 1-4) was detected in Guangdong from 1978 to 2017. DENV 1 was the dominant serotype of dengue outbreaks from 1978 to 2017, with an increasing tendency of DENV 2 since 2010. Local outbreaks of DENV 3 were rare. DENV 4 was only encountered in imported cases in Guangdong, China. The imported cases were the main source of outbreaks of DENV 1-2. Early detection, management of dengue cases, and precise vector control were the key strategies for local dengue prevention and control in Guangdong, China. Dengue has not become an endemic arboviral disease in Guangdong, China. Early detection, case management, and implementation of precise control strategies are key findings for preventing local dengue transmission, which may serve for countries still struggling to combat imported dengue in the west pacific areas.

Vaccination is the key to prevent varicella zoster virus (VZV) infection in children. Voluntary and self-funded strategies have led to variable vaccination rates against VZV in China. For low-income populations, in particular, the effects of VZV vaccination have been insufficiently estimated. Community-based serosurveillance was conducted in two less developed regions, Zhanjiang and Heyuan, of Guangdong, China. Anti-VZV IgG antibodies in serum were detected by ELISA. The vaccination data were derived from the Guangdong Immune Planning Information System. A total of 4221 participants were involved, of which 3377 were from three counties of Zhanjiang and the other 844 were from one county of Heyuan, Guangdong, China. The total VZV IgG seropositivity rate in vaccinated individuals was 34.30% and 42.76%, while it was 89.61% and 91.62% in non-vaccinated populations of Zhanjiang and Heyuan, respectively. The seropositivity rate increased gradually with age, reaching ~90% in the >20- to 30-year-old group. The VarV vaccination rates of children aged 1–14 years were 60.47% for one dose and 6.20% for two doses in Zhanjiang, and 52.24% for one dose and 4.48% for two doses in Heyuan. Compared with the non-vaccinated group (31.19%) and one-dose group (35.47%), the positivity rate of anti-VZV IgG antibodies was significantly higher in the two-dose group (67.86%). Before the VarV policy was reformed, the anti-VZV IgG positivity rate was 27.85% in the one-dose-vaccinated participants, which increased to 30.43% after October 2017. The high seroprevalence in participants was due to infection of VZV in Zhanjiang and Heyuan, not vaccination against VZV. Children aged 0–5 years are still vulnerable to varicella, so a two-dose vaccination program should be implemented to prevent onward transmission of VZV.